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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 397 records · Page 22Linked to original sources

[Visual and phonological access to the mental lexicon].

In a lexical decision experiment we investigated whether the mental lexicon is accessed directly by a visual code or by phonological mediation. Subjects were asked to make lexical decisions where phonological coding was either beneficial or detrimental. It was found that subjects used phonological coding when it was helpful and abandoned this strategy when it was a hindrance. These results support the hypothesis that lexical decisions can be based on variable coding operations. The fact that subjects were faster in classifying words when they did not rely on phonological codes is consistent with the assumption of faster visual access to the mental lexicon. Taken as a whole, these results are consistent with models which assume phonological coding to take place after lexical access as well as with models postulating parallel access to the mental lexicon. They are not compatible with models postulating mandatory prelexical phonological coding.

Decision Making↗

Enalapril treatment in a patient with impaired renal function and intolerance to captopril.

In a 36-year-old woman with malignant hypertension and moderate renal insufficiency from nephrosclerosis normotension was not achieved by the combination of a beta-blocker, a vasodilator, and a loop-diuretic. The angiotensin-converting enzyme (ACE) inhibitor captopril was then added to the therapy. The blood pressure control was good. However, due to adverse reactions, captopril had to be withdrawn. Later on, the patient was successfully treated with enalapril, another ACE inhibitor, without the relapse of any adverse reactions.

Adult↗

Suppression of cell-mediated immune responses after total lymphoid irradiation (TLI). I. Characterization of suppressor cells of the mixed lymphocyte reaction.

Total lymphoid irradiation (TLI) was administered to (BALB/c X C57BL/6)F1 mice in eight daily doses of 200 rad (total 1600 rad). Spleen cells isolated from mice after treatment with TLI do not respond to alloantigens in vitro in a one-way mixed lymphocyte reaction (MLR), but normal reactivity recovers after approximately 2 mo. Radioresistant, antigen-nonspecific suppressor cells are documented in the spleens of TLI-treated mice immediately after radiotherapy, but suppressive capacity gradually disappears within 30 days. After TLI, the spleen is repopulated with large cells, the proportion of which is greatest at a time when theta-bearing cells are still depleted. Radioresistant suppression is mediated predominantly by the large cell subset and is thymus independent. Suppressor function can be abolished by lethal physicochemical procedures including formaldehyde fixation, multiple freeze-thawing, and heating to 56 degrees C, and it cannot be conferred by supernatants of TLI-suppressed MLR suspensions. Suppression cannot be overcome by adding various cell factors including T cell growth factor (TCGF) and lymphocyte-activating factor (LAF), nor is it affected by a prostaglandin inhibitor. Equally potent radioresistant suppressive activity is documented by co-culturing cells derived from other sources enriched in large, immature hematopoietic cells, including fetal liver cells and bone marrow cells obtained from normal and congenitally athymic mice. The presence of a large cell population and MLR suppressor function is also documented in the spleens of mice treated with single dose or fractionated doses of lethal whole body irradiation, followed by reconstitution with bone marrow cells obtained from normal mice. The data suggest that MLR suppressor cells, which are large, immature and predominantly radioresistant, can be induced after a short and well-tolerated TLI regimen.

Animals↗

Busulfan-induced chronic bone marrow failure: changes in cortical bone, marrow stromal cells, and adherent cell colonies.

This study represented an effort to determine if there were quantitative or morphological changes in marrow stromal cells in busulfan-induced marrow failure and to relate these changes to other disturbances in blood and bone marrow. Mice received four busulfan (BU) injections at two-week intervals and were killed at various time points up to 40 weeks after the first injection. Evaluation techniques included complete blood counts, in vitro assay of short-term adherent cell colonies per femur (STACC per femur) and colony-forming unit-culture (CFU-C) per femur, light microscopy of sternebral marrow and spleen, and electron microscopy (EM) of sternebral marrow taken at 40 weeks. STACC per femur were acutely reduced to 25% of control, but recovered to 76% by 40 weeks. CFU-C per femur dropped to below 10% of control and never recovered. Histologically, we found that hypoplasia of acutely affected marrow was associated with heightened endosteum and cortical bone thickening. In the chronic phase of BU injury, bones became osteoporotic, and the frequency of adipocytes and mast cells rose. BU-affected spleens generally had enhanced erythropoiesis. No stromal cell changes in 40-week marrow were discernible by EM. We concluded that there were morphological changes in BU marrow stroma specifically involving endosteum, bone, adipocytes, and mast cells. Also, there was quantitative depression in stromal cells measured by the STACC assay, but this improved substantially with time, unlike damage to hematopoietic stem cells measured by the CFU-C.

