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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 271 records · Page 15Linked to original sources
PubMed1990

Sex, drugs, and HIV infection in a New York City hospital outpatient population.

Persons attending outpatient clinics at Bellevue Hospital Center in Manhattan, New York City were invited to be tested for antibodies to human immunodeficiency virus (HIV). In pretest counseling, males were asked if they had injected nonprescription drugs or engaged in sex with other men since January 1, 1977; if so, they were asked not to participate and were referred elsewhere for testing. Face-to-face interviews and HIV testing were completed for 1,119 subjects with no prior indication of HIV seropositivity. Willingness to participate in the study was significantly greater among women than men and among younger than older persons. After exclusion of two subjects with indeterminate HIV serology, seroprevalence was 6.3% (70/1,117) overall, 7.1% (26/368) among men, and 5.9% (44/749) among women. HIV seropositivity among female i.v. drug users was 37% (27/74). Among heterosexuals without other HIV risk factors, estimated seroprevalences were 2.7% (25/924) overall, 3.3% (10/305) among males, and 2.4% (15/619) among females. Among heterosexual men, the data suggested associations of HIV seropositivity with sex with prostitutes and sex with numerous partners. Multiple logistic regression analysis indicated that significant predictors of HIV infection among women were a history of sexual contact with a male intravenous drug user, recent last use of intravenous drugs, and long duration of residence in New York City. Sexual intercourse with persons from AIDS risk groups was reported by 11% of men and 18% of women. The modal method of birth control reported by both men and women was "no method".

Adult↗
PubMed1990

Immunotherapy in conjunction with autologous bone marrow transplantation.

Although high-dose chemoradiotherapy used for conditioning prior to autologous bone marrow transplantation (BMT) represent an effective tool for eradication of certain malignant hematological disorders, relapses indicate that the last tumor cell is unlikely to be completely eradicated. We are investigating several approaches for controlling residual tumor cells escaping from chemoradiotherapy by cellular adoptive immunotherapy and amplification of natural defense mechanisms, using recombinant human IL2 (Cetus, Emeryville CA), in a murine model of leukemia/lymphoma disease (BCL1).

Animals↗
PubMed1990

The frequency of aneuploidy in cultured lymphocytes is correlated with age and gender but not with reproductive history.

The clinical significance of low numbers of aneuploid cells in routine cytogenetic studies of cultured lymphocytes is not always clear. We compared the frequencies of chromosome loss and gain among five groups of subjects whose karyotypes were otherwise normal; these groups were (1) subjects studied because of multiple miscarriages, (2) parents of live borns with autosomal trisomy, (3) subjects studied because they had a relative with Down syndrome, (4) an age-matched control group of phenotypically normal adults studied for other reasons (e.g., parent of a dysmorphic child or member of a translocation family), and (5) other mostly younger and phenotypically abnormal subjects who could not be assigned to the first four groups (e.g., individuals with multiple congenital anomalies or mental retardation). No significant age, sex, or group effects were observed for autosomal loss (hypodiploidy) or gain (hyperdiploidy). Autosomal loss was inversely correlated with relative chromosome length, but autosomal gain was not. Sex-chromosome gain was significantly more frequent in females than in males, but sex-chromosome loss was not significantly different between the sexes. Significant age effects were observed for both gain and loss of sex chromosomes. When age and sex were accounted for, the frequencies of sex-chromosome loss and gain were not significantly different among the five clinical groups. In general, low numbers of aneuploid cells are not clinically important when observed in blood chromosome preparations of subjects studied because of multiple miscarriages or a family history of autosomal trisomy.

Abortion, Spontaneous↗
PubMed1990

IL-2 activated cell-mediated immunotherapy: control of minimal residual disease in malignant disorders by allogeneic lymphocytes and IL-2.

