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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 469 records · Page 26Linked to original sources

Host's immune state and kinetics of local tumor growth control--progression of postoperative lung metastasis.

In a study of the progression of lung metastases in tumor-bearing and tumor-excised mice as a function of the host's immune status and of the rate of local 3LL tumor development, the following observations were noted. 1) The total metastatic volume was larger in mice transplanted intrafootpad with the lower doses of 3LL tumor cells (1 x 10(5)--3 x 10(4)) than in mice inoculated with high doses of tumor cells (5 x 10(-6)--1 x 10(6)). 2) A dramatic acceleration of metastatic development followed surgical removal of the local tumor which developed following inoculation of low, but not high doses of 3LL tumor cells. 3) In immunoimpaired mice, growth of the local tumor induced by inoculation of 3 x 10(6) or 1 x 10(5) 3LL tumor cells was enhanced in cyclophosphamide-treated (200 mg/kg) mice and retarded in B mice, yet metastasis development was accelerated in both types of immunosuppressed tumor-bearing mice. Tumor excision was an additional stimulus for metastatic growth. In immunosuppressed animals, the growth of postoperative pulmonary metastases accelerated to the same degree, independent of whether local tumors had been produced by high or by low doses of 3LL tumor cells.

Animals↗

Absent phenylalanine hydroxylase activity without phenylketonuria.

A male infant is described who never manifested phenylketonuria even though phenylalanine hydroxylase activity was undetectable in liver tissue. Plasma phenylalanine were elevated in the range typical of PKU patients when the baby was at breast and declined with institution of a low phenylalanine diet. Physical and psychomotor development were normal with the baby on the latter treatment. The results indicate that the absence of phenylketonuria does not rule out phenylalanine hydroxylase activity.

Breast Feeding↗

Serological detection of H-2K- and H-2D-gene products. I. Principal difference between T and B lymphocytes in expression of H-2D-encoded alloantigens.

Using the fluorescence-activated cell sorter (FACS II), we have analyzed the expression of H-2K- and H-2D-gene products on the membrane of various cellular components of the murine immune system. Using this serological technique we show a basic difference between T and B lymphocytes. Whereas all cellular components analyzed--hydrocortisone-resistant thymocytes, splenic T and B lymphocytes, macrophages and bone-marrow cells--expressed H-2K-subregion-encoded alloantigens at a high density, it seems that the high density expression of H-2D-encoded alloantigens is restricted mainly to B cells and to macrophages. Hydrocortisone-resistant thymocytes, splenic T lymphocytes and bone-marrow cells, on the other hand, showed significant expression of the H-2D alloantigens only at low membrane density. These results, then, provide evidence for the existence of an imbalance in serologically detectable expression of H-2K- and H-2D-region-gene products on the cell membrane of various cells comprising the murine immune system.

Animals↗

Transport interactions of cystine and dibasic amino acids in isolated rat renal tubules.

Isolated renal cortical tubules prepared from adult male Sprague-Dawley rats were used to study the nature of cystine entry into tubule cells and its transport interactions with dibastic amino acids. The uptake of cystine over time was progressive, reaching a steady-state after 60 min of incubation. Analysis of the intracellular pool after incubation revealed that a significant fraction of the transported cystine was reduced to cysteine. A kinetic analysis of uptake demonstrated that two systems for cellular entry of cystine existed with a Km1 of 0.012 mM and Km2 of 0.55 mM. Cystine uptake was sodium dependent with an apparent Km for sodium of 36 mEq/liter. Lysine inhibited cystine uptake via the low Km system, but appeared not to inhibit cystine uptake via the high Km system. Ornithine, leucine, and isoleucine each inhibited cystine uptake via the low Km system. Arginine appeared to affect both systems for cystine uptake. Cystine inhibited the uptake of lysine by isolated renal tubules. The data suggest that cystine at physiologic concentrations is transported into renal tubule cells nearly equally by two systems, of which, the low Km system is shared with the dibasic amino acids. A defective low Km system could in part explain human cystinuria.

Amino Acids, Diamino↗

Holocarboxylase synthetase deficiency: a biotin-responsive organic acidemia.

The clinical and biochemical features of an infant affected by holocarboxylase synthetase deficiency are presented. The patient was the sibling of the deceased child in whose cultured skin fibroblasts the precise enzymatic disorder was first determined. This fact permitted administration of specific therapy in the form of oral biotin, resulting in immediate improvement from impending respiratory failure and shock. The clinical response to biotin was accompanied by recovery of the biochemical mechanisms known to be biotin-dependent, as manifested by disappearance of intermediates in urine and blood. The variability of biotin responsiveness and the diversity of clinical presentation in the patients originally thought to have a deficiency of beta methylcrotonylCoA carboxylase, a biotin-dependent enzyme, raises the question of a separate, specific apocarboxylase defect.

Amino Acid Metabolism, Inborn Errors↗

Ear injury caused by elevated intratympanic pressure during general anaesthesia.

Two cases of middle-ear injury, due to sharp fluctuations of intratympanic pressure as a result of general anaesthesia with nitrous oxide are presented. A study is reported indicating that the degree of these fluctuations is a function of the concentration of nitrous oxide. In order to reduce the risk of middle-ear injury due to nitrous oxide anaesthesia, it is suggested that the lowest concentration feasible should be used where there is a history of previous ear surgery.

Adult↗

Uptake of L-[35S]cystine by isolated rat brain capillaries.