Animals↗

Bends in human mitotic metaphase chromosomes, including a bend marking the X-inactivation center.

Bends in mitotic metaphase chromosomes are not distributed randomly throughout the karyotype. The frequency of bends at centromeres is positively correlated with the relative length of the chromosomes and negatively correlated with the centromere index (more bends in metacentrics, fewer in acrocentrics). The frequency of bends in the noncentromeric regions (except at Xq13-Xq21) is positively correlated with the relative length of chromosome arms. A bend at Xq13.3 to Xq21.1 was more frequent than a bend in any other region of the karyotype, centromeric or noncentromeric. It was observed in one member of the X-chromosome pair in 63% of 46,XX cells. In contrast, it was observed in only 2% of 46,XY cells. RBG-staining showed that this specific bend is confined to the lyonized X chromosome. These observations in cells from normal subjects were confirmed using G-banding and RBG-staining on cells from nine subjects with different X-chromosome abnormalities and on metaphases from amniotic fluid cell and lymphocyte cultures. The "center for Barr body condensation" has been localized to the region between Xq11.2 and Xq21.1. The functional and structural relationship is unclear, but we believe this highly specific bend may represent a visible manifestation of the condensation process; it could represent the first folded (and last unfolded) position, upon or around which the rest of the chromosome condenses. The late replication of this region may also be a factor. The smallest region of overlap (SRO) for the X-chromosome inactivation center and the specific chromosome bend is Xq13.3 to Xq21.1.

Centromere↗

A model of intramedullary hematopoietic microenvironments based on stereologic study of the distribution of endocloned marrow colonies.

Hematopoietic colonies were studied in the marrow of alternate fraction-irradiated mice by light microscopic stereology to investigate the microenvironmental organization of marrow. Separate analyses of the relative colony cell density of undifferentiated, granulocytic, erythrocytic, and macrophage colonies in four marrow zones were carried out at 3, 4, and 5 days postirradiation (PI) for all colonies, all periarterial colonies, and all non-periarterial colonies. The results demonstrate a differential colony cell distribution that does not appear to be due to a preferential distribution of certain colony types around arteries. Undifferentiated colony cells showed a consistent predilection for endosteal and periarterial regions, with the majority of colony cells occurring along bone. Erythrocytic colony cells proliferated initially in intermediate and central marrow zones and along arteries. Granulocytic colony cells occurred in all areas at 3 days PI, but increased in density along bone thereafter. Macrophage colony cells occurred in all zones at 4 days PI, but at 5 days were concentrated in subosteal and central regions. Macrophage colonies also occurred periarterially. To explain these findings and the organization of normal bone marrow, we present a detailed model of the microenvironmental organization of intramedullary hematopoiesis. This model portrays the stroma as engendering distinct microenvironments for stem cell replication, stem cell commitment, and early progenitor cell proliferation.

Animals↗

Metastatic patterns in patients with carcinomas of the lower esophagus and upper rectum.

The frequency of metastatic involvement of eight target organs was examined in people dying as a consequence of squamous cell carcinomas of the lower third of the esophagus or adenocarcinomas of the upper third of the rectum. In both groups, there was a stronger association of metastatic incidence in the target organs with organ blood flow per gram in patients with liver metastases than without. The results suggest that this association, which is consistent with the 'mechanical' hypothesis of metastatic pattern, is only seen in people with advanced disease and that in the others temporal limitations imposed by death or cure prevent full development of the pattern. The data suggest that in accord with the 'cascade' theory, cancer cells must first form metastases in the liver, that cells from these metastases not the primary cancer, then form metastases in the lungs; cancer cells from the lung metastases then subsequently disseminate with a trend towards an arterial pattern. Data from animal experiments suggest that owing to the inefficiency of the metastatic process in terms of cancer cells, this sequential process is slow relative to tumor development and that this time base affects expression of metastatic pattern. This proposed scheme for metastatic pattern development provides evidence in favor of Ewing's 'mechanical' hypothesis for two histologic types of cancer, each growing in one designated primary site. It does not exclude a role for 'seed and soil' effects in these and other cancers.

