- Email: [email protected]
NEGATIVE ASSOCIATION BETWEEN THE HUMAN T-CELL LEUKAEMIA VIRUS TYPE I AND LARGE GRANULAR LYMPHOCYTE LEUKAEMIA IN JAPAN
962
HNK-1antigens. The abnormal lymphoid cells from these patients showed gene rearrangement for TcR&bgr; and TcR... Anti-HTLV-1 antibodies were not found in any of the eleven cases by passive
Arterial plasma potassium changes in two renal controls during exhaustive exercise.
patients and
two
there will be a striking change in muscle membrane This potential. change may be sufficient to impair membrane and hence decrease muscle contractility.4 Such a excitability concentration would also be expected to depolarise pain afferents (C fibres), which terminate as free nerve endings around muscle. The clinical observation that fatigue and muscle pain subside quickly on recovery from exhaustive exercise may be explicable by the observed rapid clearance of potassium from the blood and consequent repolarisation of C fibres. We propose that hyperkalaemia is a limiting factor during brief periods of intensive exercise which may contribute to the fatiguing process-and that in this way the arterial plasma potassium is prevented from rising further to life-threatening levels. 7
mmol/1
Renal Unit,
Churchill Hospital, Oxford OX3 7JL
JON FRIEDLAND
University Laboratory of Physiology, Oxford 1. Breckenndge A. Jogger’s blockade. Br Med 2 Lim M, Linton RAF, Wolff CB, Band DM. potassium. Lancet 1981; ii: 591.
DAVID PATERSON J 1982; 284: 532-33. Propranolol, exercise, and arterial plasma
3. Vollestad 4.
NK, Sejersted OM. Biochemical correlates of fatigue. Eur J Appl Physiol 1988; 57: 336-47. Sjogaard G Water and electrolyte fluxes dunng exercise and their relation to muscle fatigue. Acta Physiol Scand 1986; 556 (suppl): 129-36.
NEGATIVE ASSOCIATION BETWEEN THE HUMAN T-CELL LEUKAEMIA VIRUS TYPE I AND LARGE GRANULAR LYMPHOCYTE LEUKAEMIA IN JAPAN
SIR,-Starkebaum and Pandolfi and their co-workersl,2 reported possible association of human T-cell leukaemia virus type I (HTLV-1) with large granular lymphocyte (LGL) leukaemia. Our
the
results do not support an association between HTLV-1 and LGL leukaemia. We tested eleven patients with LGL leukaemia, aged 13-78 years. The clinical courses were heterogeneous. Five patients deteriorated rapidly and died within 4 months of diagnosis. Two patients died within 32 months due to a blastic crisis following 2 years of chronic phase. Their peripheral blood leukaemic cells expressed the same surface phenotypes (ie, Ia[HLA-DR], CD2 +, CD38 +, and NKH-1I [N901] +) measured by fluorescenceactivated cell sorting with a panel of monoclonal antibodies.3,4 Some of the clinical details about one of these patients have been reported.5 Abnormal lymphoid cells of two patients with the same cell-surface phenotypes were also identified in their spleens and cultured cells. No gene rearrangements for T-cell receptors, TcRp, TcR,, or immunoglobulin were observed in peripheral blood cells and cultured cells. The clinical course of the other four cases was chronic. Phenotypes of the leukaemic cells differed from those of the other seven patients with a more acute form of LGL leukaemia as manifest by the expression of CD3, Ti(WT31), CD8, CD16, and
LGL
agglutination, immunofluorescence, ELISA, or western blotting (based on HTLV-1 antigen from culture supernatants of the human cell line MT-2). The fact that adult T-cell leukaemia (ATL) cells do not express the HTLV-1 or HTLV-1-associated antigens in vivo prompted us to study the cultured leukaemic cells from three patients with LGL leukaemia. There was no association with HTLV-1 for the cells in all three cultures measured by the use of HTLV-1 core protein monoclonal antibodies p19and p24 and electron microscopy. ATL/lymphoma and the familial occurrence of ATL6 are frequently found in endemic areas, especially the southwestern part of Japan. None of our patients with LGL leukaemia had either a family history of leukaemia/lymphoma or were born in an endemic area. Six of the patients and their ancestors were born in Hiroshima prefecture, where the incidence of ATL is extremely low/ We conclude that HTLV-1 is an unlikely aetiological agent for at least the aggressive form of LGL leukaemia. Department of Internal Medicine, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Minami-ku Hiroshima 734, Japan
NOBUTAKA IMAMURA ATSUSHI KURAMOTO
Department of Pediatrics, Osaka University Hospital
KEISEI KAWA-HA
Department of Internal Medicine, Kyoto Red Cross First Hospital
HIROSHI FUJII
Department of Internal Medicine, Hematological and Immunological Kanazawa Medical University
Division,
TOMOO TAKIGUCHI
1. Starkebaum G, Loughran TP Jr, Kalyanaraman VS, et al. Serum reactivity to human T-cell leukaemia/lymphoma virus type I proteins in patients with large granular lymphocytic leukaemia. Lancet 1987; i. 596-99. 2 Pandolfi F, Shriver K, Scarselli E, et al. HTLV-I antibodies and lymphoproliferative disease in granular lymphocytes Lancet 1987; ii: 1527 3 Imamura N, Fujimura K, Kuramoto A. Lymphocyte subpopulations in pernicious anemia N Engl J Med 1984, 311: 56 4. Imamura N, Kusunoki Y, Kajihara H, Okada K, Kuramoto A. Aggressive natural killer cell leukaemia/lymphoma with N901-positive surface phenotype evidence for the existence of a third lineage in lymphoid cells. Acta Haematol (in press). 5. Imamura N, Abe K, Kuramoto A. Malignant lymphoma-related disorder with anomalous surface phenotype. Am J Hematol 1987; 24: 115-16 6. Imamura N, Koganemaru S, Kuramoto A. T-cell leukaemia a few months apart in two brothers. Lancet 1982; i. 1361-62. 7. Imamura N, Miura K, Kuramoto A. Flow cytometric analysis of lymphocytic leukaemias and malignant lymphomas by monoclonal antibodies. First meeting of the Monoclonal Antibody Symposium m Chugoku-Shikoku Division, Monoclonal Antibody Conference, Hiroshima 1985; 1: 42-48 (in Japanese).
