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Biomedical subjects

A K Bhan

Publications and source records attributed to A K Bhan.

At least 19 recordsLinked to original sources
PubMed1992

Oligoclonality of human intestinal intraepithelial T cells.

T cells bearing the T cell receptor alpha/beta (TCR-alpha/beta) are the predominant lymphocyte population in the human intestinal epithelium. To examine if normal intestinal intraepithelial lymphocytes (IEL) have a TCR repertoire distinct from the TCR-alpha/beta repertoire in peripheral blood lymphocytes (PBL), comparative analysis of relative V beta gene usage in IEL and PBL was performed by quantitative polymerase chain reaction. In each of the six individuals examined, one to three V beta families made up more than 40% of the total V beta transcripts detected in the IEL, whereas there was a more even distribution of V beta gene usage in the paired PBL. The predominant V beta families, especially V beta 1, V beta 2, V beta 3, and V beta 6, were frequently shared among IEL of different individuals. PCR cloning and sequence analysis of the predominant V beta 6 family in two individuals revealed an identical V-D-J-C sequence in 13 of 21 clones obtained from one donor, and a different repeated sequence in 18 of 27 clones examined in the second donor. These data suggest that the V beta skewing in IEL is due to an oligoclonal T cell expansion and may reflect the response of the intestinal mucosal immune system to a restricted set of as yet undefined antigens present in the gut.

Amino Acid Sequence↗
PubMed1991

Lymphocytes with a CD4+ CD8- CD3- phenotype are effectors of experimental cutaneous graft-versus-host disease.

Graft-versus-host disease (GVHD) is known to cause profound dysregulation of the immune system, although its effector mechanisms are poorly understood. We now describe an effector lymphocyte of unusual phenotype in the skin of mice with GVHD. This cell is of donor origin and expresses several T-cell surface proteins including Thy-1, CD2, and CD4 but does not express CD8, CD3, NK1.1, or macrophage antigens. Mononuclear cells of this phenotype are the predominant lymphocyte in the epidermis of mice with GVHD 3 weeks after transplant but are not detected in transplanted mice without GVHD. Isolation and transfer of these lymphocytes into secondary recipients causes epidermal damage characteristic of GVHD. These data demonstrate that CD4+ CD8- CD3- lymphocytes are an important effector population that can be amplified outside the thymus and that can mediate target organ damage of GVHD.

Animals↗
PubMed1991

Human intestine matures as nude mouse xenograft.

This report describes a novel system for the study of the development and function of human intestine. Human fetal bowel transplanted into a subcutaneous tunnel on the back of athymic nude (nu/nu) mice develops a new microcirculation within 4 weeks. Tissues undergo morphological development, become similar to adult human bowel tissue, and may survive for 6 months after transplantation. Monoclonal antibody immunoperoxidase staining shows that the epithelial and some endothelial elements are of human phenotype, but the circulating blood cells and migrating mucosal lymphocytes are of mouse origin.

Animals↗
PubMed1991

Lymphocytes bearing the gamma delta T-cell receptor in normal human intestine and celiac disease.

Monoclonal antibodies to T-cell receptors were used to investigate the prevalence of the two distinct T-cell subpopulations (TCR alpha beta+ and TCR gamma delta+ cells) in the intestinal mucosa of children with celiac disease (gluten-sensitive enteropathy) as compared with normal intestinal mucosa. TCR gamma delta+ cells were rarely identified in the epithelium of human fetal or normal postnatal intestine and few were present in the lamina propria, whereas the number of distribution of TCR alpha beta+ cells closely resembled that of CD3+ cells. Compared with normal intestine, a significant increase in the number of CD3+, CD8+, TCR alpha beta+, and TCR gamma delta+ intraepithelial lymphocytes was present in celiac disease. Although the mucosal TCR gamma delta+ cells were less numerous than TCR alpha beta+ cells in celiac disease, there was a marked increase in the number of TCR gamma delta+ cells as compared with controls. The ligand recognized by the gamma delta T-cell receptor and the function of these cells have not been determined; however, these findings suggest a possible role for TCR gamma delta+ lymphocytes in mucosal immune responses and tissue injury as seen in celiac disease.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Studies on the cellular origin of neurothekeoma: clinical, light microscopic, immunohistochemical, and ultrastructural observations.

