Biomedical subjects

K M Das

Publications and source records attributed to K M Das.

At least 37 records · Page 2Linked to original sources

PubMed1999

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

Administration, Oral↗

PubMed1999

Intratesticular varicocele: evaluation using conventional and Doppler sonography.

OBJECTIVE: The aim of this study was to describe the conventional and Doppler sonographic appearances of intratesticular varicoceles and to determine their occurrence. SUBJECTS AND METHODS: One thousand forty men with various testicular problems were examined using conventional and Doppler sonography, and the incidence of intratesticular varicocele and other conditions was recorded. Eighteen patients with intratesticular varicoceles were further examined, allowing us to study the various sonographic and Doppler parameters of this rare entity. RESULTS: Intratesticular varicocele was identified in 18 (1.7%) patients. The condition was bilateral in seven patients and unilateral in 11. Of 25 testes involved, 12 (48%) were right-sided and 14 (56%) were isolated without any ipsilateral extratesticular varicocele. The shape of the intratesticular varicocele was tubular in 21 cases and oval in five; one patient had both oval and tubular varicoceles. Diameters ranged from 2 to 8 mm (mean, 3.1 mm). Mean venous flow velocity was 2.8 cm/sec and had an inverse relationship to the diameter of the intratesticular varicocele. CONCLUSION: Intratesticular varicocele is seen in fewer than 2% of the symptomatic population. The condition has a characteristic sonographic appearance of dilated tubular intratesticular veins with a proximity to the mediastinum testis. Variations from previously published reports included presentation with an oval shape, more frequent bilateral occurrence, greater number of isolated right-sided intratesticular varicoceles, and fewer associations with an extratesticular varicocele.

Adult↗

PubMed1998

Tropomyosin isoforms in intestinal mucosa: production of autoantibodies to tropomyosin isoforms in ulcerative colitis.

BACKGROUND & AIMS: Autoantibodies against tropomyosins (TMs) have been reported in ulcerative colitis (UC). In this study the hTM isoforms (hTM1-5) present in intestinal epithelial cells and in smooth muscle were investigated, and the immunoreactivity against hTMs by immunoglobulin G (IgG) produced in vitro by colonic mucosal lymphocytes (LPMCs) from patients with UC, Crohn's disease (CD), and controls was examined. METHODS: TMs were extracted from colonic and jejunal epithelial cells and smooth muscle, and hTM isoforms were identified using isoform-specific monoclonal antibodies by enzyme-linked immunosorbent assay and transblot analysis. The immunoreactivity of IgG produced by colonic LPMCs was analyzed against the recombinant hTM isoforms. RESULTS: The major hTM isoforms present in colonic and jejunal epithelial cells are hTM5 and hTM4, whereas intestinal smooth muscle contains the hTM1-3 isoforms. The IgG synthesized in vitro by LPMCs from UC (n = 19) recognized hTM5 and hTM1, more significantly (P < 0.04 to <0.001) when compared with CD (n = 12) and controls (n = 17). However, IgG produced by LPMCs from CD did not show such anti-hTM reactivity. Mucosal anti-hTM IgG mainly belonged to the IgG1 subclass. CONCLUSIONS: Intestinal epithelial cells and smooth muscle have distinct hTM isoforms. Patients with UC, and not CD, show mucosal autoantibody response against hTM isoforms, particularly hTM5 and hTM1.

Adult↗

PubMed1998

The monoclonal antibody 7E12H12 can differentiate primary adenocarcinoma of the bladder and prostate.