PROGRESSION OF CHRONIC RENAL FAILURE
SIR,-Your editorial (Aug 13, p 174) discusses the role of angiotensin converting enzyme (ACE) inhibitors in reduction of increased glomerular pressure in chronic glomerulopathies. Our results do not confirm the therapeutic benefit of this drug in diseases. Because of previous reports of benefits on urinary protein loss1-3 and a possible "protective effect" in progressive glomerulopathies’ (negative reports are few4,5) we studied 10 patients (7 male, 3 female, mean age 40 [SD 14 4]) with severe proteinuria due to non-diabetic nephropathy. 5 patients with chronic glomerulonephritis, 3 with amyloidosis, and 2 graft recipients with chronic rejections were also included. Renal artery stenosis was an exclusion criteria and diagnosis was confirmed histologically. When entering the study all patients had stable renal function (creatinine 0-9-5’8 mg/dl) and constant proteinuria (1 3-91 g/24 h). Antihypertensive therapy was withdrawn initially and substituted with a daily dose of 375 mg captopril. Concomitant medications (vitamin D analogues, phosphate binding agents, antacids, and frusemide) were not altered. The treatment period was 12 weeks. Blood pressure, serum creatinine, creatinine clearance, serum protein, and proteinuria were assessed every 2 weeks before, during, and after the trial. In 1 patient with amyloidosis treatment had to be discontinued because of a severe increase in serum creatinine after a week of
glomerular
HNK-1antigens. The abnormal lymphoid cells from these patients showed gene rearrangement for TcR&bgr; and TcR... Anti-HTLV-1 antibodies were not found in any of the eleven cases by passive
Arterial plasma potassium changes in two renal controls during exhaustive exercise.
patients and
two
there will be a striking change in muscle membrane This potential. change may be sufficient to impair membrane and hence decrease muscle contractility.4 Such a excitability concentration would also be expected to depolarise pain afferents (C fibres), which terminate as free nerve endings around muscle. The clinical observation that fatigue and muscle pain subside quickly on recovery from exhaustive exercise may be explicable by the observed rapid clearance of potassium from the blood and consequent repolarisation of C fibres. We propose that hyperkalaemia is a limiting factor during brief periods of intensive exercise which may contribute to the fatiguing process-and that in this way the arterial plasma potassium is prevented from rising further to life-threatening levels. 7
mmol/1
Renal Unit,
Churchill Hospital, Oxford OX3 7JL
JON FRIEDLAND
University Laboratory of Physiology, Oxford 1. Breckenndge A. Jogger’s blockade. Br Med 2 Lim M, Linton RAF, Wolff CB, Band DM. potassium. Lancet 1981; ii: 591.
DAVID PATERSON J 1982; 284: 532-33. Propranolol, exercise, and arterial plasma
3. Vollestad 4.
NK, Sejersted OM. Biochemical correlates of fatigue. Eur J Appl Physiol 1988; 57: 336-47. Sjogaard G Water and electrolyte fluxes dunng exercise and their relation to muscle fatigue. Acta Physiol Scand 1986; 556 (suppl): 129-36.