The present experiments were designed to investigate whether it might be possible to combine their therapeutic benefits of autologous BMT and allogeneic BMT following administration of T-lymphocyte depleted marrow allografts with additional immunotherapy following BMT. The tumor model used for investigating graft vs leukemia (GVL) effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. Immunotherapy with high dose recombinant human interleukin-2 (IL2) (10(5) Cetus units x 3/day intraperitoneally (IP) for 5 days) produced significant anti-tumor effects in BCL1-bearing mice. BALB/c mice inoculated with 10(3) BCL1 leukemia cells received were treated on day -1 with cyclophosphamide 100 mg/kg and transplanted with normal syngenic BM cells on day 0. High-dose IL2 (100,000 Cetus Units x 3/day IP x 5 consecutive days) was initiated on day +1, +7, or +21 following BMT. Optimal time for administration of IL2 was noted at 3 weeks post-BMT with 90% of the mice surviving with no evidence of disease greater than 1 year. An experimental model designed to study GVL effects in a state of minimal residual disease following T-cell depleted allogeneic BMT indicated that mice receiving low dose of BCL1 challenge (10(4] were successfully treated by either IL2 (2 x 10(4) Cetus units x 2/day IP x 3 days), allogeneic spleen cells (10(6) on day +1, 10(7) on day +5 and 5 x 10(7) on day +9) alone and certainly following a combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of disseminative route on the liver- and lung-colonizing efficiencies of B16 melanoma and colon-26 carcinoma in mice.

Tumor-colony formation in the liver and lungs of mice was assessed, after delivery of equal numbers of B16 melanoma or colon-26 carcinoma cells via the portal vein or the hepatic artery, and via the pulmonary artery or the bronchial artery. Significantly greater lung involvement occurred after delivery of both cell types via the bronchial artery than via the pulmonary artery. In the case of colon-26 cells, liver colonization via the hepatic artery was more efficient than via the portal vein. In the case of B16 cells, no route-dependent differences in liver colonization were detected. Our results indicate that during hematogenous metastasis, the vascular route taken by some cancer cells to the same target organ may considerably modify the efficiency with which they form metastases.

Animals↗
PubMed1989

Site-associated expression of endogenous tumor lectins.

The expression of endogenous lectins was compared in mouse Lewis lung carcinomas growing in the kidney or subcutaneously. A panel of carbohydrates coupled to a biotinylated carrier molecule (bovine serum albumin), biotinylated desialylated glycoproteins and sulfated polysaccharides were used in histochemical assays to detect the presence and distribution of carbohydrate receptors. Heterogeneous staining patterns were observed with most carbohydrates in sections of tumor tissue from both anatomic sites, and staining intensities also varied within each section. At least 2 populations of cells were identified at each site, of which one had receptors for all carbohydrates, while the other had no receptors for melibiose, sialic acid, or alpha-glucosides (maltose and glucose). There were quantitative differences in expression of endogenous lectins by tumors growing s.c. or in the kidney; 3LL cells growing in the kidney bound 6 out of 10 carbohydrates to a greater extent than 3LL cells in s.c. tumors. Conversely, 3LL cells in s.c. tumors bound heparin and asialofetuin to greater extents than cancer cells in kidney tumors. Biochemical analyses of detergent extracts of tissues subjected to affinity chromatography and subsequent SDS-PAGE revealed quantitative and also qualitative differences in lectins between tumors growing in the 2 anatomic sites.

Animals↗
PubMed1989

Mechanism of mechanical trauma to Ehrlich ascites tumor cells in vitro and its relationship to rapid intravascular death during metastasis.

