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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 343 records · Page 19Linked to original sources
PubMed1986

Familial papillary carcinoma of the thyroid.

Of 226 consecutive papillary carcinoma patients, 14 indicated that at least one other relative was similarly affected. Pathology confirmation was obtained in 8 of the 14 families. Of the eight families with documented familial papillary carcinoma, one had five members, another had four members, and yet another had three members affected. The remaining families had two members affected. In those families with two or more persons with confirmed papillary carcinomas of the thyroid, 20 first- and second-degree relatives were examined. Of those, one had a previously unidentified papillary carcinoma and 6 had a benign thyroid disease (4 primary hypothyroidism and 2 simple goiters). High-resolution chromosome studies of four patients from four different families were normal, and there was no increase in chromosome breakage in a fifth patient from yet another family. Autosomal dominant inheritance is possible. Although there was no family history of lipomas, osteomas, or intestinal polyposis to suggest Gardner syndrome, four parents of our familial papillary carcinoma patients had colon cancer. In addition, three other relatives died of unidentified intra-abdominal cancer. The apparently high frequency of colon cancer and other abdominal cancer in relatives was an additional concern. Based on our observations, three clinical recommendations can be made: obtain a family history of all patients with papillary carcinoma of the thyroid, since between 3.5 to 6.2% will have another affected relative; when two or more persons in a family have papillary carcinoma of the thyroid, all first- and second-degree relatives should have a neck palpation by an experienced examiner; and families with two or more persons with papillary carcinoma should be observed for possible colon cancer.

Adolescent↗
PubMed1986

The validity of negative necropsy reports for metastases in solid organs.

This communication concerns the statistical significance of negative reports, when solid organs are examined for metastases deep to their surfaces, by standard slicing techniques at necropsy. By taking into account factors influencing tumour detection including slice thickness, metastatic tumour size and number, the probabilities of incidence of false negative reports may be calculated and values for the undetected tumour bulk may be obtained. A graph is reproduced which facilitates the assessment.

Autopsy↗
PubMed1986

Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies.

The sequence of events in haematogenous metastasis from colonic carcinoma was analysed, using 1541 necropsy reports from 16 centres. The findings are consistent with the cascade hypothesis that metastases develop in discrete steps, first in the liver, next in the lungs and finally, in other sites. Deviations of necropsy findings from the cascade model are largely explained on the basis of false negative reports. In only 216 of 1194 cases was there suggestive evidence that metastatic patterns (excluding lymph nodes) were causally related to lymphatic or non-haematogenous pathways. The incidence of metastatic involvement in 'other' (quaternary) sites correlated with target organ blood-flow (ml min-) per g, only when bone marrow and thyroid were excluded. In the thyroid the incidence was lower than expected on the basis of blood flow per g tissue; this may indicate that the thyroid is an unfavourable site for metastatic growth of colonic carcinoma. In the bone marrow it is higher; the latter may be due to delivery of cancer cells via both arterial blood and the vertebral venous plexus. Recognition of this pattern of metastases in the bone marrow could be important with respect of diagnosis and therapy, in patients with colonic carcinoma.

Aged↗
PubMed1986

Location of the X inactivation center in primates and other mammals.

In humans, the X chromosome inactivation center and an X inactivation-associated metaphase fold are at the same location (bands Xq13----21) or are very closely associated. In other mammals, the location of the X inactivation center is unknown, but it has been suggested that the relationship between the inactivation center and the inactivation-associated fold may make it a useful marker for both identifying the inactivated X and locating the inactivation center in other mammalian species. If a similar metaphase fold is present in other mammals, the inactivation center would be located at the same site or very nearby. All of nine primate species did express an inactivation-associated fold. In most, the fold was located at the band homologous to human Xq13----q21. In one of two chimpanzees, band Xq23----q24 was implicated. In five other mammals an inactivation-associated fold was observed, but in two species, no fold was observed.

Animals↗
PubMed1986

The centromere index and relative length of human high-resolution G-banded chromosomes.

The relative length and centromere index were compared in prometaphase and midmetaphase for each human chromosome from five normal men. There were very few differences between prometaphase and midmetaphase chromosomes in these two parameters. Chromosome 7 had a significantly different centromere index between prometaphase and midmetaphase, but no difference in relative length. This was accounted for by significant differences in the relative length of both 7p and 7q between prometaphase and midmetaphase; 7p became relatively less condensed and 7q relatively more condensed with progression from prometaphase to midmetaphase. For chromosome 1, the short arm was significantly longer than the long arm in both prometaphase and midmetaphase, a finding that underscores the structural similarity of this chromosome among the hominids.

Centromere↗
PubMed1986

Depletion of human lymphocytes from peripheral blood and bone marrow by affinity ligands conjugated to agarose-polyacrolein microsphere beads.

