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G H Smith

Publications and source records attributed to G H Smith.

At least 145 records · Page 8Linked to original sources

Evidence for a precursor-product relationship between intracytoplasmic A particles and mouse mammary tumour virus cores.

This report presents evidence which supports a relationship between intracytoplasmic A particles (CAP) and mouse mammary tumour virus (MMTV). Three MMTV-specific antigenic determinants in CAP (MMTV p27, p14 and p10) uere detected by immunodiffusion. No structural proteins of comparable mol. wt. were found in CAP; however, exposure of CAP to trypsin resulted in the cleavage of the CAP structural proteins to MMTV-like polypeptides. This process was accompanied by the preservation of MMTV-specific antigen determinants. Disulphide bonds were necessary for the structural maintenance of CAP. Reducing agents destroyed the organized structure of CAP, whereupon processing of CAP proteins to MMTV-like polypeptides by trypsin was prevented. CAP p82, possessed only MMTV p27 antigenic determinants, while CAP polypeptides p20--18 possessed p10 antigenic determinants. Following processing of CAP structural proteins by trypsin, MMTV-specific p27 antigenic determinants were shifted from CAP p82 to CAP p27; MMTV-p10 antigenic determinants were found with CAP p15--10. These results suggest a model wherein CAP structural proteins are modified by protease during maturation, resulting in the shift of their proteins to sizes consistent with those which have been currently identified as the major internal components of the virion and that this phenomenon is largely predicated on the folding of CAP proteins into the morphologically intact A particle.

Antigens, Viral↗

Difference between mammary epithelial cells from mature virgin and primiparous mice.

Mammary epithelial cells from mature virgin mice are similar to those from primiparous mice in several respects. However, there is one known difference. The cells from the mature virgin must traverse the cell cycle in order to become competent to make casein and enzymatically active alpha-lactalbumin in vitro; those from the primiparous animal can make these proteins without first traversing the cycle. In this regard, cells from human placental lactogen- and prolactin-treated mature virgins are, after involution, similar to those from primiparous mice. The developemental block in the cells from the mature virgin, imposed by preventing cell cycle traversal, has been partially delineated. It does not appear to reside at the levels of ultrastructural maturation or the formation of casein messenger RNA. Rather, the lesion is postranscriptional and may be at the level of translation, or posttranslational modification, or both.

Animals↗

Transplantable granulocytic leukemia in strain 13 guinea pigs.

The occurrence of a granulocytic leukemia in 1 of 40 female strain 13/N guinea pigs given N-nitroso-N-butylurea continuously in their drinking water for 21 weeks is reported here. This leukemia has been successfully transplanted in this guinea pig strain for 13 transplant generations by i.p. inoculation of leukemic blood or marrow cells. Macroscopically and microscopically, this leukemia resembles the chronic myelogenous form in humans. Histochemical studies showed, however, that unlike the human leukemic cells those in the leukemic guinea pigs are alkaline phosphatase positive. Electron microscopic studies of the guinea pig leukemic cells revealed the presence of numerous intracisternal A-type particles that are not found in corresponding normal leukocytes.

Alkaline Phosphatase↗

The activities of 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase in hearts and mammary glands from ruminants and non-ruminants.

1. The activities of 2-oxoglutarate dehydrogenase (EC 1.2.4.2) were measured in hearts and mammary glands of rats, mice, rabbits, guinea pigs, cows, sheep, goats and in the flight muscles of several Hymenoptera. 2. The activity of 2-oxoglutarate dehydrogenase was similar to the maximum flux through the tricarboxylic acid cycle in vivo. Therefore measuring the activity of this enzyme may provide a simple method for estimating the maximum flux through the cycle for comparative investigations. 3. The activities of pyruvate dehydrogenase (EC 1.2.4.1) in mammalian hearts were similar to those of 2-oxoglutarate dehydrogenase, suggesting that in these tissues the tricarboxylic acid cycle can be supplied (under some conditions) by acetyl-CoA derived from pyruvate alone. 4. In the lactating mammary glands of the rat and mouse, the activities of pyruvate dehydrogenase exceeded those of 2-oxoglutarate dehydrogenase, reflecting a flux of pyruvate to acetyl-CoA for fatty acid synthesis in addition to that of oxidation via the tricarboxylic acid cycle. In ruminant mammary glands the activities of pyruvate dehydrogenase were similar to those of 2-oxoglutarate dehydrogenase, reflecting the absence of a significant flux of pyruvate to fatty acids in these tissues.

