- Email: [email protected]
Comparison of isoproterenol and isoproterenol-phenylephrine aerosols
ALLERGY VOL 43, NO.
ABSTRACTS JANUARY,
1
Editor-in-chief MURRAY Brooklyn,
M. ALBERT. N. Y.
M.D.
Editorial
board
EUGENE Bridgeport,
LVALZER Conn.
BERNARD Brooklyn,
HAROLD Cleveland,
FRIEDMAN Ohio
ELOISE KAILIN Washington, D. C.
MONROE Stamford,
COLEMAN Conn.
Associate KATHERINE Brooklyn,
editors NATHAN Brooklyn,
BOWMAN N. P.
BERTRAM Tyler, Texas DAVID Spring
SIEGEL N. P.
I TSU CHAO Brooklyn, N.
KAHN
STEIN Valley,
N.
1VEISS N. P.
ROBERT Brooklyn,
P.
Y.
SPIELMAN N. Y.
JAMES RUBIN New York City
ROBERT FENTON Fort Worth, Texas
JEROME SHAPIRO Santa Clara, Calif.
NEIL GOLDMAN Ossining, N. P.
Consultant MATTHEW Brooklyn,
From The
editor N.
the Jewish
%VALZER Y.
Allergy Hospital
Division and
of Medical
Center
of Brooklyn
1972
2 Abstracts
J. ALLERGY
CLIN. IMMUNOL. JANUARY 1972
Announcement rlllergy Abstracts has been published since 1936 by members of the Allergy Division of The Jewish Hospital and Medical Center of Brooklyn. The Editorial Board is comprised mainly of former residents of this department who contribute their services. Nergy ilbstracts selects and abstracts those articles in the literature which may be of clinical or theoretical interest to workers in the field of allergy. Each abstract represents a summary of the author’s findings and views, and its inclusion in Allergy ABstructs does not imply approval of its contents by the Editor. The Editor
lmmunakgy Tumor immunity: Tumor spocitkdiy stimulakd
s-ion lymp)loeyter.
in vivo
products of B. H., Istin, M., and Masen,
initkhd
Dvarchik,
by
solubk
T. H.: Science 172: 3984, 1971. may be obtained from the superA macrophage migration inhibition factor (MIF) natant fluid when sensitized lymphocytes are challenged in vitro with specific antigen. This and causes delayed hypersensitivity-like aupernatant fluid is cytotoxic and leukotaxic reactions when injected intradermally. Primary hepatomas were induced in inbred guinea pigs, and the ascites cells were harvested and injected into intradermal sites on age-matched animals of the same strain. Other syngenic animals were immunized with Y. tubero~Zosti in Freund’s adjuvant, their lymph node cells were collected, cultured, and challenged with purified protein derivative (PPD), and MIF was prepared from the resulting supernates. The MIF was purified by gel filtration on Sephadex and polyacrylamide gel. This MIF was then injected intradermally into strain-mate guinea pigs, and the ensuing reactions were. shown histologically t.o be of the delayed tuberculin type with typical mononuclear cell accumulation. Further, the MIF-containing supernate, when injected intradermally together with the hepatoma cells, prevented tumor growth at the injection sites. Tumor growth inhibition was specific for the site treated with MIF, but sites inoculated with tumor cells alone and remote from the tumor cell-MIF-treated intradermal areas showed adequate tumor cell replication and tumor growth. The authors then injected tumor cells into sites that had been treated with MIF 24 hours previously and observed that, as long as the MIF-induced delayed reaction was still in progress, tumor inhibition persisted. This MIF-induced tumor rejection reaction is caused by host factors rather than MIF. D. 8.
Immunocompetent
cells
omang
mow*
thymwyW:
A m&nor
pap&Won.
Leck-
band, E., and Boyse, E. A. : Science 172: 3989,1971. Thymocytic cells have a reduced ability to cause the graft versus host reaction (QVHR) when compared to lymph node cells. It may be postulated that QVH activity harbored by
VOLUME NUMGER
43 1
Abstracts
3
thymic cells is probably caused by the presence of a subpopulation of cells with GVH activity comparable to that of lymphocytes. The authors prepared thymic and lymph node cell suspensions from two groups of mice, one whose thymocytes carried TL antigens (TL+), and the second whose thymocytes were devoid of TL antigen (TL-) . Newborn F,, TL mice were inoculated with either TLt or TLthymocytes, or lymphocytes, respectively, and GVHR was determined by the method of Simonsen. It was thus shown that 75 times more thymocytes than lymphocytes were needed to induce GVHR. Further, the thymocytes from TL+ mice may be divided into a major population of TL+- bearing cells, and a smaller group of TLcells. Treatment of TL+ thymocyte cell population with anti-TL antiserum and complement results in survival of 12 per cent of the cells. These survivors, when injected into F, newborn mice, caused a degree of GVHR similar to that observed in mice inoculated with antibody untreated TL+ thymocytes, and control mice inoculated with antibody complement TL- thymocytes showed GVHR similar to that in the previous two experimental groups. When 95 per cent of the TLt thymocytes were killed by an anti-H-2b antibody with complement, the GVHR could be abolished. The authors were able to exclude the possib.ility that blood lymphocytes mere responsible for the experimental observations and also excluded the possibility of thymic entrapment of immunologically competent cells. It is concluded that the immunocompetent (TL-) thymoeytcs are derived within the thymus gland proper and that the GVH reactivity lies in the TLcell subpopulation, that is, cells which have lost their TL antigenieity by a process of maturation. D. S.