Protein-A or goat anti-mouse-Ig (GAMIg) covalently bound to agarose-polyacrolein microsphere beads (APAMB) were employed for the removal of T cells from human peripheral blood leukocytes (PBL) and bone marrow (BM). The cell suspensions were treated with a monoclonal anti-T cell antibody (Leu-1) or monoclonal antilymphocyte antibody (CAMPATH-1) and passed through the conjugated APAMB columns. Cell separation efficacy was determined by assaying the number and function of T cells in the final cell preparation in comparison with a sample of unseparated cells. The number of cells that form rosettes (E-RFC) with sheep red blood cells (SRBC) in a sample of PBL treated with anti-Leu-1 antibodies and subsequently passed once through GAMIg-conjugated APAMB dropped from a range of 41.5-86.0% to a range of 1.6-13.3%. The in vitro response to concanavalin-A (Con-A) dropped to a range of 0.7-27.2% (GAMIg) and a range of 1.2-21.8% (protein-A column) of the response of untreated PBL. Treatment with CAMPATH-1 antibody and passage through a protein-A-conjugated APAMB reduced E-RFC from a range of 55.6-57.4% to a range of 3.2-3.9% and abolished the Con-A induced proliferative responsiveness to background levels. Treatment of BM cells with CAMPATH-1 and passage of the cells through either GAMIg or protein-A conjugated APAMB columns resulted in reduction of E-RFC from a range of 12.4-17.7% to a range of 0-1% and from a range of 17.7-19% to a range of 1.6-3.2%, respectively. Viability of BM precursors, determined by the CFU-GM assay in semisolid medium, was not affected by these cell separation procedures. The data suggest that protein-A or GAMIg-conjugated APAMB columns may be a useful tool for separation of BM cell suspensions into specific cell subsets that can be defined by monoclonal antibodies.

Acrolein↗
PubMed1986

Congenital testicular juvenile granulosa cell tumor in a neonate with X/XY mosaicism.

A congenital sex cord-stromal tumor of the testis with morphologic features of juvenile granulosa cell tumor is reported. The tumor occurred in an abdominal testis of a newborn infant with an X/XY karyotype and ambiguous genitalia and presented as a partially cystic mass associated with ascites. Histologically the tumor was comprised of an admixture of solid, cellular, poorly differentiated lobules mimicking graafian follicles. Residual hypoplastic testicular tissue was present at the periphery. This is the 19th reported case of testicular juvenile granulosa cell tumor and the fourth with an underlying sex chromosome anomaly, further emphasizing the relationship of this uncommon neoplasm to abnormal sexual or gonadal development.

Adolescent↗
PubMed1986

Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation.

Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones.

Animals↗
PubMed1986

Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase.

Fatty-acid synthase has been purified to homogeneity from human liver by a 3-step procedure including protamine sulfate/ammonium sulfate fractionation, affinity chromatography on 2',5'-ADP-Sepharose 4B and gel filtration on Sephacryl S-300. Both the human and rat fatty-acid synthase had similar characteristics regarding molecular mass, subunit structure, amino-acid composition, and substrate affinities. In order to measure the fatty-acid synthase activities in small tissue samples it was necessary to improve the sensitivity of an isotopic assay using [14C]malonyl-CoA as tracer. Special attention was paid to the dual role of free CoASH as an activator and inhibitor of the enzyme. Considerable differences existed between the specific activities of the fatty-acid synthase complex measured in human and rat lipogenic organs. Only negligible values of about 1 mU/mg protein were found in human liver and adipose tissue, while the corresponding activities were 10- to 50-fold higher in young lean rats. Less pronounced but still remarkable differences were determined for the activity of the acetyltransferase which catalyses the initial primer reaction of the fatty-acid synthase complex. In some selected cases under long-term fat-free diet (alcoholism, parenteral nutrition) elevated values of fatty-acid synthase activities were detected in human tissues. Under usual diet, with a relatively high fat content of up to 40 percent, and even after a carbohydrate-rich diet for three days, fatty-acid synthase activity remained low. It is concluded that under the dietary conditions, common for the industrialized world, de novo lipogenesis in man is negligible.

Adipose Tissue↗
PubMed1986

Bone marrow transplantation with T-cell-depleted grafts. I. Reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted syngeneic bone marrow grafts.

The potential role of donor's mature T lymphocytes on the recovery of various immunological functions and hematopoiesis was investigated in lethally irradiated BALB/c mice by studying reconstitution with normal, as compared with T-cell-depleted, syngeneic marrow grafts. Recovery of total, as well as mononuclear, peripheral white blood cell counts, platelets, hemoglobin levels, proportion of Thy 1.2+ cells, responses to concanavalin A, phytohemagglutinin and lipopolysaccharide, mixed lymphocyte response, cell-mediated lympholysis response, anti-SRBC agglutinins and natural killer activity were basically similar in recipients of unmanipulated (as compared with T cell depleted) syngeneic marrow grafts. The data suggest that in a syngeneic murine bone marrow transplantation setting, mature donor T lymphocytes do not seem to play a major role in immunohemopoiesis. Normal T cell number and T-cell-dependent immune function can be readily regenerated out of the stem cell reservoir of adult donors following transplantation into lethally ablated recipients.

