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NUCLEOHISTONE AND THE L.E. FACTOR
297 LOSS OF ANKLE-JERK SIR,-We agree with much that Mr. London says (Aug. 15) in his remarks on our letter (July 11). Certainly the flattening of buttock, thigh, or calf is an important sign in many cases of sciatica, and while not noted in our subject has been noted in the large majority of cases one of us is now investigating.We would agree that this sign is most likely due to a disturbance of the reflex arc(s) subserving tone, but we feel it important to stress that this arc is probably not identical with that producing the
tendon jerk.2
Regarding the importance of
an
inhibitory
afferent
inflow causing the loss of the ankle-jerk we are less certain. If, as is usually conceded, the tendon reflexes in man are produced via monosynaptic arcs any incoming inhibitory impulses must act-if they are to depress the tendon reflex-at the appropriate anterior-horn-cell pool. Such an inhibition of anterior horn cells might be expected to produce some diminution in all activity utilising the final common path, including willed movement. We were interested to note no diminution in motor power, which suggested to us that there was no major inhibition at the level of the anterior horn cells. We concede, however, that the tendon reflexes may not be exclusively subserved
by monosynaptic reflex arcs in man,3 incoming inhibitory impulses might act
in which
case
internuncial level. However, the type of nerve-fibre conveying such impulses-which as Mr. London states do not reach consciousness-remains problematical. St. Thomas’s Hospital, A. J. BULLER. London, S.E.1. St. George’s Hospital, London, S.W.1.
at
The intimal layer was removed from the aorta of a fouryear-old child who had died at operation four hours previously. A homogenate in 15 ml. physiological saline was made of the intimal layers and the supernatant fluid after centrifugation was stored frozen until ready for use. This intimal extract was mixed with a polystyrene latex4 suspension, of particle size 0.81 , in the following proportions: 1000 intimal extract, 1%latex, 89’ McIlvaine’s buffer pH 5-0. Serial doubling dilutions of the sera under test from patients with systemic lupus, rheumatoid arthritis (with and without clinical evidence of arteritis), and polyarteritis nodosa were made in the range from 1:2 to 1:4096 using the pH 5-0 buffer as diluent. To each dilution was added an equal volume (0-25 ml.) of the sensitised latex particles. The tubes were incubated at 37-C for two hours, then centrifuged for three minutes at 1750 r.p.m.,
resulting agglutination
read and
graded
1
plus
to
4 plus. Agglutination in a titre of 1 : 8 or higher was regarded as positive. Any serum causing agglutination was tested against untreated latex particles. For a positive test at least a twofold dilution difference was required between the agglutination of the sensitised and unsensitised latex particle system. Titres as high as 1:1024 were obtained; most positive titres were around 1 : 64. The results (see table) suggest that the system may be a measure of the presence of vascular antibodies. Stefanini and Mendicoffin precipitation tests with aortic intimal 1. Buller, A. J., Yates, O. A. H Unpublished. 2. Buller, A. J. Lancet, 1957, ii, 1262. 3 Magladery, J. W., Teasdall, R. D. Bull. Johns Hopk. Hosp. 1958, 4. Dow Chemical Co., Michigan. 5. Stefanini, M., Mendicoff, I. B. J. clin. Invest. 1954, 33, 967.
of
saline which
was
used
to extract
the
aorta.
These results, admittedly few in number, show that there is yet another tissue component apart from nucleoprotein to which the body loses tolerance in systemic lupus. They also demonstrate another antigenic system common to lupus, polyarteritis nodosa, and rheumatoid arthritis. which this letter is based was made whilst I was in medicine at the University of California Medical Centre and was supported by a grant from the National Institutes of Health, Arthritis and Metabolic Diseases. I am very grateful to Dr. E. Engleman and Dr. W. Epstein for their kindness and encouragement of this research. The work
on
visiting fellow
Porter Neuropsychiatric San Francisco.
Institute,
W.
