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S Jothy

Publications and source records attributed to S Jothy.

At least 73 records · Page 4Linked to original sources

Definition of the human renal cell carcinoma phenotype using monoclonal and polyclonal antibodies: a tumor marker study.

Previous studies have demonstrated a high level of heterogeneity associated with human renal cell carcinoma (RCC). In order to probe further this heterogeneity monoclonal antibodies were produced after immunization of mice with extracts of fresh renal tumor specimens. Four monoclonal antibodies designated LD-M1, LD-M2, LD-M5, and LD-M8 were generated and characterized immunohistochemically on a panel of tissue sections. The LD monoclonal antibodies strongly stained paraffin sections obtained from 77 to 100% of cases of RCC. Testing the sections with a library of polyclonal and monoclonal antibodies resulted in the definition of the following immunohistochemical phenotype of RCC: positive with the LD-M1, LD-M2, Ld-M5, LD-M8, Uro-2, Uro-7, Uro-10, cytokeratin, keratin, TPA, vimentin, Fx1A, retinol binding protein, CALLA and B72 antibodies; negative with the prekeratin, desmin, A5.48, uromucoid, and CEA antibodies. The pattern of immunohistochemical activity indicates that some RCC tumor cells contain epitopes associated with distal tubules in addition to previously documented antigens present in proximal tubules. Using a solid-phase competition radioimmunoassay it was observed that the serum of patients with renal cell carcinoma contains a circulating LD-M5-reactive tumor-associated antigen.

Antibodies↗

Crescentic glomerulonephritis in Behçet's syndrome--results of therapy and review of the literature.

The syndrome initially described by Behçet in 1937 comprised the triad of ocular inflammation, oral and genital ulcers. The described manifestations have gradually expanded to include most tissues; renal involvement has been described but is usually mild. Although crescentic glomerulonephritis (GN) has been reported, it is extremely rare. We report two patients presenting with Behçet's syndrome complicated by an active crescentic GN. Their course, following the initiation of therapy with prednisone and cyclophosphamide is described. Both patients evolved to a sclerosed glomerulopathy documented by follow-up renal biopsy in spite of a dramatic clinical improvement in one patient and a stabilization of renal function in the other. Both developed nephrotic range proteinuria without amyloidosis.

Adult↗

Immunohistologic diagnosis of multiple carcinomas. The role of monoclonal antibodies against carcinoembryonic antigen.

The occurrence of multiple malignant lesions in the same patient requires that management decisions be made from an accurate pathological identification of the tumours. The authors describe five patients who had colorectal adenocarcinoma preceded or followed by adenocarcinomas in other organs. Definitive identification could not be established from routine histopathologic findings. The use of immunohistochemistry helped to clarify the relationship between the various tumours; in particular, a monoclonal antibody (D14) directed against carcinoembryonic antigen (CEA) made a notable contribution. Because of the increasing number of monoclonal antibodies with well-defined tumour specificities, their use in the documentation of multiple malignant tumours has great clinical potential.

Adenocarcinoma↗

Protein G-gold immunoelectron microscopy of colon carcinoma: the effect of tumor differentiation on carcinoembryonic antigen immunostaining.

The distribution of carcinoembryonic antigen (CEA) in human colonic cancer cells was compared to normal colonic epithelial cells by the recently introduced protein G-gold immunoelectron microscopy method. Immunostaining for CEA was obtained in glutaraldehyde-fixed tissues, but tissues fixed in osmium tetroxide failed to retain CEA immunoreactivity. In normal colonic mucosa CEA was found on the brush border and in the apical vesicles of the absorptive cells. The labeling was most intense in the cells lining the upper crypts and luminal surfaces. Mucin granules of goblet cells were also labeled. Well-differentiated adenocarcinoma cells showed cytoplasmic and apical labeling sites similar to those of normal colonic epithelial cells and in addition labeling of the basolateral membranes. The latter sites were more intensely labeled in poorly differentiated cancer cells whereas the intracytoplasmic reactivity was less intense compared to well-differentiated tumor cells. One case of poorly differentiated adenocarcinoma showed no labeling. These results indicate that the cellular site and intensity of CEA expression are closely associated with cellular differentiation in colonic cancer cells. The findings are consistent with the hypothesis that the biosynthesis and processing of CEA are different in colonic cancer cells as compared to normal colonic epithelial cells.

Carcinoembryonic Antigen↗

Brief periods of myocardial ischemia followed by reperfusion: a model in the dog of sudden cardiac death in humans.

