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Biomedical subjects

F Naeim

Publications and source records attributed to F Naeim.

At least 37 records · Page 2Linked to original sources

Detection of cytomegalovirus DNA in classic and epidemic Kaposi's sarcoma by in situ hybridization.

Several lines of evidence have suggested an etiologic association of cytomegalovirus (CMV) with Kaposi's sarcoma. This contention is supported by a pathoepidemiologic survey of 54 cases of acquired immunodeficiency syndrome (AIDS) at our own institution. Of the 27 patients with documented Kaposi's sarcoma, 24 (89%) showed histologic evidence of CMV infection (cytomegalic cells with viral inclusions), whereas only 9 (33%) of the patients with AIDS without Kaposi's sarcoma showed hallmarks of CMV infection. In an attempt to address this question further, we have searched for the presence of CMV nucleic acid sequences in a series of 25 patients with AIDS and Kaposi's sarcoma, using the technique of in situ DNA hybridization. The reliability of the in situ technique is demonstrated, and the technique is shown to be more sensitive than the detection of viral inclusions within Kaposi's sarcoma lesions by routine light microscopy. However, only 20% of our cases showed evidence of CMV involvement, and the CMV-positive cells within the affected Kaposi's sarcoma lesions were few and sparsely distributed. In addition, a companion series of 6 elderly patients with "classic" Kaposi's sarcoma showed no evidence of CMV infection by either conventional microscopy or in situ hybridization. These results do not support the notion of a strong association between Kaposi's sarcoma and CMV, unless the CMV sequences are present at a copy number too low for detection by these methods. The implications of these findings in light of current theories of CMV oncogenesis are discussed.

Acquired Immunodeficiency Syndrome↗

Histological response and antigen transmission in the lymph nodes of athymic nu/nu mice inoculated with Crohn's disease tissue filtrates.

Lymph node histology and antigen transmission in the nu/nu mouse in response to animal inoculation with Crohn's disease tissue filtrates were re-evaluated. We found that a hyperplastic lymph node response in nu/nu mice occurred with Crohn's disease (CD), ulcerative colitis (UC), or other intestinal disease (OID) tissue inoculations. In addition, antigen transmission to lymph nodes as detected by indirect immunofluorescence using CD sera was observed in all inoculation groups. The immunofluorescent reaction also occurred independently of lymph node histology. Thus, we confirm that CD sera recognize an antigen(s) expressed in lymph nodes of athymic mice inoculated with CD tissue filtrates. The antibody (or antibodies) in CD sera was not specific for this 'CD antigen or antigens', however, as tested in the nu/nu mouse system, because the CD sera antibodies also recognised antigens in UC inoculated and OID inoculated animals.

Animals↗

Reactivity of neoplastic cells of hairy cell leukemia with antisera to S-100 protein.

Rabbit antibodies to bovine S-100 protein were tested by immunoperoxidase technics against fresh hairy cell leukemia (HCL) cells obtained from nine patients (peripheral blood in six and spleen in three), as well as lymphoblastoid cell lines derived from three patients with HCL. Peripheral mononuclear cells from three normal persons and two patients with chronic lymphocytic leukemia (CLL) and cells from two melanoma lines were used as controls. The melanoma cell lines, cell lines derived from patients with HCL, and fresh HCL cells displayed cytoplasmic and nuclear positivity after exposure to anti-S-100 protein sera. By contrast, normal peripheral blood lymphocytes and CLL cells were negative for S-100 protein. Additional studies were performed by immunoperoxidase technics on representative sections of formalin-fixed splenic tissues from eight patients who had splenectomies. The cause of splenectomy was HCL in three, traumatic rupture in one, CLL in one, Hodgkin's disease in one, and hypersplenism in two patients. Sections from all three HCL patients showed moderate to marked positivity with antisera to S-100 protein. These results strongly suggest the presence of S-100 protein in HCL cells.

Animals↗

Hypocellular bone marrow with increased blasts.

Twenty patients with hypocellular bone marrow and increased blasts (HBMIB) were reviewed. The median age was 60 years with a male:female ratio of 17:3. History of alcohol abuse was noted in 30%, potential exposure to toxic chemicals in 20%, second malignancies in 20%, and aplastic anemia in 25%. Pancytopenia with marrow hypocellularity and increased marrow blast cells were characteristic hematopathologic features. Marrow hypocellularity was moderate to severe (less than or equal to 25%) in over half of the cases and mild to moderate (greater than 25, less than or equal to 35%) in the remainder. Blast cells were the predominant cellular elements in the marrow displaying scanty to moderate amounts of cytoplasm, round to oval nuclei, and one or more nucleoli. Special stains were performed in 19 cases. Blast cells morphologically displayed myeloid features, but Sudan black B and/or peroxidase positivity was noted in only ten patients. The overall mortality was high, especially in patients undergoing chemotherapy. At 1 year follow-up, 11 patients had received chemotherapy and eight of these eleven were dead compared to three of nine patients dead in those not receiving chemotherapy. Only two patients developed "overt" leukemia evidenced by hypercellular marrow and over 30% blast cells in the peripheral blood. HBMIB is a distinct clinicopathologic entity characterized by severe marrow failure and a low response rate to chemotherapy.