Anergy
and
recovery
in
a child
stage I Hodgkin’s disease. Starling, D. J. : J. Pediatr. 79: 666, 1971.
with
South, M. A., and Fernbach,
K. A.,
A 4-year-old boy with Hodgkin’s disease had negative skin test responses to mumps, streptokinase-streptodornase antigen (SKSD), Candida, and Trichophyton before radiotherapy was initiated. Challenge tests with dinitrofluorobenzene (DNFB) were also negative. There was no evidence of rejection of a skin autograft or of a graft received from another patient. His lymphocytes were not stimulated by phytohemagglutinin. While receiving radiotherapy, the patient developed meningoencephalitis with the subsequent appearance of mumps antibody in the serum. The titer of the mumps antibody was 1:64 8 months later. Tests for delayed hypersensitivity were repeated 9 months after the diagnosis of Hodgkin’s disease was made. Positive responses were obtained with the mumps, SKSD, and DNFB. A new homograft was rejected in 13 days. There was a moderate response of the patient’s lymphocytes to phytohemagglutinin at this time. When the patient’s condition deteriorated, his reactions to mumps and Candida antigens became negative. There was a poor response of the lymphocytes to phytohemagglutinin stimulation, and he failed to reject a new skin graft. The changing status of this patient’s immunologic deficiencies supports the hypothesis that the immune defect is a result rather than a cause of Hodgkin’s disease. N. w.
Variation
and
homology
in the
mu
and
gamma
heavy
chains
of
human
immuno-
Shimizu, A., Paul, C., Kohler, H., Shinoda, T., and Putnam, F. W. : Science 173: 3997, 1971.
globulins.
The authors analyzed the specific antigen-combining site on a segment of a human macroglobulin molecule (Faba) consisting of the light chain with the disulfide linkage to the terminal -NH, of the mu (h) heavy chain (the Fdp piece) and determined the amino acid sequence of 213 residues within the Fd segment on the M chain, the first 40 residues on the Fca region and the last 88 residues of the -COOH terminus of the Fe segment. A comparison was made with similar portions of the IgG molecule, and it was found that the variable regions
4
J. ALLERGY
Abstracts
CLIN. IMMUNOL. JANUARY 1972
of human p and y- 1H chains have more amino acid sequence homology th:ui do the coustant regions. The IgM precedes the appearance of IgG in neonates and during the immune response, Imt both antibodies are probably derived from a single primitive immune globulin. Not enough information is as yet availnble t.o prove whether LgM preceded IgG in evolution. However, it may be concluded from the amino acid and disulfide bond mapping t.hat the p on~l yl hear? chains diverged in evolution soou after the separntion of H and L chain genes.
Clinical use of rabbit antihuman lymphocyte globulin in cadaver kidney tranrplantation. Mannick, J. A., Davis, R. C., Cooperband, S. R., Glasgow, A. H.,
Williams, L. F., Harrington, J. T., Cavallo, T., Schmitt, G. W., Idelson, B. A., Olsson, C. A., and Nabseth, 1). C. : N. Engl. J. Med. 284: 1109, 1971. Rabbit antihuman antilymphocyte globulin (ALG) was given to 26 recipients of czadaver kidney transplants who also received conventional immunosuppressive therapy with aeathioprinc and prednisone and local radiotherapy to the transplant. The first group of 10 patients wns followed for one to 2 years, while the second group of 16 patients was observed for at least 4 months. The results of HL-A typing were not used in donor selection, although 4 patients in the first group and 11 in t.hc second group had 1) matches by serotyping. An ALG dose of approximately 100 mg. was given to an average adult in the early post,trnnsplant period. ALG administration was well tolerated. Trnnsplnnted kidneys were removed from one patient in the first group nnd 2 patients in the second group because of hyperncut,e rejection caused by preformed antibodies. Eight patients (4 in each group) showed evidence of acute rejection, but these episodes were promptly reversed by increase in the steroid dosage. In the first group, 2 patients showed histologic changes on one-year renal biopsy, consistent with moderately severe chronic rejection. One of these patient.s and 7 other patients had satisfactory renal function at the end of one year. Profound lymphopenia appenred within 6 hours of the first ALG injection and persisted for 4 to 6 weeks in most reeipcnts. Thrre were no consistent changes seen in serum immunoglobulin levels or complement. Among the 26 patients, there were 2 deaths (one in each group) associated with infection. The authors conclude that rabbit ALG is well tolerated and effective in reducing the frequency and severity of acute transplant rejections.
J. 8.
Systemic and local immunological with antilymphocyte serum.
activity
of lymph-node
Smith, J. J., III, Proc. Sot. Exp. Biol. Med. 137: 388, 1971..
Hilgard,
cells from mice treated H. R., and Sell, K. IV. :
The immunosuppressive action of antilymphocyte serum (ALS) resulting in prolonged survival of allografts and suppression of the graft. versus host react,ion has been demonstrated. It has been postnlated that immunosuppression in such cases is associated with nn inhibition of migration of ALS-exposed lymphoid cells to the sites where they may 1.x immunologically active. Rabbit antimouse lymphocyte serum (RAMLS) or normal rabbit sera (NRS) was injected intraperitoneally in t.wo groups of mice. A third group received neither preparation. Skin allografts were applied to all three groups with median survival times for these grafts of 9.6, 9.8, and 28.5 days for the untreated, NRS-treated, and RAMLS-treated mice, respectively. The immunosuppressive action of the RAMLS was also demonstrated by a significant decrease in the ability of lymph node cells obtained from RAMLS-treated mice to produce splenomegaly after these cells were injected intraperitoneally into young mice when compared to the erect of the injection of lymph node cells obtained from untreated or NRS-treated mice. However, local reactivity of lymph node cells obtained from RAMLS-treated mice was demonstrated when x-irradiated hamsters were injected intradermally with these cells.
VOLUME NUMBER
This treated locally.
43 1
Abstracts
investigation mice display
indicated suppressed
that, although immunocompetence
lymph
node cells systemically,
5
obtained from RAMLSthese cells are reactive A’. a.
Quantitation
of
immunoglobulins
in
gastric
juice
by
electroimmunodiffusion.
McClelland, D. B. L., Finlayson, N. D. C., Samson, R. R., Nairn, I. Shearman, D. J. C. : Gastroenterology 60: 509, 1971.