Adenocarcinoma↗

Differences in the peripheries of Lewis lung tumor cells growing in different sites in the mouse.

The peripheries of Lewis lung (3LL) tumor cells growing in different organs of the mouse were studied by cell electrophoresis and electron microscopic quantitation of colloid iron hydroxide (CIH) adsorption before and after incubation with neuraminidase. The results show that cells growing in the kidney after direct injection have significantly higher anodic mobilities than cells growing in the subcutaneous sites from which they were derived, or in intramuscular sites, liver or spleen. The proportional contributions of cell surface sialic acids were similar in all sites. Electron microscopy of cells reacted with CIH indicates that the increased surface charge density of the tumor cells growing in the kidney is due to the presence of increased densities of non-CIH-binding ionogenic groups. Before neuraminidase treatment, the surface distribution patterns of CIH were indistinguishably random for 3LL cells growing in all sites. After neuraminidase treatment, significantly more clustering of CIH particles was observed on 3LL cells with a history of growth in the kidney than in subcutaneous sites. The changes observed in the 3LL cells growing in the kidney were irreversible, and persisted on multiple back-transplantation to subcutaneous sites. Detailed analysis of the results shows the changes to be due to the preferential selection of a subpopulation consisting of approximately 10% of the original (subcutaneous) tumor-cell population. This evidence for an irreversible site-induced selection of a pre-existing sub-population of 3LL cells contrasts with the reversible (modulation) site-induced adaptation previously observed by us in Walker-256 cancer cells, and therefore indicates that both selective and adaptive processes can occur. Even in the case of the 3LL cells, site-specific selection is not general, since the changes were observed in tumors growing in the kidney but not in the other anatomic sites. At present we cannot comment on the relevance of these reported changes to naturally occurring metastasis.

Animals↗

Purification and physical-chemical properties of acetyl-CoA:arylamine N-acetyltransferase from pigeon liver.

Acetyl-CoA:arylamine N-acetyltransferase (EC 2.3.1.5) from pigeon liver was purified by protamine sulfate precipitation, ion exchange chromatography on DEAE-A-25 Sephadex, gel filtration on Sephadex G-75, amethopterin-AH-Sepharose 4B affinity chromatography, and finally, gel filtration on Sephadex G-100. The enzyme preparation was homogeneous as judged by ultracentrifugation studies, SDS-polyacrylamide gel electrophoresis and gel filtration. The N-terminal amino acid was detected to be histidine and the complete amino acid composition is reported. The enzyme contains one disulfide bridge and two cysteine residues/mol monomer. The isoelectric point was estimated to be 4.8. The molecular weight was determined to be 32900 by high-speed sedimentation equilibrium analysis, 33000 by Sephadex G-100 gel filtration and 31600 by SDS-disc gel electrophoresis. The sedimentation coefficient from conventional sedimentation velocity runs was 3.1 S observed by ultraviolet optics. 'Active enzyme centrifugation' showed a sedimentation constant of 5.0 and 4.8 S for the purified enzyme and crude extract from pigeon liver, respectively, indicating that the enzyme forms a dimer under conditions of catalysis. It could be demonstrated that the inhibitor amethopterin was noncompetitive with respect to the acetyl donor and the acetyl acceptor. Acetyl-CoA:arylamine N-acetyltransferase was examined in different organs of pigeon. The enzyme was not inducible by 1,3-phenylenediamine and hexobarbital in vivo.

Acetyltransferases↗

Characterization of the active site, substrate specificity and kinetic properties of acetyl-CoA:arylamine N-acetyltransferase from pigeon liver.

