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Biomedical subjects

H L Ioachim

Publications and source records attributed to H L Ioachim.

At least 37 records · Page 2Linked to original sources

Disseminated pneumocystosis without pulmonary involvement during prophylactic aerosolized pentamidine therapy in a patient with the acquired immunodeficiency syndrome.

Pneumocystosis, the most common opportunistic infection associated with the acquired immunodeficiency syndrome, is usually restricted to the lungs and results in severe bilateral pneumonia, which is fatal unless vigorously treated. Rare cases have been reported in which involvement of other organs or disseminated disease occurred in addition to the pulmonary lesions. Pentamidine, an efficient drug used intravenously for the treatment of pulmonary pneumocystosis, has also recently been used in aerosolized form for the prevention of Pneumocystis infection in patients with the acquired immunodeficiency syndrome. In the present case, widely disseminated, though symptomless, pneumocystosis developed in a human immunodeficiency virus-positive individual treated prophylactically with aerosolized pentamidine. Despite heavy multiorgan infection with Pneumocystis carinii, the lungs revealed no microorganisms or characteristic inflammatory lesions. This case indicates that aerosolized pentamidine, while efficient against the pulmonary infection, may not produce fungicidal blood levels sufficient for the prevention of disseminated pneumocystosis.

Acquired Immunodeficiency Syndrome↗

Immunobiology of metastases.

The role of immunity in the control of tumor metastasis is unclear, although various evidence suggests its existence. Immunosuppressive treatment is associated with increase in metastasis in both experimental animals and humans. Infiltration by T-lymphocytes is substantial in primary tumors while minimal or absent in their metastases. The capacity for metastasis is related to histologic type and grade of differentiation; small cell carcinomas of the lung are more metastatic than large cell carcinomas; small cell lymphomas are more metastatic than large cell lymphomas. Organ selectivity is evident in the patterns of metastasis; the spleen is common site of metastasis for lymphomas but not for carcinomas. In an experimental system, a virus-induced lymphoma invariably metastasized to the thymus while chemical-induced lymphomas metastasized to the liver; immunosuppression did not alter the patterns. Malignant tumors may exhibit years-long intervals of dormancy before metastasis and established metastases may regress spontaneously, both phenomena being altered by changes in immune status. Malignant tumors in persons with immune deficiency, particularly AIDS, like the opportunistic infections, have a tendency for early dissemination, including organs not usually affected.

Animals↗

Immunopathogenesis of human immunodeficiency virus infection.

The acquired immunodeficiency syndrome (AIDS) is associated with a broad spectrum of opportunistic infections and neoplasias that differ from those occurring in the general population by their high aggressiveness, unusual location, early tendency to generalization, frequent relapse, and short survival. The severe complications of AIDS, however, represent only the last phase in a prolonged course of progressive dysfunction and destruction of the immune system set in motion by the infection with the human immunodeficiency virus (HIV). While substantial progress was achieved in the ultrastructural identification and biochemical characterization of HIV, its mode of action in the causation of AIDS is not yet fully understood. This article explores the main processes involved in the HIV infection and in its role in the origin of AIDS. It describes the phases of HIV infection, investigates the effects of HIV on the various components of the immune system, and analyzes the pathogenesis of the HIV-induced lymphadenopathies and encephalopathy, as well as the causes and mechanisms of AIDS-associated opportunistic infections and opportunistic neoplasias. The total failure of immune surveillance against a host of infectious and oncogenic agents, unprecedented in human pathology, is thus traced to the initial event of specific HIV infection of the CD4 T-lymphocytes.

B-Lymphocytes↗

Ovarian cancer-associated antibodies recovered from ascites: their use for the isolation of ovarian cancer-associated antigen to produce monoclonal antibodies.