Most experimental interest has focused on the electrophysiologic mechanisms which may underlie sudden death. The purpose of the present study was to develop a model in the dog where ischemia would produce not just ventricular fibrillation but also histologic abnormalities similar to those previously reported in sudden death in humans. First, the collateral blood flow to a portion of the ventricle was surgically abolished and then the arterial blood supply to this region was interrupted for 15 minutes after which nutrient flow was restored for 30 minutes. If the animal survived, this cycle was repeated up to seven times. Thirty-six animals were studied: 15 controls (Group A) survived an average of 1.75 +/- 0.8 cycles (mean +/- SD); 11 others (Group B) received a loading dose of sodium verapamil and survived 3.7 +/- 1.8 cycles while 10 (Group C) received a continuous infusion as well as the loading dose of sodium verapamil and survived 4.4 +/- 2.6 cycles--the difference between each group being significant (p less than 0.05). Four animals in Group C survived all 7 cycles; out of the other 32, 27 fibrillated just after reperfusion and the rest during ischemia. Histological examination revealed small foci of contraction band necrosis widely interspersed amongst large areas of morphologically normal tissue. The beneficial effect of verapamil and the histologic findings suggest cellular calcium overload may be important in the genesis of the fatal arrhythmias produced by reperfusion.

Animals↗

Dyazide-induced reversible acute renal failure associated with intracellular crystal deposition.

Acute interstitial nephritis due to Dyazide therapy, ie, a combination of hydrochlorothiazide (25 mg) and triamterene (50 mg), has been recently reported in the literature. This had been characterized by nonoliguric renal failure after a long latent period (weeks) following exposure to the drug. Pathologic data have indicated a drug-induced hypersensitivity reaction. We report here one case of oliguric acute renal failure after a massive Dyazide intoxication. Based on the results of the renal biopsy and clinical course, we propose that the oliguria was secondary to a direct toxic effect on the tubules, and intrarenal obstruction was secondary to triamterene crystals and crystal-laden cells. In addition, pathologic findings also suggested a moderate hypersensitivity reaction. After hemodialysis and short-term steroid therapy, the patient achieved complete recovery of renal function within 12 days. Recent knowledge of triamterene-induced nephrolithiasis helps to explain the pathogenesis of acute renal failure in this patient, and is briefly reviewed here.

Acute Kidney Injury↗

Granulomatous nephritis and chronic renal failure in sarcoidosis. Long-term follow-up studies in two patients.

Sarcoid granulomatous nephritis was observed in 2 patients. Renal failure was present in both patients in the absence of hypercalcemia or nephrocalcinosis. Specific tubular dysfunction manifested as an acquired Fanconi syndrome in 1 patient. Steroid therapy was effective in causing regression of the renal granuloma, but there were significant interstitial changes on repeat renal biopsy which were accompanied by persistent tubular dysfunction. Sarcoid granulomatous nephritis may be a not infrequent cause of renal dysfunction in sarcoidosis.

Female↗

Characterization of monoclonal antibodies to carcinoembryonic antigen with increased tumor specificity.

Nine monoclonal antibodies reacting with carcinoembryonic antigen (CEA) were produced after immunization of mice with either purified CEA or a CEA-producing human cell line. Their specificities were assessed by immunohistochemistry on tissue sections of neoplastic and nonneoplastic lesions. These monoclonal antibodies have different patterns of tissue reactivity. Two of them, D14 and B18, were found to have a high degree of specificity for colonic carcinoma and did not react with formalin-fixed paraffin-embedded sections of normal colon with standardized staining conditions. Most cases of noncolonic adenocarcinomas and normal epithelial structures were not stained by these two monoclonal antibodies. The specificity of the monoclonal antibodies was further investigated immunochemically using intact, reduced, and alkylated or chemically fragmented CEA. Liquid phase radioimmunoassays and antibody competition immunoenzymatic assays confirmed that the antibodies recognize different epitopes of CEA. These data support the concept of CEA heterogeneity and the reactivity of the D14 and B18 monoclonal antibodies with colonic adenocarcinomas indicates that they are useful immunohistochemical probes.

Animals↗

A prospective study on the impact of the renal biopsy in clinical management.

A three year prospective study involving 80 patients was conducted to assess the impact of renal biopsy on clinical management. Pre-biopsy predicted histologic diagnosis was changed in 35 (44%) of the patients as a result of the biopsy. Prognosis changed in 45 (57%) of the patients. Therapy changed in 25 (31%) of the patients. These results suggest that, overall, renal biopsy had a marked effect on management. However, we identified subgroups of patients who were unlikely to have their management changed as a result of the biopsy: of 16 patients with a pre-biopsy diagnosis of IgA nephropathy, 1 (6%) had treatment changed because of the biopsy; and of the 50 patients without heavy proteinuria (greater than 3 g/24 h), 10 (20%) had treatment changed because of the biopsy. Although our overall results suggest an important role for renal biopsy in clinical management, renal biopsy has the least apparent impact in patients with a pre-biopsy diagnosis of IgA nephropathy or without heavy proteinuria.