Acetyl Coenzyme A↗

Experience with counterpulsation in cardiac surgical patients.

At Sheffield Regional Cardiothoracic Unit, the AVCO intra-aortic balloon pump has been used on 25 occasions in 21 months. Of the 25 patients, 12 survived and left hospital. The procedure is particularly beneficial in patients who have suffered some failure of myocardial protection during operation and to those who are suffering from acute ischaemia or the sequelae of myocardial infarction. The place of preoperative counterpulsation is discussed. Patients with long-standing cardiac disease who have emergency surgery benefit less from counterpulsation. Those patients with chronic ischaemic damage to the heart have nothing to gain from the use of counterpulsation.

Adolescent↗

Further characterization of intracytoplasmic A particle-associated DNA.

A DNA species with buoyant densities greater than mouse cellular DNA was found associated with intracytoplasmic A particles (CAP) isolated from mouse mammary tumor virus-infected mouse mammary tumors and mouse Leydig cell tumors which produce CAP but no complete mouse mammary tumor virus virions. This DNA species was absent in identically prepared tissue fractions from tumors which did not contain CAP. Treatment of CAP-associated DNA with pancreatic RNase A did not alter the buoyant density although a reduction in apparent molecular weight (broadening of the DNA band at equilibrium) was observed upon analytical equilibrium sedimentation in CsCl. The molecular weight of untreated CAP-associated DNA was estimated to range from 0.8 x 10(6) to 3.1 x 10(6). Base composition analysis showed CAP-DNA to possess an approximate guanine plus cytosine content of 38%. Ninety percent of CAP-associated DNA eluted as single-stranded molecules upon hydroxyapatite column chromatography, a characteristic that accounts in part for its higher buoyant density in neutral CsCl compared to native double-stranded mouse DNA. In two preparations, CAP-DNA had a sedimentation coefficient of 7 to 8S.

Animals↗

Determinant competition during the immune response to N-acyl derivatives of ox insulin in the Hartley guinea-pig.

Subgroups of female Hartley guinea-pigs were immunized with N-carbamylated ox insulin, N-maleylated ox insulin, N-phthaloylated ox insulin, or with the crystalline ox insulin from which the N-acylated insulins had been prepared. The immunogens were administered in water-in-oil emulsions containing pertussis vaccine as adjuvant. Sera obtained 20 days after secondary immunization were assayed for their antibody titres to iodo-ox insulin and their insulin-binding capacities. The data were log transformed for statistical comparison. N-carbamylated ox insulin seemed to be as immunogenic as crystalline ox insulin and no specific carbamyl hapten antibody could be found. N-maleylated and N-phthaloylated ox insulins yelded significantly less antibody cross-reactingwith iodo-ox insulin, but produced a complementary quantity of specific maleyl and phthaloyl hapten antibody respectively. Thus it was shown that in the system used the immune response was partitioned between different determinants, ox insulin and its N-acylated derivatives being equipotent immunogens.

Acylation↗

Comparison of intracytoplasmic A particles and intracisternal A particles.

Intracytoplasmic A particles and intracisternal A particles are associated with mouse tumors of various types, and both can coexist in the cytoplasm of the same cell. The designation of both as A particles is based on the recognition that they share morphological similarities. A comparison of purified isolates of these two particles reveals that the structural protein profiles are different, but that there is some antigenic cross-reaction as demonstrated by immunodiffusion and complement fixation. This result does not appear to involve the major structural protein of intracisternal A particles, but may reflect the presence of common antigenic determinants located on minor proteins.

Animals↗

Ulcreative colitis.

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Adrenal Cortex Hormones↗

Protein and glycoprotein electrophoretic patterns of enriched fractions of primary and secondary granules from guinea pig polymorphonuclear leukocytes.