Immune complexes (ICs) were recovered from the ascites of a patient with stage IV endometrioid ovarian cancer by sequential precipitation with 33% saturated ammonium sulfate and 2.5% polyethylene glycol 6000 (PEG 6000), followed by affinity chromatography on protein A-Sepharose CL-4B. The IgG-containing ICs were dissociated using 8 M urea, separated by ion-exchange chromatography on Sephadex QAE-50, and subsequently analyzed for purity by immunoelectrophoresis (IEP) and radial immunodiffusion (RID). Recovered antibody was tested for reactivity by immunohistologic techniques against paraffin-embedded tumor tissue and acetone-fixed cell suspensions of epithelial tumors. The antibody which demonstrated ovarian cancer-associated activity was absorbed with antigen extracts of breast, colon, and lung cancers as well as keratin to reduce cross-reactivity. The absorbed endometrioid ovarian cancer-associated antibody (OCAAb) was used to produce an immunoadsorbent column for the recovery of tumor-associated antigens. A mouse monoclonal antibody designated FEN-1 was produced using this antigen-containing fraction, and preliminary screening has demonstrated ovarian tumor-associated reactivity. The use of autologous ICs as reagents for preparing tumor antigen-rich immunogens may provide a valuable tool in the search for tumor-associated antigens.

Antibodies, Monoclonal↗

Detection of HIV-related protein in testes and prostates of patients with AIDS.

The testes and prostates of 14 patients with acquired immune deficiency syndrome (AIDS) for whom autopsies were performed were examined for the presence of human immunodeficiency virus (HIV) and the pathologic alterations seen in AIDS. Histologically, the testes contained peritubular fibrosis and variable spermatogenic arrest, which were inconsistent with the young age of these patients. There were also numerous foci of germ cell degeneration and occasional germ cell loss. The Leydig cells were atrophic and decreased in number. The prostates contained increased numbers of concretions. Sections of testis and prostate were stained with an anti-HIV P17 monoclonal antibody with the use of the avidin-biotin technique. Small scattered foci of positive staining were identified in 8 of 14 testes (57%). They were located over one or several degenerating germ cells and the surrounding Sertoli cells. In addition, in 9 of 14 prostates (64%) there were a few minute foci of positive staining in several adjacent glandular epithelial cells. In one case the testis was positive and the prostate was negative, whereas in two cases the testes were negative and the prostate positive. In contrast, 22 testes and 22 prostates of control non-AIDS patients, read double-blind, were negative. The positive controls were HIV-infected tissue culture HUT 78 lymphoma cells in which there were many scattered positive cells. The results indicate the presence of focal HIV-associated protein in the testes and prostates of patients with AIDS, particularly within the foci of germ cell degeneration. The present observations are in accordance with previous research demonstrating the presence of HIV in the seminal fluid of patients with AIDS and appears to indicate the presence of an infection of the male genital tract by the HIV virus.

Acquired Immunodeficiency Syndrome↗

Persistent lymphadenopathies in people at high risk for HIV infection. Clinicopathologic correlations and long-term follow-up in 79 cases.

Clinicopathologic correlations were explored in 79 patients at high risk for human immunodeficiency virus (HIV) infection who had lymph node biopsy for persistent lymphadenopathies and were followed for intervals of up to 7.2 years. Three histologic patterns, follicular hyperplasia with cytolysis (A), follicular involution with hypervascularity (C), and a combination of the previous two (B), were recognized. Ninety lymph node biopsies (79 primary and 11 sequential) were classified into the three histologic patterns and the results correlated with the immunologic data and clinical course. Of 31 patients who showed a pattern A at the initial biopsy, the condition of 58% remained stationary and 42% progressed to acquired immune deficiency syndrome (AIDS); of 31 patients who had initial B pattern, the condition of 36% remained stationary and 64% progressed to AIDS; and of 17 patients who initially had histologic pattern C, the condition of 6% remained stationary and 94% progressed to AIDS. Forty-one patients died during this follow-up, representing 32% of those who had a pattern A, 52% of those who had a pattern B, and 88% of those who had a pattern C at the initial lymph node biopsy. Medial survival times were 54.4 months for pattern A, 35.6 months for pattern B, and 8.4 months for pattern C. Sequential biopsies showed persistence of the same pattern or changes generally in the direction of pattern A to pattern C over variable amounts of time. Lymphocyte evaluation expressed by total counts of T4 cells, T8 cells, T4/T8 cell ratios, and anti-lymphocyte antibody levels expressed by increases in counts of surface immunoglobulin-positive lymphocytes showed positive correlations with lymph node histologic patterns. All three parameters proved to be useful prognostic indicators for the course of the HIV infection. The pathogenetic significance of lymph node histologic patterns, although not clearly understood, suggests the relation of follicular hyperplasia (pattern A) to acute viral lymphadenitis and of follicular involution with hypervascularity (pattern C) to cellular immune deficiency.

