Cyclosporine A inhibits lymphocyte activation at more than one site in vivo.
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Cells, Cultured↗
Biomedical subjects
F M Lai
Publications and source records attributed to F M Lai.
Immunohistochemical study of the membrane attack complex of complement and S-protein in idiopathic and secondary membranous nephropathy.
Twenty-eight renal biopsies from 12 patients with idiopathic membranous nephropathy (MN), eight patients with lupus MN, and eight patients with hepatitis B virus-(HBV) related MN were investigated by immunofluorescence for the presence of C5b-C9 neoantigens of the terminal sequence of complement and for S-protein, which is a regulatory component of the membrane attack complex (MAC). Glomerular MAC was detected in 50% of patients with idiopathic MN, in 75% of patients with lupus MN, and in only 12.5% of the HBsAg carrier with MN. Glomerular adhesions to Bowman's capsule were associated with a high incidence of glomerular MAC deposition only in patients with idiopathic MN. Lupus patients had a high incidence of MAC deposition and patients with HBV-related MN had a low incidence of MAC deposition, in both cases regardless of the presence of glomerular capsular adhesions. It is unlikely that deposition of S-protein could inhibit the glomerular damage in idiopathic or lupus MN because significant glomerular capsular adhesions and MAC deposition were observed despite the concomitant glomerular deposition of S-protein. It was concluded that activation of terminal components of complement may play a role in glomerular injuries in idiopathic and lupus MN. The rare occurrence of glomerular MAC deposition in HBV-related MN could be related to its distinct immunopathogenetic mechanism and its indolent clinical course.
Complement Membrane Attack Complex↗
Relaxant actions of viprostol and prostaglandin E2 on tracheal muscle and their effects on calcium influx.
The relaxant effect of viprostol was studied in monkey and guinea-pig tracheal muscle rings in vitro and compared to that of prostaglandin E2 (PGE2), isoproterenol (ISO) and verapamil (guinea-pig trachea only). Viprostol, PGE2, ISO and verapamil produced a concentration-dependent relaxation of carbachol-contracted tracheal preparations. The rank order of potency in monkey trachea was viprostol = ISO greater than PGE2, while in guinea-pig treachea it was ISO greater than viprostol greater than PGE2 greater than verapamil. The relaxant effect of viprostol or PGE2 was not antagonized by propranolol, suggesting that beta-adrenoceptors are not involved. Epithelium removal did not affect the bronchorelaxant effects of viprostol, PGE2 or ISO. In K+-rich, Ca++-free Krebs solution, preincubation with an IC30 of verapamil antagonized CaCl2-induced contractions while an IC30 of viprostol, PGE2 or ISO did not. Preincubation with an IC90 of viprostol, PGE2 or ISO produced 0.5, 0.5 and 1.0 log unit shifts to the right of the CaCl2 concentration response curves, respectively. At this concentration, viprostol did not reduce the maximum effect of CaCl2, but PGE2 and ISO reduced it approximately 20%. However, preincubation with an IC90 of verapamil completely abolished the CaCl2 contraction. In conclusion, viprostol is a potent bronchodilator whose effect does not depend on the epithelium, beta-adrenoceptors or antagonism of Ca++ influx. Whether the bronchodilator effect of viprostol is via intracellular sequestration of calcium as that of PGE2 remains to be studied.
Animals↗
Light chain composition of IgA in IgA nephropathy.
The immunochemical nature of the light chains of the mesangial IgA deposits were studied in 13 IgA nephritic patients with only IgA isotype in their renal biopsies. Direct immunofluorescence (IF) using rabbit and goat antihuman monospecific antibodies demonstrated lambda light chain IF in all 13 biopsies (100%). Kappa light chain IF was detected in ten renal biopsies by the rabbit antihuman antisera and in eight renal biopsies by the goat antihuman antisera. Monoclonal antibodies studies showed lambda IF in all 13 biopsies and kappa IF in eight biopsies. Twelve biopsies showed a predominance of lambda light chain IF staining in the mesangial deposits. Identical IF patterns were observed when double IF technique with rhodamine-conjugated antihuman alpha heavy chain antiserum and fluorescein-conjugated antihuman light chain antisera were employed, and these findings confirmed that the light chains IF arose directly from the IgA deposits. These IgA nephritic patients had a significantly higher serum concentration of lambda light chain-IgA and a distinct alteration of kappa/lambda ratio of IgA compared with healthy controls. Our results support our preliminary observation that mesangial IgA deposits in IgA nephropathy consist mostly of IgA with lambda light chain.
Fluorescent Antibody Technique↗
Predominant synthesis of IgA with lambda light chain in IgA nephropathy.