Acute Disease↗

Diagnostic immunopathology.

The application of immunologic techniques to tissue sections has added a new dimension to the investigation and classification of various processes. Virtually every section of diagnostic pathology has been enhanced by using specific monoclonal antibodies or polyclonal antiserum. Neoplasms formerly diagnosed as poorly differentiated or anaplastic may be precisely identified as to their origin through the use of specific membrane or cytoplasmic markers. Other cellular products, including viruses, hormones, enzymes or highly specific proteins, are also available to study neoplastic and nonneoplastic processes. New and more specific reagents are regularly becoming available for the diagnostic repertoire of pathologists. We present some of the principles of diagnostic immunopathology to show the scope and importance of the techniques.

Adult↗

Pathologic evaluation of thymic hyperplasia in myasthenia gravis and Lambert-Eaton myasthenic syndrome.

Eleven thymectomy specimens from patients with myasthenia gravis or Lambert-Eaton myasthenic syndrome were thoroughly sectioned. The results were compared with the routine surgical pathology reports that were based on a median of four sections. Routine sampling was found to be inadequate because the thymectomy specimens were inhomogeneous--some random sections contained germinal centers while others did not. Thus, on more thorough examination, about half of the specimens should have been diagnosed as showing "follicular hyperplasia" rather than "no diagnostic change" or "involution." This helps explain the conflicting results of previous studies, based when stated on a mean of three sections, in which favorable response to thymectomy in patients with myasthenia gravis was either not correlated with the thymus histologic state or correlated variously with few or numerous germinal centers. Thus, nondiagnostic histologic findings based on only one or two thymus sections should be suspect, and if in doubt a larger number of sections should be examined for accurate pathologic diagnosis.

Adolescent↗

Bone marrow changes in patients with hairy cell leukemia treated by recombinant alpha 2-interferon.

Bone marrow specimens from 21 patients with hairy cell leukemia (HCL) who were entered into a program to study the efficacy of treatment with recombinant alpha 2-interferon were evaluated. Patients were treated with the interferon, 2 X 10(6) U/m2 subcutaneously three times weekly, and were scheduled to undergo bone marrow aspiration and biopsy at study entry and after three (21 patients) and six (16 patients) months of treatment. Bone marrow samples after three months of treatment showed an overall decline in cellularity, from an average of 77 +/- 20 to 57 +/- 22 per cent, with a marked decrease in the percentage of neoplastic mass (from 87 +/- 9 to 59 +/- 24 per cent). The bone marrow changes were associated with significant improvement in hematologic values, including hemoglobin levels and granulocyte and platelet counts. The bone marrow changes and improved hematologic values remained stable with continuation of interferon therapy. However complete bone marrow remission did not occur in any of the patients after three or six months of interferon therapy. The HCL cell mass in more than 60 per cent of the patients remained at or above 50 per cent of the marrow cellularity and dropped to less than 25 per cent in 14 per cent of the patients. In all of the patients increased amounts of reticulin fibers were identified in the bone marrow prior to therapy, and 89 per cent of bone marrow aspirations failed (dry tap). The amounts of reticulin fibers remained increased in most of the patients (91 per cent), with a high incidence of dry taps (73 per cent), after therapy. Interferon therapy also changed the tartrate-resistant acid phosphatase(TRAP)-positive HCL cells to TRAP-negative, suggesting inhibition of activity and/or production of TRAP in HCL cells.

Acid Phosphatase↗

Thymus involution in the acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in AIDS may be a crucial element in the pathogenesis of this syndrome.

Acquired Immunodeficiency Syndrome↗

Acute megakaryocytic leukemia following chemotherapy for a malignant teratoma.

A 20-year-old man underwent systemic chemotherapy (four cycles of vinblastine sulfate, bleomycin sulfate, and cisplatin) following full resection of a malignant mediastinal teratoma without evidence of metastatic spread. Five months following this resection, pancytopenia, circulating blast cells, and bone marrow necrosis developed. An autopsy disclosed a disseminated megakaryocytic neoplasm. Although a cause-effect relationship is suggested, the duration between the institution of therapy and the appearance of this megakaryocytic malignant neoplasm is less than the latent periods previously reported for cases of therapy-related leukemias. This case is also compared with other reports of therapy-related hematopoietic disorders with prominent megakaryocytic proliferations.

Adult↗

Strong HLA-DR expression in T cell cultures after activation is necessary for IL-2-dependent proliferation.

We have examined the appearance of DR antigens on human T cells activated by PHA, using a monoclonal anti-DR framework antibody and a large panel of human HLA typing sera. Strong DR expression within the culture by day 8 was associated with the ability of cells to grow for long periods in IL-2 containing medium, whereas weak or absent DR expression was predictive of poor in vitro growth. All the cells responded equivalently to initial stimulation with PHA. These data support the hypothesis proposed by Moretta et al. to explain blocking of IL-2-dependent proliferation by an anti-DR antibody--that DR molecules may be involved in the transmission of signals by IL-2.

Cells, Cultured↗

Clinicopathological subtypes in hairy-cell leukemia.