Biopsy↗

Decreased population of Leu-7+ natural killer cells in lymph nodes of homosexual men with AIDS-related persistent lymphadenopathy.

Natural killer (NK) cells were studied in the lymph nodes of homosexual men with the persistent lymphadenopathy syndrome (PLS) and other signs of the disease complex related to the acquired immune deficiency syndrome (AIDS). The NK cells were identified by their Leu-7+ phenotype and enumerated in frozen sections of lymph nodes in conjunction with the quantification of T-lymphocyte subsets. Lymph nodes from patients with AIDS-related PLS contained 91% and 81% fewer NK cells than normal lymph nodes and lymph nodes from patients with non-AIDS-related hyperplastic lymphadenopathy respectively. This decrease in NK cells in PLS is consistent with the immune dysregulation leading to persistent infection and neoplasia in AIDS.

Acquired Immunodeficiency Syndrome↗

Aggressive angiomyxoma of pelvic soft parts: a clinicopathologic study of nine cases.

Nine cases of aggressive angiomyxoma (AAM) of the pelvic soft parts were studied by light and electron microscopy and immunohistochemistry. The tumors were confined to the vulva, vagina, pelvic floor, and perineum in the seven women. The perineum and the para-anal region were involved in the two men. The patients ranged in age from 18 to 63 years. Aggressive angiomyxoma presented as a slowly growing, polypoid or cyst-like tumor. Six of the nine cases were followed up; all of the tumors recurred within nine to 84 months, and one recurred for the second time at 144 months. Recurrences were attributed to incomplete tumor excision. None of the six patients died or had metastases. The aggressive angiomyxomas had infiltrative borders and rubbery, white or soft, gelatinous cut surfaces. Histologically, the lesions were composed of stellate and spindle-shaped neoplastic cells embedded in a collagenous and hyaluronic acid-containing stroma. Nuclear atypia and mitoses were absent. Typically, the lesions had an important vascular component, often displaying medial hypertrophy and vascular grouping. Ultrastructurally, the neoplastic cells resembled fibroblasts rather than myofibroblasts. They showed strong immunoreactivity for actin but were negative for S-100 protein, Factor VIII, carcinoembryonic antigen, and keratin. The morphoimmunocytochemical characteristics of AAM cells favor a fibroblastic origin and differentiation. Aggressive angiomyxoma should be distinguished from the more common benign and malignant myxoid neoplasms or tumor-like conditions of the pelvic soft parts. Recurrence of AAM may be avoided by wide, local excision.

Adolescent↗

Immunohistochemical demonstration of T-lymphocyte subsets in tissue sections using monoclonal antibodies: a 3-layer PAP system and comparison of three immunoperoxidase methods.

Several immunohistochemical systems have been described to study T cells and their subsets in cryostat sections using monoclonal antibodies. In this report tonsils were studied by 2-layer and 4-layer immunoperoxidase techniques. In addition a 3-layer immunoperoxidase method using mouse PAP is proposed. The 2-layer technique proved unsatisfactory due to insufficient sensitivity. The other methods were characterized by comparably high sensitivity. The mouse PAP 3-layer system gave the most specific results due in particular to the complete absence of immunoglobulin staining in the germinal centers.

Antibodies, Monoclonal↗

The spectrum of diseases associated with necrotizing glomerulonephritis and its prognosis.

Necrotizing glomerulonephritis (NGN) represents small-vessel vasculitis in the kidney. To assess the diseases associated with necrotizing glomerular changes and their prognosis we studied all 32 patients who had this histologic finding on kidney biopsy from 1969 to 1982 and compared them to those patients who had crescentic, diffuse, or focal and segmental glomerulonephritis without necrosis (n = 29). The diseases associated with NGN were systemic lupus erythematosus (n = 6/15), Henoch-Schönlein purpura (n = 3/4) Goodpasture's syndrome (n = 4/7), Wegener's granulomatosis (n = 6/6), polyarteritis (n = 4/5), infective endocarditis (n = 2/3), and idiopathic rapidly progressive glomerulonephritis (n = 7/21). Necrotizing glomerulonephritis occurred significantly more often in the vasculitides than in all the other disorders put together. The most difficult diagnosis problem occurred in patients with renal disease and pulmonary hemorrhage (n = 9), in three of whom diagnosis was uncertain even after autopsy (two autopsies done within one month and one within three months of presentation). A fourth patient had a linear staining for IgG along the glomerular basement membrane (GBM) on kidney biopsy but was subsequently diagnosed as having Wegener's granulomatosis. Comparison of patients with without NGN revealed no difference in outcome (death or dialysis) one year after biopsy (38% v 43%) or in serum creatinine levels one year later (4.6 v 4.8 mg/dL). The prognostic effect of NGN was not obscured by unequal distribution of other adverse prognostic factors in the two groups. The most important prognostic characteristics we identified for outcome were serum creatinine at biopsy (chi 2 = 24.0, P less than .0004) and the sum of activity and chronicity indexes on biopsy (chi 2 = 12.7, P = .0004). These variables were similarly distributed in patients with and without necrosis, mean serum creatinine levels at biopsy being 4.3 v 4.2 mg/dL and sum of indexes 7.8 v 8.0. Other factors such as clinical diagnosis and therapy were not important prognostically and therefore could not explain our results. We conclude that NGN in patients with active proliferative glomerulonephritis has multiple causes. Diagnostic difficulties occurred in those with anti-GBM-negative pulmonary hemorrhage. The appearances of small-vessel vasculitis in the kidney did not appear to have prognostic significance.