M.,
and
Immunoglobulins in gastric juice fro.m 65 achlorhydric patients, 4 normal volunteers, and one achlorhydric hypogammaglobulinemic patient were quantitated by radial immunodiff’usion ‘r: stimulation was used to obtain specirncns. and electroimmunodiffusion techniques. Pontagastri Thirty samples of achlorhydric gastric juice were examined by the two techniques. Problems encountered with the radial immunodiffusion method but not with electroimmunodiffusion were lack of sensitivity for immunoglobulin levels below 10 mg. per 100 ml., inaccuracies in reading plates, and nonspecific precipitates. The levels of immunoglobulins were similar as measured by both techniques. Immunoglobulins were not detected in gastric juice of the hypogammaglobulinemic patient, while in aehlorhydric patients, IgA and IgG levels each ranged from 10 to 200 mg. per 100 ml. (most were in 20 to 100 mg. per 100 ml. range) and IgM levels were 0 to 35 mg. per 100 ml. In the volunteers, measurements were performed on gastric juice either aspirated at 5 minute intervals and then brought to pH 7 to 7.5 by 5 per cent sodium bicarbonate or on gastric juice neutralized intragastrically by continuous infusion of sodium bicarbonate to maintain pH of aspirates between 7 and 7.5. Immunoglobulins were not detected by the extragastric neutralization methods but were found to be in the same ranges as those of achlorhydric patients when the gastric aspirates were neutralized intragastrically. The authors conclude that immunoglobulins may be detected in gastric juice of all but hypogammaglobulinemic patients and that the electroimmunodiffusion method of quantitating these immunoglobulins has advantages over the radial immunodiffusion technique. J. As.
Subtle
immunologic cephalitis.
abnormalities
in four
boys
with
subacute
sclerosing
panen-
Gerson, K. L., and Haslam, R. H. A.: N. Engl. J. Med. 285: 78,
1971. Immunologic studies were performed on 4 boys with proved subacute sclerosing panencephalitis (SSPE) following rubeola infection or vaccination. One patient had an absence of serum IgA, and 2 had deficient serum IgA. Each patient was given a booster dose of diphtheria-tetanus toxoid subcutaneously into the right thigh, and a right inguinal lymph node was examined 5 days later. The serum antibody response was normal. In the lymph nodes, germinal centers were rare and small, and there was an increased concentration of lymphocytes of inflammatory response with the use of in the cortex and paracortical zone. An evaluation Rebuck skin window showed normal cellular response. Delayed reactions following intradermal skin testing with Candida alhicnns, streptokinase-streptodornase, and live measles vaccine were absent or greatly decreased. In addition, the patients failed to develop contact sensitivity after application of 2 mg. of 2,4-dinitrochlorobenzene (DNCB). Full-thickness grafts from nonrelated donors were rejected after a moderately prolonged rejection time by the eighteenth to twenty-seventh day. Lymphocyte stimulation was measured by the uptake of tritiated thymidine after a 5 day incubation period with measles and Candida antigen. Phytohemagglutination (PHA) and Candida elicited normal lymphocyte stimulation. Measles virus caused neither stimulation or inhibition of the lymphocytes. The authors believe these studies show that subtle abnormalities may be present in the immune system in patients who develop subacute sclerosing panencephalitis which follows rubeola. J. S.
6
J. ALLERGY
Abstracts
Measles
antibodies
in the cemkoepiclal
Brown, I’., Cathala, F., Gajdusek, Exp. Biol. Med. 137: 956, 1971.
fiuii
-of patients
with
CLIN. IMMUNOL. JANUARY 1972
mvltiplr
D. C., and Gibbs, C. J., Jr.:
sclerosis.
Proc. Sot.
Previous investigations have demonstrated increased measles antibody titers in the scra and spinal fluid of multiple sclerosis (MS) patients when compared to healthy adults or patients with other neurologic diseases. The c.erehrospinal fluid (CSF) specimens of 61 MS patients were tested for the presence of measles antibody with the following methods: measles neutralizing (N) antibody, complement-fixing (CF) antibody, hemagglutination-inhibiting (HI) antibody, fluorescent antibody (FA), and mixed hemadsorbing (HAd) antibody. Measles antibody was detected by at least. one of these tests in 45 (74 per cent) of the patients. Positive CSF tests for measles antibody in a control group of 59 patients with other types of neurologic diseases were obtained in 29 patients (49 per cent). With the exception of neutralizing antibody, each type of antibody was found significantly more often in t.he MS patients than in the cont.rol group. There was no apparently significant correlation beetween CSF and serum antibody titers. No significant occurrence of CSF antibodies to myxoviruses other than measles was detected. This investigation suggests that t.here is no Lvidence for measles virus being the etiologic cause of MS in at least half of the MS patients. The possibility exists that if measles virus is involved in causing MS, the virus may be present in a defective, latent, or imperfect condition. Other different latent agents may also be etiologically involved in cases of MS. N. w.
Hirtocompatibilty A possible
&U-AI anti+nr orsocioted with genetic predisposition to disease.
Bodmer, 6. G., Bodmer, W. F., and McDevitt, 1971.
systemic
lupus
eythematosus.
Grumet, F. C., Coukell, A., H. : N. Engl. J. Med. 285: 193,
The HL-A antigens were determined in -10 unrelated patients, 25 Caucasian patients with systemic lupus (SLE), and 82 normal Caucasian control subjects by a standard lymphocyte cytotoxicity assay. In the “LA series” antigens (first locus), the frequency of the antigens was not significantly different between control subjects and patients. However, in the “-I series” (second locus), HLA8 was present in 33 per cent of SLE patients and 16 per cent of the control subjects, while W15 (LND) was found in 40 per cent of patients and 10 per cent of control subjects. There was no significant difference in frequency of the other antigens of the “4 series.” Since antigens HL-A8 and W15 (LND) were presentin SLE patients in significantly higher frequency than in a normal Caucasian population, the authors conclude that there may be an association between SLE and the HL-A histocompatibility antigen system. J. s.
Relevance of HL-A on&igenr to acute humoral m&-Men of mqlt@k mmal ellotranspkts. Pierce, J. C., Cobb, G. W., and Hume, D. M. : N. Engl. J. Med.
285: 142, 1971. Acute humoral rejections are uncommon in recipients of first renal transplants but not uncommon in recipients of multiple renal transplants. Immunologic indexes were eomputed in terms of the HL-A histocompatibility antigen system to predict the likelihood of acute humoral rejection in patients receiving multiple renal transplants from randomly selected related or unrelated donors. The indexes were also calcula&d for various donor-recipient combinations based on the number of transplants, relation of donors, and race of donors.