Acquired Immunodeficiency Syndrome↗

Immunohistochemical characterization of a monoclonal antibody detecting an endometrioid ovarian cancer-associated antigen.

Murine monoclonal antibody FEN-1 was derived by immunizing Balb/c mice with an affinity-purified endometrioid ovarian cancer-associated antigen recovered from ascites-derived immune complexes. Splenic lymphocytes from the immunized mouse were fused with the myeloma cells SP2/0-AG14 in the presence of PEG 1500. The hybrid cultures were screened for production of immunoglobulins reactive with an extract preparation of an endometrioid ovarian tumor by enzyme-linked immunosorbent assay and flow cytometry. One of the hybrids secretes a monoclonal antibody of the IgG3 subtype designated FEN-1, which reacts with 100% of endometrioid ovarian cancer containing adenoacanthoma by indirect immunoperoxidase on paraffin-embedded tissue. No detectable levels of antigen were found in squamous metaplasia associated with nonendometrioid tumors, and no reactivity occurred against endometrial adenocarcinomas, endometriosis, or normal ovary and endometrium. The antibody does not cross-react with mucinous tumors, nonepithelial tumors of the ovary, or gastrointestinal tissue. This antibody may be used as an aid in the diagnosis of nonmucinous ovarian carcinomas by immunohistology.

Animals↗

Presence and prognostic significance of antilymphocyte antibodies in symptomatic and asymptomatic human immunodeficiency virus infection.

The presence of antilymphocyte antibody (ALA) in patients with the acquired immunodeficiency syndrome (AIDS), identified in a previous study, was confirmed by testing a population of 200 patients with AIDS. Of these, 88% had significant levels of ALA vs only 8% of a control group of patients with non-AIDS-related diseases. In a prospective study, the levels of ALA were determined in 61 patients with AIDS-related complex who were followed up for 18 to 30 months. During this interval, 31 (67%) of 46 patients with significant elevation of ALA levels developed AIDS, while none of 15 patients without elevation of ALA levels progressed to AIDS. In a group of 85 apparently healthy homosexual men, also followed up for 18 to 30 months, a significant number of those with high levels of ALA developed clinically apparent disease, while those with low levels did not. These results show that the amount of ALA correlates with the present clinical status as well as the future risk of developing immune deficiency.

AIDS-Related Complex↗

Biopsy diagnosis in human immunodeficiency virus infection and acquired immunodeficiency syndrome.

Human immunodeficiency virus infection and the complications of the acquired immunodeficiency syndrome produce a broad spectrum of lesions affecting all organs and tissues. They are caused by uncommon etiologic agents and characterized by unusual location, multiplicity, rapid progression, and tendency to generalization. Cellular reactions are inefficient and histologic appearances frequently atypical. Tissue biopsy, most often endoscopic, with microscopic examination, is the method predominantly used for achieving the required rapid, definitive diagnosis. This article reviews the lesions commonly seen in biopsy specimens of human immunodeficiency virus infection and acquired immunodeficiency disease syndrome, their characteristic histologic features, and their differential diagnosis.

Acquired Immunodeficiency Syndrome↗

Description of an endometrioid ovarian cancer cell line.

A human cell line, designated L-1, has been established from the ascites of an untreated patient with stage IV (FIGO) endometrioid ovarian cancer. This cell line initially grew uninterupted for 6 months without fibroblast contamination and contact inhibition, and has been subcultured weekly for the past 7 years. L-1 does not contain steroid hormone receptors nor does it demonstrate the presence of oncofetal antigens by immunohistochemical techniques. The doubling time of L-1 is 11.8 hr. Flow cytometric analysis reveals an aneuploid DNA peak, and an abnormal karyotype demonstrates hyperdiploidy, translocations, and deletions. Morphology, growth patterns, cytogenetic analysis, and other features of L-1 are characterized.

