- Email: [email protected]
SERUM AMYLOID A, ABNORMAL HDL APOLIPOPROTEINS, AND ACUTE PHASE SERA
192 concentration in patients with low 1,25(OH)2D levels when different assays or different laboratories are used. This multicentre study shows that the two assay methods are fairly comparable, provide reproducible results when done in different laboratories, and can be used with confidence in clinical
practice. Department of Medicine, University of California, San Diego, V.A. Hospital, La Jolla, California 92161, U.S.A.; Endocrine Metabolic Center,
S. C. MANOLAGAS R. REITZ
Oakland, California; National Animal Disease Center,
R. HORST
Ames, Iowa; and
J. HADDAD L. J. DEFTOS
of Medicine,
Department University of Pennsylvania
We find, by contrast, that the pI values for apoT-I to apoT-IV range from around 6 - 9 to 9 -5(±0.20) (see figure) when we use a tailormade gradient of a 1:1 mixture of ’Ampholine’ pH 4-6 and pH 3-5-10 and the method of Eriksen and Bendittfor pI determination of the gradient. The results from isoelectric focusing thus indicate that only one of the four SAAs might be identical with apoT-I and none with apoT-II, III, or IV. Similarly the apo-SAAs isolated from HDL by Eriksen and Benditt1 had much lower pI values (5’ 6 and 6-1) than did the apoTs. (2) ApoT has an apparent molecular weight of about 15000 (see figure) which is higher than the values of about 11 500 (Eriksen and Bendittl) or 12 000 (Marhaug et a1.2) reported for SAA. Despite the non-identity of physiochemical properties between reported SAAs and the apoT group, the apoTs may well be related to SAA or other acute phase proteins. They may, however, equally well represent an independent, trauma dependent group of
SERUM AMYLOID A, ABNORMAL HDL APOLIPOPROTEINS, AND ACUTE PHASE SERA SIR,—Dr Marhaug and Professor Husby (Dec. 25, p. 1463), commenting on our Oct. 2 letter on the abnormal apoplipoproteins of high density lipoproteins (HDL) in trauma, designated apoT, claim that the apoTs "obviously represent species of serum amyloid A protein (SAA)", another acute phase protein.
peptides.
Because of the clinical conditions studied an obvious possibility is that apoT is related to or identical with one or more acute phase proteins. So far we have only tested this for C-reactive protein (CRP) and ApoT did not react with antisera against CRP. We have not had access to antisera against SAA but for two reasons would hesitate to identify apoT with SAA. (1) Only one of the four SAA bands in the isoelectric focusing experiments described by Marhaug and Husby had a pI above 6.
SIR,—After pneumonectomy the space previously occupied by the lung usually becomes filled, partly by shift of the mediastinum and partly with fibrous tissue and loculated fluid,3and the clinical and radiological signs resemble those of collapse of a lung. I report a case in which the patient might not have died had it been appreciated that these signs were masking a potentially treatable empyema. A 67-year-old man was admitted with a 1 month history of loss of energy, increased breathlessness, loss of appetite, and 4 kg weight loss. He had a cough productive of white sputum, and had been generally short of breath since a right pneumonectomy for carcinoma of the bronchus in 1970. He had not received any antibiotics. He was thin (though of average height he weighed only 58 kg). Temperature and blood pressure were normal. The trachea was deviated to the right and the right side of the chest was dull to percussion. Otherwise, apart from cataracts, clinical examination was normal. He had normochromic anaemia (Hb 9.44 g/dl, white cells 9 . 4 x 1091) and an erythrocyte sedimentation rate of 104 mm/h. Biochemical results were normal except for a reduced albumin (26 g/1), reduced calcium (2 -04 mmol/1), and much increased alkaline phosphatase (>350 U/1) which, since the y-glutamyltransferase was normal, was thought to be of non-hepatic origin. The chest X-ray (a completely opaque right hemithorax) was consistent with a previous pneumonectomy and the left lung appeared clear. Spirometry revealed both obstruction and restriction, with forced expiratory volume in 1 s of 0.65 litres and a forced vital capacity of 1 -3litres. The following investigations, directed towards elucidating the anaemia and high ESR, were normal or negative: Coombs, rheumatoid factor, and Mantoux tests; sigmoidoscopy, barium enema and meal; intravenous pyelogram; urine and four blood cultures; and isotope scan and ultrasound of the liver. Serum protein electrophoresis showed reduced albumin and increased Y2-globulin. At bronchoscopy both the pneumonectomy stump and the left bronchial tree appeared normal. Because the patient was slowly deteriorating, after 4 weeks of investigation, antibiotics (oral ampicillin 1 g four times daily and oral metronidazole 200 mg three times daily) were tried. Spikes of low-grade pyrexia persisted, and 3 weeks later a cough productive of green sputum developed with crackles at the base of the left lung.