The clinical, histopathologic, and immunohistochemical features of 11 cases of neurothekeoma are reported. One case was examined by electron microscopy. The mean age of the patients was 27.1 years; the study comprised eight female and three male patients. Most lesions were nondescript papules and located on the upper part of the body, seven cases of neurothekeoma on the head. Eight cases were classified as cellular neurothekeoma on the basis of a striking fascicular pattern and three cases as myxomatous neurothekeoma because of prominent myxoid stromal change. All cellular neurothekeomas failed to express S-100 protein, whereas the three myxomatous types were strongly positive for this marker. Other than vimentin, there was no significant immunoreactivity with other immunohistochemical markers. Ultrastructural study of one case of cellular neurothekeoma was inconclusive for cell type although a perineurial origin could not be excluded. On the basis of these results, we conclude that cellular neurothekeoma differs from myxomatous neurothekeoma not only by clinical and histologic findings but also by immunoreactivity with S-100 protein. These findings also suggest the existence of two distinct subtypes of neurothekeoma and possible origin of the two variants of neurothekeoma from different cell types or at least variation in phenotypic expression of a common cell type. On the other hand, it cannot be excluded that these two variants are different stages in the natural history of neurothekeoma.

Adolescent↗
PubMed1991

Autoimmune enteropathy and nephropathy with circulating anti-epithelial cell antibodies.

We describe a child with circulating anti-epithelial cell antibodies, autoimmune enteropathy with intestinal villous atrophy, and membranous glomerulonephritis. The patient had persistent diarrhea at 6 months of age, and a small bowel biopsy showed active enteritis, villous atrophy, and crypt hyperplasia. When the patient was, 10 months of age, nephrotic syndrome developed because of membranous glomerulonephritis. Results of tests for circulating immune complexes were negative. Indirect immunofluorescence studies revealed a circulating antibody directed against renal epithelial cells. Circulating antibodies directed against normal small intestine epithelial cells were also detected by the immunoperoxidase technique. Western blot and immunoprecipitation identified a 55-kd antigen, in both small bowel and kidney, that reacted with an antibody in the patient's serum. High-dose prednisone therapy induced a clinical remission, resolution of the small bowel injury, and diminished serum anti-epithelial cell antibodies; after dose reduction, clinical relapse occurred with villous atrophy and reappearance of anti-epithelial cell antibodies. When the patient was 45 months of age, persistent diarrhea recurred despite intravenous administration of corticosteroids, cyclosporine, and total parenteral nutrition. Autoantibodies to a 55-kd epithelial cell protein are temporally related to the development of enteropathy and nephropathy. Study of similar patients is needed to determine the role of such antibodies in this disorder.

Atrophy↗
PubMed1991

Estrogen receptors in skin appendage tumors and extramammary Paget's disease.

Determination of estrogen receptors (ER) in breast carcinoma is valuable in the management of patients. However, little is known about the presence of these receptors in other tumors. Normal skin appendages and their neoplasms, including extramammary Paget's disease (EPD), might be expected to express ER since the breast is histogenetically related to sweat glands. In this study, 41 cases of skin appendage tumors (SAT) and 11 cases of EPD were stained using the ER-ICA monoclonal kit (Abbott, Chicago, IL) with a modified technique for paraffin-embedded sections. Controls included 10 biopsies of primary breast carcinoma and 4 cases of metastatic breast carcinoma to skin, all positive for ER. None of the samples of SAT or EPD showed staining for ER. Normal skin appendages were also negative. Normal vaginal epithelium in one case of EPD showed positive nuclear staining for ER. ER determination using immunohistochemical technique in paraffin-embedded sections may be useful in the differential diagnosis between malignant SAT and metastatic breast carcinoma in the skin. The absence of ER in normal skin appendages suggests that its apparition is a feature of specialized differentiation of breast epithelium.

