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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 307 records · Page 17Linked to original sources
PubMed1988

Cephalosporin-induced changes in the ultrastructure of canine bone marrow.

Fourteen healthy dogs were given 540 to 840 mg/kg of cefazedone (Refosporen) intravenously for up to 4 months or until peripheral blood cell count were depressed. Within 6 to 10 weeks treated dogs developed pancytopenia (5/14), thrombocytopenia (11/14), moderate to severe neutropenia (8/14), and/or normocytic anemia with erythroblastemia (8/14). Ultrastructural changes in bone marrow of severely cytopenic dogs included mitochondrial damage in hematopoietic and nonhematopoietic cells, thickening of endosteal bone lining layers, increased adventitial coverage of vascular sinuses, and an increased number of active macrophages. Swollen, ruptured mitochondria were in erythroid, granulocytic, and megakaryocytic cells, and, to a lesser extent, in macrophages, reticular endothelial, and bone lining cells. Maturation arrest was evident in both erythroid and granulocytic cell lines. There was also evidence of ineffective erythropoiesis and granulopoiesis. None of these changes were observed in bone marrow of controls, treated dogs that did not develop cytopenia, or dogs allowed to recover after cessation of dosing.

Anemia↗
PubMed1988

Reproducible cloning assays for in vitro growth of canine hematopoietic progenitor cells and their potential applications in investigative hematotoxicity.

A variety of in vitro cloning assays have been used for studying hematopoiesis in mice and human beings. However, these techniques have had limited use in dogs, a species used extensively as a model for hematopoietic research, particularly hematotoxicity. We have adopted cloning assays for in vitro growth of canine colony-forming unit-erythroid (CFU-E) and colony-forming unit-granulocyte/macrophage (CFU-GM) progenitor cells, using modified microplasma clot and soft agar culture systems, respectively. Marrow mononuclear cells separated by density-gradient centrifugation were added to the aforementioned culture systems. Erythroid colonies were stimulated with sheep plasma erythropoietin and incubated at 37 C in 5% CO2 for 2 days. The CFU-E colonies were fixed with 5% glutaraldehyde, stained with benzidine, counted, and expressed as a mean of 8 replicates. The CFU-GM colonies were stimulated with pooled serum from endotoxin-treated dogs and incubated for 8 days at 37 C in 10% CO2. Using an inverted microscope, the CFU-GM colonies were counted and expressed as a mean of 6 replicates. The number of colonies was proportional to the plated cell concentrations. The addition of 10% autologous serum to CFU-GM cultures increased the number of colonies by 80 to 100%, but markedly reduced the size and number of CFU-E colonies. The marrow cloning capacity among dogs of comparable age was similar, and little variation was noticed when bone marrow cells from the same dogs were cultured repeatedly over a period of 3 to 4 months. We concluded that these cloning assays are fast, reliable, and reproducible and that they allow quantitative determination of canine hematopoietic progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Optimal time interval between myeloablative whole body irradiation and reconstitution with syngeneic bone marrow graft.

The optimal time interval between termination of radiation therapy and marrow grafting has been studied in an animal model of syngeneic bone marrow transplantation, using a limiting number of bone marrow cells. Optimal survival was achieved when reconstitution took place 24 h following termination of radiation therapy at all cell doses studied, including 5 x 10(4), 2 x 10(5) and 1 x 10(6) cells/recipient. The worst results were observed when bone marrow cells were infused immediately after irradiation. These results suggest that reconstitution of lethally irradiated recipients requires migration of irradiated host marrow cells and establishment of adequate 'bone marrow space', which is optimal at 24 h following termination of whole body irradiation.

Animals↗
PubMed1988

Campylobacter pylori and gastroduodenal disease: a prospective endoscopic study and comparison of diagnostic tests.

A series of 72 adult patients undergoing 76 upper gastrointestinal (GI) endoscopies because of GI signs or symptoms were studied for the presence of Campylobacter pylori by culture, histology, and rapid urease determination of gastric antral biopsy specimens. C. pylori was found by culture or histology in all 10 cases of gastric and duodenal ulcer, and in 77% of endoscopies with histologically proven active gastritis. Positive culture for C. pylori was highly correlated pathologically with active gastritis, but not endoscopically, and was rarely seen in the absence of acute inflammation on biopsy. There was no correlation between C. pylori and alcohol ingestion, smoking, age, sex, antibiotics, or nonsteroidal anti-inflammatory drug use. The rapid urease test was positive in 70% of cases with positive cultures and 89% with positive cultures or acridine orange stains. Acridine orange-stained histological samples were positive in 97% of cases with positive cultures. In addition, 31% of endoscopies with negative cultures were also positive by acridine orange stain. Acridine orange stain, culture, and urease reaction of antral mucosal biopsies all are effective methods for demonstration of mucosal C. pylori-like organisms. However, of the three methods used, acridine orange staining is positive in the largest group of patients and is the most sensitive method for detecting colonization of gastric antral mucosa. In general, positive urease and culture identify those patients with larger numbers of organisms on the mucosa. Differences in urease and culture positivity from case to case suggest that factors other than numbers of organisms, such as viability and urease levels, affect the results. All these results support a role for C. pylori as an aggressive factor in peptic ulcer disease and gastritis.

