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Biomedical subjects

R Carroll

Publications and source records attributed to R Carroll.

At least 19 recordsLinked to original sources
PubMed1992

Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3.

Experiments using recombinant vaccinia viruses expressing rat proinsulin I coinfected into COS-7 cells with recombinant vaccinia virus expressing human furin, human PC2, mouse PC3 (subtilisin-related proprotein convertases 1-3, respectively), or yeast Kex2 indicate that in this system both Kex2 and furin produce mature insulin, whereas PC2 selectively cleaves proinsulin at the C-peptide-A-chain junction. This is a property consistent with its probable identity with the rat insulinoma granule type II proinsulin processing activity as described by Davidson et al. [Davidson, H. W., Rhodes, C. J. & Hutton, J. C. (1988) Nature (London) 333, 93-96]. PC3 generates mature insulin but cleaves preferentially at the proinsulin B-chain-C-peptide junction. This pattern of cleavage by PC3 is similar, but not identical, to that of the highly B-chain-C-peptide junction-selective type I activity as described by Davidson et al., perhaps due to the presence of a P4 arginine residue near the C-peptide-A-chain junction unique to the rat proinsulins. These results along with data presented on the expression of both PC2 and PC3 in islet beta cells strongly support the conclusion that these proteases are involved in the conversion of proinsulin to insulin in vivo.

Amino Acid Sequence↗
PubMed1992

Activation of lipoprotein lipase in cardiac myocytes by glycosylation requires trimming of glucose residues in the endoplasmic reticulum.

Incubation of cycloheximide-treated cardiac myocytes results in a time-dependent increase in cellular and heparin-releasable lipoprotein lipase (LPL) activities. N-Methyldeoxynojirimycin (1 mM) and castanospermine (100 micrograms/ml), inhibitors of glucosidases in the endoplasmic reticulum (ER), prevented the increase in cellular LPL activity. The glucosidase inhibitors did not influence the synthesis or turnover of LPL protein. Therefore activation of LPL by glycosylation in cardiac myocytes requires the trimming of glucose residues in oligosaccharide chains by glucosidases of the ER.

1-Deoxynojirimycin↗
PubMed1992

Inhibition of myocardial lipoprotein lipase by U-57,908 (RHC 80267).

U-57,908 (RHC 80267) was shown to inhibit lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts; the concentrations required for inhibition to 50% of control activity were 1.1 microM and 2.5 microM for myocyte homogenates and a post-heparin medium preparation, respectively. The inhibition of LPL activity by U-57,908 was not changed when the concentration of the triolein substrate and apolipoprotein CII activator in the assay was reduced. The availability of U-57,908 as a potent and selective LPL inhibitor may provide a useful experimental approach in studies on lipoprotein metabolism.

Animals↗
PubMed1992

Inhibition of human immunodeficiency virus type 1 Tat activity by coexpression of heterologous trans activators.

We examined the mechanism of Tat-mediated trans activation through competition experiments employing Tat proteins of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV). EIAV Tat, as well as chimeric EIAV/HIV-1 Tat proteins, inhibited HIV-1 Tat-mediated trans activation in a cell-type-dependent fashion. Furthermore, these proteins inhibited trans activation by Tat-bacteriophage R17 coat protein chimeras. Inhibition resulted from competition between activation domains of effectors and competitors for a limiting cellular cofactor. The context in which competitor activation domains were expressed contributed to the extent of inhibition. In transfected cells, EIAV Tat and all chimeric competitors were located primarily in the cytoplasm, whereas HIV-1 Tat was primarily located in the nucleus. These data are consistent with a model for trans activation in which the activation domain of Tat associates with and conveys a cellular factor to the transcription complex via the trans-acting-responsive element (TAR).

Amino Acid Sequence↗
PubMed1991

A minimal lentivirus Tat.

Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of bacteriophage R17 and tested on the long terminal repeat of EIAV, where TAR was replaced by the R17 operator, the target of the coat protein. This independent RNA-tethering mechanism mapped activation domains of Tats from HIV-1 and EIAV to 47 and 15 amino acids and RNA-binding domains to 10 and 26 amino acids, respectively. Thus, a minimal lentivirus Tat consists of 25 amino acids, of which 15 modify viral transcription and 10 bind to the target RNA stem-loop.