The postnuclear supernatant fraction of sucrose homogenates of guinea pig polymorphonuclear leukocytes (PMNL) was subjected to differential centrifugation to obtain a total particulate fraction, a particle-free supernatant fraction, highly enriched fractions of primary and secondary granules, and a membrane-rich fraction. The various fractions were solubilized in buffer containing sodium dodecyl sulfate (SDS) and analyzed for protein and glycoproteincomponents by SDS -polyacrylamide gel electrophoresis. The major glycoprotein components of the postnuclear supernatant fraction were found mainly associated with the enriched fraction of secondary granules and, to a lesser extent, with the membrane-rich fraction. No major glycoprotein components were visible in the polypeptide electrophoretic patterns of the primary granule fraction or of the particle-free supernate. Attempts at separation of guinea pig granules by zonal sucrose density gradient centrifugation were only partially successful. Data supporting a species difference in this regard between rabbit and guinea pig PMNL granules are presented.

Alkaline Phosphatase↗

Autoradiographic evidence for the association of DNA with intracytoplasmic A-particle inclusions in situ.

Mice with subcutaneous transplants of a Leydig cell tumor were given tritiated thymidine sc proximal to the tumor mass. The labeled tissue was collected and samples for autoradiography were taken. Nuclei and intracytoplasmic. A particle(s) (CAP) were purified from the remainder of the tumor pool. The distribution of radioisotopic grains over electron microscopic autoradiography was semiquantitated and analyzed. Granin were found over CAP inclusions in situ. Comparison of the relative frequency of CAP-associated grains to nuclear grains by probability on a planar area basis revealed a higher frequency of thymidine incorporation into these structures. Isolation and comparison of the DNA(s) associated with CAP and nuclei showed a higher specific activity for CAP-associated DNA than for nuclear DNA, which was in good agreement with the autoradiographic analysis. The DNA associated with the purified CAP possessed a significantly higher buoyant density in CsCl than did the nuclear DNA. These reslult implied that this DNA was present in CAP inclusions in situ.

Animals↗

Physician attitudes toward drug information resources.

A survey of the drug information needs of physicians in western Washington State is discussed. Of 5006 questionnaires mailed to physicians, 1227 were returned completed. The results showed that physicians depended primarily on journals and texts for drug information. Pharmacists were seldom considered as sources of drug information which would directly affect patient therapy. Slightly more than a third of the respondents indicated a willingness to pay for drug information services

Attitude of Health Personnel↗

Virion-associated and cellular RNA methylase activity in normal and neoplastic mammary tissue from mammary tumor virus-infected and -uninfected mice.

A comparison of cellular RNA methylase activities and patterns between normal and neoplastic mouse mammary tissue indicated the following. The rna methylases of mammary tumor tissue extracts are qualitatively different from those of normal lactating mammary tissue, based on differences in extent of methylation; the normal lactating tissue extracts have a greater capacity of methylate RNA than do the tumor extracts studied to date. There is no correlation between capacity and either the malignant state or the etiological agent. There is a qualitative effect on methylation patterns attributable to the presence of virus. Finally, both the etiological agent, mouse mammary tumor virus, and its putative nucleoprotein core, intracytoplasmic A particles, have a N-2-guanine RNA methyltransferase integrally associated with them. These conclusions are consistent with the aberrant nucleic acid methylation hypothesis, with the reservation that aberrant does not imply hypermethylation.

Animals↗

Mouse mammary tumor virus polypeptide precursors in intracytoplasmic A particles.

Intracytoplasmic A particles were analyzed by immunodiffusion and sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) before and after enzymatic cleavage with trypsin. A common antigen in A particles was detected by antisera prepared against purified intracytoplasmic A particles, purified mouse mammary tumor virus (MMTV), and a purified MMTV core polypeptide (p28). Despite this correlation, no SDS--polyacrylamide band migrating at p28 was observed in purified intracytoplasmic A particles. However, after incubation with trypsin, A particles subjected to SDS--PAGE produced only two polypeptide bands. They were observed at p28 and p15-10. Ouchterlony analysis of the trypsin-cleaved A particles revealed no alteration in the antigenicity of the particles. These results suggested that some structural components of intracytoplasmic A particles are polypeptide precursors of MMTV core proteins.

Animals↗