Carcinoembryonic Antigen↗

Salivary gland lymph nodes. The site of lymphadenopathies and lymphomas associated with human immunodeficiency virus infection.

Normally, lymph nodes are intimately associated with the salivary glands, particularly the parotid gland. Several lymph nodes are embedded in the parotid gland, other lymph nodes are adjacent to the submaxillary gland, and ectopic salivary gland acini and ducts are commonly present in cervical lymph nodes. These salivary gland lymph nodes may become the primary site of the benign lymphadenopathy and the malignant lymphomas characteristically associated with human immunodeficiency virus (HIV) infection. This report of a series of HIV-associated lymphatic lesions originating in salivary gland lymph nodes comprises nine cases of salivary gland masses that were surgically excised, it includes six cases of lymphadenitides and three cases of lymphoma--all originating in salivary gland lymph nodes and showing the histologic lesions known to occur in association with the acquired immunodeficiency syndrome. The HIV-related infections and neoplasias located in the salivary gland lymph nodes raise interesting questions about the possible etiologic role of an oral portal of entry and of the virus-infected saliva. The recognition of their clinical and pathologic features is indispensable to enable correct diagnosis and treatment.

Acquired Immunodeficiency Syndrome↗

Primary anorectal lymphoma. A new manifestation of the acquired immune deficiency syndrome (AIDS).

Non-Hodgkin's lymphomas with particular clinicopathologic features occur with a high incidence in homosexual men affected by AIDS. More frequently than in the general population, these lymphomas have an extranodal location including the gastrointestinal tract. We have recently observed four cases of AIDS-associated lymphomas whose primary location is in the lower rectum and anus. The patients were 27 to 44 years of age, had greatly depressed helper-suppressor T-cell ratios, and antibodies to human immunodeficiency virus (HIV). All four presented with anorectal symptoms and originally had surgery for anorectal fistulas or tumor masses. When staged, three patients had no other organ involvement, the fourth only had lymphoma in an axillary lymph node, and all four had large tumor masses confined within the rectum. In terms of histology, the lymphomas were of undifferentiated or of large cell type and of B-cell phenotype. Lymphomas with primary or major location in the rectum are a rare occurrence in the general population, and until recently, are rare even among the lymphomas associated with the immune deficiency syndrome. At the Lenox Hill Hospital in New York City, no rectal lymphoma among the 58 cases of AIDS-related lymphoma diagnosed during the past 4 years was recorded until 10 months ago. The recognition of the new feature in presentation, a neoplasm associated with AIDS, is obviously important for its early diagnosis and treatment. Its unusual occurrence at the suspected portal of entry of the HIV infection is of interest because it may provide new clues to the association between AIDS and neoplasia.

Acquired Immunodeficiency Syndrome↗

Lymphomas associated with the acquired immune deficiency syndrome (AIDS): a study of 35 cases.

An increased incidence of lymphoid neoplasias is associated with the states of immune deficiency both congenital and acquired. Thirty-five cases of lymphoma in males at high risk for AIDS were diagnosed in one community hospital in New York City within the past 2 years. The mean age of these patients was 39.6 years; 34 were homosexual, and one was an intravenous drug abuser. There were four Hodgkin and 31 non-Hodgkin lymphomas of various histologic types but almost all of high-grade categories. The proportion of extranodal lymphomas, the involvement of the gastrointestinal tract, central nervous system, bone marrow, and myocardium were significantly higher than in the lymphomas of the general population. The phenotypes were B-cell and non-B-non-T-cell types without any T-cell lymphomas. All patients had reversed helper-suppressor T-cell ratios, and all those tested had circulating HTLV-III and antilymphocyte antibodies. Nine patients have had previous lymph node biopsies showing the lesions of AIDS-related lymphadenopathies that were often directly associated with lymphoma. A variety of severe opportunistic infections and Kaposi sarcoma affected these patients. All lymphomas associated with immune deficiency were highly aggressive, involved multiple organs, and responded poorly to treatment resulting in early deaths.

Acquired Immunodeficiency Syndrome↗