OBJECTIVE: To determine if the monoclonal antibody 7E12H12, which reacts with a 40 kDa protein in normal human enterocytes and has been shown to be a marker for intestinal metaplasia and adenocarcinoma arising in the bladder, could assist in distinguishing prostatic, urachal and vesical adenocarcinoma, using a sensitive immunohistochemical assay. MATERIALS AND METHODS: Fifteen primary prostatic adenocarcinomas and five adenocarcinomas of the urinary bladder were selected for a retrospective evaluation. The monoclonal antibody 7E12H12 (IgM isotype) was used in an immunoperoxidase assay to survey formalin-fixed, paraffin-embedded archival tissue specimens. RESULTS: All vesical adenocarcinomas reacted positively with the antibody, regardless of grade; none of the 15 prostatic specimens reacted positively in either the benign or malignant glandular epithelium. CONCLUSION: The monoclonal antibody 7E12H12 can differentiate primary adenocarcinoma of the bladder from secondary adenocarcinoma arising in the prostate and may be a useful tool in diagnostic pathology.

Adenocarcinoma↗

PubMed1997

Adenocarcinoma of the urachus and bladder expresses a unique colonic epithelial epitope: an immunohistochemical study.

PURPOSE: Primary adenocarcinoma of the bladder is a rare neoplasm whose histogenesis is poorly understood. Current data support the concept that adenocarcinoma of the bladder and urachus evolves from zones of intestinal metaplasia that become dysplastic and invasive. To address this hypothesis further we determined the immunoreactivity of benign and malignant epithelial tissue from the bladder and urachus with a monoclonal antibody that is reactive with colonic epithelium to evaluate the presence of a common reactive epitope. MATERIALS AND METHODS: The monoclonal antibody 7E12H12 (IgM isotype), developed against a colonic epithelial protein, was used in an immunoperoxidase assay to survey formalin fixed, paraffin embedded archival tissue specimens. A total of 26 specimens obtained by endoscopic biopsy or extirpative surgery, including benign and malignant bladder and urachal epithelial abnormalities, was chosen for retrospective evaluation. RESULTS: All adenocarcinoma reacted positively regardless of the histological variant, differentiation, or bladder or urachal origin. In contrast, transitional cell and squamous cell carcinomas were nonreactive. Also, the pattern of reactivity in tissues that contained benign epithelial proliferations suggested a stepwise transition with no reactivity in normal urothelium or Brunn's epithelial nests, rare staining of cystitis cystica, and uniformly positive reactivity in cystitis glandularis and frank colonic intestinal metaplasia of the bladder and urachus. CONCLUSIONS: The shared, aberrant phenotypic expression of a unique colonic epitope in benign epithelial metaplasia, and adenocarcinoma of the bladder and urachus suggests a common underlying pathway toward adenocarcinoma in cystic and urachal adenocarcinoma. The implications for diagnostic pathology are discussed.

Adenocarcinoma↗

PubMed1997

Computed tomography features of lung parenchymal changes in pulmonary tuberculosis.

Twenty-five patients with active pulmonary tuberculosis were prospectively studied with CT. Three major parenchymal patterns were noted. The nodular opacities pattern was seen in all cases. Confluent consolidation was seen in 37% of patients and consolidation with associated loss of volume (CWALV) was seen in 69% of patients. High-resolution CT (HRCT) features of bronchogenic spread included (i) a centrilobular nodule or a branching linear structure (92.3%); (ii) bronchial wall thickening (61.5%); (iii) a 'tree in bud' appearance (92.3%); and (iv) poorly marginated 5-8 mm nodules (61.5%). Most of the patterns showed satellite lesions in the form of small nodules or peripheral areas of increased attenuation. Cavitation was most common in CWALV lesions. Bronchiectasis was a common accompaniment (81.3%), and its occurrence paralleled the distribution of parenchymal lesions. Associated pleural thickening was noted in half the cases. To conclude, distinctive parenchymal changes were noted with CT in cases of pulmonary tuberculosis, which may suggest the diagnosis in the appropriate clinical setting.

Adult↗

PubMed1996

Characterization of the mucins produced by normal human colonocytes in primary culture.