The nature of the light chains in mesangial IgA deposits and serum IgA was studied in patients with IgA nephropathy. Immunofluorescence (IF) studies using murine monoclonal antibodies, rabbit and goat anti-human monospecific antisera were performed in kidney sections from 15 IgA nephritic patients with only IgA isotype detected in the renal biopsy. Lambda light chain IF was demonstrated in all biopsy specimens and kappa light chain IF in 11 renal biopsy specimens. The majority of renal biopsies showed a predominance of lambda light chain IF staining in the mesangial deposits. The concentration of individual immunoglobulins and their light chain fractions, and the kappa/lambda ratio were determined in the serum and the supernate from peripheral blood mononuclear cells culture of 30 IgA nephritic patients and 30 age-matched healthy controls. The IgA nephritic patients had a higher serum concentration of total IgA (P less than 0.001) and a significantly lower IgA kappa/lambda ratio (P less than 0.001) compared with the controls. The kappa/lambda ratio of supernatant IgA from IgA nephritic patients (N = 20) was also significantly lower than that of the normal subjects (N = 14), both in the unstimulated (P less than 0.01) and pokeweed mitogen stimulated, peripheral blood mononuclear-cell culture (P less than 0.05). Our results showed that patients with primary IgA nephropathy displayed a unique immunologic response characterized by a predominance of IgA with lambda light chain in circulation.
Cells, Cultured↗
Effect of gamma-aminobutyric acid (GABA) on vasodilation in resistance-sized arteries isolated from the monkey, rabbit, and rat.
The effect of gamma-aminobutyric acid (GABA) and papaverine on cerebral arteries of rat, rabbit, and monkey and the small mesenteric arteries of the rat were studied in vitro with a microvessel apparatus. GABA (1 x 10(-7) to 1 x 10(-3) M) did not affect the basal tension of arteries of rats at rest. In PGF2 alpha-contracted monkey basilar artery and middle cerebral artery and rat basilar artery, cumulative addition of GABA (1 x 10(-7) to 1 x 10(-3) M) did not produce any relaxation. Also in K+-contracted rat basilar artery and small mesenteric artery, cumulative additions of GABA, muscimol, or bicuculline did not result in relaxation. In K+-contracted rabbit basilar artery, GABA did not produce relaxation. However, the addition of papaverine (1 x 10(-7) to 1 x 10(-4) M) in either PGF2 alpha- or K+-contracted arteries, produced a concentration-dependent relaxation in all arteries tested. These results suggest that the failure of GABA or muscimol to induce relaxation is not due to a defect of the arterial smooth muscle relaxant mechanism, but rather is due to the inability of GABA or muscimol to directly relax the artery in this in vitro preparation. Therefore, the hypotensive effect of GABA seen in the rat is probably not due to direct vasodilation of mesenteric or cerebral arteries. These findings lend further support to the idea that GABA mediates its hypotensive effect through its action as an inhibitory neurotransmitter, as previously suggested by others.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The ultrastructural changes of the mucosa of blocked fallopian tubes.
The ultrastructure of the epithelium was studied in four blocked fallopian tubes which differed in the site of blockage and the degree of luminal distension. In all four specimens, there were large areas of the luminal surface which became barren and devoid of both the secretory and ciliated cells. Necrotic secretory cells and partially sloughed ciliated cells were observed in the remaining epithelium. Isolated patches of attenuated epithelium decorated with ciliated cells were sometimes found in the crypt of the mucosal folds. Results of this study suggest that pathological changes in the epithelium are common to tubes of both the terminal and cornual blockage.
Fallopian Tube Diseases↗
Studies on the effects of viprostol in isolated small blood vessels and thoracic aorta of the rat.
1. The effects of viprostol, prostaglandin E2 (PGE2) and nitroglycerin were studied in basilar artery, small mesenteric artery and the vein parallel to it as well as thoracic aorta of the rat. 2. In KCl-contracted basilar artery, viprostol produced a concentration-related biphasic response, contraction at concentrations less than 3 X 10(-6) M and relaxation at concentrations greater than 3 X 10(-6) M. PGE2 produced a concentration-related contraction while nitroglycerin produced a concentration-related relaxation. 3. In KCl-contracted small mesenteric artery, viprostol produced a biphasic response which was similar to that in the basilar artery. PGE2 produced a contraction and nitroglycerin produced relaxation in a concentration-dependent manner. 4. In KCl-contracted small mesenteric vein, in contrast to basilar and mesenteric artery, viprostol produced only a concentration-related relaxation in the range of 1 X 10(-6) to 1 X 10(-4) M. PGE2 produced a contraction and nitroglycerin produced a concentration-related relaxation. 5. In KCl-contracted thoracic aorta, PGE2 produced a biphasic response, relaxation at concentrations less than 3 X 10(-7) M and a concentration-related contraction at concentrations greater than 3 X 10(-7) M. Viprostol only produced a concentration-related contraction at concentrations greater than 1 X 10(-6) M, which was significantly less in magnitude than the contraction produced by PGE2. Nitroglycerin produced a concentration-related relaxation as seen in the small vessels. 6. In conclusion, the present data demonstrate that viprostol is a vasorelaxant agent which effectively dilates KCl-contracted basilar, small mesenteric artery and vein, but not the thoracic aorta of rat. The potent antihypertensive action of viprostol is probably due to its relaxant effect on the small arteries and veins but not on the large conduit artery.