Acridine Orange↗
PubMed1988

Biomechanical destruction of cancer cells in the heart: a rate regulator for hematogenous metastasis.

B16 and Ehrlich ascites tumor cells were introduced into the myocardium via the coronary arteries, following injection into the left ventricular cavity of mice. Bioassays show that the vast majority of the injected cells reaching the beating myocardium were destroyed in less than 5 min. The results support the hypothesis that rapid biomechanical destruction of cancer cells within the microvasculature of the heart is a significant rate regulator of hematogenous metastasis to this organ.

Animals↗
PubMed1988

Selenium status and the polyp-cancer sequence: a colonoscopically controlled study.

Diminished blood selenium levels have been associated with increased risk of gastrointestinal cancers in man, while dietary selenium supplementation reduces the incidence of experimental colon cancer in rats. However, no previously published data are available concerning selenium and the evolution of colon cancer from benign neoplastic colonic polyps through localized and metastatic cancer. To assess any influence of selenium on this polyp to cancer sequence, we measured plasma and erythrocyte selenium levels in colonoscopically and histologically evaluated patients with adenomatous polyps (group I), locally resectable colon cancer (group II), metastatic colon cancer (group III), and selected colonoscopy negative controls (group IV). We found no difference in selenium levels between groups IV versus groups I or II. Likewise, within group I, no difference in selenium was present for different polyp histologies or numbers of polyps. However, selenium levels did drop progressively (p = 0.028, ANOVA) from polyp (group I) to local cancer (group II, p = NS vs group I) to metastatic cancer (group III, p less than 0.05 vs group I or group II). Parallel changes were seen in both plasma and erythrocyte levels, suggesting that these selenium abnormalities are of long duration, reflecting tissue stores, and therefore capable of influencing cancer risk. We conclude that selenium stores may not be an important factor in the de novo formation of benign neoplastic colonic polyps. Although these data suggest that selenium does not affect the polyp-cancer sequence, it is possible that a subset of patients with polyps and the lowest selenium levels are at higher risk for malignant transformation. However, these human data do not support a significant role for selenium in colon carcinogenesis.

Aged↗
PubMed1987

Tumor behavior in transitional cell carcinoma of the bladder in relation to chromosomal markers and histopathology.

Tumor cells from direct harvests and short term cultures were karyotyped from 15 patients with transitional cell carcinoma of the bladder. There were two tumors with an apparently normal diploid karyotype, eight with counts up to 50 and with marker chromosomes, and five with counts of 60 or more and with markers. The median duration between recurrences was 3 months for the near-diploid, and 3 months for the near-polyploid tumors. One patient whose tumor was normal diploid had a recurrence at 5 months and the second patient whose tumor had normal diploid tumor had no recurrence over 15 months. Four tumors (27% of the series) had a rearrangement involving band 3p14: three had +der(5)t(3;5)(p14;p14) and one had +der(6)t(1;3;6)(q21;p14;p23). Duplication 3p14----3pter was observed in four tumors, and deletion 11p15----11pter in five. Three other abnormalities were observed in three cases each: deletion 5p14----5pter, duplication 1q23----1q32 and deletion 6q21----6qter. Trisomy 7 was observed as a sole clonal abnormality in one carcinoma in situ. Thirteen of 15 patients had recurrence of their tumor. Tumor progression (either in stage or grade) was evident in seven recurrent tumors. Among the seven with tumor progression, three had 11p deletion, two had 11p deletion plus 3p duplication, one had 3p duplication, and one had trisomy 7. Four of the five that had 11p deletion underwent cystectomy and three have died. Three of eight near-diploid tumors progressed and four of five near-tetraploid tumors progressed. It will be important to characterize any cytogenetic changes that are of prognostic value, since the categorization of bladder tumors by other methods has been problematic.

Adult↗
PubMed1987

Lymphogenous and hematogenous metastasis of Lewis lung carcinoma in the mouse.

