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M A Conant

Publications and source records attributed to M A Conant.

At least 55 records · Page 3Linked to original sources

Basement membrane and connective tissue proteins in early lesions of Kaposi's sarcoma associated with AIDS.

Nearly one-third of all young homosexual men diagnosed as having acquired immune-deficiency syndrome (AIDS) develop a disseminated form of dermal Kaposi's sarcoma (KS). Although the histogenesis of KS cells is unclear, certain evidence suggests that the aberrant cells are of endothelial derivation. We have examined the presence and distribution of connective tissue-specific and basement membrane-specific macromolecules by indirect immunofluorescence and immunoperoxidase staining of frozen sections in early cutaneous lesions of KS from individuals with AIDS. The KS cells typically line the spaces between collagen bundles of the reticular dermis. When stained for the connective tissue-specific glycoprotein fibronectin, all Kaposi's sarcoma lesions showed an intense staining pattern, revealing a complex array of linear deposits of antigen that outlined the exterior surface of the collagen bundles. Antibodies to laminin and type IV collagen, both basement membrane-specific macromolecules, produced an intense staining pattern similar to that found with the anti-fibronectin antiserum, indicating that all 3 antigens are closely codistributed. In contrast, antibodies to type I collagen, the major collagen of the dermis, uniformly stained the collagen bundles in the KS lesions and in the normal control skin. Antiserum to factor VIII-associated antigen, an antigen specific to blood vascular endothelium, frequently stained the KS lesions but the staining pattern was diffuse and of variable intensity. The results suggest that KS cells are derived from the endothelium of the blood microvasculature and maintain their secretory phenotype of secreting basement membrane-specific macromolecules.

Acquired Immunodeficiency Syndrome↗

AIDS: a new disease.

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Acquired Immunodeficiency Syndrome↗

Herpes zoster ophthalmicus and acquired immune deficiency syndrome.

Acquired immune deficiency syndrome (AIDS) is a recently recognized disease characterized by abnormalities in cell-mediated immunity that predispose affected persons to severe opportunistic infections and unusual malignant neoplasms. We describe four cases of herpes zoster ophthalmicus in four previously healthy homosexual men. Two had signs and symptoms consistent with AIDS, and two had signs and symptoms of a lymphadenopathic syndrome associated with AIDS. We suggest that underlying AIDS be considered in young, healthy persons with herpes zoster ophthalmicus and no known cause of immunosuppression.

Acquired Immunodeficiency Syndrome↗

Hematologic manifestations in homosexual men with Kaposi's sarcoma.

Peripheral blood and bone marrow findings are presented for six homosexual males with Kaposi's sarcoma. Cytopenia in one or more cell lines was common in this group of patients, including two individuals with pancytopenia. Bone marrow findings in all patients, while not specific, were similar in that adequate numbers of normal appearing erythroid, myeloid, and megakaryocytic elements were present. Mild plasmacytosis as well as reticulin fiber increase were common findings. No patient, at time of study, demonstrated marrow involvement with Kaposi's sarcoma. We conclude that depression of peripheral blood counts in these patients was not due to marrow underproduction, and discuss possible mechanisms for increased blood cell destruction.

Acquired Immunodeficiency Syndrome↗

Speculations on the viral etiology of acquired immune deficiency syndrome and Kaposi's sarcoma.

The acquired immune deficiency syndrome (AIDS) appeared in the United States in late 1978 and has spread at an epidemic rate through the four major coastal cities of this country. The disease appears to show the same epidemiologic distribution as hepatitis B virus infection, and for this reason, most investigators feel that this new disease is caused by a blood-borne sexually transmitted virus. A number of viral agents have been suggested as the cause of AIDS, but to date, no virus has been consistently isolated. The most likely candidate is a retrovirus that has recently been introduced into the human population and has found its way into two extremely high-risk groups, namely, promiscuous male homosexuals and intravenous drug abusers. The relationship between Kaposi's sarcoma and cytomegalovirus is still unclear, but evidence is mounting that cytomegalovirus may be the agent that initiates this multifocal malignancy. Multiple factors must be involved in this process. It is known that some immunosuppressed individuals develop Kaposi's sarcoma, which completely resolves when the immunosuppression is reversed; however, in individuals with classical Kaposi's sarcoma, the profound degree of helper T-cell depression that characterizes the acquired immune deficiency syndrome is not seen.

Acquired Immunodeficiency Syndrome↗

Recombinant alpha-2 interferon therapy for Kaposi's sarcoma associated with the acquired immunodeficiency syndrome.

In a randomized prospective study we tested the toxicity and efficacy of recombinant alpha-2 interferon in the treatment of Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. High doses (50 X 10(6) U/m2 body surface area, intravenously) or low doses (1 X 10(6) U/m2, subcutaneously) of recombinant alpha-2 interferon were administered to 20 patients for 5 days/wk, every other week, for four treatment cycles. Therapy was well tolerated subjectively and caused only mild hematologic and hepatic toxicity at both dose levels. No consistent or sustained changes were seen in immunologic variables during or after treatment. Six patients with Kaposi's sarcoma, four at high dose and two at low dose, had objective responses (complete or partial) to treatment. However, therapy did not appear to eradicate cytomegalovirus carriage or prevent opportunistic infections related to cytomegalovirus.

Acquired Immunodeficiency Syndrome↗

T-lymphocyte subsets in lymph nodes from homosexual men.