Many, if not most, of the cancer cells arrested in the microvasculature during metastasis appear to be rapidly killed by mechanical trauma, associated with shape-transitions, which require increases in cell surface area. The hypothesis has been advanced that such increases in surface area occur in 2 phases: First, there is an apparent increase due to surface unfolding, which is reversible and non-lethal. Second, there is a true increase, during which cell surface membranes are stretched, with an increase in membrane tension. When tension exceeds a critical level, the surface membranes rupture and this irreversible change is lethal. In the present study, cell surface area has been incrementally increased by a hypotonic environment. Down to approximately 70 mM/kg, a reversible, non-lethal increase in cell volume was observed, associated with electron microscopic evidence of unfolding. At and below 70 mM/kg, irreversible, lethal changes occurred, associated with increased susceptibility to the mechanical trauma associated with membrane-filtration. These observations are consistent with the hypothesis in question.

Animals↗
PubMed1989

Electron microscopic study of subcutaneous and intraperitoneal splenules in the mouse.

The development of splenules derived from slices of freshly removed autologous spleen implanted subcutaneously or intraperitoneally was followed by light and electron microscopy from day 2 to day 70. Within 48 hr after transplantation, a rough space filled with blood, unlined by endothelium, formed just under the surface of the splenic fragment. The tissue central to this vascular space was disrupted and necrotic. In the outer portion of the vascular space, fibroblasts appeared and created locules which developed into a highly vascular, hematopoietic red pulp. From the inner portion, blood percolated into the central necrotic tissue. At 1 week the splenule was divisible into concentric structures. The capsule was outermost. A shell of vascularized, highly hematopoietic red pulp lay within the capsule, having replaced the vascular space. Central to the red pulp lay a band of fibroblasts and macrophages. Next was a layer of fibroblasts in a matrix of degenerating cells, and, at the center, a necrotic core. As fibroblasts and macrophages moved centrad, the red pulp moved with them, expanding and replacing the necrotic tissue. The splenule differed in character from the original spleen. Splenular red pulp, especially near the surface, was unusually hematopoietic. The circumferential reticulum of white pulp was reduced or absent, and the boundary between red and white pulp was sometimes indistinct. Some white pulp was subcapsular, and the capsule and surrounding connective tissue were infiltrated by lymphocytes. The necrotic core of the splenule was typically surrounded by a zone containing large blood vessels, connective tissue, and adipocytes.

Animals↗
PubMed1989

Human T cells and interleukin 4 inhibit the release of interleukin 1 induced by lipopolysaccharide in serum-free cultures of autologous monocytes.

Stimulation with lipopolysaccharide (LPS) of unfractionated peripheral blood mononuclear cells in serum-free cultures resulted in the release of lower amounts of interleukin (IL) 1 as compared with those induced in cultures of purified monocytes. In addition, a dose-dependent decrease in IL 1 production was observed when purified autologous T cells were added to cultures of LPS-stimulated monocytes. The inhibitory effect of T cells on IL 1 production was reproduced by adding human recombinant IL 4 to monocyte cultures. IL 4 optimally inhibited the generation of cell-associated IL 1 and the extracellular release of IL 1 in monocyte cultures performed in the presence of low doses of LPS. IL 4 inhibited the generation of IL 1 activity and that of IL 1 alpha and IL 1 beta antigens indicating that IL 4 interfered with IL 1 transcription and/or processing rather than induced the synthesis of an IL 1 inhibitor. IL 2 and IL 3 enhanced IL 1 production by LPS-stimulated cells whereas granulocyte-monocyte colony-stimulating factor had no effect. IL 4 inhibited the production and the release of tumor necrosis factor alpha activity by monocytes stimulated with LPS. Thus, T cells and IL 4 may down-regulate the production of monokines which induce their proliferation and exert a suppressive effect on the generation of potent proinflammatory mediators.

Cells, Cultured↗
PubMed1989

Metachronous seeding of lymph node metastases in rats bearing the MT-100-TC mammary carcinoma: the effect of elective lymph node dissection.