VOLUME NUMBER
43 1
Abstracts
7
These predictions were then compared to the clinical results. There rrere only 5 acute humoral rejections, 2 with ABO-incompatible donors, among 153 recipients of first transplants. The predicted figure for multiple transplants was 12.2 rejections. Eleven of 31 (35 per cent) acute rejections for multiple transplants were observed clinically. Predicted figures for acute rejections were 7.9 rejections in 24 second transplants, 3.5 rejections in 6 third transplants, and 0.7 rejections in one fourth transplant. In comparison, there were 7 acute rejections observed clinically among the recipients of second transplants, 3 acute rejections among third transplants, and one acute rejection among fourth transplants. Similar close agreement between predicted and clinical figures were seen among various subgroups (race, donor-recipient relationship) for multiple renal transplants. The authors conclude that immunization to the HL-A antigen system could account for the observed frequency of acute humoral rejections in recipients of second, third, or fourth transplants without involvement of other histocompatibility antigen systems. J. 5’.
Pharmacology, physiology, and pathology Phosphatidylserine:
Selective
H. R., and Knookuizen,
enhancer
of histamine release. M. : Science 173: 1034, 19’71.
Goth, A., Adams,
Phosphatidylserine, a phosphatide present in brain acetone powder, and cell membranes enhance the release of histamine from rat peritoneal mast cells caused by the addition of dextran or specific antigen. Histamine release induced by compound 48/80, chymotrypsin, 01 other nonimmunologic agents is not enhanced by this phosphatide. The authors fractionated brain acetone powder on silica gel and by column chromatography, respectively, and obtained a mixture of phosphatides whose only single active histamine-releasing property was vested in the phosphatidylserine portion. Of interest is the finding that this compound does not, by itself, release histamine from the mast cells but must act in concert with a histamine releaser and has to be added to the cells just prior to their treatment with dextran or, in the case of bovine serum albumin-(BSA) sensitized rats, with BSA. Also, the addition of the phospholipid enhancer prior to challenge with specific antigen caused a greater cell release of histamine than did treatment of comparable cells with specific antigen alone. It was further observed that treatment of rat mast cells with fatty acid-poor BSA reduces the histamine release response of the cells to challenge with dextran. The supernate from this system was found to contain phosphatidylserine which, in turn, could enhance histamine release from other dextran-treated mast cells. The difference between antigen-mediated and 48/80-induced histamine release is discussed in light of these new findings. D. S.
Screening for heterozygous diethylstilbestrol and
a,-antitrypsin deficiency. effect of oral contraceptives. C., and Kent, J. R. : J. A. M. A. 217: 1198,19’71.
III. A provocative
Lieberman,
test with
J., Mittman,
The effect of diethylstilbestrol medroxyprogesterone and corticosteroids on serum trypsin inhibitory capacity (STIC) and cu,-globulin levels was studied in heterozygous and homoaygous cu,-antitrypsin-deficient patients and in normal subjects. The STIC was determined with crystalline trypsin and benzoly-L-arginine ethyl ester substrate. Normal values are greater than 0.85 units of inhibitory activity. The a,-globulin serum levels were determined by electrophoresis on cellulose acetate membranes. The normal level is above 0.2 Gm. per 100 ml. A dose of 3 mg. of diethylstilbestrol daily for 14 days was found to cause a significant elevation of STIC and cu,-globulin levels in normal subjects and heterozygous patients. Anti-
8
1. ALLERGY
Abstracts
CLIN. IMMUNOL. JANUARY 1972
trypsin levels could also be stimulated by an acute pulmonary infection such as tuberculosis. Nine of 12 heterozygous individuals attained a low normal STIC when stimulated with diethylstilbestrol. Ten of the 12 also attained a normal level of cr,-globulin. However, nom of the heterozygous patients had a BTIC greater than 1.3 units. Homozygous patients had no significant elevation of STIC when given diethylstilbestrol. Medroxyprogesterone and corticosteroids did not elevate BTIC values in hoth homozygous and heterozygous types. The authors then studied the differences between women receiving oral contraceptives and control women. The control subjects had a mean level of 1.162, whereas the contraceptive group had a mean level of 1.550. Therefore, oral contraceptives cause a significant elevation in STIC. It may be concluded that women receiving oral contraceptives having a BTIC below 1.2 units should be further inv&igated for a,-antitrypsin deficiency. Furthermore, diethylstilbeutrol may be used as a provocative screening method for heterozygous a,-antitrypsin deficiency. N. G.
Comparison
of isoprokrenol
J., Werfelman,
and
isoproterenol-pkenylephrlne
N., Cook, M., and Metherall,
aerosols.
Grant,
W.: Chest 60: 129, 1971.
The effects of isoproterenol versus isoproterenol-phenylephrine aerosols on the vital capacity (VC) and one-second forced expiratory volume (FEV,) were investigated in 30 male patients with chronic obstructive pulmonary disease. Patients received isoproterenol hydrochloride alone, isoproterenol hydrochloride with phenylephrine bitartrate, or a placebo in freon-powdered aerosol cartridges. The treatments consisted of two inhalations; the second was given 2 minutes after the first. The VC and FEV, were measured on a 13 L. Collins spirometer at 1, hour and 2% hour intervals following treatment. Isoproterenol hydrochloride alone was found to increase the VC 16.75 per cent, whereas the isoproterenol with phenylephrine bitartrate increased the VC by 12.6 per cent after W hour. The FEV, rose 23.3 per cent with isoproterenol alone and 15.3 per cent with isoproterenol The placebo resulted in negligible changes in the combined with phenylephrine bitartrate. FEV, and VC. After 21,4 hours there still was a significant increase in the VC and FEV, with either cartridge containing isoproterenol. However, there was no statistically signifkant difference between the two. The authors concluded, therefore, that both forms of isoproterenol cartridge produce a notable improvement in the FEV, and VC and the slight difference in effectiveness of the isoproterenol-phenylephrine combination does not warrant its being the preferred dosage form. N. G.