Adult↗
PubMed1991

Expression of MHC class II (Ia) antigen by the neonatal enterocyte: the effect of treatment with interferon-gamma.

Immunohistochemical techniques were used to probe the expression and inducibility of class II major histocompatibility complex (MHC) (Ia) antigens by the mouse enterocyte at various stages postpartum. Expression of Ia was related to both age and intestinal location. Ia antigen was not detected until at least 1 week post-weaning and was noted thereafter in both proximal and distal intestine. Both crypt and villus enterocytes were stained in the distal small intestine, but staining was restricted to the upper portion of the villus in the proximal small intestine. Moreover, the extent of staining and the intensity of staining were greater in the distal small intestine. The effect of a single injection of recombinant mouse interferon-gamma (IFN-gamma) on Ia expression by enterocytes of 16-day-old, suckling BDF1 mice was examined. Injection of distilled water (DW) or 1 to 2 x 10(4) U IFN-gamma did not induce enterocyte Ia expression. Doses of 4-10 x 10(4) U were effective inducers of Ia on crypt and, occasionally, on lower villus cells examined 24 hr later. Staining did not persist on the enterocyte beyond 48 hr. In conclusion, Ia is not normally expressed on small intestinal enterocytes of the mouse until after weaning; however, Ia expression can be induced earlier by treatment with IFN-gamma. It is not known whether failure to detect Ia expression prior to weaning reflects a lack of positive stimuli and/or the presence of inhibitory stimuli, possibly carried in the breast milk.

Aging↗
PubMed1990

Central nervous system neurocytoma and neuroblastoma in adults--report of eight cases.

The clinical features, pathologic findings and treatment courses of eight adults with central nervous system small-cell neuronal tumors were reviewed. Five patients had central neurocytomas, two patients central nervous system neuroblastomas, and one patient a neurocytoma-like spinal cord tumor. The neurocytomas were intraventricular, moderately cellular tumors with bland nuclei and perinuclear halos. Patients with neurocytoma were treated with surgery, radiation therapy, and/or chemotherapy, and have followed favorable clinical courses. The neuroblastomas were intraparenchymal, hypercellular tumors with necrosis and frequent mitoses. Patients with neuroblastomas were treated with surgery, radiation therapy and chemotherapy, with some clinical response, but overall poor survival. One of the two patients developed extracranial metastasis. The spinal cord tumor had histologic features of neurocytoma, and responded well to biopsy and radiation therapy. The cases are compared with the varieties of small-celled neuronal tumors described in the literature, and pathologic, histogenetic and treatment implications are discussed.

Adult↗
PubMed1990

Cytokeratin expression in epithelioid vascular neoplasms.

Seven epithelioid and eight non-epithelioid vascular tumors were studied by the avidin-biotin-peroxidase method for the presence of endothelial- and epithelial-associated markers, using Ulex europaeus agglutinin-1 (UEA-1) lectin, and antibodies directed against factor VIII-related antigen, (FVIII-RA), vimentin, keratin, carcinoembryonic antigen, and epithelial membrane antigen. The cases included four epithelioid hemangiomas, two epithelioid hemangioendotheliomas (EHE), one epithelioid angiosarcoma (EAS), four common non-epithelioid capillary hemangiomas, and four non-epithelioid angiosarcomas. Staining for FVIII-RA, UEA-1, and vimentin were observed in all cases. The EAS showed staining for keratin in formalin-fixed, paraffin-embedded sections and in frozen sections. Staining for keratin was also observed in frozen sections of one EHE. Both keratin-positive vascular tumors were confirmed with electron microscopy. Carcinoembryonic antigen and epithelial membrane antigen stains were negative in all cases. Our results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin. This is important since these tumors may closely resemble carcinomas by routine light microscopy. This study further underscores the importance of using a broad panel of immunohistochemical markers in the diagnostic workup of soft-tissue neoplasms.

Biomarkers, Tumor↗
PubMed1990

The distribution of T and B lymphocyte populations and MHC class II expression in human fetal and postnatal intestine.

