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Biomedical subjects

R Bass

Publications and source records attributed to R Bass.

At least 55 records · Page 3Linked to original sources

Venous malformation of the neck secondary to a plunging ranula of the mouth.

An unusual case of plunging ranula, with development into a venous malformation, is presented. The patient was successfully treated by excision of one venous aneurysm and malformation and submandibular gland in one session followed by exteriorization of ranula and removal of a sublingual gland two months later.

Adult↗

Distribution of T lymphocyte subsets in human colostrum.

Lymphocytes were isolated from human colostrum and peripheral blood collected within 7 days postpartum. A 20-fold enrichment of lymphocytes from colostrum was achieved by centrifugal elutriation followed by equilibrium density gradient centrifugation. The distribution of T lymphocyte subsets was determined by immunofluorescence analysis of reactivity with monoclonal antibodies of the OKT series. In confirmation of previous reports employing sheep erythrocyte rosette assays, the majority of colostral lymphocytes reacted with OKT3 monoclonal antibody, a reagent that detects a surface antigen on mature T cells. Neither colostral nor blood lymphocytes from postpartum donors expressed the OKT6 antigen that is found in immature thymocytes. A novel finding is that the T lymphocyte population in colostrum contains both OKT4 (helper/inducer phenotype) and OKT8- (cytotoxic/suppressor phenotype) positive subsets. The relative ratio of OKT4 to OKT8-positive T cell subsets in colostrum, however, is generally lower than that observed for peripheral blood T cells.

Antibodies, Monoclonal↗

Placental transfer of thiamphenicol in the rat.

Measurement of thiamphenicol transfer to the rat embryo during organogenesis was performed as one step of the determination of possible drug embryotoxicity in man. Extrapolation of data on animal embryotoxicity to man will only become possible when data on the toxicokinetic properties of the substance under investigation are available for both animal and man. 1) Thiamphenicol, given between day 11.5 and 14 of rat gestation, rapidly reached the embryo; 4--6 h after single i.v. or s.c. injection, embryonic and maternal thiamphenicol levels became equal and decreased from that time on at the same rate. 2) No evidence was found for development of a placenta barrier with increasing placental function. The same dose applied at different developmental stages yielded the same embryonic drug concentrations. 3) Elimination via kidney (unchanged) or bile (glucuronide), may become rate-limiting for thiamphenicol excretion. Doses exceeding 50 mg/kg (i.v.) or approx. 100 mg/kg (s.c.) yielded thiamphenicol levels higher than those expected from linear dose-concentration relationships. 4) Drug concentrations (greater than 3--5 micrograms/g wet weight) obtained with dosing regimens (greater than 100 mg/kg/day) used for experimental induction of embryolethality in rats are equal to those necessary for inhibition of mitochondrial protein synthesis in vitro and to those necessary for treatment of bacterial infections in man.

Animals↗

Amyloidosis in systemic lupus erythematosus.

Amyloidosis occurs in a significant proportion of patients with rheumatologic diseases. The fibrillar amyloid proteins in such patients are composed predominantly of amyloid A protein, which is characteristic of the amyloid deposits associated with chronic inflammatory diseases. Only four patients with amyloidosis associated with systemic lupus erythematosus (SLE) have been described previously; analyses of their fibrillar amyloid proteins were not reported. We present herein, a patient with SLE and amyloidosis. Histochemical staining of our patient's renal tissue with Congo red demonstrated that the amyloid deposits contained amyloid A protein, as defined by permanganate sensitivity. In addition, the patient's serum contained increased concentrations of serum amyloid A proteins. In review, each of the previously described patients with amyloidosis associated with SLE had renal amyloid deposits, with diagnosis in three during evaluation of proteinuria. Thus, although rare, amyloidosis should be considered in the differential diagnosis of proteinuria in patients with SLE.

Adult↗

Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the mouse embryo and fetus.

(1) Following the administration of the highly toxic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pregnant mice, exceedingly low concentrations of this substance were found in the embryo and fetus between gestational days 11 and 18 (between 0.04 and 0.14% of the maternal dose/g tissue). (2) Tissue levels of tCDD in embryos on days 9 and 10 exceeded those of later gestational stages. (3) TCDD levels in fetal livers were 2--4 times higher than those in other fetal organs. (4) Maternal liver contained the highest concentrations of TCDD (4 -10% of the dose/g). A comparison of the results obtained following oral, s.c. and i.p. applications indicated that there was no major first pass effect involved following oral administration. (5) Placenta and other extrahepatic maternal organs exhibited TCDD levels, which were approximately 1, embryos and features 2 orders of magnitude lower than maternal liver concentrations. (6) Good correlation was found between the doses applied (5, 12.5 and 25 microgram/kg) and the tissue levels observed. (7) A single dose of 25 microgram/kg given on day 10 or 5 doses of 5 microgram/kg, 1/day from days 7-11, resulted in higher levels of TCDD in embryos on day 13 than did a singly dose of 25 microgram/kg on day 7; cleft palate was induced at different rates by these treatment schedules.

Animals↗

Inhibition of growth of cells in culture by L-phenylalanine as a model system for the analysis of phenylketonuria. I. aminoacid antagonism and the inhibition of protein synthesis.

