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Biomedical subjects

A K Bhan

Publications and source records attributed to A K Bhan.

At least 73 records · Page 4Linked to original sources
PubMed1994

Importance of recording lead V1 in the seventh right intercostal space in diagnosing corpulmonale.

Right-sided chest leads V1 to V6R were recorded in the 4th to 7th intercostal spaces in 25 cases of corpulmonale secondary to chronic obstructive pulmonary disease and in an equal number of age-matched controls. Results were compared with findings in the conventional electrocardiogram. Chest leads recorded in the seventh right intercostal space along the right sternal border could detect 24% of cases of corpulmonale that were missed by conventional leads.

Adult↗
PubMed1994

Chondroid chordoma--a variant of chordoma. A morphologic and immunohistochemical study.

In 1973, Heffelfinger and coworkers described a variant of chordoma that contained cartilaginous areas indistinguishable from hyaline type chondrosarcoma. They designated these tumors chondroid chordomas and found that they had a better prognosis than classic (nonchondroid) chordomas. Since that time, there has been an ongoing debate over whether chondroid chordoma is best considered a distinct clinicopathologic entity separable from chondrosarcoma or a misdiagnosed chondrosarcoma whose concept developed from the erroneous interpretation of morphology. In an attempt to clarify the issue, the authors used light microscopy and immunohistochemistry to study 12 chondroid chordomas, 38 classic chordomas, and 28 chondrosarcomas that arose in the base of the skull or spine. As a reference, they also analyzed the immunohistochemical profile of fetal notochord, ecchordosis physaliphora, and fetal hyaline cartilage. They found that all chondroid and nonchondroid chordomas were positive for cytokeratin, and the majority were also positive for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). In contrast, none of the chondrosarcomas stained for cytokeratin, EMA or CEA. Vimentin and S-100 were positive in more than 95% of both classic and chondroid chordomas and chondrosarcomas. The immunohistochemical profile of these tumors was similar to the pattern of immunoreactivity of their nonneoplastic counterparts. The authors conclude that chondroid chordomas is a variant of chordoma and should not be confused with chondrosarcoma. Because chondroid chordomas have been reported to have a better prognosis, they felt that this nosologic term should be preserved and that chondroid chordoma should continue to be a focus of clinical and pathologic study.

Adolescent↗
PubMed1994

Peripheral lymphoid development and function in TCR mutant mice.

We describe the development and function of the peripheral lymphoid system of mutant mice rendered deficient in either alpha beta or gamma delta T cells via targeting of TCR genes in embryonic stem cells. In the spleen of alpha beta T cell-deficient mice, gamma delta T cells do not compensate in numbers for the lack of alpha beta T cells, but B cells do. alpha beta T cell-deficient mice are unable to mount an antibody response to ovalbumin and do not reject skin allografts. Natural killer cell function is not impaired in any of the mutant mice. TCR mutant mice will prove useful in dissecting differential functions of alpha beta and gamma delta T cells in vivo.

Animals↗
PubMed1993

Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.

We describe the spontaneous development of inflammatory bowel disease (IBD) in several immunodeficient mouse strains created via gene targeting in embryonic stem cells. Chronic colitis was observed in T cell receptor (TCR) alpha mutant, TCR beta mutant, TCR beta x delta double mutant, or class II major histocompatibility complex (MHC) mutant mice, but not in recombination-activating gene RAG-1 mutant mice or nude mice kept in the same specific pathogen-free animal facility. This clinical pattern suggests that the disease requires the presence of B lymphocytes and the absence of class II MHC-restricted CD4+ alpha beta T cells. IBD in the mutant mice has some of the features of the human disease ulcerative colitis. Based on these results, we suggest that dysfunction of the mucosal immune system may underly the pathogenesis of some types of IBD in humans.

Aging↗
PubMed1993

Anti-KCA-3, a monoclonal antibody reactive with a rat complement C3 receptor, distinguishes Kupffer cells from other macrophages.