Mature goblet cells filled with mucin ready for secretion represent about one third of the cells in primary cultures of human colonocytes. In the present study characterization of the mucins produced by cultured human colonocytes was made by histochemical methods by lectin and monoclonal antibody binding. Two monoclonal antibodies and three lectins (Dolichos biflorus (DBA), Helix pomatia (HPA) and Arachis hypogea (PNA) recognizing epitopes or sugar haptens characteristic of different stages of mucin glycoprotein maturation, were employed. The reactivity to these probes was tested both on cultured colonocytes and on tissue sections of the normal colon mucosa. The results show that the mucins produced in culture are glycosylated to the mature form, as they show the same reactivity to lectins and antibodies of the mucins expressed in tissue sections of the normal colon mucosa. In addition, it is demonstrated that cultured human colonocytes do not express mucins reactive to PNA, which are characteristic of tumors. Since the cultured colonocytes maintain the expression of differentiated functions for at least three days, they may offer a useful model to study metabolism, function and regulation of colon mucins in health and disease.

Adult↗

PubMed1996

Ulcerative colitis: pathogenesis, diagnosis, and current treatment.

Ulcerative colitis is a chronic inflammatory disease of the colon that affects the rectum and a variable length of contiguous colon. The disease is characterized by rectal bleeding and diarrhea during periods of exacerbation; these symptoms usually abate with treatment. The pathogenic mechanism of ulcerative colitis is believed to be an aberrant immune response in which antibodies are formed against colonic epithelial protein(s). The disease usually presents during the second and third decades of life, with a smaller peak after the age of 60 years. There is a genetic component to ulcerative colitis, with a higher incidence among family members and, particularly, first-degree relatives. Diagnosis depends on several factors, most notably symptoms, demonstration of uniformly inflamed mucosa beginning in the rectum, and exclusion of other causes of colitis, such as infection. There is no medical cure for ulcerative colitis, but medical therapy is effective and can improve or eliminate symptoms in more than 80% of patients. Surgery offers a cure but carries the high price of total colectomy. New surgical methods, such as ileoanal anastomosis, allow for maintenance of bowel continuity and better patient satisfaction.

Aminosalicylic Acids↗

PubMed1995

Development of ulcerative colitis-associated anti-idiotype antibody using a novel monoclonal antibody against a colonic autoantigen.

Earlier studies have established reactivity of ulcerative colitis colon-bound IgG antibody with an autoantigen recognized by a novel monoclonal antibody, 7E12H12 (IgM isotype). Purified 7E12H12-IgM was used to raise anti-idiotype antibody in the rabbit, and the presence of disease-specific idiotype(s) was evaluated in patients with ulcerative colitis. F(ab')2 fragments were prepared from serum-IgG of the rabbit immunized with 7E12H12-IgM and extensively absorbed against unrelated mouse IgM and purified serum IgG from 4 normal subjects. The reactivity of the absorbed F(ab')2 fragment was tested in an ELISA against the serum from 19 patients with ulcerative colitis, 15 patients with Crohn's disease, and 10 normal subjects. The OD values with ulcerative colitis sera were significantly (P < 0.0005) higher than those with Crohn's disease and normal sera. Blood serum from 84% of patients with ulcerative colitis contains antibodies that are reactive to the F(ab')2 fragments of the immune rabbit serum-IgG. Further studies of the anti-idiotype antibodies may elucidate autoimmune processes in ulcerative colitis and may have diagnostic and therapeutic values.

Animals↗

PubMed1995

Production of immunoglobulin G and G1 antibodies to cytoskeletal protein by lamina propria cells in ulcerative colitis.