To evaluate further the immunodeficiency of homosexual men, blood and lymph node specimens were obtained from five homosexual men with lymphadenopathy and from seven homosexual men with Kaposi's sarcoma. Monoclonal antibodies were used to identify T-lymphocyte subsets in blood by cytofluorometry and in frozen sections of nodes by immunoperoxidase techniques. The homosexuals with Kaposi's sarcoma had a T-helper/suppressor ratio in blood of 0.7; the homosexuals with lymphadenopathy had a ratio of 0.6, compared with controls of 2.1. Control lymphoid tissue had a ratio of 3.0 in the interfollicular areas compared with the reactive lymph nodes in the homosexuals with lymphadenopathy, which was 0.7, and nodes from patients with Kaposi's sarcoma, 0.9. The nodes from homosexual men had evident numerous suppressor cells in the follicular center and mantle regions, locations in normal lymphoid tissue where suppressor cells were uncommon.

Flow Cytometry↗

Chemotherapy in advanced Kaposi's sarcoma. Implications for current cases in homosexual men.

Kaposi's sarcoma has recently appeared in an aggressive form in young, previously healthy, homosexual men. The disease in these patients corresponds most closely to disseminated Kaposi's sarcoma common in areas of Africa. This and the underlying acquired immune deficiency in the current patients in the United States affect the choice of appropriate therapy. Because Kaposi's sarcoma in these patients is rapidly progressive, it often requires aggressive systemic therapy, but this can be difficult given the patients' susceptibility to opportunistic infections. Reports from Africa suggest that Kaposi's sarcoma is very responsive to several chemotherapeutic agents, but these data must be interpreted cautiously because of problems in study design and differences between cases in Africa and the United States. This report reviews the clinical classification of Kaposi's sarcoma and the reported results of chemotherapy in patients with advanced disease. Implications of this experience in the treatment of recent cases in the United States are discussed.

Acquired Immunodeficiency Syndrome↗

Oral manifestations of tumor and opportunistic infections in the acquired immunodeficiency syndrome (AIDS): findings in 53 homosexual men with Kaposi's sarcoma.

Fifty-three homosexual men with Kaposi's sarcoma (KS) were studied. Twenty-seven had biopsy-proved oral KS, the palate being the most common site. Past or present infections with cytomegalovirus, hepatitis, venereal diseases, and gastrointestinal microorganisms occurred in more than 70%. Oral candidiasis was confirmed in 57%. Heavy marijuana smoking was the most common habit. Transmission of AIDS is thought to be by a viral agent. Precautions involving the use of gloves, eyeglasses, and masks, similar to those recommended for the management of patients with hepatitis B, are urged.

Acquired Immunodeficiency Syndrome↗

Kaposi's sarcoma in homosexual men: an immunohistochemical study.

A recent outbreak of disseminated Kaposi's sarcoma has been recognized in homosexual men in New York, San Francisco, and Los Angeles. Biopsy specimens of skin lesions were obtained from nine of these homosexual men in Los Angeles and San Francisco. T lymphocyte subset antigens, factor VIII-related antigen, and HLA-Dr antigen were evaluated in situ in frozen sections using immunoperoxidase technics. Factor VIII-related antigen and HLA-Dr antigen were present on tumor cells, supporting a vascular endothelial origin of this neoplasm. Langerhans cells and T lymphocytes were present in numbers similar to that of normal skin in skin specimens from seven patients with Kaposi's sarcoma with visceral dissemination, but were increased in specimens from two patients with only cutaneous involvement.

Antigens↗

Early lesions of Kaposi's sarcoma in homosexual men. An ultrastructural comparison with other vascular proliferations in skin.

An aggressive variant of Kaposi's sarcoma (KS) has appeared in young homosexual men with evidence of systemic immunosuppression. The ultrastructure in biopsy specimens from 8 KS cases in young homosexual men has been compared with that in biopsy specimens from 4 KS cases in elderly heterosexuals and with that in biopsy specimens from 23 cases of benign vascular disorders of skin. In all cases of KS the small blood vessels lacked a prominent investment of pericytes and their processes, had a fragmented and often absent basal lamina, had frequent discontinuities in the endothelial lining, and had only a few small junctional densities between endothelial cells. Some clinically aggressive cases of KS also had necrosis of individual endothelial cells and had prominent cytoplasmic processes entrapping individual collagen fibers. The benign disorders lacked these features. These differences in the structure of the small vessels may be of diagnostic value in some early cases of KS. The loss of dendritic pericytes in blood capillaries in KS might relate to the telangiectasia which is a prominent feature of the early lesions of KS.

Adult↗

Cytomegalovirus and Kaposi's sarcoma in young homosexual men.

10 homosexual men with Kaposi's sarcoma (KS) were studied for evidence of cytomegalovirus (CMV) infection. IgG and IgM antibodies to CMV were detected in 9 out of 9 and in 7 out of 9 of these patients, respectively. CMV was recovered from body secretions or peripheral blood of 7 patients. Viral cultures of KS tumour biopsy specimens were negative in 8 out of 8 patients, but CMV RNA was detected by in-situ hybridisation in 2 out of 3 and CMV antigen(s) by immunofluorescence in 6 out of 9. Normal tissue specimens from 3 KS patients were negative for CMV antigen. These observations suggest an association of CMV with KS.

Adult↗