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Biomedical subjects

S Alexander

Publications and source records attributed to S Alexander.

At least 199 records · Page 11Linked to original sources

Immunogenic structure of the influenza virus hemagglutinin.

We chemically synthesized 20 peptides corresponding to 75% of the HA1 molecule of the influenza virus. Antibodies to the majority (18) of these peptides were capable of reacting with the hemagglutinin molecule. These 18 peptides are not confined to the known antigenic determinants of the hemagglutinin molecule, but rather are scattered throughout its three-dimensional structure. In contrast, antibody raised to intact hemagglutinin did not react with any of the 20 peptides. Taken together these results suggest that the immunogenicity of an intact protein molecule is not the sum of the immunogenicity of its pieces.

Amino Acid Sequence↗

Concurrent thymoma and lymphoma: a report of two cases.

Two patients presenting with mediastinal masses that proved to be thymomas were found to have concurrent evidence of lymphoma. One patient also developed another malignancy (of the stomach) one year later. Review of the literature shows a marked increase in the frequency of other malignancies with thymomas and suggests the possibility of decreased natural killer cell function resulting from increased suppressor T cell activity.

Adenocarcinoma↗

endo-beta-N-acetylglucosaminidase F: endoglycosidase from Flavobacterium meningosepticum that cleaves both high-mannose and complex glycoproteins.

We have detected an endoglycosidase activity produced by Flavobacterium meningosepticum. This enzyme, named endo F, cleaves glycans of both the high-mannose and the complex type linked through asparagine to the protein backbone. The data indicate that cleavage occurs via hydrolysis of the glycosidic bond of the N,N'-diacetylchitobiose core structure adjacent to asparagine, similar to that due to endo H and endo D. Extreme variability was noted in the availability of this cleavage site among N-linked glycoproteins. Glycoproteins of retrovirus, lymphocytic choriomeningitis virus, Pichinde virus, and HLA-A and -B antigens were readily cleaved in the presence of nonionic detergent. Others, such as ovalbumin, fetuin, bromelain, ovomucoid, alpha 1-acid glycoprotein, immunoglobulin G, and influenza virus hemagglutinin became susceptible only after reduction and alkylation or when cleavage was performed in the presence of 1% 2-mercaptoethanol. Endo F should prove useful in the study of glycans and protein backbones as discrete entities and for defining the nature of the glycan-protein interface.

Acetylglucosaminidase↗

Radioimmunoassay and in-vitro bioassay of serum LH throughout the equine oestrous cycle.

Mares were bled once daily throughout a cycle, or 3 times daily from the first day of oestrus to the 2nd day after ovulation. LH was measured by heterologous radioimmunoassay and by an in-vitro bioassay based on LH-stimulated testosterone production by mouse Leydig cells. The patterns of bio- and immuno-active LH during the oestrous cycle were similar but not identical, so that in both groups of mares the ratio of biological: immunological (B:I) activity during the LH surge was significantly higher before than after ovulation (P less than 0 . 001). Considerable individual variation in cycle mean B:I ratio, and extent and duration of the peri-ovulatory change in ratio was observed. While the similarity between bio- and immuno-assay LH profiles indicates that the RIA system used can provide useful measurements of LH in the normal cycle, the significant differences between the two profiles suggest that there are circumstances in which RIA alone may not give adequate information on the level of LH stimulation at target tissues. These changes in B:I ratio during the LH surge suggest qualitative differences in the circulating molecule which may be physiologically important in the control of ovulation. The in-vitro bioassay appears to be a useful method to study the biological role of LH in the mare and investigate the roles of the various forms of this polymorphic hormone.

Animals↗

Importance of testicular hormones in maintaining the annual pattern of LH secretion in the male horse.

Serum LH was measured by radioimmunoassay in 5 long-term (greater than or equal to 3 years) castrated male horses bled at 30-min intervals for 2 h twice a month from March to February. There was no significant effect of month on LH levels; however, mean levels were significantly lower in spring than autumn (P less than 0.05). By contrast, stallions in the same environment showed a markedly seasonal pattern of LH secretion, with LH rising at the onset of the breeding season to reach levels in late spring 3-4 times those in early winter. Despite differences in seasonal patterns of secretion, annual mean LH levels in geldings (19.6 ng/ml) and stallions (20.4 ng/ml) were similar. In mid-summer, LH was measured in 6 geldings castrated 4-6 weeks previously, 25 geldings castrated 3-25 years previously, and 8 stallions; mean +/- s.e.m. LH values were 62.2 +/- 8.0, 14.0 +/- 1.6, and 13.0 +/- 2.2 ng/ml respectively. In the long-term geldings, LH was not affected by age, indicating that, after the rapid 4-fold post-castration rise, LH falls to within the normal range of pre-castration values and stabilizes. These results show that testicular hormones are necessary to maintain the normal seasonal pattern of LH secretion in the male horse, including the increase in LH at the onset of the breeding season. It is suggested that the effects of testicular hormones on LH secretion include (1) a negative feedback at the hypothalamus/pituitary as observed in other species, and (2) a positive component in the pathway by which LH is increased at the onset of the breeding season.

Androgens↗

Characterization, by immunoprecipitation, of myeloid- and monocyte-specific antigens present on the human promyelocytic cell line (HL-60) in three stages of differentiation.