Phenylalanine in high concentrations inhibits the growth of mouse A9 cells. Protein synthesis is inhibited earlier and more severely than RNA or DNA synthesis. Phenylalanine inhibits the uptake and decreases the intracellular pool of several amino acids. Certain amino acids added in excess reverse the phenylalanine inhibition. The strongest reversing amino acids appear to function by excluding phenylalanine. The phenylalanine inhibition does not appear to be due to a deficiency of any amino acid, but to the high intracellular phenylalanine concentration and/or an amino acid imbalance resulting from the large ratio of phenylalanine to other amino acids.

Amino Acids↗

Testing for embryotoxicity.

No animal species exists with which the situation in man can be completely mimicked. This also holds true for non-human primates. With animal experiments only certain aspects of the whole complex situation can be analyzed. In order to achieve this successfully, animal species and experimental set-ups have to be chosen carefully to represent the situation existing in humans in as suitable a model as possible. The more the model deviates from the situation existing in humans, the less will be the predictability. It has to be decided, and this is mainly a political decision, what risk is acceptable. Both terms "risk" and "acceptable" have to be specified. Animal studies beyond routine procedures will have to include the use of more and other species (e.g., primates), and in vitro systems adjusted to the special problem to be solved. Today more information is needed on the pharmacokinetic and "toxico" dynamic properties of old and new chemicals. This will supply data on the embryotoxic/teratogenic doses of a substance or on their non-embryotoxic/teratogenic doses relevant to man. A drastic reduction in the number of chemicals pregnant women are exposed to will greatly enhance the chance to perform experiments on the remaining substances successfully and the chance to obtain valid data.

Animals↗

Mammalian mitochondrial ribosomes. Studies on the exchangeability of polypeptide chain elongation factors from bacterial and mitochondrial systems.

Mammalian mitochondrial ribosomes from rat liver synthesised poly(phenylalanine) from [14C]-Phe-tRNA in the presence of a homologous 10(5) X gav supernatent fraction. The activity depended on the addition of synthetic template and was resistant to cycloheximide. The polyanion spermidine had a stimulatory effect on peptide synthesis in vitro. In contrast to Escherichia coli ribosomes, which also functioned with heterologous supernatant fractions, 55-S mitochondrial ribosomes were inactive when supplemented with heterologous supernatant fractions from E. coli or with purified bacterial elongation factors. EF-T slightly stimulated polyphenylalanine synthesis when added in combination with mitochondrial supernatant fractions. Two-dimensional electrophoretic analysis of the protein content of both supernatant fractions revealed considerable differences in the distribution of the species-specific proteins according to their isoelectric points. The mitochondrial supernatant proteins were in general more basic, and the few acidic proteins did not co-migrate with EF-Tu or EF-G from E. coli.

Animals↗

Elucidation of an A and L system for amino acid transport in the human lymphoblast using a membrane filtration technique.

Optimum conditions have been established for the measurement of amino acid transport by human lymphoblastoid cell lines using a membrane-filtration technique. The parameters we found to be important for the reproducibility of the method are: the types and combination of filters, the strength of the vacuum applied to the filters and the density of the cultures at the time of harvesting and during uptake and filtration. We found that bovine serum albumin added to phosphate buffered saline (PBS) glucose in which the cells are washed, resuspended and assayed is essential for the maintenance of viability, the prevention of clumping and the retention of the accumulated amino acid. Using this procedure we have characterized two transport systems for the neutral amino acids; an A and an L system, which are similar but not identical to the A and L systems characterized in rodent cell lines. These A and L systems have characteristically lower Km's and Vm's for alanine and phenylalanine, when compared to rodent cell lines. In addition, we find alpha-AIB to be a poor competitor of alanine and phenylalanine uptake.

Alanine↗

Effect of intact parathyroid hormone on hepatic glucose release in the dog.

The liver has been shown to remove parathyroid hormone (PTH) from its arterial circulation by a mechanism that is selective for the intact form of the peptide (PTH 1-84). The present studies demonstrate that PTH has biologic effects on the liver in vivo. Bovine PTH 1-84 stimulated hepatic glucose release in dogs with indwelling hepatic vein catheters from basal values of 31+/-8 to 68+/-9 mg/min per kg after bolus injections of PTH. The effect on hepatic glucose release was apparent by 5 min and persisted for the 80 min of observation. The NH(2)-terminal PTH fragment (syn b-PTH 1-34) had no effect. Bovine PTH 1-84 administered in doses designed to produce circulating levels of immunoreactive PTH similar to the endogenous levels observed in uremic dogs also increased the incorporation of (14)C from infused [(14)C]alanine into glucose, and increased estimated hepatic uptake of both chemical and [(14)C]alanine, while increasing hepatic glucose release. Thus, administration of "physiologic levels" of b-PTH 1-84 stimulated hepatic glucose release in part through increased gluconeogenesis in vivo, whereas syn b-PTH 1-34 had no demonstrable effect. Circulating levels of insulin rose after PTH administration, an increase which presumably represents a secondary response to the rise in glucose release. These results suggest that the liver is a target organ of PTH, and that PTH might potentially alter carbohydrate metabolism during hypersecretion. They also suggest that hepatic uptake of PTH may be related in part to production of a specific biologic effect rather than just simple peptide degradation.

Animals↗