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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 469 records · Page 26Linked to original sources

Genetic screening for mental retardation in Michigan.

The Michigan Department of Mental Health established a genetic screening laboratory in 1977 to provide diagnostic information on retarded patients. Of 727 patients screened during a 2-year period, a genetic diagnosis was established for 121 moderately to severely retarded patients. Genetic counseling was provided for 40 percent of their parents. A wide variety of chromosomal abnormalities, inborn errors of metabolism, and dysmorphic syndromes was discovered, including 16 instances of previously unknown familial conditions. This program has demonstrated a cost-effective method for determining genetic etiology in mental retardation and, in some instances, has led to prevention of mental retardation.

Abnormalities, Multiple↗

Properties and organ distribution of ATP citrate (pro-3S)-lyase.

1. The lipogenic enzyme ATP citrate lyase (ATP:citrate oxaloacetate-lyase (pro-3S-CH2COO-acetyl-CoA; ATP-dephosphorylating), EC 4.1.3.8) is partially purified from human liver by ammonium sulfate fractionation and anionexchange chromatography. 2. Km values for the substrates are 1.1 x 10(-5) 1.3 x 10(-3), and 1.2 x 10(-4) M for CoASH, ATP and citrate, respectively. The hypolipidemic drug L(-)-hydroxycitrate is a competitive inhibitor with respect to citrate (Ki = 3 x 10(-4) M). 3. Specific activities measured in liver, adipose tissue and intestinal mucosa (autopsic and biopsic material) are in the range of 1 mU/mg protein suggesting that the citrate pathway does not significantly contribute to human lipogenesis. No stimulation is found after a 3-day carbohydrate-rich diet. 4. Specific activities of other key-enzymes of the acetyl-CoA production from carbohydrates (pyruvate dehydrogenase, cytosolic acetyl-CoA synthetase) are of the same low magnitude.

ATP Citrate (pro-S)-Lyase↗

Cell interactions between hematopoietic and stromal cells in the embryonic chick bone marrow.

Light microscopic, scanning electron microscopic, and transmission electron microscopic studies of the early developmental stages of chick embryonic bone marrow disclose characteristic associations of the first hematopoietic cells with stromal cells. The first hematopoietic cells, large basophilic cells that we have termed presumptive stem cells, segregate into erythropoietic and granulopoietic regions. Intravascular erythropoietic cells associate with sinusoidal endothelial cells, while granulopoietic cells associate with extravascular reticular cells. Extensive, intimate contacts between erythroid and endothelial cells are maintained, in part, by marginal arrays of microtubules, which promote a flattening of the adherent erythroid cell surface. In addition, cell surface components of opposing cells, visualized by ruthenium red staining, appear to merge and possibly to interact. Granulopoietic cells establish intimate but less extensive associations with reticular cells through cell-surface interactions. Stationary granuloid cells appear to be held in place by small, thin processes emanating from the sheet-like reticular cells. Granuloid cells are capable of moving within the extravascular region, using reticular cell surfaces as a substrate. Intimate associations also occur among granulopoietic cells, the significance of which is unclear. Thus, sinusoidal endothelial cells and reticular cells comprise the critical non-hematopoietic or stromal elements of avian bone marrow, where they have a putative role in segregating presumptive stem cells into erythrocyteic and granulocytic compartments. They serve as an architectual, and possibly regulatory, framework on which hematopoiesis occurs.

Animals↗

A light and electron microscopic study of the region of cartilage resorption in the embryonic chick femur.

