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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 253 records · Page 14Linked to original sources
PubMed1990

Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression.

Infection of confluent human umbilical vein endothelial cells by the parasite Trypanosoma cruzi results in the appearance of an altered heparan sulfate proteoglycan (HSPG) isolated from the extracellular matrix of infected endothelial cells (ECMi). HSPG from ECMi differed from HSPG obtained from the extracellular matrix of uninfected endothelial cells (ECMu) by virtue of an 8-10-fold increase in sulfation and a different elution pattern using DEAE Sepharose chromatography. Analysis of the HSPG that binds to acidic fibroblast growth factor (aFGF) revealed that infection increased the proportion of HSPG that binds to aFGF by 35%. Heparitinase and alkaline borohydride treatment of aFGF-binding HSPG and chromatographic resolution on Sepharose CL4B column revealed an infection-associated 10-fold increase in sulfation of the GAG side chain with no significant change in the migration of the core protein. In addition, the aFGF binding HSPG isolated from ECMi demonstrated a markedly attenuated synergistic mitogenic activity with aFGF in a cell proliferation assay. All of the infection associated changes in HSPG could be demonstrated in HSPG obtained from uninfected endothelial cell cultures grown on ECMi. Hence, the ECMi is associated with signals capable of modulating the ECM associated metabolism of uninfected endothelial cells. This facility of ECMi was also shown to extend to patterns of Gs protein synthesis as revealed by Western blot analysis. The observation that the ECM produced by infected endothelial cells can direct the synthetic patterns of uninfected endothelial cells in a manner uniquely observed in infected endothelial cells suggests a plausible pathway by which infection of only a few cells can ultimately result in the coordinate responses of neighboring uninfected cells.

Chagas Disease↗
PubMed1990

A molecular analysis of terminase cuts in headful packaging of Salmonella phage P22.

Fragments of DNA molecules of Salmonella phage 22 which represent the molecular termini created by the terminase reaction have been cloned and sequenced. The terminase cleavage separates a headful-sized piece of DNA from the concatemeric precursor; by successful cloning strategy it was shown that the terminase produces blunt ends. The termini of 20 different phage DNA molecules fall into a region located between about 600 and 4000 bp from the pac signal and show a Gaussian distribution. The average terminal redundancy was calculated to be about 2230 bp (= 5.3%) and is therefore higher than was previously reported. A comparison of the nucleotides flanking the terminal bases of 20 different end clones does not support the suggestion that the terminase recognizes some specific sequence and/or structural information in determining the actual cleavage site.

Base Sequence↗
PubMed1990

Characterization of effector cells of graft vs leukemia following allogeneic bone marrow transplantation in mice inoculated with murine B-cell leukemia.

It is now widely accepted that immunocompetent lymphocytes in allogeneic bone marrow grafts exert an antileukemic effect that contributes to the cure of leukemia. Graft vs leukemia (GVL) effects independent of graft vs host disease were investigated in allogeneic bone marrow chimeras tolerant of host and donor alloantigens. The role of Thy1.2, L3T4 and Lyt2 T lymphocytes as effector cells of GVL were investigated in (BALB/c x C57BL/6)F1 mice inoculated with murine B-cell leukemia and subsequently conditioned with total lymphoid irradiation and cyclophosphamide (200 mg/kg). Mice were reconstituted with C57BL/6 bone marrow cells depleted of well-defined T-cell subsets or enriched for stem cells by the soybean agglutination method. Detection of residual tumor cells, an indicator for efficacy of GVL, was carried out by adoptive transfer of peripheral blood or spleen cells obtained from treated chimeras into secondary naive BALB/c recipients at different time intervals following bone marrow transplantation. Treatment of the primary marrow inoculum with monoclonal anti-Thy1.2 or anti-Lyt2 abolished the GVL effects and all secondary BALB/c recipients developed leukemia within 60 days. On the other hand, the treatment with monoclonal anti-L3T4 did not influence the effect of GVL and all treated recipients remained without leukemia. The data suggest that T cells may mediate GVL effects in the absence of graft vs host disease and in circumstances where tolerance to conventional alloantigens is elicited. Effector cells of GVL across the major histocompatibility complex (MHC) in the murine B-cell leukemia tumor model system appear to be Thy1.2+ Lyt2+ L3T4-. Induction of GVL effects by allogeneic cells tolerant of host MHC suggests that these effects may be independent of graft vs host disease.