ABSTRACTS JANUARY,
1
Editor-in-chief MURRAY Brooklyn,
M. ALBERT. N. Y.
M.D.
Editorial
board
EUGENE Bridgeport,
LVALZER Conn.
BERNARD Brooklyn,
HAROLD Cleveland,
FRIEDMAN Ohio
ELOISE KAILIN Washington, D. C.
MONROE Stamford,
COLEMAN Conn.
Associate KATHERINE Brooklyn,
editors NATHAN Brooklyn,
BOWMAN N. P.
BERTRAM Tyler, Texas DAVID Spring
SIEGEL N. P.
I TSU CHAO Brooklyn, N.
KAHN
STEIN Valley,
N.
1VEISS N. P.
ROBERT Brooklyn,
P.
Y.
SPIELMAN N. Y.
JAMES RUBIN New York City
ROBERT FENTON Fort Worth, Texas
JEROME SHAPIRO Santa Clara, Calif.
NEIL GOLDMAN Ossining, N. P.
Consultant MATTHEW Brooklyn,
From The
editor N.
the Jewish
%VALZER Y.
Allergy Hospital
Division and
of Medical
Center
of Brooklyn
1972
2 Abstracts
J. ALLERGY
CLIN. IMMUNOL. JANUARY 1972
Announcement rlllergy Abstracts has been published since 1936 by members of the Allergy Division of The Jewish Hospital and Medical Center of Brooklyn. The Editorial Board is comprised mainly of former residents of this department who contribute their services. Nergy ilbstracts selects and abstracts those articles in the literature which may be of clinical or theoretical interest to workers in the field of allergy. Each abstract represents a summary of the author’s findings and views, and its inclusion in Allergy ABstructs does not imply approval of its contents by the Editor. The Editor
lmmunakgy Tumor immunity: Tumor spocitkdiy stimulakd
s-ion lymp)loeyter.
in vivo
products of B. H., Istin, M., and Masen,
initkhd
Dvarchik,
by
solubk
T. H.: Science 172: 3984, 1971. may be obtained from the superA macrophage migration inhibition factor (MIF) natant fluid when sensitized lymphocytes are challenged in vitro with specific antigen. This and causes delayed hypersensitivity-like aupernatant fluid is cytotoxic and leukotaxic reactions when injected intradermally. Primary hepatomas were induced in inbred guinea pigs, and the ascites cells were harvested and injected into intradermal sites on age-matched animals of the same strain. Other syngenic animals were immunized with Y. tubero~Zosti in Freund’s adjuvant, their lymph node cells were collected, cultured, and challenged with purified protein derivative (PPD), and MIF was prepared from the resulting supernates. The MIF was purified by gel filtration on Sephadex and polyacrylamide gel. This MIF was then injected intradermally into strain-mate guinea pigs, and the ensuing reactions were. shown histologically t.o be of the delayed tuberculin type with typical mononuclear cell accumulation. Further, the MIF-containing supernate, when injected intradermally together with the hepatoma cells, prevented tumor growth at the injection sites. Tumor growth inhibition was specific for the site treated with MIF, but sites inoculated with tumor cells alone and remote from the tumor cell-MIF-treated intradermal areas showed adequate tumor cell replication and tumor growth. The authors then injected tumor cells into sites that had been treated with MIF 24 hours previously and observed that, as long as the MIF-induced delayed reaction was still in progress, tumor inhibition persisted. This MIF-induced tumor rejection reaction is caused by host factors rather than MIF. D. 8.
Immunocompetent
cells
omang
mow*
thymwyW:
A m&nor
pap&Won.
Leck-
band, E., and Boyse, E. A. : Science 172: 3989,1971. Thymocytic cells have a reduced ability to cause the graft versus host reaction (QVHR) when compared to lymph node cells. It may be postulated that QVH activity harbored by
VOLUME NUMGER
43 1
Abstracts
3
thymic cells is probably caused by the presence of a subpopulation of cells with GVH activity comparable to that of lymphocytes. The authors prepared thymic and lymph node cell suspensions from two groups of mice, one whose thymocytes carried TL antigens (TL+), and the second whose thymocytes were devoid of TL antigen (TL-) . Newborn F,, TL mice were inoculated with either TLt or TLthymocytes, or lymphocytes, respectively, and GVHR was determined by the method of Simonsen. It was thus shown that 75 times more thymocytes than lymphocytes were needed to induce GVHR. Further, the thymocytes from TL+ mice may be divided into a major population of TL+- bearing cells, and a smaller group of TLcells. Treatment of TL+ thymocyte cell population with anti-TL antiserum and complement results in survival of 12 per cent of the cells. These survivors, when injected into F, newborn mice, caused a degree of GVHR similar to that observed in mice inoculated with antibody untreated TL+ thymocytes, and control mice inoculated with antibody complement TL- thymocytes showed GVHR similar to that in the previous two experimental groups. When 95 per cent of the TLt thymocytes were killed by an anti-H-2b antibody with complement, the GVHR could be abolished. The authors were able to exclude the possib.ility that blood lymphocytes mere responsible for the experimental observations and also excluded the possibility of thymic entrapment of immunologically competent cells. It is concluded that the immunocompetent (TL-) thymoeytcs are derived within the thymus gland proper and that the GVH reactivity lies in the TLcell subpopulation, that is, cells which have lost their TL antigenieity by a process of maturation. D. S.