Quantitative and temporal comparisons were made between lymphogenous and hematogenous metastasis in the non-immunogenic model system of mice bearing transplanted 3LL tumors in their hind feet. The experimental evidence indicates that cancer cells disseminate from clinically detectable primary cancers by non-exclusive routes in the blood-stream and in the lymphatics. Following a delay of approximately 2 weeks after injection of 3LL cancer cells into the foot, local lymph-node micrometastases occur, together with the first appearance of overt hematogenous metastases in the lungs. The anatomic extent of lymph-node involvement, determined by bioassays of orthotopic grafts, of ipsilateral popliteal, inguinal and lumbar nodes, provides an accurate indicator of hematogenous metastasis, even though lymphogenous and hematogenous metastasis are operationally independent in this tumor/host system.

Animals↗
PubMed1987

Perfusion characteristics and norepinephrine reactivity of human renal carcinoma.

Kidneys, surgically removed due to carcinoma, were subjected to perfusion in vitro. The perfusion distribution was studied by means of labeled microspheres injected during maximal vascular dilation and during two different norepinephrine concentrations. The perfusion concluded with injection of barium sulfate. Two-mm-thick slices of tissue were autoradiographed and microangiographed for visualization of perfusion and distribution of vascular density, respectively. Multiple specimens from tumor and cortical tissues were subjected to quantitative perfusate flow analysis. In spite of regionally high vascular density, perfusion through "normal-sized" capillaries was very low in tumor tissue as compared to cortex (during maximal dilation, one-tenth of the cortical flow). During moderate norepinephrine infusion, the perfusate flow decreased, and the resistance of the cortex increased. The flow to tumor tissue increased while the vascular resistance remained constant. During higher norepinephrine concentrations, the flow was redistributed; i.e., the cortical flow increased while that of the tumor decreased, due to a marked increase in tumor vascular resistance while the cortical tissue showed a very moderate rise in resistance. The thin-walled tumor vessels might be collapsed under a high tissue pressure at low perfusion pressures. At higher perfusion pressure, the vessels might open up, and contractile activity may not be expressed until then. The tumor vascular resistance increased 3 to 4 times, while that of cortex showed a 7-fold increase. Indications that a considerable fraction of the perfusate passes arteriovenous passages larger than 15 micron were obtained in individual experiments, this fraction increasing upon norepinephrine infusion.

Carcinoma↗
PubMed1987

Comparative distribution of mRNAs for glutamic acid decarboxylase, tyrosine hydroxylase, and tachykinins in the basal ganglia: an in situ hybridization study in the rodent brain.

Neurotransmitter-related messenger RNAs were detected by in situ hybridization in sections of rat and mouse brains by using 35S-radiolabelled RNA probes transcribed from cDNAs cloned in SP6 promoter-containing vectors. The distribution of messenger RNAs for glutamic acid decarboxylase, tachykinins (substance P and K), and tyrosine hydroxylase was examined in the striatum, pallidum, and substantia nigra. Dense clusters of silver grains were observed with the RNA probe complementary of the cellular messenger RNA for glutamic acid decarboxylase (antisense RNA) over most large neurons in the substantia nigra pars reticulata and medium-sized to large neurons in all pallidal subdivisions. A few very densely and numerous lightly labelled medium-sized neurons were present in the striatum. Among the areas examined, only the striatum contained neurons labelled with the antisense tachykinin RNA. Most of these neurons were of medium size, and a few were large. With the antisense tyrosine hydroxylase RNA, silver grains were found over neurons of the substantia nigra pars compacta and adjacent A10 and A8 dopaminergic cell groups. No signal was observed with RNAs identical to the cellular messenger RNA for glutamic acid decarboxylase or tachykinin (sense RNA). These results show a good correlation with immunohistochemical studies, suggesting that documented differences in the distribution and the level of glutamic acid decarboxylase, tyrosine hydroxylase, and substance P immunoreactivities in neurons of the basal ganglia are related to differences in the level of expression of the corresponding genes rather than to translation accessibility, stability, or transport of the gene products.

Animals↗
PubMed1987

Monoclonal antibodies to the human C3b/C4b receptor (CR1) enhance specific B cell differentiation.