Agglutinins↗
PubMed1990

Mechanisms for the biomechanical destruction of L1210 leukemia cells: a rate regulator for metastasis.

Mechanical trauma appears to be one significant cause of the rapid intravascular death of cancer cells and, as such, could act as an important rate regulator for the metastatic process. Intravascular mechanical trauma to cancer cells is thought to be a consequence of shape transitions, occurring when they are deformed from spherical shape by entry into, and passage along, capillaries having smaller diameters than themselves. These transitions from spherical shape require increases in surface area; first, an apparent increase in surface area is accomplished by a reversible, nonlethal surface membrane unfolding. If this is insufficient to meet geometric demands, it is followed by a true increase in surface area, resulting in increased tension in the cancer cell surface membrane, leading to its lethal rupture.

Animals↗
PubMed1990

The spleen in malaria: the role of barrier cells.

I believe that my laboratory has developed a construct of the spleen useful in understanding its range of normal and pathologic functions. The elements in the construct include recognition of an anatomically open vasculature with the interposition of reticular cell-reticular fiber filtration beds between terminal arterial vessels and proximal venules. The central function of the spleen, moreover--selective clearance of cells, microbes and other particles from the blood--depends upon these filtration beds. Such functions of the spleen as phagocytosis, immunologic reactivity, hematopoiesis, and blood cell storage derive from its clearance capacities. The reticular filtration beds offer but modest levels of basal clearance. The wide ranges of filtration that characterize the stressed spleen depend upon arming or augmenting the basic reticular filtration beds with responsive cells which can rapidly appear, and rapidly disappear. These include macrophages, salient phagocytic cells of rich repertoire, which have been accorded the major, even exclusive, role in splenic clearance. But other stromal cells participate in splenic clearance. I have identified a system of fibroblastic, contractile, granulated cells which fuse to form complex, branched syncytial sheets which, deployed as diverse barriers, augment the basic reticular filtration beds. Hence, I term these cells barrier cells. Barrier cells effectively interact with macrophages, reticular cells, other stromal and blood cells, contributing to the extraordinary range of splenic clearance capacities. Barrier cells may be elicited by a variety of infectious processes, damaged blood cells and hematopoietic factors. Interleukin-1-alpha evokes a strong barrier cell response, and may be the common denominator in splenic stress, stimulated by activated macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Polyarticular symmetric tophaceous joint inflammation as the initial presentation of gout.

A 76-year-old woman suffered from bilateral distal index finger pain and swelling. The patient had been initially treated with antibiotics for herpetic whitlow complicated by a secondary bacterial infection. Gout was diagnosed through clinical history, physical examination and identification of monosodium urate crystals in the joint aspirate. Gout appearing as polyarticular, symmetric tophi involving the periungual region and distal interphalangeal joint has not been previously described.

Aged↗
PubMed1990

Zidovudine inhibits functional extracellular monocytic interleukin-1.

Zidovudine (AZT) penetrates human monocytes to exert its antiretroviral activity at the level of reverse transcriptase in infected cells. Stimulation of normal human monocytes with lipopolysaccharide (LPS) results in the transcription of interleukin-1 (IL-1) genes, the intracellular accumulation of IL-1 alpha and IL-1 beta precursors, and the subsequent extracellular release of functional IL-1 beta. The present study demonstrates that zidovudine inhibits the extracellular release of IL-1 activity without affecting the generation of intracellular IL-1 or the amount of released IL-1 beta protein. Similar results were observed with monocytes from normal individuals and monocytes from patients with AIDS. Since IL-1 may upregulate the expression of HIV genes in infected cells, the inhibitory effect of zidovudine on the release of functional IL-1 may be relevant for the beneficial effect of the drug in HIV infection.

Extracellular Space↗
PubMed1990

Low-back pain in pregnancy. Abdominal muscles, sit-up performance, and back pain.

An attempt was made to determine the effect of pregnancy on the abdominal muscles and to correlate changes in abdominal muscles strength with low-back pain during pregnancy. The study included 328 women. Group A consisted of 164 pregnant women; group B consisted of 164 non-pregnant women. The race, age, height, weight, parity, profession, time devoted to physical fitness per week, abdominal length, and relation between the abdominal length to height were recorded. A detailed history relating to backache prior to and during pregnancy was obtained. Each woman was asked to perform a single sit-up. The results of the study indicate that about 10% of pregnant women develop severe low-back pain that interferes with daily life activities. About 49% of the non-pregnant women complained of LBP. The pain did not interfere with activities of daily living. During pregnancy, due to overstretching of the abdominal muscles, the ability to perform a sit-up is significantly decreased. Whereas all non-pregnant women could perform a sit-up, 16.6% of pregnant women could not perform a single sit-up. There was no statistically significant correlation between the sit-up performance and backache. It may be concluded that during pregnancy the abdominal muscles become insufficient.