It could be demonstrated that a sulfhydryl group is involved in the catalysis of acetyl-CoA:arylamine N-acetyltransferase from pigeon liver (EC 2.3.1.5). From ping-pong kinetics it was concluded that there is a covalent acetyl-enzyme intermediate. The respective intermediate could be isolated and chemically characterized as a cysteinyl thioester. Electrophoretically homogeneous acetyl-CoA:acylamine N-acetyltransferase from pigeon liver was able to acetylate a broad variety of aromatic and aliphatic amines from different acetyldonors such as acetyl-CoA, p-nitroacetanilide and p-nitrophenylacetate. Apparent Km values were determined for a number of acetyl donors and acetyl acceptors. Additionally, Ki values were evaluated for CoA, 3',5'-ADP and AMP. Correlation studies of basicity of acceptor amines and acetylation rate demonstrated that there is a limit of the pKa value (about pKa = 1) where the covalently-bound acetyl-enzyme intermediate can still be saponified. Testing crude liver homogenates of several animals including turkey, duck, chicken, cow, pig, horse, sheep, carp, trout and herring the outstanding nature of the pigeon liver enzyme in acetylating very weakly basic amines could be demonstrated. It is shown that the enzyme is quite flexible concerning sterically different acceptor amines, because arylamines whose amino group was effected by large o-substituents could be quantitatively acetylated. After enzymatic acetylation of the first amino group, 1,2-phenylendiamine formed the heterocyclic compound 2-methylbenzimidazole by a spontaneous condensation reaction. There is evidence that with distinct amines formation of heterocyclic compounds may also occur in vivo.

Acetyl Coenzyme A↗

Liver-to-lung traffic of cancer cells.

Following the injection of B16 melanoma cells into the portal veins of mice, all animals developed liver tumors, but only 16% developed lung tumors. Portal vein injections of radiolabelled B16 and Walker 256 cancer cells into mice and rats, respectively, revealed that all of the cells were temporarily arrested in the liver and most were then slowly released. Bioassays indicated that of 8 X 10(4) B16 cells released from the liver over 24 h after portal vein injections of 10(5) cells, only approximately 1% were delivered to the lungs in a viable state. Experiments made with radiolabelled B16 cells showed that transit through either the liver or lungs following portal vein or tail vein injections, respectively, resulted in massive death of cancer cells. It is suggested that the death of most circulating cancer cells passing through the first organ encountered after leaving their primary tumor, serves to severely limit their further direct spread to other organs. It is therefore expected that metastases to these other organs would, to a large extent, be generated by cancer cells from metastases in the "first organs" as distinct from direct seeding from cancer cells released from the primary tumor. If the results of the present experiments have general application, they serve to emphasize the importance of metastasis of metastases in the natural history of the spread of cancer. In a previous publication (Weiss, 1980), studies of lung-to-liver traffic of cancer cells in rats revealed that, after tail vein injections, most Walker 256 cells were temporarily arrested in the pulmonary vasculature and then slowly released. A large proportion of the released cancer cells were dead or lethally injured on release from the lungs, and this "first organ processing" apparently accounted for the comparative rarity of extrapulmonary tumors following tail vein injections. In this communication, the concept of "first organ processing" of circulating cancer cells is further examined with respect to the liver-to-lung traffic of B16 melanoma and Walker 256 cells injected into the portal veins of mice or rats respectively. Both of these cell types grow well in the lungs following tail-vein injection.

Animals↗

Studies on the organization and regeneration of bone marrow: origin, growth, and differentiation of endocloned hematopoietic colonies.