The addition of monoclonal antibodies against the human C3b/C4b receptor (CR1) to cultures of peripheral blood lymphocytes in the presence of suboptimal amounts of TNP bound to polyacrylamide beads enhanced by 150 to 400% the specific anti-TNP response, as measured by a plaque-forming cell assay on day 7. Anti-CR1 antibodies similarly enhanced the anti-fluorescein antibody response. Enhancement only occurred in cultures performed in the presence of the relevant antigen. No enhancing effect on the anti-TNP response was observed on addition to cultures of monoclonal antibodies directed against other surface antigens of B cells or an anti-T cell antibody of the same subclass as that of anti-CR1 antibodies. Anti-CR1 antibodies alone did not induce nonspecific B cell proliferation and did not provide B cells with a first signal for proliferation in the presence of a source of B cell growth factors. Anti-CR1 antibodies did not enhance the nonspecific proliferative response of B cells to growth factors derived from PHA-stimulated T cells, semi-purified BCGF 20 KD, BCGF 50 KD, or recombinant IL 2 in the presence of anti-mu. In this respect, the effect of anti-CR1 antibodies differs from that of anti-CR2 antibodies which interact with early stages of B cell activation. In contrast, anti-CR1 antibodies enhanced specific differentiation of antigen-activated B cells in the absence of T cells when soluble T cell factors were provided. Similar results were obtained by using either of two sources of differentiation factors, the MLA-144 supernatant or a 30 to 15 KD fraction from PHA-stimulated T cells. These results indicate that triggering of CR1 on B cells positively regulates the specific antibody response to low doses of antigen by enhancing B cell differentiation whether T cell help is provided by intact T cells or by T cell-derived differentiation factors.

Antibodies, Monoclonal↗
PubMed1987

Controversy in the management of optic nerve glioma.

The records of 16 patients with optic nerve glioma treated between 1961 and 1984 were reviewed. All patients except two had extension of tumor beyond the chiasm to the hypothalamus, adjacent brain and/or along the posterior optic tract. Eleven of 16 cases were biopsy-proven, two patients had craniotomy and visual inspection but no biopsy was performed, and in two cases the biopsy was not diagnostic. Fourteen patients received radiation therapy, usually consisting of 50 Gy in 5 weeks (range 40-56 Gy), one patient was treated surgically and one with chemotherapy. With a follow-up of 1 to 20 years, 7 of the 14 patients irradiated are alive, three patients are dead of disease at 3, 6 and 9 years post-treatment, three were lost to follow-up at 1, 8, and 8 years, and one is dead of intercurrent disease at 5.5 years. Overall vision was improved in five patients and stable in seven following treatment. In two patients, vision could not be evaluated because of young age at presentation. Four patients had recurrences. One was retreated with 30 Gy in 3 weeks and shows no evidence of disease at 20 years. The three other patients died of their disease. There is controversy over the best treatment for these patients. Based on these results and a review of the literature, the authors recommendation is to irradiate tumors with extension beyond the chiasm at the time of presentation rather than waiting for increasing symptoms because function that is lost may not always be recovered. Chemotherapy needs to be further investigated but holds promise, especially for the younger children.

Adolescent↗
PubMed1987

Ultrastructural localization of heparan sulfate and chondroitin sulfates associated with granulopoiesis in embryonic chick bone marrow.

Sulfated glycoconjugates were ultrastructurally localized within embryonic chick marrow by using the high iron diamine-silver proteinate stain. Stain was concentrated in the extravascular, granulopoietic compartment, indicating that granulopoiesis, but not erythropoiesis, proceeded in a highly sulfated environment. It was likely that most of the stainable material represented sulfated proteoglycans since staining was abrogated by predigesting tissue with enzymes and other treatments known to degrade specific glycosaminoglycan chains. Chondroitinase/hyaluronidase digestion resulted in the removal of most of the stainable material associated with the extracellular matrix and a portion of the stainable material associated with fibroblastic cell surfaces. Unaffected material lay in close proximity to fibroblastic cell membranes. Heparitinase/heparinase digestion had essentially the opposite effect. Sulfated material associated with matrix components was largely unaffected, but the fibroblastic plasmalemmal material was now absent. These results suggest that there are at least two categories of sulfated proteoglycans in the granulopoietic compartment, each differentially distributed. The plasmalemmal material likely represented heparan sulfate which in this tissue appeared to be associated in a uniform layer with fibroblastic stromal cell membranes and not with blood or endothelial cell membranes. Material identified as chondroitin sulfates was found within patches of amorphous matrix that was located on fibroblastic stromal cell surfaces and that was interspersed with fibrils in the extracellular matrix. Chondroitin sulfates were sparsely distributed on granulocytic cell surfaces.

Animals↗
PubMed1987

Duplication 3p21----3pter and cyclopia.

We report on a patient with an interchromosomal duplication of 3p, from 3p21 to 3pter, which apparently arose de novo. The infant had multiple malformations including holoprosencephaly and cyclopia. It is possible that duplication 3p has a generalized effect on the holoprosencephalon or the cleavage of the embryonic forebrain. Fibroblasts from the patient are available from the NIGMS Human Genetic Mutant Cell Repository (GM 7216).

Abnormalities, Multiple↗