BACKGROUND & AIMS: Recent studies suggest an autoantigenic role for tropomyosin-related protein(s) in ulcerative colitis (UC). This study examined whether immunoglobulin G and G1 subclass antibodies against tropomyosins are produced spontaneously by the lamina propria mononuclear cells (LPMCs) that infiltrate the inflamed UC tissue. METHODS: LPMCs were isolated from colonic biopsy specimens from 29 patients with UC, 15 with colonic Crohn's disease (CD), and 13 with non-inflammatory bowel disease (IBD). The autologous peripheral blood mononuclear cells (PBMCs) were obtained. Cells were cultured in vitro and unstimulated for 10 days. Spontaneous production of immunoglobulin G and G1 antibodies against tropomyosins was measured by enzyme-linked immunosorbent assays using highly enriched tropomyosins from skeletal muscle and colonic mucosa. RESULTS: The total immunoglobulin G produced by LPMCs from both patients with UC and CD was comparable but higher than from patients with non-IBD (P < 0.05). However, immunoglobulin G antibodies to tropomyosins were higher in patients with UC than in patients with CD (P < 0.04) and non-IBD (P < 0.02). LPMCs from patients with symptomatic UC produced higher immunoglobulin G antibodies to tropomyosins than patients with UC in remission (P < 0.03), symptomatic CD (P < 0.04), and non-IBD (P < 0.02). Immunoglobulin G antibodies to tropomyosins predominantly belonged to immunoglobulin G1 subclass. The autologous PBMCs showed comparable results. CONCLUSIONS: Immunoglobulin G antibodies predominantly belonging to immunoglobulin G1 subclass and reactive against tropomyosin-related protein(s) are spontaneously produced by LPMCs from the colonic mucosa in patients with UC.

Adolescent↗

PubMed1995

Expression of a unique protein on colon cancer cells that reacts with a novel monoclonal antibody and ulcerative colitis serum.

We earlier developed a MoAb, 7E12H12 (IgM isotype), against a protein present in normal colonic epithelial cells. To examine if 7E12H12-reactive protein is expressed in colon cancer cells and is recognized by ulcerative colitis (UC)-associated autoantibody, we investigated several colon cancer cell lines. 7E12H12 reactivity against the cells was examined by indirect immunofluorescence assay and whole cell ELISA against six colon cancer cell lines HT-29, LoVo, COLO 205, DLD-1, LS 180 and SW 1116. A competitive ELISA was developed using 7E12H12 MoAb and patients' serum to examine the cross-reactive antibodies in the serum. Among the six colon cancer cell lines only LS 180, DLD-1 and SW 1116 reacted with 7E12H12 MoAb, while others did not. The mean (+/- s.e.m.) inhibition of the binding of 7E12H12 MoAb to LS 180 cells by UC serum (n = 51) was 42 +/- 2.1%, whereas in normal subjects (n = 17) it was 14 +/- 2.6%, in Crohn's disease (n = 19) it was 15.3 +/- 2.5%, in infectious diarrhoea (n = 10) it was 11% +/- 3%, and in systemic lupus erythematosus (n = 10) it was 2% +/- 0.6%. The inhibition by the UC group was significantly (P < 0.001 - < 0.0001) higher than any of the non-UC groups, and this inhibition was mainly by IgG1 antibody. The protein in the specific colon cancer cells recognized by the 7E12H12 MoAb cross-reacts with UC-IgG1 antibody and may provide an in vitro system to examine the autoimmune mechanisms in UC.

Adolescent↗

PubMed1995

Epithelial deposits of immunoglobulin G1 and activated complement co-localize with the "M(r) 40kD" putative auto-antigen in ulcerative colitis.

In conclusion, the "M(r) 40kD" antigen is expressed on the apical face of colonic enterocytes often in spatial relation to immune complexes in active UC, apparently targeting an IgG1-mediated autoimmune attack. Thus, our findings support the notion that an autoimmune response to the "M(r) 40kD" antigen, with local production of specific IgG1, is a possible immunopathological mechanism(s) in UC.

Autoantigens↗

PubMed1994

Detection of a shared colon epithelial epitope on Barrett epithelium by a novel monoclonal antibody.