J. FESSEL.
THE MEDICAL SUPERINTENDENT
of
April 18 pointed out that the L.E. factor behaves in many ways as though it might be an autoantibody towards deoxyribose nucleoprotein. The following results tend to show that in systemic lupus erythematosus, rheumatoid arthritis, and polyarteritis nodosa, vascular antibodies may also be involved in the pathogenesis of the disease.
and the
reached the same conclusion. It is unlikely that traces gamma-globulin present in the extract (shown by zone electrophoresis) are responsible for the positive tests, since 9 out of 16 rheumatoid sera were negative when tested with intima-latex suspension, yet all had FII1 hxmagglutination titres in excess of 156,000. Nor is it likely that deoxyribose nucleic acid present in the extract was responsible for the positive tests since that substance unassociated with its histone cannot be made to sensitise latex particles to produce a positive test with systemic lupus sera-only the associated nucleoprotein can be used and this, of course, is insoluble in isotonic
extract
Langley
A. C. DORNHORST.
NUCLEOHISTONE AND THE L.E. FACTOR
SIR,-Your annotation
RESULTS OF THE INTIMA-LATEX TESTS
103, 236.
SIR,—Your authoritative and statesmanlike leader (Aug. 22) could well be the preliminary of a note from the Editor of The Lancet in the interesting correspondence about medical superintendents of mental hospitals which he has encouraged in his columns: This correspondence "
cease." before it does, may I add one note-that, although But the Mental Health Act has been widely acclaimed as following closely the recommendations of the Royal Commission, we on that Commission, according to my recollection, never talked about nor even thought about any possibility of any change in the status quo of the medical superintendent, and nothing of that appears in our report. Guildhall, J. GREENWOOD WILSON. London, E.C.2.
must now
MEDICAL ADMINISTRATION IN PSYCHIATRIC HOSPITALS SIR,—In your issue of Aug. 22 Dr. Shaw and Dr. Samuel describe the administrative experiment at Belmont Hospital and say that " there is general agreement that the arrangement has worked well ". I should perhaps point out that neither the Hospital Management Committee nor the Regional Hospital Board has yet officially
formulated any
opinion in the
matter. -
St. Ebba’s and Belmont
Hospital Group, Sutton, Surrev.
G. H.
SHREEVE,
Chairman, Hospital Management Committee.
GENERAL INFIRMARY AT LEEDS
Dr. S. T. ANNING
(42, Park Square, Leeds, 1) writes:
"I am working on the history of the General Infirmary at Leeds. I would be most grateful for information about any If any such were relevant letters, documents, portraits, &c. lent to me they would be copied and returned without delay and due acknowledgment to the owner would be made in the text."
tendon jerk.2
Regarding the importance of
an
inhibitory
afferent
inflow causing the loss of the ankle-jerk we are less certain. If, as is usually conceded, the tendon reflexes in man are produced via monosynaptic arcs any incoming inhibitory impulses must act-if they are to depress the tendon reflex-at the appropriate anterior-horn-cell pool. Such an inhibition of anterior horn cells might be expected to produce some diminution in all activity utilising the final common path, including willed movement. We were interested to note no diminution in motor power, which suggested to us that there was no major inhibition at the level of the anterior horn cells. We concede, however, that the tendon reflexes may not be exclusively subserved
by monosynaptic reflex arcs in man,3 incoming inhibitory impulses might act
in which
case
internuncial level. However, the type of nerve-fibre conveying such impulses-which as Mr. London states do not reach consciousness-remains problematical. St. Thomas’s Hospital, A. J. BULLER. London, S.E.1. St. George’s Hospital, London, S.W.1.