Adolescent↗

Diagnostic value of kidney biopsy in heterozygous Fabry's disease.

We studied a case of abnormal renal pathologic findings in a female patient that were suggestive of Fabry's disease. Except for corneal clouding, no other clinical findings were consistent with this diagnosis. The serum and urinary enzyme levels were all within normal limits; the ceramide trihexoside level was slightly increased in the urine. We examined the pathologic changes in the context of the present knowledge of renal lesions in storage diseases.

Adult↗

Late development of purpura in a patient with glomerulonephritis.

A 20-year-old man with a 10-year history of glomerulonephritis presented with a purpuric rash on his legs. A renal biopsy specimen obtained when he was 11 years old had shown mesangial glomerulonephritis; staining 9 years later for IgA had negative results. A second renal biopsy, performed when the rash was present, revealed mesangial glomerulonephritis and mesangial deposits of IgA; biopsies of the involved skin showed leukocytoclastic vasculitis. In this case isolated glomerulonephritis appeared to change to a multisystem illness, with a different immunologic character, through one of several possible pathogenetic mechanisms.

Adult↗

Ultrastructural markers of lymph nodes in patients with acquired immune deficiency syndrome and in homosexual males with unexplained persistent lymphadenopathy. A quantitative study.

To determine if vesicular rosettes (VR), tubuloreticular structures (TRS), and "test-tube and ring-shaped forms" (TRF) are characteristic ultrastructural features of the syndromes of acquired immune deficiency (AIDS) or of unexplained persistent lymphadenopathy (PLS), the authors studied lymph nodes from nine patients with PLS, two patients with AIDS, and seven controls by electron microscopy. An average of 122 lymphocytes per case were photographed. VR were present in only 0.37% of lymphocytes in 4 of 11 index cases and were mimicked by grouped vesicles and degenerating multivesicular bodies (MVB). TRS were found in 10 of 11 index cases, compared with only one of seven controls (P less than 0.01). In the index cases, they were more frequent in AIDS (mean 21%) than in PLS lymphocytes (mean 4%) (P less than 0.05). MVB were found in all index cases and five of seven controls and were more frequent in index lymphocytes (mean 19%) than in controls (mean 5%) (P less than 0.01). TRF were found in one Haitian male with AIDS, where they were present in 4% of lymphocytes. VR are infrequent and indistinct. MVB probably reflect the reactivity of the lymphocytes. TRF is not a feature of PLS. The authors conclude that there are no pathognomonic ultrastructural markers of AIDS or PLS but that TRS are characteristic of both syndromes and occur frequently enough to be supportive to the diagnosis of AIDS and PLS.

Acquired Immunodeficiency Syndrome↗

Persistent generalized lymphadenopathy in homosexual men: clinical, pathological and immunologic characteristics.

Eighteen homosexual men who had had lymphadenopathy in two or more extrainguinal sites for more than 5 months but had no evidence of other illnesses or infections were studied. All had extreme malaise, and 90% had additional symptoms (fever, night sweats, weight loss or gastrointestinal dysfunction). They were compared with 10 healthy homosexual and 10 healthy heterosexual male controls. The mean numbers of circulating T8 (suppressor) lymphocytes were increased equally in the two homosexual groups, but the mean number of T4 (helper) lymphocytes was decreased only in the group with lymphadenopathy. The response to testing for recall anergy was diminished in both homosexual groups but was significantly lower in the group with lymphadenopathy. The serum immunoglobulin and complement concentrations and the numbers of circulating B lymphocytes were normal in each group. Seven of nine lymph node biopsy specimens showed characteristic hyperplasia and confluence of follicles. Thus, idiopathic persistent, generalized lymphadenopathy in homosexual men without opportunistic infections or malignant diseases appears to be a distinct syndrome; it may also be related to the acquired immune deficiency syndrome.

Adult↗