Animals↗
Acute renal failure due to postpartum haemolytic uraemic syndrome.
A patient developed the haemolytic uraemic syndrome after an uncomplicated Caesarean section. Escherichia coli species producing verotoxin was not isolated from the stool and the verotoxin was not demonstrated in the renal biopsy. The patient recovered with supportive dialysis. The clinical features of 66 cases of postpartum haemolytic uraemic syndrome reported in the literature are reviewed.
Acute Kidney Injury↗
Relapse of idiopathic pulmonary haemorrhage and glomerulonephritis associated with cytomegalovirus (CMV) infection.
A 49 year old man who developed idiopathic pulmonary haemorrhage and glomerulonephritis responded initially to immunosuppressive treatment and plasmapheresis. However, he died later from massive pulmonary haemorrhage and necropsy showed cytomegalovirus infection of the lungs. We propose that relapse of pulmonary haemorrhage may be associated with cytomegalovirus infection and that preventive measures against acquiring the virus through blood products should be considered for elective transfusions in view of the relatively good long term prognosis of this syndrome.
Cross Infection↗
Acute renal failure, eosinophilia thrombocytopenia and exfoliative dermatitis associated with captopril therapy.
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Acute Kidney Injury↗
In vitro study of expression of interleukin-2 receptors in T-lymphocytes from patients with IgA nephropathy.
The present study was undertaken to examine the expression of interleukin-2 receptor (IL-2R)/CD25 antigen in cultured T-lymphocyte subsets in IgA nephropathy. Twenty-four IgA nephritic patients, 12 patients with chronic glomerulonephritis (non-IgA nephropathy), and 17 healthy controls were studied in an infection-free interval. T-cell subsets in peripheral blood mononuclear cells (PBMC) and activated T-lymphocyte subsets expressing IL-2R were determined by double immunofluorescence staining with fluorochromes conjugated to monoclonal antibodies against T-helper/inducer (CD4+) cell, T-suppressor/cytotoxic (CD8+) cell, B (CD20+) lymphocytes, and IL-2R. The percentages of CD4+ and CD8+ lymphocytes, CD4/CD8 ratio, and total activated lymphocytes (with IL-2R/CD25 antigen) did not differ between the IgA nephritic patients, patients with chronic glomerulonephritis, and healthy controls in freshly isolated, unstimulated lymphocytes or PBMC cultured with pokeweed mitogen. Following pokeweed mitogen stimulation for 5 days, 17.3 +/- 10.3%, 16.6 +/- 8.4%, and 16.7 +/- 9.4% of PBMC from IgA nephritic patients, patients with chronic glomerulonephritis, and controls respectively expressed IL-2R (p greater than 0.05). However, the individual T-cell subsets bearing IL-2R were distinctly different between the IgA nephritic patients and patients with chronic glomerulonephritis or healthy controls. IgA nephritic patients had increased activated CD4+ lymphocytes (with IL-2R) (p less than 0.025) and reduced activated CD8+ lymphocytes (p less than 0.025). Our study suggests a defective immunoregulation in IgA nephropathy with enhanced T-helper/inducer and reduced T-suppressor/cytotoxic activity when stimulated with mitogen and probably, during clinical exacerbation.
Adult↗
Distribution of interleukin-2 receptors in activated T-lymphocyte subsets in vitro.
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Adult↗
Strong association between IgA nephropathy and hepatitis B surface antigenemia in endemic areas.