The human promyelocytic leukemia cell line HL-60 is reactive with an antiserum raised against normal human granulocytes (AGS). Immunoprecipitation with AGS on [35S]methionine-labeled HL-60 cell lysates with subsequent analysis by NaDodSO4/polyacrylamide slab gel electrophoresis shows a major antigenic doublet with molecular weights of 88,000 and 86,000, together with some minor antigens of lower molecular weight. Upon stimulation with dimethyl sulfoxide or 12-O-tetradecanoylphorbol 13-acetate, which induces HL-60 to differentiate to mature granulocytes or monocytes/macrophages, respectively, this antigenic doublet disappears. 12-O-Tetradecanoylphorbol 13-acetate induces the synthesis of an antigen, molecular weight 83,000, reactive with an antimonocyte serum. Neutrophil-specific alloantigens were not detected on HL-60 or its differentiated derivatives.

Animals↗

Field-induced trapping as a probe of dimensionality in molecular crystals.

The combined effect of an electric field and reduced dimensionality on the hopping motion of a charge carrier in an anisotropic molecular crystal is determined. New, exact expressions for S(t), the number of distinct sites occupied by a carrier in time t, are presented for two-dimensional and three-dimensional anisotropic lattices. The general results are used to model the unusual phenomenon of field-induced charge carrier trapping reported to occur in a quasi-one-dimensional molecular crystal. An analytic expression for the carrier lifetime tau, as a function of the anisotropy in the molecular hopping rates and electric field, is developed and is shown to be in excellent agreement with experimental results. A major conclusion of the theory is that E(c), the electric field characterizing the E dependence of tau, can be a more direct probe of the intrinsic anisotropy than is the observed mobility ratio.

Journal Article↗

Regulation of glycolytic enzyme activity during chronic hypoxia by changes in rate-limiting enzyme content. Use of monoclonal antibodies to quantitate changes in pyruvate kinase content.

Monoclonal antibodies were prepared against pyruvate kinase (PyKi; ATP: pyruvate phosphotransferase, EC 2.7.1.40) and used to quantitate PyKi content in L2 lung cells and WI-38 fibroblasts cultivated under hypoxic and normoxic conditions. After 96 h of hypoxic cultivation, PyKi activity was significantly increased in both cell types (L2: normoxia [Po2 = 142 torr], 0.11 +/- 0.01 [SD]; hypoxia [Po2 = 14 torr], 0.25 +/- 0.04 U/microgram DNA, P < 0.01). PyKi content increased proportionately in both cell lines (L2: normoxia, 0.44 +/- 0.13; hypoxia, 0.94 +/- 0.13 microgram enzyme protein/microgram DNA). Specific activity was not significantly different after 96 h (L2: normoxia, 261 +/- 11; hypoxia, 261 +/- 14 U/mg enzyme protein). These results indicate that regulation of glycolysis during chronic hypoxia occurs at the level of enzyme content. Chronic O2 depletion leads to either an increased rate of biosynthesis or a decreased rate of biodegradation of PyKi, causing augmented glycolytic capacity. Monoclonal antibodies provide a highly specific, convenient approach to charcterizing enzymes, as well as quantitating cellular enzyme content.

Animals↗

Ewing sarcoma: phalangeal primary with fatal cardiac metastases.

A 39-year-old man had pain and swelling of the terminal phalanx of a finger. Radiograph was interpreted as osteomyelitis, and amputation through the mid-phalanx was performed. Histology revealed Ewing sarcoma. Lung metastases rapidly developed. Right lung irradiation and systemic chemotherapy, including doxorubicin, were instituted. He developed progressive severe right ventricular failure which was attributed to effects of large pulmonary metastases. Autopsy showed massive right ventricular metastases, the primary pathological cause of the heart failure, without evidence of doxorubicin cardiomyopathy.

Adult↗

Renal clearance of estriol and its conjugates in normal and abnormal pregnancies.

Renal clearance of estriol (E3), E3-3-sulfate (E3S), E3-16-glucuronide (E316G), E3-3-glucuronide (E33G), and E3-3-sulfate-16-glucuronide (E3SG) has been measured in 13 normal and 17 abnormal pregnancies between the 33rd and 40th weeks of gestation. The methodology involved a chromatographic separation on a celite column in the presence of tritiated tracers, enzymic hydrolysis of the conjugates, and measurement of the E3 moiety by a specific RIA. Preeclampsia (eight patients) was characterized by a significant decrease of renal clearance for all conjugates except E33G. In contrast to that pattern, a patient with cholestatic icterus had normal clearances except for E33G, which was reduced to less than 15% of its normal mean value. Administration of ampicillin to a pregnant woman induced an important decrease of all E3 clearances, especially for E33G which decreased to nearly 1% of its initial value; normal clearances were resumed within a week after the end of the treatment. In a small number of complicated pregnancies, E3 clearances were normal. A significant correlation between the renal clearance of E316G and that of urea and creatinine has been demonstrated.

Estriol↗

Serum unconjugated estriol after intravenous cortisol administration in late pregnancy.

Serum unconjugated estriol levels were measured in 44 pregnant women treated with corticoids for the prevention of respiratory distress syndrome (RDS) in premature infants. Intravenous administration of cortisol (1 g every 6 hours for 24 hours) decreased the level of circulating unconjugated estriol to 40% of the initial value after 6 hours and to 27% after 24 hours. During the 2 succeeding days, all the results remain below the pretreatment values. On the third day, the mean value is no longer different from the control value, but in some patients recovery takes more than 3 days.

Estriol↗