Anergy
and
recovery
in
a child
stage I Hodgkin’s disease. Starling, D. J. : J. Pediatr. 79: 666, 1971.
with
South, M. A., and Fernbach,
K. A.,
A 4-year-old boy with Hodgkin’s disease had negative skin test responses to mumps, streptokinase-streptodornase antigen (SKSD), Candida, and Trichophyton before radiotherapy was initiated. Challenge tests with dinitrofluorobenzene (DNFB) were also negative. There was no evidence of rejection of a skin autograft or of a graft received from another patient. His lymphocytes were not stimulated by phytohemagglutinin. While receiving radiotherapy, the patient developed meningoencephalitis with the subsequent appearance of mumps antibody in the serum. The titer of the mumps antibody was 1:64 8 months later. Tests for delayed hypersensitivity were repeated 9 months after the diagnosis of Hodgkin’s disease was made. Positive responses were obtained with the mumps, SKSD, and DNFB. A new homograft was rejected in 13 days. There was a moderate response of the patient’s lymphocytes to phytohemagglutinin at this time. When the patient’s condition deteriorated, his reactions to mumps and Candida antigens became negative. There was a poor response of the lymphocytes to phytohemagglutinin stimulation, and he failed to reject a new skin graft. The changing status of this patient’s immunologic deficiencies supports the hypothesis that the immune defect is a result rather than a cause of Hodgkin’s disease. N. w.
Variation
and
homology
in the
mu
and
gamma
heavy
chains
of
human
immuno-
Shimizu, A., Paul, C., Kohler, H., Shinoda, T., and Putnam, F. W. : Science 173: 3997, 1971.
globulins.
The authors analyzed the specific antigen-combining site on a segment of a human macroglobulin molecule (Faba) consisting of the light chain with the disulfide linkage to the terminal -NH, of the mu (h) heavy chain (the Fdp piece) and determined the amino acid sequence of 213 residues within the Fd segment on the M chain, the first 40 residues on the Fca region and the last 88 residues of the -COOH terminus of the Fe segment. A comparison was made with similar portions of the IgG molecule, and it was found that the variable regions
4
J. ALLERGY
Abstracts
CLIN. IMMUNOL. JANUARY 1972
of human p and y- 1H chains have more amino acid sequence homology th:ui do the coustant regions. The IgM precedes the appearance of IgG in neonates and during the immune response, Imt both antibodies are probably derived from a single primitive immune globulin. Not enough information is as yet availnble t.o prove whether LgM preceded IgG in evolution. However, it may be concluded from the amino acid and disulfide bond mapping t.hat the p on~l yl hear? chains diverged in evolution soou after the separntion of H and L chain genes.
Clinical use of rabbit antihuman lymphocyte globulin in cadaver kidney tranrplantation. Mannick, J. A., Davis, R. C., Cooperband, S. R., Glasgow, A. H.,
Williams, L. F., Harrington, J. T., Cavallo, T., Schmitt, G. W., Idelson, B. A., Olsson, C. A., and Nabseth, 1). C. : N. Engl. J. Med. 284: 1109, 1971. Rabbit antihuman antilymphocyte globulin (ALG) was given to 26 recipients of czadaver kidney transplants who also received conventional immunosuppressive therapy with aeathioprinc and prednisone and local radiotherapy to the transplant. The first group of 10 patients wns followed for one to 2 years, while the second group of 16 patients was observed for at least 4 months. The results of HL-A typing were not used in donor selection, although 4 patients in the first group and 11 in t.hc second group had 1) matches by serotyping. An ALG dose of approximately 100 mg. was given to an average adult in the early post,trnnsplant period. ALG administration was well tolerated. Trnnsplnnted kidneys were removed from one patient in the first group nnd 2 patients in the second group because of hyperncut,e rejection caused by preformed antibodies. Eight patients (4 in each group) showed evidence of acute rejection, but these episodes were promptly reversed by increase in the steroid dosage. In the first group, 2 patients showed histologic changes on one-year renal biopsy, consistent with moderately severe chronic rejection. One of these patient.s and 7 other patients had satisfactory renal function at the end of one year. Profound lymphopenia appenred within 6 hours of the first ALG injection and persisted for 4 to 6 weeks in most reeipcnts. Thrre were no consistent changes seen in serum immunoglobulin levels or complement. Among the 26 patients, there were 2 deaths (one in each group) associated with infection. The authors conclude that rabbit ALG is well tolerated and effective in reducing the frequency and severity of acute transplant rejections.
J. 8.
Systemic and local immunological with antilymphocyte serum.
activity
of lymph-node
Smith, J. J., III, Proc. Sot. Exp. Biol. Med. 137: 388, 1971..
Hilgard,
cells from mice treated H. R., and Sell, K. IV. :
The immunosuppressive action of antilymphocyte serum (ALS) resulting in prolonged survival of allografts and suppression of the graft. versus host react,ion has been demonstrated. It has been postnlated that immunosuppression in such cases is associated with nn inhibition of migration of ALS-exposed lymphoid cells to the sites where they may 1.x immunologically active. Rabbit antimouse lymphocyte serum (RAMLS) or normal rabbit sera (NRS) was injected intraperitoneally in t.wo groups of mice. A third group received neither preparation. Skin allografts were applied to all three groups with median survival times for these grafts of 9.6, 9.8, and 28.5 days for the untreated, NRS-treated, and RAMLS-treated mice, respectively. The immunosuppressive action of the RAMLS was also demonstrated by a significant decrease in the ability of lymph node cells obtained from RAMLS-treated mice to produce splenomegaly after these cells were injected intraperitoneally into young mice when compared to the erect of the injection of lymph node cells obtained from untreated or NRS-treated mice. However, local reactivity of lymph node cells obtained from RAMLS-treated mice was demonstrated when x-irradiated hamsters were injected intradermally with these cells.
VOLUME NUMBER
This treated locally.
43 1
Abstracts
investigation mice display
indicated suppressed
that, although immunocompetence
lymph
node cells systemically,
5
obtained from RAMLSthese cells are reactive A’. a.
Quantitation
of
immunoglobulins
in
gastric
juice
by
electroimmunodiffusion.
McClelland, D. B. L., Finlayson, N. D. C., Samson, R. R., Nairn, I. Shearman, D. J. C. : Gastroenterology 60: 509, 1971.