Abdomen↗
PubMed1990

Prenatal identification of a girl with a t(X;4)(p21;q35) translocation: molecular characterisation, paternal origin, and association with muscular dystrophy.

There are 23 females known with Duchenne or Becker muscular dystrophy (DMD or BMD) who have X;autosome translocations that disrupt the X chromosome within band p21. A female with a t(X;4)(p21;q35) translocation was identified prenatally at routine amniocentesis. At birth, she was found to have a raised CK level, consistent with a diagnosis of Duchenne muscular dystrophy. Her cells were fused with mouse RAG cells and the translocated chromosomes were separated from one another and from the normal X chromosome by segregation in the resulting somatic cell hybrids. Southern blot analysis of the hybrids indicated that the translocation occurred on the X chromosome between genomic probes GMGX11 and J-66, both of which lie within the DMD gene. Further localisation with a subfragment of the DMD cDNA clone placed the translocation breakpoint in an intron towards the middle of the gene, confirming that the de novo translocation disrupted the DMD gene. RFLP analysis of the patient, her parents, and the hybrid cell lines showed that the translocation originated in the paternal genome. This brings to six out of six the number of DMD gene translocations of paternal origin, a fact that may be an important clue in future studies of the mechanism by which X;autosome translocations arise.

Adult↗
PubMed1990

Effects on serum parathyroid hormone of intravenous treatment with alphacalcidol in patients on chronic hemodialysis.

Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D. Intravenous administration of alphacalcidol, a synthetic analogue which is metabolized to calcitriol, was given during 12 weeks to 51 patients on chronic hemodialysis in doses between 1 and 4 micrograms/dialysis session. The treatment caused a modest rise, by 0.25 mmol/l, in serum calcium but a 60% reduction of intact serum PTH concentrations. Most patients acquired normal PTH values and hypercalcemia was easily avoided by dose adjustments. There was a significant reduction in serum PTH within the 1st week before the serum calcium concentrations were increased, but after that time the induced suppression of PTH was correlated to the induced rise in serum calcium. These observations are compatible with the view that calcitriol exerts both a direct inhibition of PTH release and increases the gland's sensitivity to calcium. The major implication of the study is that intravenous treatment with alphacalcidol is of great clinical value since it is easy to administer and provides suppression of hypersecretion of PTH with few side effects.

Aluminum↗
PubMed1990

Chlorpromazine-induced hypothermia in tumour-bearing mice, acute cytotoxic drug lethality and long-term survival.

The acute lethality of various cytotoxic drugs (doxorubicin, vinblastine and nitrogen mustard) and long-term survival in a syngenic mouse-tumour system were studied at normal body temperature and at 28 degrees C induced by chlorpromazine. Chlorpromazine-induced hypothermia itself neither caused acute toxicity nor influenced long-term survival. Doxorubicin (15 mg/kg) and nitrogen mustard (6 mg/kg) lethality was reduced at decreased temperature. The median survival time increased significantly from 35 days in normothermic to 52 days in hypothermic doxorubicin-treated mice. With nitrogen mustard, no increase in long-term survival was seen in the hypothermic group. The acute lethality of vinblastine was enhanced by hypothermia and the long-term tumour survival was unaffected. Hypothermia or possibly chlorpromazine considerably modulates drug toxicity and possibly anti-tumoural activity.

Animals↗
PubMed1990

Effect of cyclosporine A and methylprednisolone on the graft-versus-leukemia effects across major histocompatibility barriers in mice following allogeneic bone marrow transplantation.