Adult rat brain capillaries were isolated by a simplified procedure and showed an enrichment of the marker enzyme, gamma-glutamyltranspeptidase. The uptake of [35S]cystine at 37 degrees C by this preparation can be divided into two components, a sodium- and energy-dependent transport process for the free amino acid pool, with an apparent Km of 36 microM, and a binding process, with an apparent Km of 1.13 mM. Chemical analysis of the amino acid pool indicates that cystine is the major from of intracapillary 35S. Cystine transport was not inhibited by lysine, but glycine, alpha-methylaminoisobutyric acid and beta-2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid were inhibitory to a small extent.

Amino Acids↗

Ease of solubilization of five marker enzymes in three preparations of rat renal brush border membranes.

The ability of eight stripping agents to solubilize five marker enzymes from rat renal brush border membranes isolated by three different preparative methods was examined. Protein and enzyme activities - alkaline phosphatase (APase), L-leucine aminopeptidase (LAPase), gamma-glutamyl transpeptidase (GGTase), gamma-glutamyl hydrolase (GGHase) and maltase - solubilized by the treatments were expressed as percent of total activity recovered in excess of control values. The relative enzyme activity and the solubilization factor were determined for each marker enzyme in every treated sample and the treatments with the eight agents compared. Trypsin treatment released > 80% of LAPase and < 10% of total membrane protein. Papain treatment released only 16--23% of total membrane protein but most of the enzyme activities except APase. Neuraminidase had no solubilizing effect. 4--10% of total membrane protein was solubilized by LiCl treatment but no marker enzyme activities were released. Less total membrane protein was released by treatment with proteolytic enzymes or LiCl than with the detergents Triton X-100, hexadecyltrimethylammonium bromide, sodium deoxycholate, and sodium dodecylsulfate. APase activity was the least readily solubilized. Correlating the degree of solubilization for five marker enzymes with the types of stripping agents used and with the appearance of the membrane surface when examined by electron microscopy led to the suggestion that LAPase, GGTase, GGHase and maltase molecules are part of an interwoven surface layer of membrane proteins which can be disrupted by transamidation and transesterification reactions. APase appears to be more strongly associated with the intact lipid matrix than the bulk of the membrane protein.

Alkaline Phosphatase↗

Male pseudohermaphroditism due to 5 alpha-reductase deficiency. Ultrastructure of the gonads.

We report here the results of the endocrine studies and the morphological findings of the gonads in two male pseudohermaphrodite siblings with 5 alpha-reductase deficiency. Basal levels of luteinizing hormone, follicle-stimulating hormone, and prolactin were elevated and rose to very high levels in response to gonadotropin-releasing hormone and thyrotropin-releasing hormone,, when compared to those in normal males, while thyroid-stimulating hormone response was normal. Serum testosterone levels were within the normal range, and estradiol values were modestly elevated. Diagnosis was confirmed by lack of conversion of 3H-testoterone to 3H-dihydrotestosterone by fibroblasts taken from perineal skin. Pathologic examination of the testes in both patients disclosed tubular atrophy and complete arrest of spermatogenesis, with numberous hyperplastic Leydig cells containing large Reinke crystalloids.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Control of lung metastasis progression in mice: role of growth kinetics of 3LL Lewis lung carcinoma and host immune reactivity.

Studies were made of the growth of metastases of the 3LL Lewis lung carcinoma in tumor-bearing and tumor-excised C57BL/6 mice after intrafootpad inoculation of different cell doses to the intact or immunosuppressed host. The total metastatic volume was higher in tumor-bearing mice given transplants of low doses of 3LL cells (3 X 10(4)- 1 X 10(5)) than in mice receiving high doses of cells (1 X 10(6)-5 X 10(6)). The growth of postoperative lung metastases depends on the size of the removal of local tumors and the rate of their development. Surgical removal of small, medium, or large local tumors, respectively, resulted in the development of smaller, similar, or larger volumes of pulmonary metastases compared to the metastases in tumor-bearing mice not having surgery. Accelerated growth of postoperative metastases in mice inoculated with low doses of 3LL cells was observed following removal of the local tumors of more than 310 mm3. The same effect was observed on mice given transplants of high doses of 3LL cells only when the removed local tumors had reached a volume of more than 550 mm3. In immunologically suppressed tumor-bearing mice, acceleration of the metastatic growth in the lungs was observed independently of the inoculum size. Even in the immunosuppressed mice, the growth of metastases was not optimal, and an additional stimulus for their growth was achieved following the removal of local tumors. This finding suggested that immunologic and nonimmunologic mechanisms were involved in the control of the metastatic growth of 3LL tumors in mice.

Animals↗

Superiority of bromocriptine over pyridoxine in the treatment of patients with acromegaly or galactorrhea.

Sixteen patients, eight with acromegaly and eight with galactorrhea, were treated with pyridoxine (600 mg/day) for a three-month period. The clinical and biochemical changes induced by the drug were compared with those induced by bromocriptine (2.5 to 50 mg/day) administered for the same length of time to the same patients. Pyridoxine induced lowering of growth hormone and prolactin levels in two acromegalic patients. In only one patient with galactorrhea after irradiation of the hypophysis for active acromegaly did pyridoxine treatment stop and galactorrhea and induce renewal of menstrual bleeding without significantly changing the basal prolactin levels. In another patient with a chromophobe adenoma of the hypophysis, it reduced the excessively elevated prolactin levels. On bromocriptine therapy, all the patients reported signifcant clinical improvement paralleled by significant drops in plasma growth hormone and prolactin. It appears that at the dosages administered bromocriptine is preferable to pyridoxine in the treatment of patients with acromegaly or galactorrhea.

Acromegaly↗