M.,
and
Immunoglobulins in gastric juice fro.m 65 achlorhydric patients, 4 normal volunteers, and one achlorhydric hypogammaglobulinemic patient were quantitated by radial immunodiff’usion ‘r: stimulation was used to obtain specirncns. and electroimmunodiffusion techniques. Pontagastri Thirty samples of achlorhydric gastric juice were examined by the two techniques. Problems encountered with the radial immunodiffusion method but not with electroimmunodiffusion were lack of sensitivity for immunoglobulin levels below 10 mg. per 100 ml., inaccuracies in reading plates, and nonspecific precipitates. The levels of immunoglobulins were similar as measured by both techniques. Immunoglobulins were not detected in gastric juice of the hypogammaglobulinemic patient, while in aehlorhydric patients, IgA and IgG levels each ranged from 10 to 200 mg. per 100 ml. (most were in 20 to 100 mg. per 100 ml. range) and IgM levels were 0 to 35 mg. per 100 ml. In the volunteers, measurements were performed on gastric juice either aspirated at 5 minute intervals and then brought to pH 7 to 7.5 by 5 per cent sodium bicarbonate or on gastric juice neutralized intragastrically by continuous infusion of sodium bicarbonate to maintain pH of aspirates between 7 and 7.5. Immunoglobulins were not detected by the extragastric neutralization methods but were found to be in the same ranges as those of achlorhydric patients when the gastric aspirates were neutralized intragastrically. The authors conclude that immunoglobulins may be detected in gastric juice of all but hypogammaglobulinemic patients and that the electroimmunodiffusion method of quantitating these immunoglobulins has advantages over the radial immunodiffusion technique. J. As.
Subtle
immunologic cephalitis.
abnormalities
in four
boys
with
subacute
sclerosing
panen-
Gerson, K. L., and Haslam, R. H. A.: N. Engl. J. Med. 285: 78,
1971. Immunologic studies were performed on 4 boys with proved subacute sclerosing panencephalitis (SSPE) following rubeola infection or vaccination. One patient had an absence of serum IgA, and 2 had deficient serum IgA. Each patient was given a booster dose of diphtheria-tetanus toxoid subcutaneously into the right thigh, and a right inguinal lymph node was examined 5 days later. The serum antibody response was normal. In the lymph nodes, germinal centers were rare and small, and there was an increased concentration of lymphocytes of inflammatory response with the use of in the cortex and paracortical zone. An evaluation Rebuck skin window showed normal cellular response. Delayed reactions following intradermal skin testing with Candida alhicnns, streptokinase-streptodornase, and live measles vaccine were absent or greatly decreased. In addition, the patients failed to develop contact sensitivity after application of 2 mg. of 2,4-dinitrochlorobenzene (DNCB). Full-thickness grafts from nonrelated donors were rejected after a moderately prolonged rejection time by the eighteenth to twenty-seventh day. Lymphocyte stimulation was measured by the uptake of tritiated thymidine after a 5 day incubation period with measles and Candida antigen. Phytohemagglutination (PHA) and Candida elicited normal lymphocyte stimulation. Measles virus caused neither stimulation or inhibition of the lymphocytes. The authors believe these studies show that subtle abnormalities may be present in the immune system in patients who develop subacute sclerosing panencephalitis which follows rubeola. J. S.
6
J. ALLERGY
Abstracts
Measles
antibodies
in the cemkoepiclal
Brown, I’., Cathala, F., Gajdusek, Exp. Biol. Med. 137: 956, 1971.
fiuii
-of patients
with
CLIN. IMMUNOL. JANUARY 1972
mvltiplr
D. C., and Gibbs, C. J., Jr.:
sclerosis.
Proc. Sot.
Previous investigations have demonstrated increased measles antibody titers in the scra and spinal fluid of multiple sclerosis (MS) patients when compared to healthy adults or patients with other neurologic diseases. The c.erehrospinal fluid (CSF) specimens of 61 MS patients were tested for the presence of measles antibody with the following methods: measles neutralizing (N) antibody, complement-fixing (CF) antibody, hemagglutination-inhibiting (HI) antibody, fluorescent antibody (FA), and mixed hemadsorbing (HAd) antibody. Measles antibody was detected by at least. one of these tests in 45 (74 per cent) of the patients. Positive CSF tests for measles antibody in a control group of 59 patients with other types of neurologic diseases were obtained in 29 patients (49 per cent). With the exception of neutralizing antibody, each type of antibody was found significantly more often in t.he MS patients than in the cont.rol group. There was no apparently significant correlation beetween CSF and serum antibody titers. No significant occurrence of CSF antibodies to myxoviruses other than measles was detected. This investigation suggests that t.here is no Lvidence for measles virus being the etiologic cause of MS in at least half of the MS patients. The possibility exists that if measles virus is involved in causing MS, the virus may be present in a defective, latent, or imperfect condition. Other different latent agents may also be etiologically involved in cases of MS. N. w.
Hirtocompatibilty A possible
&U-AI anti+nr orsocioted with genetic predisposition to disease.
Bodmer, 6. G., Bodmer, W. F., and McDevitt, 1971.
systemic
lupus
eythematosus.
Grumet, F. C., Coukell, A., H. : N. Engl. J. Med. 285: 193,
The HL-A antigens were determined in -10 unrelated patients, 25 Caucasian patients with systemic lupus (SLE), and 82 normal Caucasian control subjects by a standard lymphocyte cytotoxicity assay. In the “LA series” antigens (first locus), the frequency of the antigens was not significantly different between control subjects and patients. However, in the “-I series” (second locus), HLA8 was present in 33 per cent of SLE patients and 16 per cent of the control subjects, while W15 (LND) was found in 40 per cent of patients and 10 per cent of control subjects. There was no significant difference in frequency of the other antigens of the “4 series.” Since antigens HL-A8 and W15 (LND) were presentin SLE patients in significantly higher frequency than in a normal Caucasian population, the authors conclude that there may be an association between SLE and the HL-A histocompatibility antigen system. J. s.
Relevance of HL-A on&igenr to acute humoral m&-Men of mqlt@k mmal ellotranspkts. Pierce, J. C., Cobb, G. W., and Hume, D. M. : N. Engl. J. Med.
285: 142, 1971. Acute humoral rejections are uncommon in recipients of first renal transplants but not uncommon in recipients of multiple renal transplants. Immunologic indexes were eomputed in terms of the HL-A histocompatibility antigen system to predict the likelihood of acute humoral rejection in patients receiving multiple renal transplants from randomly selected related or unrelated donors. The indexes were also calcula&d for various donor-recipient combinations based on the number of transplants, relation of donors, and race of donors.