A new mAb, designated anti-KCA-3, was developed against rat Kupffer cells. The reactivity of anti-KCA-3 was restricted to macrophages with preferential binding to Kupffer cells; only a few macrophages in the spleen, lymph nodes, lungs, and intestine stained with the antibody. A very small number of peritoneal resident and exudate macrophages reacted with the antibody and no reactivity was seen within the thymus, skin, heart, kidneys, brain, peripheral blood, and bone marrow. KCA-3 was expressed predominantly by the Kupffer cells in the periportal region rather than in the centrilobular region of the hepatic lobules. The cells in the portal tract did not stain with the antibody. The staining of the cytosmears and FACS analysis of the Kupffer cell fraction isolated from hepatic sinusoidal cells by centrifugal elutriation revealed that as many as 62% and 49% of the cells were stained with anti-KCA-3, respectively. Immunoelectron microscopic study of the liver indicated that expression of KCA-3 on Kupffer cells was limited to the plasma membrane facing the sinusoid rather than the space of Disse. Immunoprecipitation and SDS-PAGE analysis demonstrated KCA-3 to have a m.w. of approximately 50 kDa under both reducing and nonreducing conditions. After treatment of KCA-3 with N-glycanase, there was no significant change in the m.w., indicating KCA-3 was not highly glycosylated. C3b- and iC3b-mediated rosette formation between Kupffer cells and sensitized SRBC was inhibited by the antibody, implying that KCA-3 functioned as a complement C3 receptor or complement receptor-associated molecule. Furthermore, KCA-3 was eluted from C3b-Sepharose but not HSA-Sepharose after incubation with Kupffer cell lysate, indicating that KCA-3 directly binds C3b. The cell distribution, ligand-binding specificity, and biochemical properties of the protein were found to be different from the complement C3 receptors previously described. Because OX42 (antibody reactive with the rat CR3 receptor) inhibited complement C3-mediated rosette formation with peritoneal resident macrophages but not with Kupffer cells, the findings suggest that C3-mediated binding to Kupffer cells and to peritoneal macrophages is mediated by two different receptors. We conclude that anti-KCA-3 recognizes a novel type of complement C3 receptor preferentially expressed on Kupffer cells.

Animals↗
PubMed1993

Expression of epithelial markers in malignant fibrous histiocytoma of the musculoskeletal system: an immunohistochemical and electron microscopic study.

We performed an immunohistochemical and ultrastructural study on 67 specimens of malignant fibrous histiocytoma (MFH) from 65 patients. Most of the tumors were musculoskeletal in origin and all presented clinically as a primary malignancy. The tumors were high grade and 57 of 67 were the storiform-pleomorphic subtype. Immunohistochemical studies were performed in 34 cases with both fresh-frozen and formalin-fixed tissue; in 33 cases only formalin-fixed tissue was available. The immunohistochemical panel included vimentin, various molecular weight keratins, epithelial membrane antigen (EMA), desmin, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Seventeen of 67 (25.4%) cases stained with one or more keratin antibodies. The low molecular weight cytokeratins demonstrated the most widespread and intense staining and, using fresh-frozen tissue, increased sensitivity. Epithelial membrane antigen was detected in 20.6% of cases and six of these cases also stained with keratin. The EMA staining was more focal and less intense than the keratin reactivity. The keratin- or EMA-positive cases were not distinguished by their light microscopic or ultrastructural features. Desmin staining was focally present in 16.9% of cases. The vast majority of tumors stained with vimentin and alpha-1-antitrypsin or alpha-1-antichymotrypsin. There was no staining of tumor cells for S-100. Appropriately fixed tissue was available for electron microscopic evaluation in 15 of 23 MFHs that stained with keratin or EMA. Ultrastructurally, all tumors were composed of an admixture of cells that had the features of fibroblasts, myofibroblasts, and histiocytes; no epithelial structures were identified. This study confirms that MFH may express epithelial markers. It emphasizes the importance of using electron microscopy and clinical findings to distinguish keratin or EMA-positive MFH from carcinoma. This distinction is important because of the significant differences in therapy and prognosis.

Adult↗
PubMed1993

Tissue distribution of the non-polymorphic major histocompatibility complex class I-like molecule, CD1d.

The CD1 gene family is composed of five distinct molecules: CD1a, b, c, d and e. CD1a, b and c are primarily expressed thymically with limited extrathymic expression. Preliminary studies have shown that CD1d is primarily expressed extrathymically in gastrointestinal epithelial cells, renal tubular epithelial cells and B cells. This report characterizes the expression of CD1d in a variety of human tissues by immunohistochemistry using two anti-human CD1d monoclonal antibodies (mAb). CD1d was found in a wide range of tissues including the intestine, liver, pancreas, skin, kidney, uterus, conjunctiva, epididymis, thymus and tonsil. Within those tissues CD1d was mainly present in epithelial cells, vascular smooth muscle cells and parenchymal cells. Therefore, the tissue distribution of CD1d is distinct from CD1a-c and classical major histocompatibility complex (MHC) proteins implicating a unique role for CD1d in the immune system.

Antibodies, Monoclonal↗
PubMed1993

Hyaluronate is a component of crescents in rat autoimmune glomerulonephritis.