OBJECTIVE: To determine if there is a reactive epitope common to colonic epithelium and Barrett epithelium, a premalignant metaplastic columnar-lined esophagus, usually arising as a complication of chronic reflux esophagitis. DESIGN: A monoclonal antibody, 7E12H12 (IgM isotype), developed against a colonic epithelial protein was used in a sensitive immunoperoxidase assay using formalin-fixed, paraffin-embedded tissue. One hundred sixteen tissue specimens from the esophagus, stomach, duodenum, and jejunum were examined. Twenty-two biopsy specimens were taken from 22 patients with benign Barrett epithelium, and 12 specimens were obtained from 12 patients with adenocarcinoma of the esophagus arising in Barrett epithelium. The remaining 85 tissue specimens were obtained from various parts of the upper gastrointestinal tract of patients with or without disease states. RESULTS: 21 of 22 (95%) Barrett epithelium specimens and all 12 adenocarcinomas arising from Barrett epithelium reacted with the 7E12H12 monoclonal antibody. Other tissues from esophagus, gastroesophageal junction, stomach, duodenum, or jejunum did not react. Squamous cell carcinoma of the esophagus also did not react. CONCLUSIONS: Barrett epithelium shares phenotypic expression of colonic epithelium. The 7E12H12 monoclonal antibody may provide insight into the origin and cellular lineage of Barrett epithelium.

Adenocarcinoma↗

PubMed1994

A shared and unique peptide in the human colon, eye, and joint detected by a monoclonal antibody.

BACKGROUND/AIMS: Extraintestinal manifestations of inflammatory bowel disease include involvement of the eye and joint. However, the pathogenesis of ocular and joint complications is unknown. The aim of the current study is to examine the presence of cross-reactive peptide in the colon and ocular and joint tissue. METHODS: Using a murine monoclonal antibody (7E12H12; immunoglobulin M isotype) developed against a colon epithelial protein, various parts of the eyes (n = 10) and joints (n = 8) were examined. A sensitive immunoperoxidase assay was used. RESULTS: In the ocular and joint tissues, the reactivity of 7E12H12 monoclonal antibody was exclusively present in the nonpigmented epithelial cells of the ciliary processes and chondrocytes, respectively. Other structures of the eyeball, such as the sclera, cornea, iris, and retina, and the synovium of the joints did not react with 7E12H12 monoclonal antibody. Colonic epithelial cells examined in parallel also reacted with the monoclonal antibody. CONCLUSIONS: The colon epithelial cells share a unique peptide with the nonpigmented ciliary epithelial cells and chondrocytes. Future studies of the peptide(s) expressing this common epitope shared by the colon and extracolonic organs known to be involved in colitis may provide further understanding of the pathogenesis of extraintestinal complications in patients with ulcerative colitis.

Antibodies, Monoclonal↗

PubMed1994

Autoantibodies in sclerosing cholangitis against a shared peptide in biliary and colon epithelium.

BACKGROUND/AIMS: A strong association exists between ulcerative colitis and primary sclerosing cholangitis (PSC). Previously, the presence of a unique epitope shared by colon and biliary epithelial cells was shown by using the novel monoclonal antibody (MAb) 7E12H12 developed against a colonic epithelial protein. In the present study, the presence of circulating autoantibody in PSC against this peptide was examined. METHODS: Sera from 16 patients with PSC, 13 with primary biliary cirrhosis, 6 with secondary biliary stricture, and 6 with chronic liver diseases and 10 normal subjects were used. An inhibition immunoperoxidase assay using the 7E12H12 MAb was developed against sections of bile duct and gallbladder. Sera were also examined in an enzyme-linked immunosorbent assay (ELISA) against the gallbladder extract enriched in 7E12H12-reactive protein. RESULTS: About two thirds of the sera from patients with PSC blocked the binding of 7E12H12 MAb on the bile duct and gallbladder, whereas non-PSC sera did not. In the ELISA, 93% of PSC sera had circulating immunoglobulin G antibodies against the enriched gallbladder extract. The reactivity of sera from the PSC group was significantly (P < 0.01 to P < 0.0001) higher than in each of the non-PSC groups. CONCLUSIONS: Sera from patients with PSC contains autoantibodies against a cross-reactive peptide shared by colon and biliary epithelial cells.

Adult↗

PubMed1994

Circulating immunoglobulin G1 antibody in patients with ulcerative colitis against the colonic epithelial protein detected by a novel monoclonal antibody.