Gel
electrophoresis
and isoelectric
focusing
studies of
apo-HDL
King Gustav V Research Institute, S-104 01 Stockholm, Sweden
OCCULT EMPYEMA PRESENTING TEN YEARS AFTER PNEUMONECTOMY
of
1. Eriksen N, Benditt EP. Isolation and characterization of the amyloid-related apoprotein (SAA) from human high density lipoproteins. Proc Natl Acad Sci(USA)
trauma.
(A) SDS-polyacrylamide gel electrophoresis (Laemmli) of: (1) molecular markers; (2) total apo-HDL of trauma, and (3) total apo-HDL of normal. Molecular weight markers from Pharmacia LMW kit. KD=kilodalton. (B) Isoelectric focusing in polyacrylamide m 8 mol/I urea of: (3) total apoHDL of normal and (4) total apo-HDL of trauma. pI=isoelectric point.
LARS A. CARLSON LEIF HOLMQUIST
2
1980; 77: 6860-64 Marhaug G, Sletten K, Husby G. Characterization of amyloid related protein SAA complexed with serum lipoproteins (apoSAA). Clin Exp Immunol 1982; 50: 382-89.
3
Suarez J,Clagett OT, Brown AL The post pneumonectomy space. Factors influencing its obliteration J Thorac Cardiovasc Surg 1969; 57: 539-42.
practice. Department of Medicine, University of California, San Diego, V.A. Hospital, La Jolla, California 92161, U.S.A.; Endocrine Metabolic Center,
S. C. MANOLAGAS R. REITZ
Oakland, California; National Animal Disease Center,
R. HORST
Ames, Iowa; and
J. HADDAD L. J. DEFTOS
of Medicine,
Department University of Pennsylvania
We find, by contrast, that the pI values for apoT-I to apoT-IV range from around 6 - 9 to 9 -5(±0.20) (see figure) when we use a tailormade gradient of a 1:1 mixture of ’Ampholine’ pH 4-6 and pH 3-5-10 and the method of Eriksen and Bendittfor pI determination of the gradient. The results from isoelectric focusing thus indicate that only one of the four SAAs might be identical with apoT-I and none with apoT-II, III, or IV. Similarly the apo-SAAs isolated from HDL by Eriksen and Benditt1 had much lower pI values (5’ 6 and 6-1) than did the apoTs. (2) ApoT has an apparent molecular weight of about 15000 (see figure) which is higher than the values of about 11 500 (Eriksen and Bendittl) or 12 000 (Marhaug et a1.2) reported for SAA. Despite the non-identity of physiochemical properties between reported SAAs and the apoT group, the apoTs may well be related to SAA or other acute phase proteins. They may, however, equally well represent an independent, trauma dependent group of
SERUM AMYLOID A, ABNORMAL HDL APOLIPOPROTEINS, AND ACUTE PHASE SERA SIR,—Dr Marhaug and Professor Husby (Dec. 25, p. 1463), commenting on our Oct. 2 letter on the abnormal apoplipoproteins of high density lipoproteins (HDL) in trauma, designated apoT, claim that the apoTs "obviously represent species of serum amyloid A protein (SAA)", another acute phase protein.
peptides.