at
The intimal layer was removed from the aorta of a fouryear-old child who had died at operation four hours previously. A homogenate in 15 ml. physiological saline was made of the intimal layers and the supernatant fluid after centrifugation was stored frozen until ready for use. This intimal extract was mixed with a polystyrene latex4 suspension, of particle size 0.81 , in the following proportions: 1000 intimal extract, 1%latex, 89’ McIlvaine’s buffer pH 5-0. Serial doubling dilutions of the sera under test from patients with systemic lupus, rheumatoid arthritis (with and without clinical evidence of arteritis), and polyarteritis nodosa were made in the range from 1:2 to 1:4096 using the pH 5-0 buffer as diluent. To each dilution was added an equal volume (0-25 ml.) of the sensitised latex particles. The tubes were incubated at 37-C for two hours, then centrifuged for three minutes at 1750 r.p.m.,
resulting agglutination
read and
graded
1
plus
to
4 plus. Agglutination in a titre of 1 : 8 or higher was regarded as positive. Any serum causing agglutination was tested against untreated latex particles. For a positive test at least a twofold dilution difference was required between the agglutination of the sensitised and unsensitised latex particle system. Titres as high as 1:1024 were obtained; most positive titres were around 1 : 64. The results (see table) suggest that the system may be a measure of the presence of vascular antibodies. Stefanini and Mendicoffin precipitation tests with aortic intimal 1. Buller, A. J., Yates, O. A. H Unpublished. 2. Buller, A. J. Lancet, 1957, ii, 1262. 3 Magladery, J. W., Teasdall, R. D. Bull. Johns Hopk. Hosp. 1958, 4. Dow Chemical Co., Michigan. 5. Stefanini, M., Mendicoff, I. B. J. clin. Invest. 1954, 33, 967.
of
saline which
was
used
to extract
the
aorta.
These results, admittedly few in number, show that there is yet another tissue component apart from nucleoprotein to which the body loses tolerance in systemic lupus. They also demonstrate another antigenic system common to lupus, polyarteritis nodosa, and rheumatoid arthritis. which this letter is based was made whilst I was in medicine at the University of California Medical Centre and was supported by a grant from the National Institutes of Health, Arthritis and Metabolic Diseases. I am very grateful to Dr. E. Engleman and Dr. W. Epstein for their kindness and encouragement of this research. The work
on
visiting fellow
Porter Neuropsychiatric San Francisco.
Institute,
W.
J. FESSEL.
THE MEDICAL SUPERINTENDENT
of
April 18 pointed out that the L.E. factor behaves in many ways as though it might be an autoantibody towards deoxyribose nucleoprotein. The following results tend to show that in systemic lupus erythematosus, rheumatoid arthritis, and polyarteritis nodosa, vascular antibodies may also be involved in the pathogenesis of the disease.
and the
reached the same conclusion. It is unlikely that traces gamma-globulin present in the extract (shown by zone electrophoresis) are responsible for the positive tests, since 9 out of 16 rheumatoid sera were negative when tested with intima-latex suspension, yet all had FII1 hxmagglutination titres in excess of 156,000. Nor is it likely that deoxyribose nucleic acid present in the extract was responsible for the positive tests since that substance unassociated with its histone cannot be made to sensitise latex particles to produce a positive test with systemic lupus sera-only the associated nucleoprotein can be used and this, of course, is insoluble in isotonic
extract
Langley
A. C. DORNHORST.
NUCLEOHISTONE AND THE L.E. FACTOR
SIR,-Your annotation
RESULTS OF THE INTIMA-LATEX TESTS
103, 236.
SIR,—Your authoritative and statesmanlike leader (Aug. 22) could well be the preliminary of a note from the Editor of The Lancet in the interesting correspondence about medical superintendents of mental hospitals which he has encouraged in his columns: This correspondence "
cease." before it does, may I add one note-that, although But the Mental Health Act has been widely acclaimed as following closely the recommendations of the Royal Commission, we on that Commission, according to my recollection, never talked about nor even thought about any possibility of any change in the status quo of the medical superintendent, and nothing of that appears in our report. Guildhall, J. GREENWOOD WILSON. London, E.C.2.
must now
MEDICAL ADMINISTRATION IN PSYCHIATRIC HOSPITALS SIR,—In your issue of Aug. 22 Dr. Shaw and Dr. Samuel describe the administrative experiment at Belmont Hospital and say that " there is general agreement that the arrangement has worked well ". I should perhaps point out that neither the Hospital Management Committee nor the Regional Hospital Board has yet officially
formulated any
opinion in the
matter. -
St. Ebba’s and Belmont
Hospital Group, Sutton, Surrev.
G. H.
SHREEVE,
Chairman, Hospital Management Committee.
GENERAL INFIRMARY AT LEEDS
Dr. S. T. ANNING
(42, Park Square, Leeds, 1) writes:
"I am working on the history of the General Infirmary at Leeds. I would be most grateful for information about any If any such were relevant letters, documents, portraits, &c. lent to me they would be copied and returned without delay and due acknowledgment to the owner would be made in the text."