VOLUME NUMBER
43 1
Abstracts
7
These predictions were then compared to the clinical results. There rrere only 5 acute humoral rejections, 2 with ABO-incompatible donors, among 153 recipients of first transplants. The predicted figure for multiple transplants was 12.2 rejections. Eleven of 31 (35 per cent) acute rejections for multiple transplants were observed clinically. Predicted figures for acute rejections were 7.9 rejections in 24 second transplants, 3.5 rejections in 6 third transplants, and 0.7 rejections in one fourth transplant. In comparison, there were 7 acute rejections observed clinically among the recipients of second transplants, 3 acute rejections among third transplants, and one acute rejection among fourth transplants. Similar close agreement between predicted and clinical figures were seen among various subgroups (race, donor-recipient relationship) for multiple renal transplants. The authors conclude that immunization to the HL-A antigen system could account for the observed frequency of acute humoral rejections in recipients of second, third, or fourth transplants without involvement of other histocompatibility antigen systems. J. 5’.
Pharmacology, physiology, and pathology Phosphatidylserine:
Selective
H. R., and Knookuizen,
enhancer
of histamine release. M. : Science 173: 1034, 19’71.
Goth, A., Adams,
Phosphatidylserine, a phosphatide present in brain acetone powder, and cell membranes enhance the release of histamine from rat peritoneal mast cells caused by the addition of dextran or specific antigen. Histamine release induced by compound 48/80, chymotrypsin, 01 other nonimmunologic agents is not enhanced by this phosphatide. The authors fractionated brain acetone powder on silica gel and by column chromatography, respectively, and obtained a mixture of phosphatides whose only single active histamine-releasing property was vested in the phosphatidylserine portion. Of interest is the finding that this compound does not, by itself, release histamine from the mast cells but must act in concert with a histamine releaser and has to be added to the cells just prior to their treatment with dextran or, in the case of bovine serum albumin-(BSA) sensitized rats, with BSA. Also, the addition of the phospholipid enhancer prior to challenge with specific antigen caused a greater cell release of histamine than did treatment of comparable cells with specific antigen alone. It was further observed that treatment of rat mast cells with fatty acid-poor BSA reduces the histamine release response of the cells to challenge with dextran. The supernate from this system was found to contain phosphatidylserine which, in turn, could enhance histamine release from other dextran-treated mast cells. The difference between antigen-mediated and 48/80-induced histamine release is discussed in light of these new findings. D. S.
Screening for heterozygous diethylstilbestrol and
a,-antitrypsin deficiency. effect of oral contraceptives. C., and Kent, J. R. : J. A. M. A. 217: 1198,19’71.
III. A provocative
Lieberman,
test with
J., Mittman,
The effect of diethylstilbestrol medroxyprogesterone and corticosteroids on serum trypsin inhibitory capacity (STIC) and cu,-globulin levels was studied in heterozygous and homoaygous cu,-antitrypsin-deficient patients and in normal subjects. The STIC was determined with crystalline trypsin and benzoly-L-arginine ethyl ester substrate. Normal values are greater than 0.85 units of inhibitory activity. The a,-globulin serum levels were determined by electrophoresis on cellulose acetate membranes. The normal level is above 0.2 Gm. per 100 ml. A dose of 3 mg. of diethylstilbestrol daily for 14 days was found to cause a significant elevation of STIC and cu,-globulin levels in normal subjects and heterozygous patients. Anti-
8
1. ALLERGY
Abstracts
CLIN. IMMUNOL. JANUARY 1972
trypsin levels could also be stimulated by an acute pulmonary infection such as tuberculosis. Nine of 12 heterozygous individuals attained a low normal STIC when stimulated with diethylstilbestrol. Ten of the 12 also attained a normal level of cr,-globulin. However, nom of the heterozygous patients had a BTIC greater than 1.3 units. Homozygous patients had no significant elevation of STIC when given diethylstilbestrol. Medroxyprogesterone and corticosteroids did not elevate BTIC values in hoth homozygous and heterozygous types. The authors then studied the differences between women receiving oral contraceptives and control women. The control subjects had a mean level of 1.162, whereas the contraceptive group had a mean level of 1.550. Therefore, oral contraceptives cause a significant elevation in STIC. It may be concluded that women receiving oral contraceptives having a BTIC below 1.2 units should be further inv&igated for a,-antitrypsin deficiency. Furthermore, diethylstilbeutrol may be used as a provocative screening method for heterozygous a,-antitrypsin deficiency. N. G.
Comparison
of isoprokrenol
J., Werfelman,
and
isoproterenol-pkenylephrlne
N., Cook, M., and Metherall,
aerosols.
Grant,
W.: Chest 60: 129, 1971.
The effects of isoproterenol versus isoproterenol-phenylephrine aerosols on the vital capacity (VC) and one-second forced expiratory volume (FEV,) were investigated in 30 male patients with chronic obstructive pulmonary disease. Patients received isoproterenol hydrochloride alone, isoproterenol hydrochloride with phenylephrine bitartrate, or a placebo in freon-powdered aerosol cartridges. The treatments consisted of two inhalations; the second was given 2 minutes after the first. The VC and FEV, were measured on a 13 L. Collins spirometer at 1, hour and 2% hour intervals following treatment. Isoproterenol hydrochloride alone was found to increase the VC 16.75 per cent, whereas the isoproterenol with phenylephrine bitartrate increased the VC by 12.6 per cent after W hour. The FEV, rose 23.3 per cent with isoproterenol alone and 15.3 per cent with isoproterenol The placebo resulted in negligible changes in the combined with phenylephrine bitartrate. FEV, and VC. After 21,4 hours there still was a significant increase in the VC and FEV, with either cartridge containing isoproterenol. However, there was no statistically signifkant difference between the two. The authors concluded, therefore, that both forms of isoproterenol cartridge produce a notable improvement in the FEV, and VC and the slight difference in effectiveness of the isoproterenol-phenylephrine combination does not warrant its being the preferred dosage form. N. G.