Following the introduction of cancer cells into the lymphatic system, metastases in 'down-stream' lymph nodes often appear in a sequential manner. This could be due to synchronous seeding of the in-line nodes with progressively diminishing numbers of tumorigenic cancer cells, or alternatively, by discrete, stepwise (metachronous) seeding of 'down-stream' nodes by 'up-stream' nodal metastases acting as 'generalizing' sites. Metachronous seeding to local lymph nodes is potentially curable by elective lymph node dissection; synchronous seeding is not. Synchronous versus metachronous seeding of lymph node metastases was investigated using the MT-100-TC mammary carcinoma injected into the hind foot-webs of rats. When the primary tumor was removed by amputation one week after injection, 1/15 animals survived; in contrast, removal of the draining popliteal lymph node in addition to the primary lesion, resulted in 8/19 long-term survivors. At this time, occult metastases detectable by bioassay but not by conventional histology, were present in all draining popliteal nodes and in 60 percent of lungs. The fact that some amputees were cured when the popliteal node was removed, indicated the metachronous nature of nodal metastases in this system. Further, recurrence of nodal and lung metastases in those amputees in which the popliteal node was left intact, identified the popliteal node as a 'generalizing' site. By the time popliteal node involvement was evident by conventional histology, micrometastases were present in 'down-stream' nodes, and accordingly, removal of the popliteal node and the primary lesion at this time was not curative.

Amputation, Surgical↗
PubMed1989

Biomechanical interactions of cancer cells with the microvasculature during metastasis.

Metastasis is a major, life-threatening complication of cancer. The bloodstream is the most important disseminative route for cancer cells liberated from their parent tumors. Single circulating cancer cells are arrested in the microvasculature, where the vast majority are killed by rapid or slow processes, and the relatively few survivors grow into micrometastases. We review the underlying causes of one type of rapid cancer cell death in the microcirculation, namely, that caused by biomechanical interactions of cancer cells with microvessel walls, which may result in cell surface membrane expansion and lethal rupture. These lethal interactions appear to be important rate-regulators in hematogenous metastasis, and to dictate some aspects of metastatic patterns. Although these are not the only interactions involving cancer cells, in contrast to others involving cellular and humoral defense mechanisms, they have received comparatively little attention.

Animals↗
PubMed1989

Lymphoepithelioma-like carcinoma of the lung.

Originally described in the nasopharynx, lymphoepitheliomas are undifferentiated carcinomas with prominent lymphoid infiltration. Recently this tumor has been described in a number of other sites. An association with prior infection by the Epstein-Barr virus has been recognized in cases from the nasopharynx. We report four cases of lymphoepithelioma-like carcinoma arising in the lung. Epstein-Barr virus serology indicated prior infection in two cases, one of which was also found by in situ hybridization to have the virus genome. Lymphoepithelioma-like carcinoma must be considered in the differential diagnosis of primary lung tumors, particularly when an extensive infiltrate by lymphoid tissue is present and may even suggest lymphoma.

Aged↗
PubMed1989

HIV infection is associated with the spontaneous production of interleukin-1 (IL-1) in vivo and with an abnormal release of IL-1 alpha in vitro.

Interleukin-1 (IL-1) is not constitutively produced by normal human monocytes. We have investigated the production of cell-associated IL-1 in uncultured unstimulated adherent monocytes from HIV-infected patients, which reflects ongoing generation of IL-1 by the cells in vivo. High levels of cell-associated IL-1 activity and of cell-associated IL-1 alpha and IL-1 beta antigens were found in monocytes from HIV-infected patients as compared with those found in monocytes from normal individuals. Amounts of cell-associated IL-1 were high in patients with AIDS and in patients from Centers for Disease Control groups II and III. Serum-free culture for 24 h of monocytes from HIV-infected individuals in the absence of lipopolysaccharides (LPS) resulted in spontaneous release of IL-1 activity from the cells whereas no release occurred upon culture of normal cells. Stimulation of monocytes with LPS induced the release of IL-1 alpha and IL-1 beta from cells of infected patients. Only IL-1 beta was released from cells of normal individuals. Thus, circulating monocytes from HIV-infected patients are triggered to produce IL-1 in vivo. The present study also indicates that HIV infection is associated with an acquired defect in the intracellular processes regulating IL-1 secretion.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Night backache in pregnancy. Hypothetical pathophysiological mechanisms.