Amino Acid Sequence↗
PubMed1991

Identification of lentivirus tat functional domains through generation of equine infectious anemia virus/human immunodeficiency virus type 1 tat gene chimeras.

The structural regions that comprise the functional domains of lentivirus Tat proteins were examined. Chimeric tat genes and chimeric viral promoters were constructed between the distantly related human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV). These exchange experiments revealed that the EIAV Tat-responsive element recognition domain is formed by two distinct structural regions. Activation domains of both HIV-1 and EIAV Tat contain a conserved core element, but at least HIV-1 Tat requires the presence of additional structural regions. The interchangeable nature of Tat activation domains suggests that these domains act through a common or ubiquitous cellular transcription factor.

Amino Acid Sequence↗
PubMed1991

Recurrent ovarian carcinoma: presentation as idiopathic thrombocytopenic purpura and a splenic mass.

We report a case of a 38 year old female who was treated for a Stage IIIb serous cystadenocarcinoma of the ovary with cytoreduction, combination chemotherapy, negative second look laparotomy, and adjuvant chemotherapy, who eight months later presented with Idiopathic Thrombocytopenic Purpura (ITP) and an isolated splenic recurrence. Review of the literature shows only four other cases of gynecologic malignancy which exhibited this pattern of recurrence. This case is the first where the primary lesion was an ovarian carcinoma and the patient presented with thrombocytopenia.

Adult↗
PubMed1990

The immunosuppressive action of FK506. In vitro induction of allogeneic unresponsiveness in human CTL precursors.

FK506 is an unusually potent new immunosuppressive agent that inhibits T cell-mediated immunity in vivo and in vitro. In these studies we sought to further elucidate the immunosuppressive mechanism of action of FK506 on human allogeneic MLR-induced CTL activation. FK506 induced suppression of cell-mediated lympholysis by PBMC was optimal at 1-2-nM concentrations, if added at the initiation of 6 day CML cultures. The sensitivity to suppression decreased with time, and fully differentiated effectors were resistant to inhibition by FK506. Suppression of CML was not reversed by washing the cultures, adding exogenous IL-2, or restimulating with fresh cells. Pretreatment of unfractionated or adherent allogeneic PBMC with FK506 blocked the stimulating activity of these cells. Furthermore, addition of FK506-treated stimulator cells to cocultures containing untreated responder and stimulator cells resulted in suppression of CML. The inhibition in the cocultures was greatest if the FK506-pretreated cells were autologous to the original stimulator, suggesting a relative specificity in the suppression obtained under these conditions. These studies suggest that, in addition to suppressing the response of alloreactive CTL precursors, FK506 reduces the ability of irradiated allogeneic PBMC to induce CTL generation.

Anti-Bacterial Agents↗
PubMed1979

[Ultrasonography of the pancreas. Diagnostic problems and findings in cases of solid pancreatic masses (author's transl)].

By using rigourous examination techniques and interpretive criteria, ultrasonography of the pancreas can, in many cases, confirm the etiological diagnosis of solid pancreatic masses. Factors influencing diagnosis are the volume and shape of the pancreas, the ultrasound structure, the attenuation of ultrasounds, the outline of the pancreas, and the effect on neighbouring structures. The association of signs is often characteristic and can differentiate benign from malignant masses.

Acute Disease↗
PubMed1978

Promotion of monolayer formation in cultured whole pancreatic islets by 3-isobutyl-1-methylxanthine.

Normal adult rat islets usually remained intact and encapsulated, even after many days in culture. In contrast, islets cultured in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 mM) attached more readily to the surface of plastic culture dishes and almost uniformly formed monolayers of endocrine cells. The mechanism of this effect is not known but presumably involves increases in cellular cyclic AMP content. Fibroblast growth did not appear to be stimulated by the inhibitor. These adult pancreatic endocrine monolayer cultures can be produced readily and provide useful preparations for further morphological and biochemical studies of factors affecting the differentiation, growth, and regenerative capacity of islet cells.

Animals↗
PubMed1978

A comparison of depression and physical illness in men and women.

A limited self-rating depression scale given to male and female factory workers indicated that subclinical depressive symptoms were correlated with visits to the factory health service for females and with absenteeism from work for males. In general, the females acknowledged more depression symptoms.

Absenteeism↗