The development of the intestinal mucosal immune barrier is an important protective adaptation for postnatal life. The distribution and phenotype of T and B lymphocytes in human fetal intestine and lymphoid tissues have been characterized and compared to the distribution and phenotype of lymphocytes in postnatal intestine. The characterization of lymphocyte phenotype and MHC class II antigen distribution was done using MAb and an avidin-biotin complex immunohistochemical staining technique. Intraepithelial lymphocytes were occasionally present in fetal intestine and were primarily CD3+, CD8+. T lymphocytes were readily identified in the lamina propria of fetal intestine, but most were clustered in lymphoid aggregates. Cells identified by anti-IgA1 and anti-IgA2 were the most numerous cells of B cell lineage in the lamina propria of postnatal intestine, whereas IgM+ and IgD+ lymphocytes predominated in fetal tissues. However, IgA-bearing cells were identified in lymphoid aggregates of the intestine or spleen of some fetuses. This finding suggests that B lymphocytes can undergo Ig switching in utero. Additionally, fetal intestinal epithelial cells did not express MHC class II antigens, unlike some postnatal intestinal tissues. It is possible that postnatal events such as antigen exposure may be important for the induction of these class II antigens on intestinal epithelial cells.

B-Lymphocytes↗
PubMed1990

Application of immunohistochemistry in the differential diagnosis of skin tumors.

As with neoplasms in any tissue, skin tumors may be categorized as epithelial or mesenchymal, benign or malignant, and primary or metastatic. Immunoperoxidase stains are useful in elucidating the nature of the tumor cells, especially in poorly differentiated tumors. It is important to consider that tumors may exhibit staining patterns different from the typical or reported results. This may be because of intrinsic features of the neoplasm such as the aberrant expression of antigens (markers). Furthermore, the staining of the tumor may be affected by tissue preservation and fixation as well as by the selection of antibodies used for staining. For this reason, the pathologist should be vigilant in comparing the results of unknown tumors with standard controls, with results in the literature, and with his or her own experience. Unusual neoplasms may require additional tissue for analysis, study by other ancillary methods such as electron microscopy, or consultation by more experienced laboratories. These guidelines should be helpful in providing accurate diagnosis of skin tumors.

Biomarkers, Tumor↗
PubMed1990

Prolactinoma in wall of ovarian dermoid cyst with hyperprolactinemia.

A 41-year-old woman with long-standing amenorrhea and hyperprolactinemia that disappeared after hysterectomy and bilateral salpingo-oophorectomy was found to have a prolactinoma in the wall of a dermoid cyst. Prolactin was demonstrated in the tumor cells by immunohistochemical staining.

Adult↗
PubMed1990

Sinonasal hemangiopericytoma. A reassessment with electron microscopy, immunohistochemistry, and long-term follow-up.

Sinonasal hemangiopericytomas are rare, occasionally misdiagnosed neoplasms that have often been considered distinct from hemangiopericytomas of other sites. Eleven cases were studied. Nine arose from the nasal cavity and two from the paranasal sinuses. The patients' mean age was 58 years. In nine cases there were no appreciable mitoses; in two, mitoses were frequent. Of 10 cases studied by immunostaining, all were positive for vimentin; two had faint focal staining for actin; one focally expressed S-100 protein; all were negative for cytokeratins, desmin, and Factor VIII-related antigen; and none bound Ulex europaeus agglutinin 1. Five cases were studied by electron microscopy. The most consistent features were basal lamina-like material partly surrounding tumor cells and completely separating them from endothelium, tapered cytoplasmic extensions, and orderly bundles of filaments. Intercellular junctions and pinocytotic vesicles were present in some tumors. Of nine cases with adequate follow-up, tumors recurred in four cases (44%) after a mean of 6.5 years, and none metastasized. A review of the literature showed that high local recurrence rates, late recurrences, and low rates of metastasis were features of tumors in this location. This might be a reflection of early presentation, small tumor bulk, and difficulty of complete resection, rather than evidence for a biologically distinct neoplasm.

Adult↗
PubMed1990

Monoclonal antibodies to rat Kupffer cells. Anti-KCA-1 distinguishes Kupffer cells from other macrophages.