BACKGROUND: Crescent formation is a major feature of rapidly progressive glomerulonephritis and is generally associated with a poor prognosis. Crescents are formed by accumulation of monocyte/macrophages and plasma proteins in Bowman's space, by proliferation of parietal epithelial cells and fibroblasts, and by deposition of the extracellular matrix. Interactions of components of the extracellular matrix with surface receptors of inflammatory cells may be important in crescent formation. One such receptor is the glycoprotein, CD44, whose main ligand is hyaluronate. We performed the present study to determine if hyaluronate is a component of crescents in a model of autoimmune anti-glomerular basement membrane nephritis in rats. EXPERIMENTAL DESIGN: Wistar-Kyoto rats were immunized with bovine glomerular basement membrane, that resulted in severe crescentic glomerulonephritis. Sections of renal tissue were studied with two probes to detect hyaluronate: (a) a soluble CD44-human immunoglobulin fusion protein; and (b) a hyaluronic acid-binding protein. Both probes were revealed by immunofluorescence techniques. The specificity of the reactions was established by selective enzymatic digestions. RESULTS: Marked accumulation of hyaluronate was demonstrated in developing and sclerosing crescents, in association with local infiltration of T lymphocytes and monocyte/macrophages, cells known to express CD44. Lesser amounts of hyaluronate were found in periglomerular infiltrates. CONCLUSIONS: Hyaluronate is an abundant extracellular component of crescents, and may play a critical role in their formation, by its effects on migration and activation of CD44+ lymphocytes, monocyte/macrophages, fibroblasts and epithelial cells.

Animals↗
PubMed1993

Immunohistochemical characterization of intraepithelial and subepithelial mononuclear cells of the upper airways.

The upper airway is the first site of exposure to inhaled antigens and the site of initiation of mucosal immunity to certain antigens; however, the intraepithelial lymphoid populations of this region have not been well characterized. We studied 6-mu frozen tissue sections from tonsils, adenoids, and nasal mucosae using immunohistochemistry and a panel of antibodies to mononuclear antigens to determine whether nasal mucosa contained distinctive populations of mononuclear cells. Intraepithelial lymphocytes (IELs) of nasal mucosa were CD3+, CD8+, and mainly CD5+. Tonsil and adenoid both showed diffuse CD8+ IELs; clusters of CD4+ IELs were associated with B cells within the crypt epithelium. All nasal IELs were uniformly negative for Leu8 (homing receptor analog of Mel14). Scattered Leu8-positive cells were present within tonsil and adenoid crypt epithelium only. Nasal IELs rarely expressed HML1 and were often CD7-, whereas the majority of tonsillar and adenoidal IELs were HML1+ and variably CD7+. In nasal mucosa and in deep submucosa of tonsil and adenoid, 80 to 90% of T cell receptor expression was of alpha/beta type. There was a concentration of gamma/delta T cell receptor-positive cells in intraepithelial and subepithelial zones of tonsil and adenoid, with areas of up to 30% gamma/delta T cell receptor positivity. A population of intraepithelial dendritic cells was identified in all three tissues expressing mononuclear phagocyte system antigens CD14 and KiM1P, but lacking CD1a. Virtually no B cells and no organized subepithelial lymphoid tissue were identified in nasal mucosa. Nasal mucosal lymphoid tissue seems to differ from that of endodermally derived mucosae, tonsil, and adenoids to share similarities with both mucosa-associated lymphoid tissue and peripheral lymph nodes.

Adenoids↗
PubMed1993

Epithelioid hemangioma of bone. A tumor often mistaken for low-grade angiosarcoma or malignant hemangioendothelioma.

Epithelioid hemangiomas are benign vascular tumors that usually occur in the skin and subcutis. They have been infrequently recognized in bone. Because of their unusual cytologic appearance and growth patterns, they are commonly confused with malignant tumors. We report a series of 12 epithelioid hemangiomas of bone occurring in adult patients, including five males and seven females whose ages at presentation ranged from 24 to 74 years, with a mean of 46 years. Five tumors were associated with involvement of the adjacent soft tissue. A single patient had multifocal bone disease. The most common presenting symptom was localized pain. Treatment of the patients varied widely; however, none of the tumors behaved aggressively. In 11 cases, adequate tissue was available for immunohistochemical analysis, which revealed positive staining for the epithelial markers cytokeratin and epithelial membrane antigen in nine cases. All 11 tumors stained for factor VIII-related antigen and Ulex europeus agglutinin. We believe that many of the vascular tumors of bone that have been reported as low-grade malignant hemangioendotheliomas probably represent examples of epithelioid hemangiomas. We recommend that the criteria for diagnosing vascular tumors of bone conform to those used for morphologically similar tumors that arise in the soft tissues.

Adult↗
PubMed1993

Cytotoxic potential of intraepithelial lymphocytes (IELs). Presence of TIA-1, the cytolytic granule-associated protein, in human IELs in normal and diseased intestine.

Human intestinal intraepithelial lymphocytes (IELs) have phenotypic characteristics of cytotoxic T cells, yet a cytotoxic function has not been demonstrated in redirected lysis assays. A monoclonal antibody that reacts with a cytotoxic granule-associated protein, TIA-1, was used in this study to identify this protein in many, but not all, IELs of normal human proximal small intestine. Furthermore, in active celiac disease, in which the number of IELs is significantly increased, a corresponding increase in the number of TIA-1 cells was found. These results indicate that whereas cytotoxicity of human IELs has been difficult to demonstrate, they contain at least one of the proteins associated with cytotoxicity, and a failure to demonstrate this function may be related to the in vitro assay system used.

CD3 Complex↗
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↗