One hundred women responded to a questionnaire dealing with night backache during pregnancy. All the women were in the second half of their pregnancy. Sixty seven per cent of the women reported discomfort and/or backache during the night. We hypothesize that hypervolemia combined with obstruction of the inferior vena cava, caused by the enlarging uterus, is the underlying pathomechanism leading to night backache. Patients with inadequate venous collateral circulation may develop excessive pressure within the venous system, the vertebral bodies and overdistension of venous channels distal to the occluded zone. These changes may lead to hypoxemia, metabolic disturbances, irritation of unmyelinated nerves and result in night backache.

Back Pain↗
PubMed1989

Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of type I collagen determines the clinical phenotype.

Skin fibroblasts grown from three individuals with osteogenesis imperfecta (OI) each synthesized a population of normal type I collagen molecules and additional molecules that had one or two alpha 1(I) chains that contained a cysteine residue within the triple-helical domain, a region from which cysteine normally is excluded. The patients had very different phenotypes. One patient with OI type I had a population of alpha 1(I) chains in which glycine at position 94 of the triple helix was substituted by cysteine; a patient with OI type III had a population of alpha 1(I) chains in which glycine at position 526 of the triple helix was substituted by cysteine; and the third patient, with OI type II, had a cysteine for glycine substitution at position 718 of the alpha 1(I) chain. From all three patients, molecules that contained two mutant chains formed interchain, intramolecular disulfide bonds, and although less stable to thermal denaturation than normal molecules, they were more stable than molecules that contained only a single mutant chain. These findings indicate that substitutions for glycine within the triple-helical domain of the alpha 1(I) chain are not invariably lethal and that their phenotypic effect largely depends on the nature of the substituting residue and its location in the chain.

Adult↗
PubMed1989

Mechanisms of splenic control of murine malaria: cellular reactions of the spleen in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice, and the consequences of pre-infective splenectomy.

The splenic response in lethal 17XL Plasmodium yoelii murine malaria is vigorous, displaying marked phagocytosis, erythropoiesis, lymphopoiesis, plasmacytopoiesis, and, from day 3 of infection, increasing levels of parasitized erythrocytes. There is also a pronounced response of newly characterized fibroblastic stromal cells which branch and fuse with one another, forming extensive, complex, irregular, syncytial membranous sheets which provide a variety of barriers. Hence, I term these barrier cells (BC), and their fusion results in barrier-forming complexes (BFC). BC form adherent surfaces, trapping parasitized erythrocytes and monocytes-macrophages, facilitating phagocytosis. They envelop single plasma cells, erythrocytes, erythroblasts, lymphocytes, reticulocytes, monocytes-macrophages, or clusters of them. They surround blood vessels, forming blood-spleen barriers. They are insinuated into the circumferential reticulum at the periphery of white pulp, isolating white pulp. They form channels in red pulp, directing blood flow. They are associated with collagen. There appear to be several sources of BC. They may originate by activation of established reticular cells which form the filtration beds, by activation of reticular cells covering the pulp surface of capsule and trabeculae, and as a major source in this malaria, from circulating progenitors entering the splenic pulp from the vasculature. In non-lethal malaria, these barrier systems protect splenic reticulocytes from parasitization. In the lethal 17XL malaria they do not, and there follows a considerable increase in parasitization in the spleen with a corresponding increase in active macrophages. Large-scale parasitization and parasite recycling through the great stores of splenic reticulocytes in the lethal malaria, and the failure of parasitization of these splenic reticulocytes reserves on the non-lethal malaria, suggests that the actions of the spleen aggravate the lethal malaria and ameliorate the non-lethal. This is supported by the finding that non-lethal malaria is aggravated and lethal malaria ameliorated by splenectomy.

Animals↗