It has long been known that uncalcified cartilage of embryonic chick long bones is removed to make way for invading marrow. However, no one has clearly established which cells are responsible for this erosion. Using the light and electron microscopes, we have studied the cartilage-marrow interface, which we presume to be the region of resorption. Here, we found two types of mononuclear cells in intimate contact with cartilage matrix. 1. The predominate cell type had a euchromatic nucleus with a nucleolus and a cytoplasm containing extensive profiles of rough endoplasmic reticulum; also, processes extended from these cells into the adjoining cartilage matrix. 2. Macrophages containing many lysosomal vesicles, which often became swollen, were found on or near the surface of cartilage. In addition, a few cells with an intermediate appearance were present. A decrease in the amount of sulfated material in a 25-30 micrometer zone of cartilage in advance of the interface and an alteration in the orientation, and in some cases the integrity, of collagenous fibers were associated with the presence of the above mentioned cells. These alterations in cartilage were not due to the synthesis of sulfated or of collagenous material. The above evidence, although not conclusive, suggests that these mononuclear cells are responsible for cartilage resorption. In this respect, the removal of avian uncalcified cartilage is similar to the resorption of uncalcified articular cartilage which occurs in rheumatoid arthritis.

Animals↗

Some effects of products from necrotic regions of tumours on the in vitro migration of cancer and peritoneal exudate cells.

The invasion of normal tissues by cancer cells and the infiltration of tumours by macrophages to some degree involves active translatory movements by these cells. As necrosis is a common occurrence in solid tumours, we have studied the interactions of saline extracts from the necrotic regions of rat Walker-256 tumours and mouse Gardner lymphosarcomas on the transmembrane, in vitro migration of Walker and Gardner cancer cells, and rat and mouse peritoneal macrophages. Necrotic extracts enhanced cell migration independently of chemotactic activity, an effect which was partially reduced by Trasylol, an inhibitor of neutral proteases. Rat liver lysosomal preparations which contain lower levels of neutral proteases than necrotic extract, inhibited or had no effects on cell migration, and the lysosomal stabilizer hydrocortisone did not inhibit the action of necrotic extracts. The results indicate that necrosis may enhance the migration of cancer cells out of tumours and the migration of macrophages into them. The extracts act partially through their neutral protease content. In contrast to the enhancement of cell detachment by necrotic extracts, which previous work has shown to be partially mediated by their indirect effect in causing lysosomal labilization and which is partially inhibited by hydrocortisone, this indirect mechanism is not demonstrable in the enhancement of cell migration. The results indicate that the consequences of necrosis are worthy of consideration in attempts at understanding the biology of solid tumours.

Animals↗

Megakaryocytes in steel mutant mice.

The megakaryocytes in the bone marrow of steel mutant mice (S1/S1d) and their normal littermates (+/+) were studied by light and electron microscopy with special emphasis on their maturity and distribution in the hematopoietic cords. A higher percentage of megakaryocytes lying against the sinus wall, a higher percentage of the sinus perimeter covered by megakaryocytes and a higher percentage of large megakaryocytes were found in S1/S1d mice than in +/+ mice. In addition, more large megakaryocytes as well as senile megakaryocytes were observed in the spleen of S1/S1d mice than in that of +/+ mice. These observations suggest that more platelets are produced in S1/S1d mice than in +/+ mice on the basis of per unit area of the marrow tissue. Heretofore, the fate of the senile megakaryocytes in the marrow was not known. However, in S1/S1d mice senile megakaryocytes were often found entering the marrow sinuses from the hematopoietic cords. They were also seen in the lung and the spleen where degradation of senile megakaryocytes was observed. These observations suggest that senile megakaryocytes in S1/S1d mice leave the marrow and are removed by the reticuloendothelial system outside the marrow.

Anemia↗

Blood flow and reactivity to noradrenaline in DMBA-induced rat mammary neoplasia.

Blood flow during "resting condition' and during noradrenaline infusion were studied by microsphere tracer technique in DMBA-induced mammary tumors, hindpaw, muscle and liver in rats. During "resting condition' the mean tumor blood flow was relatively high and in the same range as that of the hindpaw representing mainly skinflow, but during noradrenaline infusion there was a marked decrease in tumor blood flow as was the case for hindpaw, while cardiac output, muscle flow and arterial liver flow remained essentially unaltered. There was an inverse relation between tumor size and blood flow.