Thirty-six patients with hairy-cell leukemia (HCL) were evaluated, and were divided in two major subtypes: leukopenic (WBC less than 3000/microliters) and non-leukopenic (WBC greater than or equal to 3000/microliters). There were 22 leukopenic and 14 non-leukopenic patients. The leukopenic group were older than the non-leukopenic group, with an average age of 58.4 years compared with 47.6 years. The male/female ratio was higher in the leukopenic (6.3) than the non-leukopenic (2.0) patients. Splenomegaly, hepatomegaly and lymphadenopathy were found in 66%, 32%, and 18% of the leukopenic patients, compared with 92%, 57%, and 35% in the non-leukopenic patients. The leukopenic HCL was associated with more severe anemia, granulocytopenia, monocytopenia, and thrombocytopenia, and higher incidence of serious infections than the non-leukopenic HCL. Increased bone marrow reticulin fibers and unsuccessful marrow aspirations (dry taps) were more frequently associated with the leukopenic than the non-leukopenic HCL.

Bone Marrow Examination↗

Burkitt's lymphoma with cranial nerve involvement.

A 22-year-old white native Californian acquired multiple cranial nerve palsies. He was found to have a Burkitt's-type lymphoma involving the ethmoid and sphenoid sinuses, with orbital invasion. Bone marrow involvement developed. Despite aggressive therapy, he died 18 weeks after the onset of his illness. Poor prognostic indicators included CNS symptoms at the time of initial onset, bone marrow involvement, and postadolescent occurrence. The absence of viable tumor at autopsy indicates sensitivity of Burkitt's lymphoma cells to combination chemotherapy and irradiation treatment.

Adult↗

Acute lymphoblastic leukemia with giant intracytoplasmic inclusions.

Leukemic cells of bone marrow and peripheral blood showing clusters of distinctive, large, uniform, rounded intracytoplasmic inclusions were found in a patient who had acute lymphoblastic leukemia. These membrane-bound inclusions ranged from 0.8 to 1.4 microgram in diameter and were clearly demonstrated on routinely stained preparations. Electron microscopy disclosed transitions between well-developed mitochondria and the electron-dense structures. The functional significance of these presumably altered mitochondria is uncertain. Whorled lamellar internal structures, in occasional fingerprintlike arrangements, may represent duplication of mitochondrial cristae and, functionally, may reflect increased metabolic rate or otherwise abnormal metabolism. Cytochemical studies demonstrated the presence of both periodic acid-Schiff positivity and nonspecific esterase activity in these inclusions, but no peroxidase or acid phosphatase was found. These findings support the lymphoid nature of the disorder. Immunologic surface membrane markers are consistent with this case being, as with the majority of acute lymphoblastic leukemias, of non-B, non-T cell type. Cytogenetic studies on cultured leukemic cells from bone marrow and peripheral blood showed a consistently abnormal karyotype associated with the presence of an XXY chromosomal constitution. Since no other tissues (e.g., dermal fibroblasts) were examined, the diagnosis of Klinefelter's syndrome cannot be confirmed. A causal relationship between the coexistence of the abnormal karyotype and the acute leukemia was not proven but was suspected.

Bone Marrow↗

Cytoskeletal control of redistribution of surface membrane receptors in hairy cells.

The redistribution of surface membrane immunoglobulin (SmIg) and concanavalin A (Con-A) was studied in peripheral mononuclear cells of three patients who had hairy cell leukemia. Fluorescein-labeled polyvalent goat antihuman immunoglobulin and fluoresceinated Con-A were used as ligands. The capping of ligand-receptor complexes was temperature-dependent and was more prominent at 37 C. A significant drop in the percentages of SmIg and Con-A capping was observed when cytochalasin B was added. In contrast, no decline in the percentages of SmIg and Con-A capping was seen in the presence of colchicine. The inhibitory action of cytochalasin B on the capping of SmIg and Con-A receptors in hairy cells suggests that these receptors are integral macromolecules of the plasma membrane and their redistribution is regulated by cytoskeletal structures.

Cell Membrane↗

Disturbance of redistribution of surface membrane receptors on peripheral mononuclear cells of patients with Down's syndrome and of aged individuals.

Redistribution of surface membrane immunoglobulins (SmIg) and concanavalin A (Con-A) receptor sites were studied in the peripheral mononuclear cells of institutionalized patients with Down's syndrome (DS), non-DS patients from the same institution, normal hospital staff members, and a group of healthy-appearing older volunteers averaging over 85 years of age. Two ligands were chosen: fluorescein-labeled polyvalant goat anti-human immunoglobulin for T-depleted mononuclear cells, and fluoresceinated Con-A for unfractionated peripheral mononuclear cells. The percentage of cells showing capping of SmIg and Con-A receptor sites was significantly lower in aged persons and in DS patients than in non-DS patients and normal staff members. Such a disturbance of mobility of cell membrane receptors in aged persons indicates the existence of alterations in surface membrane and associated structures of peripheral mononuclear (lymphoid) cells with aging in humans. The finding of a lower degree of capping in DS than in controls of similar age supports the supposition that DS shows features of accelerated aging.

Adult↗