Hematopoietic colonies were studied by light microscopy in the marrow of alternate fraction x-irradiated mice (C576J/B1) to investigate the microenvironmental organization of marrow and identify early hematopoietic cell-stromal cell interactions. Undifferentiated colonies (UC) were detected at 3 days postirradiation, showed a marked predilection for bone surfaces, and disappeared as differentiated colonies developed. Some UC occurred along marrow arteries. Neutrophilic granulocyte colonies (GC) occurred in all areas at 3 days but grew rapidly only subosteally. Few eosinophilic colonies (GCe) occurred. Erythrocytic colonies (EC) appeared at 4 days as dispersed populations of motile cells within a localized area of marrow; these tended to proliferate initially in intermediate and central marrow zones. Macrophage colonies (M phi C) of two "subtypes" were detected, peaking in relative frequency at 4 days. These appeared active in stromal repair and monocytopoiesis. Megakaryocyte colonies (MC) originated along bone and differentiated away from bone. From 3-5 days, the frequency of GC greater than UC greater than M phi C much greater than MC approximately equal to GCe. All colony types except UC, M phi C, and central GC increased in size and became mixed in differentiation by 12-14 days. For several weeks, however, erythropoiesis concentrated toward central areas, whereas granulopoiesis and thrombopoiesis concentrated along bone. Some mixed colonies showed an abrupt transition from erythrocytic, centrally, to granulocytic, subosteally. These results were interpreted as evidence that in x-irradiated marrow: (1) hematopoietic microenvironments (HMs) for stem-cell proliferation and commitment to differentiation, with the possible exception of HMs determining erythroid differentiation, occur in endosteal and periarterial regions; (2) a proliferative and/or chemotactic stimulus to erythroid progenitors exists in intermediate and central marrow regions; and (3) some subosteal regions may exclude erythropoiesis, or preferentially support nonerythroid differentiation. Elaborate associations occurred between macrophages and early UC, GC, and EC, but not MC hematopoietic cells. UC and GC often associated with osteoclasts. Reticular and other fibroblastic cells associated with the cells of all colony types.

Animals↗

The equine spleen: an electron microscopic analysis.

The capacity of the equine spleen to store and rapidly release as much as half the circulating blood volume after adrenergic stimulation depends upon the size of the spleen, its muscular capsule, and the distinctive structure of its red pulp. The unit, or lobule, of red pulp is a cylinder of pulp spaces organized in a reticular meshwork, supplied by a peripheral ring of arterial capillaries, and drained by a central venule. Reticular cells, which make up the meshwork of the pulp, contain an extraordinarily large complement of microfilaments and intermediate filaments and are richly innervated by nerves containing both dense and lucent core vesicles typical of adrenergic nerves. The wall of the pulp venule contains large apertures. The capacious red pulp would thus appear capable both of large-scale blood storage and, by the contractile adrenergic innervated reticulum and open venous vasculature, of rapid expression of stored blood into the circulation. Antigen-presenting cells are present not only in B and T cell zones in white pulp but in the periarterial macrophage sheath of red pulp as well. The periarterial macrophage sheath is one of the first sites of antigen capture, and the presence of these cells confers on it an immunological role.

Animals↗

The origin of inverted tandem duplications, and phenotypic effects of tandem duplication of the X chromosome long arm.

Tandem repeats of chromosome material can arise as inverted or as direct duplications. Such duplications of the X chromosome are instructive regarding X-linked genetic determinants of phenotype. We describe a 40-year-old woman with a direct duplication Xq13.3 to Xq27.2, short stature, gonadal dysgenesis, and secondary amenorrhea. Comparison of her phenotype with that of two other women with a direct duplication of part of Xq confirms the existence of statural determinants within the region X13 to Xq21, determinants of ovarian function within X22 to X27, and the X inactivation center within or proximal to band Xq13.3. In humans, direct duplications are more frequent than inverted, but both forms are rare. The mean age of parents is normal in subjects with direct duplications, but is advanced in subjects with inverted duplications. An inverted duplication can arise from a three-break rearrangement that includes a U-type exchange; a similar origin (two breaks and a U-type exchange) and a parental age association can be postulated for dicentric inverted duplications including dicentric isochromosome X.

Adult↗

Ultrastructure of the bone marrow in three murine strains with non-malignant lymphoproliferative syndromes NZBxW, BXSB, and MRL/lpr.

Three mouse strains, NZBxW, BXSB, and MRL/lpr have well documented congenital lymphoproliferative syndromes and lupus-like disease. We studied the ultrastructures of the marrows of these mice searching for a model for intramedullary lymphopoiesis. In MRL/lpr, the strain with the most severe disease, the marrow was largely populated by large lymphocytes associated with dark branching stromal cells. These stromal cells are apparently of a recently recognized cell type which has been associated with extremely accelerated eosinophilopoiesis and erythropoiesis. They did not appear in the lymph nodes and spleens of the MRL/lpr mice or in the marrows of the other strains. BXSB marrows showed some non-proliferant lymphocytic infiltrates and heightened erythropoiesis while NZBxW marrows resembled controls. We suggest that the dark stromal cells in the MRL/lpr marrows were important in supporting the production or differentiation of lymphoid precursor cells.

Animals↗