9,10-Dimethyl-1,2-benzanthracene↗

Overestimation of glucose in uranyl acetate-treated samples: modification of the deproteinization method.

It is demonstrated that uranyl ions remaining in deproteinized supernatants of blood, serum, or liquor cerebrospinalis lead to falsely elevated glucose values by forming insoluble precipitates of uranyl phosphate. Furthermore, glucose is overestimated in hemolytic blood samples because of the UV-absorption of incompletely precipitated hemoglobin. A modified deproteinization method is recommended which overcomes these problems: the specimen volume is reduced to one half of the usual volume (0.05 instead of 0.1 ml) and excess uranyl ions are removed from the deproteinized supernatant by precipitation as uranyl phosphate, using phosphate-coated tubes. The supernatant obtained after centrifugation is free of uranyl ions and hemoglobin. Therefore, a sample blank may be omitted.

Blood Glucose↗

The role of the spleen in tumor growth kinetics of the murine B cell leukemia (BCL1).

BCL1 is a transplantable B cell leukemia resembling human chronic lymphocytic leukemia-lymphoma maintained by cell passage in BALB/c mice. After BCL1 inoculation (10(7) cells), all mice developed extreme B lymphocytosis in the blood (less than or equal to 440,000 lymphocytes/mm3) and marked splenomegaly (50 times normal nucleated cell numbers). BCL1 infiltrated the spleen before peripheral leukemia was overt (3 days vs 28 days, respectively). BCL1 development in splenectomized mice was characterized by a delayed onset of leukemia (greater than 20,000 cells/ mm3 at 59 vs 28 days in intact mice), doubled median survival (102 vs 53 days, respectively), and reduced peak level of leukemic counts in the blood (125,000 vs 440,000 cells/mm3). Early splenectomy at different time intervals, ranging between 1 hr to 3 days after BCL1 inoculation, significantly delayed onset of the disease and prolonged survival, indicating that homing to the spleen occurred as early as 1 hr after inoculation. Splenectomy at 7 days still delayed onset of leukemia but did not affect survival. No significant effect on BCL1 kinetics was noticed when splenectomy was done on day 21. All splenectomized mice showed significantly lower peripheral blood counts as compared to intact mice (98,000/mm3 vs 440,000/mm3, respectively). The data show that the spleen plays a major role in the pathogenesis and prognosis of BCL1.

Animals↗

Specific serum pancreatic lipase determination, with use of purified colipase.

We show that the turbidimetric method of Ziegenhorn et al. (Clin. Chem. 25: 1067, 1979) for determination of pancreatic lipase is not influenced by lipoprotein lipase. This improved specificity as compared to standard lipase methods is explained by the presence of purified colipase and the high concentration of bile acids in the substrate emulsion.

Bile Acids and Salts↗

Isolation and identification of biologically active contaminants from soft contact lenses. I. Nicotine deposits on worn lenses.

A method for elution of contaminants deposited onto soft contact lenses during wear utilizing a nondestructive cleaning procedure is presented. Twenty-five soft contact lenses supplied by American Optical Corp. were pooled and subjected to 20% H2O2 (hydrogen peroxide). The resulting wash was extracted with organic solvents, hydrolyzed, and re-extracted. The organic-soluble fraction was further divided into strong acids, intermediate acids, neutrals, and bases. Sequential separation, isolation, characterization, and confirmation of constituents were achieved with thin-layer chromatography, ultraviolet spectrophotometry, and microcrystallography. Photomicrographs before and after cleaning were obtained to assess the optical quality of the lenses. Initial emphasis has been to characterize naturally occurring, biologically active constituents and common environmental toxins of molecular weight 150 to 500. We find that nicotine, a common environmental pollutant and a significant component of the blood of people who smoke regularly, is one of the contaminants present on a worn soft contact lens.

Chemistry, Organic↗