Animals↗
PubMed1986

Vascular reactivity to norepinephrine of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and normal tissue as studied in vitro.

Vascular reactivity to norepinephrine has been studied in dimethyl-benz(a)anthracene-induced rat mammary neoplasia and compared with that of skeletal muscle, salivary gland, kidney, and uterus by means of an artificial perfusion technique. Perfusion of tissues and organs was measured with the microsphere tracer technique during smooth muscle relaxation and infusion of norepinephrine at two different dose levels. This procedure makes possible a dose-response analysis of several tissues under controlled conditions without confounding endogenous vasoregulation. The tumor vascular bed has a low perfusion capacity during smooth muscle relaxation and responds rapidly with an increased resistance to norepinephrine infusion. The results indicate a hypersensitivity, although the relative maximal constrictor response is equal to or less than that of other vascular beds studied.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Perturbations in cancer cell deformability and resistance to shear forces.

During hematogenous metastasis, circulating cancer cells appear to be killed in the microcirculation by a non-exclusive mechanism, involving the mechanical trauma consequent upon cancer cell interactions with the vessel wall. Various observations by others indicate that with increased cell deformability, there is decreased intravascular cell killing. We have therefore critically examined the effects of agents previously shown to modify cell deformability, on the susceptibility of Ehrlich ascites tumor and L1210 leukemia cells to mechanical damage on passage through polycarbonate membranes in vitro. Treatment with neuraminidase, trypsin or EGTA, was previously shown to increase cell deformability. However, in the present studies, neuraminidase treatment was associated with increased cell loss on filtration; trypsin treatment with small decreases in cell loss, and EGTA treatment with decreased loss. Consideration of the effects of these agents on cell deformability and membrane strength suggests that under the described experimental conditions, the latter appears more important for survival than the former. As proteolytic and glycolytic enzymes and calcium ions are involved in the release of cancer cells from tumors and invasive events, the effects described here may be relevant to the variability of cancer cells with respect to the metastatic process.

Animals↗
PubMed1986

A practical metaphase marker of the inactive X chromosome.

It is paradoxical that the inactivated X is the only chromosome that can be identified in the interphase nucleus, yet in metaphase, it is indistinguishable from its genetically active homolog unless special culture and staining procedures are employed. A specific inactivation-associated fold in proximal Xq resolves that paradox. We describe here how the fold in the proximal long arm can be used as a simple and reliable marker to identify the inactivated X in G-, Q-, or R-banded preparations. Several examples are given, including localization of the inactivation center to band Xq13 or q21.1, identification of nonrandom inactivation in X-chromosome rearrangements, identification of multiple active X chromosomes in tumor cell lines, analysis of X-inactivation patterns in female carriers of the fragile site at Xq27, and comparison of X-inactivation patterns among primate species.

Chromosome Banding↗
PubMed1986

Drug delivery to tumors. A problem requiring microscopic resolution.

One factor in the effectiveness of chemotherapy for both primary tumors and their metastases is the delivery of the drug to the cancer cells within the tumor. The uptake of Adriamycin, assayed in 8 cu mm samples from primary tumors, lung metastases and "normal" lung tissue (unaffected by the metastases) in mice, showed wide variations between different tumors, between primary tumors and their metastases and between different metastases. The heterogeneity of uptake was greater in tumors than in normal lung tissues, whose uptake was in the range of the metastases, i.e., higher than in the tumor itself. Studies of Adriamycin uptake within individual tumors showed a wide range of values; this variability was statistically significantly increased as compared with the variation in normal lung tissues. Since the lower levels found in some tumor areas were below the cytotoxic level, those areas may represent "drug-resistant" cells from which tumor recurrence could ensue. In a three-dimensional reconstruction, the areas of lowest uptake were found at both peripheral and internal regions, a finding not in accord with the concentric zonal concentration expected on the basis of considerations of tumor vascularity. It is suggested that the problem of drug delivery to tumors needs further study at the microscopic level and that automated microscopic image analysis and three-dimensional reconstructions of serial sections could greatly extend the macroscopic findings of this study.

Animals↗
PubMed1986

[Acute degenerative mitral insufficiency caused by rupture of the chordae in the elderly patient].

Five cases of degenerative mitral incompetence due to rupture of the chordae tendinae in patients over 70 years of age were reviewed to determine the clinical features of this pathology which is not rare in elderly patients. Chordal rupture usually involves the posterior leaflet and is a sign of generalised disease of the mitral apparatus of two main types: myxoid infiltration or pellucid degeneration. Although the clinical syndrome of rupture is rare (10 p. 100), the mechanism of the mitral regurgitation can be identified by 2D echocardiography with a sensitivity of 92 p. 100, and the consequences of regurgitation on the left ventricle can also be evaluated. Rapid progression to acute cardiac failure is often observed and early surgical cure may be necessary (valvular replacement with a bioprosthesis is more common than mitral valvuloplasty). Further justification for this surgical approach is the improved myocardial protection which has reduced the perioperative mortality rate to less than 10 p. 100.

Acute Disease↗