Autoimmunity has been implicated in the pathogenesis of ulcerative colitis (UC). Several studies have shown amplified immunoglobulin G1 (IgG1) antibody response in UC; however the immunoreactive antigen(s) is unknown. To study this antigen(s), mucosal colonic extract was prepared by sonication, ultracentrifugation followed by ion exchange chromatography in fast protein liquid chromatography. The fraction (enriched colonic peptide), that was most reactive to a novel monoclonal antibody, 7E12H12 (IgM isotype), was isolated and used to examine the immunoreactivity against the patients' serum samples. Two hundred and thirteen coded samples from 111 patients with UC (symptomatic and untreated (63), symptomatic and treated (26), remission (22)); 47 with Crohn's disease (CD) (40 were symptomatic and untreated, and 30 had colonic disease); 29 with acute diarrhoea caused by specific pathogen(s); 10 with systemic lupus erythematosus, and 16 normal subjects were examined against the enriched colonic peptide by IgG subtype specific enzyme linked immunosorbent assays (ELISAs). Total IgG antibody reactivity was significantly (p < 0.01) higher only in symptomatic and untreated UC patients compared with each of the non-UC group, but the sensitivity was only 50%. IgG2 and IgG3 reactivities were not different among various groups. The IgG1 antibody reactivity against the enriched colonic peptide, however, differentiated UC patients from CD and each of the other non-UC groups. Seventy nine per cent of the patients with UC, treated or untreated, symptomatic or in remission, had significantly (p < 0.0001) higher IgG1 antibody against the enriched colonic peptide when compared with each of the other non-UC groups. Only 12% of CD serum samples and none of the other control serum samples reacted. Using purified serum IgG1 and 7E12H12-IgM, by 7E12H12 reactive peptide indeed reacts with UC-IgG1 antibody but not with control IgG1.

Adolescent↗

PubMed1993

Autoimmunity to cytoskeletal protein tropomyosin. A clue to the pathogenetic mechanism for ulcerative colitis.

Autoimmunity has been emphasized in the pathogenesis of ulcerative colitis and various anticolon antibodies have been described. Nevertheless, the nature of the autoantigens has been elusive. Using ulcerative colitis colon-eluted IgG antibody, we earlier detected an M(r) 40,000 protein, P40, in colon extract. In our study, we purified P40 from human colon to apparent homogeneity, sequenced two peptides after proteolytic digestion, and demonstrated that the P40 belongs to the tropomyosin family. Furthermore, we demonstrated that blood serum from 95% of patients with ulcerative colitis contains antibodies that are reactive to tropomyosin.

Adolescent↗

PubMed1993

Amplified expression of intercellular adhesion molecule-1 (ICAM-1) and M(r) 40K protein by DLD-1 colon tumor cells by interferon-gamma.

Inflammatory bowel disease, in particular ulcerative colitis, is characterized by localization of leukocytes in close proximity to the colonic epithelium, which may be mediated by the expression of intercellular adhesion molecules (ICAM-1; CD 54). We previously reported the presence of an organ-specific M(r) 40K colonic protein that acts as an autoantigen in ulcerative colitis and is present on the surface of colonic epithelial cells and also in DLD-1 colon cancer cells. Using the colon tumor cell line DLD-1 and flow cytometry, ICAM-1 antibody binding by untreated cultured DLD-1 cells was similar to background antibody binding (mean channel number, MCN = 9.77 +/- 2.13). Interferon-gamma (100 U) induced a 1-2 log increase in anti-ICAM-1 antibody binding from as early as 12 hr after exposure up to 72 hr and a moderate increase (up to about 100%) in the binding of anti-M(r) 40K antibody. Additional studies showed that anti-ICAM-1 and anti-M(r) 40K antibodies bound to DLD-1 cells regardless of the presence of the other antibody. Taken together, the present observations suggest that the epitopes of ICAM-1 and M(r) 40K molecules are coexpressed by colonic epithelial cells, regardless of the presence of the other molecule. Furthermore, lymphocytes in the colonic mucosa that are activated to produce interferon-gamma may upregulate the expression of both of these molecules.

Autoantigens↗