Because of the clinical conditions studied an obvious possibility is that apoT is related to or identical with one or more acute phase proteins. So far we have only tested this for C-reactive protein (CRP) and ApoT did not react with antisera against CRP. We have not had access to antisera against SAA but for two reasons would hesitate to identify apoT with SAA. (1) Only one of the four SAA bands in the isoelectric focusing experiments described by Marhaug and Husby had a pI above 6.
SIR,—After pneumonectomy the space previously occupied by the lung usually becomes filled, partly by shift of the mediastinum and partly with fibrous tissue and loculated fluid,3and the clinical and radiological signs resemble those of collapse of a lung. I report a case in which the patient might not have died had it been appreciated that these signs were masking a potentially treatable empyema. A 67-year-old man was admitted with a 1 month history of loss of energy, increased breathlessness, loss of appetite, and 4 kg weight loss. He had a cough productive of white sputum, and had been generally short of breath since a right pneumonectomy for carcinoma of the bronchus in 1970. He had not received any antibiotics. He was thin (though of average height he weighed only 58 kg). Temperature and blood pressure were normal. The trachea was deviated to the right and the right side of the chest was dull to percussion. Otherwise, apart from cataracts, clinical examination was normal. He had normochromic anaemia (Hb 9.44 g/dl, white cells 9 . 4 x 1091) and an erythrocyte sedimentation rate of 104 mm/h. Biochemical results were normal except for a reduced albumin (26 g/1), reduced calcium (2 -04 mmol/1), and much increased alkaline phosphatase (>350 U/1) which, since the y-glutamyltransferase was normal, was thought to be of non-hepatic origin. The chest X-ray (a completely opaque right hemithorax) was consistent with a previous pneumonectomy and the left lung appeared clear. Spirometry revealed both obstruction and restriction, with forced expiratory volume in 1 s of 0.65 litres and a forced vital capacity of 1 -3litres. The following investigations, directed towards elucidating the anaemia and high ESR, were normal or negative: Coombs, rheumatoid factor, and Mantoux tests; sigmoidoscopy, barium enema and meal; intravenous pyelogram; urine and four blood cultures; and isotope scan and ultrasound of the liver. Serum protein electrophoresis showed reduced albumin and increased Y2-globulin. At bronchoscopy both the pneumonectomy stump and the left bronchial tree appeared normal. Because the patient was slowly deteriorating, after 4 weeks of investigation, antibiotics (oral ampicillin 1 g four times daily and oral metronidazole 200 mg three times daily) were tried. Spikes of low-grade pyrexia persisted, and 3 weeks later a cough productive of green sputum developed with crackles at the base of the left lung.
Gel
electrophoresis
and isoelectric
focusing
studies of
apo-HDL
King Gustav V Research Institute, S-104 01 Stockholm, Sweden
OCCULT EMPYEMA PRESENTING TEN YEARS AFTER PNEUMONECTOMY
of
1. Eriksen N, Benditt EP. Isolation and characterization of the amyloid-related apoprotein (SAA) from human high density lipoproteins. Proc Natl Acad Sci(USA)
trauma.
(A) SDS-polyacrylamide gel electrophoresis (Laemmli) of: (1) molecular markers; (2) total apo-HDL of trauma, and (3) total apo-HDL of normal. Molecular weight markers from Pharmacia LMW kit. KD=kilodalton. (B) Isoelectric focusing in polyacrylamide m 8 mol/I urea of: (3) total apoHDL of normal and (4) total apo-HDL of trauma. pI=isoelectric point.
LARS A. CARLSON LEIF HOLMQUIST
2
1980; 77: 6860-64 Marhaug G, Sletten K, Husby G. Characterization of amyloid related protein SAA complexed with serum lipoproteins (apoSAA). Clin Exp Immunol 1982; 50: 382-89.
3
Suarez J,Clagett OT, Brown AL The post pneumonectomy space. Factors influencing its obliteration J Thorac Cardiovasc Surg 1969; 57: 539-42.