The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 122 patients with primary IgA nephropathy. Hepatitis B surface (HBs) antigenemia was detected in 21 patients (17.2%) and this was significantly higher than the prevalence of HBsAg carrier in the general population (p less than 0.01). These patients had no clinical or laboratory findings to suggest acute or chronic liver diseases. Two glomerulopathic entities: mesangial proliferative glomerulonephritis with predominant mesangial IgA deposits and a mixed picture of membranous nephropathy with capillary IgG deposits and mesangial proliferative glomerulonephritis with mesangial IgA deposits, were observed in this group of patients. Glomerular deposits of HBsAg, hepatitis B core antigen (HBcAg), and both HBsAg and HBcAg were detected in three, five and four renal biopsy specimens respectively. Replication of hepatitis B virus (HBV) was suggested in two of the six renal biopsy specimens examined by HBV DNA gene probe. During the mean study period of 40 months (range 12-84), 19% of these patients with hepatitis B virus-associated IgA nephropathy developed progressive renal deterioration and one required maintenance dialysis therapy. Our study suggests that hepatitis B virus antigenemia may play a significant pathogenetic role in the development of IgA nephropathy in areas of high HBV endemicity and these HBV-associated IgA nephropathies can run an indolent but relentless slowly progressive clinical course.
Adult↗
Cyclosporin treatment of IgA nephropathy: a short term controlled trial.
Cyclosporin's known regulatory effects on the immune system suggest that it may be useful in treating patients with IgA nephropathy. A randomised prospective single blind study of 19 patients with IgA nephropathy and proteinuria (greater than 1.5 g/day) was conducted to determine the therapeutic value of cyclosporin. The patients were divided into two groups: nine patients were given oral cyclosporin (5 mg/kg/day) for 12 weeks and 10 patients a placebo. The two groups were comparable in age of presentation, ratio of men to women, plasma creatinine and serum IgA concentrations, creatinine clearance, daily urinary protein excretion, severity of renal histopathological changes, and prevalence of hypertension. A significant reduction of proteinuria and an increase of plasma albumin concentration was observed with treatment with cyclosporin. Nevertheless, a significant rise of plasma creatinine concentration and a fall in creatinine clearance was found in patients after six weeks' treatment with cyclosporin, although the plasma cyclosporin concentrations were maintained within a narrow therapeutic range. Serum IgA concentrations were reduced in seven patients. Renal function improved within eight weeks after treatment was stopped. Three months after treatment was stopped proteinuria remained less than half of the pretreatment values in three patients. No similar biochemical changes were observed in the controls. Short term cyclosporin therapy may be beneficial in reducing proteinuria in some patients with IgA nephropathy. As transient renal impairment was seen, despite cyclosporin concentrations being maintained within a narrow therapeutic range, indiscriminate use of cyclosporin in glomerulonephritis should be discouraged.
Adolescent↗
Multiple use of plasmafilters.
The practice of multiple use of membrane plasmafilters was examined in six patients receiving intermittent or regular plasmapheresis treatment. The plasmafilters were cleaned by flushing and ultrafiltration using positive pressure in the blood and filtrate compartments of the plasmafilter. Twenty-six plasmafilters were studied and the membrane permeability characteristics were examined during 56 plasmapheresis treatments with reused plasmafilters. The clearances of nitrogen urea and creatinine, and the sieving coefficients of albumin and immunoglobulins remained unchanged with the reuse of plasmafilters. The practice is safe, efficient, and can contribute to cost containment in plasmapheresis treatment.
Disposable Equipment↗
IgA nephropathy and membranous nephropathy associated with hepatitis B surface antigenemia.
This is the first report of glomerular disease in a 13-year-old boy who was a carrier of hepatitis B virus both mesangial IgA and subepithelial IgG deposits in the glomeruli at the same time. The clinical findings resembled those of IgA nephropathy. On electron microscopy, electron-dense deposits were identified not only in the mesangium but also on the epithelial side of the glomerular basement membrane. Immunofluorescence and immunoperoxidase staining demonstrated hepatitis B surface antigen and hepatitis B core antigen in the glomeruli but hepatitis B e antigen was not detected. Our findings suggest hepatitis B virus antigens have a pathogenetic role in the simultaneous development of these two glomerulopathies.
Adolescent↗
Plasma exchange in patients with rapidly progressive idiopathic IgA nephropathy: a report of two cases and review of literature.
Primary IgA nephropathy is generally considered an indolent disease, but progression to chronic renal failure is not uncommon, and a rapidly progressive course is observed in some cases, especially when extensive fibrocellular crescents are present. The therapeutic benefit of immunosuppression and plasma exchange remains controversial. We described two patients with primary IgA nephropathy and rapidly progressive renal failure. Both patients showed extensive glomerulosclerosis and crescent formation in their renal biopsies. Corticosteroid and immunosuppressive therapy failed to control the progression of the disease, and plasma exchanges were performed. In both cases, the serum creatinine and creatinine clearance initially improved with plasma exchange and the rapid progression of renal failure was apparently halted. In one patient, the serum creatinine rose when treatment was discontinued and fell again when plasma exchange was recommenced. Nevertheless, the long-term benefit of plasma exchange in crescentic IgA nephropathy was unsatisfactory as the renal function continued to deteriorate in the following 12 months despite an initial stabilization.
Adult↗