Two monoclonal antibodies, anti-KCA-1 and anti-KCA-2, directed against rat Kupffer cells (hepatic sinusoidal macrophages) were developed. Immunohistologic studies of the liver and analysis of isolated hepatic cells by immunofluorescence and flow cytometry showed that the reactivity of these antibodies was restricted to macrophages. Both KCA-1+ and KCA-2+ cells were located predominantly in the periportal region; in contrast, Ia+ sinusoidal cells were located primarily in the centrilobular region. Macrophagelike cells within the portal tracts expressed KCA-2 but not KCA-1. These findings indicate the presence of heterogeneity within the macrophage population of the liver. Anti-KCA-1 reactivity appeared to be almost entirely restricted to Kupffer cells; only a few macrophages in the thymus and a small number of cells in the bone marrow expressed KCA-1. In contrast, KCA-2 was more widely distributed; splenic, lymph node, and intestinal macrophages were intensely stained with anti-KCA-2. These studies indicate that KCA-1 is a marker of Kupffer cells.

Animals↗
PubMed1989

Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system.

A direct quantitative and phenotypic cytofluorographic analysis of TCR-gamma/delta+ lymphocytes as well as an immunohistologic study of their tissue distribution and microanatomy was made possible by the availability of two mAbs (anti-TCR-delta 1 and anti-C gamma M1) specific for framework determinants on human TCR gamma and delta chains, respectively. TCR-gamma/delta+ lymphocytes, ranging between greater than 0.5 and 16% of CD3+ cells, were found in fetal and postnatal thymus, fetal and adult peripheral lymphoid organs, and adult peripheral blood. While TCR-gamma/delta+ lymphocytes comprised a small subpopulation of T cells (mean, approximately 4%) occasionally greater than 10-16% of CD3+ cells expressed TCR-gamma/delta. Virtually all TCR-gamma/delta+ thymocytes/lymphocytes expressed CD7, CD2, and CD5 but were heterogeneous with respect to their expression of CD1, CD4, CD8, CD28, CD11b, CD16, and Leu-7. Human TCR-gamma/delta+ cells populate both organized lymphoid tissues (thymus, tonsil, lymphnode, and spleen) as well as the gut- and skin-associated lymphoid systems at similar frequencies without obvious tropism for epithelial microenvironments. TCR-gamma/delta+ lymphocytes tend to be located within a given organ wherever TCR-alpha/beta+ lymphocytes are found. This study shows that TCR-gamma/delta+ lymphocytes constitute a small but numerically important, phenotypically diverse T cell population distributed throughout the body. These results support the concept that TCR-gamma/delta+ cells comprise a distinct, functionally heterogeneous, mature T cell sublineage that may substantially broaden the T cell repertoire at all immunologically relevant sites.

Antibodies, Monoclonal↗
PubMed1989

Glial fibrillary acidic protein and keratin expression by benign and malignant nerve sheath tumors.

Formalin-fixed, paraffin-embedded sections of 59 ultrastructurally confirmed nerve sheath tumors (NSTs) that included 27 benign schwannomas, five neurofibromas, and 27 malignant schwannomas were studied by the avidin-biotin-peroxidase complex method using antibodies directed against glial fibrillary acidic protein (GFAP), keratin, S-100 protein, vimentin, and desmin. GFAP was expressed by 33% of the benign schwannomas, 40% of the neurofibromas, and 7% of the malignant schwannomas. Keratin was expressed by 7% of the benign schwannomas and 4% of the malignant schwannomas. S-100 protein was expressed by 100% of the benign NSTs and by 40% of the malignant schwannomas. Vimentin was observed in 100% of the benign NSTs and in 85% of the malignant schwannomas. None of the cases stained for desmin. GFAP and cytokeratin expression could not be predicted on the basis of tumor light microscopy or ultrastructure. These findings are of practical importance in routine surgical pathology, particularly with respect to the differential diagnosis of gliomas located in the central nervous system and in immunohistochemical studies of peripherally located, poorly differentiated neoplasms.

Desmin↗