The effect of post-transplant immunosuppressive agents used in anti-GVHD prophylaxis on leukemic relapse was tested using a murine model of originally spontaneous, subsequently transplantable and non-immunogenic B cell leukemia (BCL1). (BALB/c x C57BL/6)F1 mice inoculated with 10(7) BCL1 cells were conditioned by total lymphoid irradiation (TLI) (1600 cGy), cyclophosphamide (200 mg/kg) or total body irradiation (TBI) 750 cGy and reconstituted with C57BL/6 (C57) bone marrow cells (30 x 10(6] or 10 x 10(6) bone marrow cells with additional 2 x 10(6) donor-type spleen cells, respectively. Mice were treated by cyclosporine A (CSA) 20 mg/kg i.p., or methylprednisolone (MP) 10 mg/kg i.p. for 10 days each and one group of controls received no post-transplant therapy. Stable chimerism was documented in all recipients with greater than or equal to 90% donor-type C57 cells in the peripheral blood. Eighty-nine percent of the mice treated by CSA following conditioning with TLI developed leukemia within 70 days, whereas none of the MP-treated mice and none of untreated chimeras showed any evidence of leukemia for more than 150 days. Adoptive transfer experiments using 10(5) spleen cells obtained from recipients conditioned with TBI were done to monitor residual leukemic cells following different post-transplant treatments. Eight-five percent of recipients of spleen cells obtained from mice treated with CSA developed leukemia in contrast with 33% and 25% when spleen cells were obtained from mice treated with MP or untreated controls, respectively (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Some effects of mechanical trauma on the development of primary cancers and their metastases.

Posttraumatic inflammation and, much less commonly, mechanical trauma itself may affect the clinical course of cancer. There is no evidence that a single incident of trauma can cause cancer, although posttraumatic chronic inflammation may be associated with carcinogenesis. In patients with cancer at the time of trauma, inflammation and repair processes may inhibit or enhance cancer growth, and trauma and its sequelae may increase the rates of invasion and dissemination.

Humans↗
PubMed1990

Long-term function of persons with atherosclerotic bilateral below-knee amputation living in the inner city.

Long-term function of 24 elderly persons with atherosclerotic bilateral below-knee amputation living in an inner city for at least six months after the second amputation, was determined. Twenty-one (87.6%) subjects were living at home; three were living in nursing homes. Fourteen (70%) of 20 subjects who received bilateral prostheses were ambulators. At interview, the mean age was 75.2 years; 4.87 years was the mean time since the second amputation. Ten (50%) subjects remained ambulatory. Among the other ten who received prosthesis, loss of ambulation occurred mostly due to medical factors, at an average of 3.47 years after the second amputation. Those no longer ambulatory were older and "sicker," and the interval between amputations was shorter. Fifteen (62.5%) subjects were independent in dressing, 14 (58.4%) in toileting, and only nine (33.3%) in bathing. All but one subject required housekeeping assistance. The anticipated effect on function of environmental and socioeconomic factors could not be demonstrated in this sample. Survival time and retention of ambulatory skills for an average of nine years after the second amputation in eight (33.3%) subjects who died before the end of the study was longer than previously described. The high rate of success in rehabilitation and in maintenance of ambulatory skills fully justifies intensive restorative efforts for this group of amputees.

Activities of Daily Living↗
PubMed1990

The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD?

Graft-versus-leukemia (GVL) is a major component of the overall beneficial effects of allogeneic bone marrow transplantation (BMT) in the treatment of leukemia. Although several clinical trials have suggested a direct relationship between GVL effects and acute and chronic graft-versus-host disease (GVHD), it is not yet known whether GVL can be separated from GVHD. However, several investigations in murine models of human leukemia indicate that the two may be at least partially separable. Moreover, analysis of clinical data from the International Bone Marrow Transplant Registry suggest that allogeneic BMT may be more advantageous than syngeneic BMT, regardless of the GVHD. Likewise, T lymphocyte depletion is associated with an increased incidence of relapse, independently of GVHD. Recent investigations in murine leukemia suggest that GVL-like effects may be inducible following syngeneic BMT by recombinant cytokines with no overt GVHD. Taken together, current data in experimental animals and man suggest that GVL may be at least partially separable from GVHD. Hence, further understanding of effector and target cells of GVL as well as our ability to induce antitumor effector cells, especially those that are MHC nonrestricted, may lead to new approaches for potentiating anti-tumor effector mechanisms without inducing severe, clinically overt GVHD. Successful attempts in these directions may also lead to improved results following autologous BMT as a result of activation of GVL-like effects by recombinant cytokines that are capable of activating effector cells with anti-leukemic activity in vivo, such as recombinant human IL2, alpha interferon or perhaps a synergistic combination of factors.

Animals↗