NEGATIVE ASSOCIATION BETWEEN THE HUMAN T-CELL LEUKAEMIA VIRUS TYPE I AND LARGE GRANULAR LYMPHOCYTE LEUKAEMIA IN JAPAN
SIR,-Starkebaum and Pandolfi and their co-workersl,2 reported possible association of human T-cell leukaemia virus type I (HTLV-1) with large granular lymphocyte (LGL) leukaemia. Our
the
results do not support an association between HTLV-1 and LGL leukaemia. We tested eleven patients with LGL leukaemia, aged 13-78 years. The clinical courses were heterogeneous. Five patients deteriorated rapidly and died within 4 months of diagnosis. Two patients died within 32 months due to a blastic crisis following 2 years of chronic phase. Their peripheral blood leukaemic cells expressed the same surface phenotypes (ie, Ia[HLA-DR], CD2 +, CD38 +, and NKH-1I [N901] +) measured by fluorescenceactivated cell sorting with a panel of monoclonal antibodies.3,4 Some of the clinical details about one of these patients have been reported.5 Abnormal lymphoid cells of two patients with the same cell-surface phenotypes were also identified in their spleens and cultured cells. No gene rearrangements for T-cell receptors, TcRp, TcR,, or immunoglobulin were observed in peripheral blood cells and cultured cells. The clinical course of the other four cases was chronic. Phenotypes of the leukaemic cells differed from those of the other seven patients with a more acute form of LGL leukaemia as manifest by the expression of CD3, Ti(WT31), CD8, CD16, and
LGL
agglutination, immunofluorescence, ELISA, or western blotting (based on HTLV-1 antigen from culture supernatants of the human cell line MT-2). The fact that adult T-cell leukaemia (ATL) cells do not express the HTLV-1 or HTLV-1-associated antigens in vivo prompted us to study the cultured leukaemic cells from three patients with LGL leukaemia. There was no association with HTLV-1 for the cells in all three cultures measured by the use of HTLV-1 core protein monoclonal antibodies p19and p24 and electron microscopy. ATL/lymphoma and the familial occurrence of ATL6 are frequently found in endemic areas, especially the southwestern part of Japan. None of our patients with LGL leukaemia had either a family history of leukaemia/lymphoma or were born in an endemic area. Six of the patients and their ancestors were born in Hiroshima prefecture, where the incidence of ATL is extremely low/ We conclude that HTLV-1 is an unlikely aetiological agent for at least the aggressive form of LGL leukaemia. Department of Internal Medicine, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Minami-ku Hiroshima 734, Japan
NOBUTAKA IMAMURA ATSUSHI KURAMOTO
Department of Pediatrics, Osaka University Hospital
KEISEI KAWA-HA
Department of Internal Medicine, Kyoto Red Cross First Hospital
HIROSHI FUJII
Department of Internal Medicine, Hematological and Immunological Kanazawa Medical University
Division,
TOMOO TAKIGUCHI
1. Starkebaum G, Loughran TP Jr, Kalyanaraman VS, et al. Serum reactivity to human T-cell leukaemia/lymphoma virus type I proteins in patients with large granular lymphocytic leukaemia. Lancet 1987; i. 596-99. 2 Pandolfi F, Shriver K, Scarselli E, et al. HTLV-I antibodies and lymphoproliferative disease in granular lymphocytes Lancet 1987; ii: 1527 3 Imamura N, Fujimura K, Kuramoto A. Lymphocyte subpopulations in pernicious anemia N Engl J Med 1984, 311: 56 4. Imamura N, Kusunoki Y, Kajihara H, Okada K, Kuramoto A. Aggressive natural killer cell leukaemia/lymphoma with N901-positive surface phenotype evidence for the existence of a third lineage in lymphoid cells. Acta Haematol (in press). 5. Imamura N, Abe K, Kuramoto A. Malignant lymphoma-related disorder with anomalous surface phenotype. Am J Hematol 1987; 24: 115-16 6. Imamura N, Koganemaru S, Kuramoto A. T-cell leukaemia a few months apart in two brothers. Lancet 1982; i. 1361-62. 7. Imamura N, Miura K, Kuramoto A. Flow cytometric analysis of lymphocytic leukaemias and malignant lymphomas by monoclonal antibodies. First meeting of the Monoclonal Antibody Symposium m Chugoku-Shikoku Division, Monoclonal Antibody Conference, Hiroshima 1985; 1: 42-48 (in Japanese).
PROGRESSION OF CHRONIC RENAL FAILURE
SIR,-Your editorial (Aug 13, p 174) discusses the role of angiotensin converting enzyme (ACE) inhibitors in reduction of increased glomerular pressure in chronic glomerulopathies. Our results do not confirm the therapeutic benefit of this drug in diseases. Because of previous reports of benefits on urinary protein loss1-3 and a possible "protective effect" in progressive glomerulopathies’ (negative reports are few4,5) we studied 10 patients (7 male, 3 female, mean age 40 [SD 14 4]) with severe proteinuria due to non-diabetic nephropathy. 5 patients with chronic glomerulonephritis, 3 with amyloidosis, and 2 graft recipients with chronic rejections were also included. Renal artery stenosis was an exclusion criteria and diagnosis was confirmed histologically. When entering the study all patients had stable renal function (creatinine 0-9-5’8 mg/dl) and constant proteinuria (1 3-91 g/24 h). Antihypertensive therapy was withdrawn initially and substituted with a daily dose of 375 mg captopril. Concomitant medications (vitamin D analogues, phosphate binding agents, antacids, and frusemide) were not altered. The treatment period was 12 weeks. Blood pressure, serum creatinine, creatinine clearance, serum protein, and proteinuria were assessed every 2 weeks before, during, and after the trial. In 1 patient with amyloidosis treatment had to be discontinued because of a severe increase in serum creatinine after a week of
glomerular