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Biomedical subjects

J Ellis

Publications and source records attributed to J Ellis.

At least 253 records · Page 14Linked to original sources
PubMed1990

Hepatic steatosis during convalescence from influenza B infection in ferrets with postprandial hyperinsulinemia.

The possibility that postprandial hyperinsulinemia could play a role in the development of hepatic lipid disturbances during convalescence from influenza B infection was explored in the ferret as a possible model of the steatosis of Reye's syndrome. Postprandial hyperinsulinemia was produced by feeding young ferrets glucose/water and a regular diet (glucose-treated group), as reflected by the mean serum insulin levels attained, which were 57 and 135 microU/ml during control and postinfluenza periods, respectively. By comparison, ferrets fed water and a regular diet (untreated group) had mean insulin levels of 19 and 22 microU/ml, while postprandial glucose levels were comparable in the two groups of animals for each period. In contrast to untreated animals, grossly visible fatty livers were found in glucose-treated ferrets during convalescence. The total lipid content of these livers had doubled compared with preinfection samples and compared with livers of untreated ferrets. By electron microscopy hepatic mitochondria showed striking changes with diminution of matrix density and reduction in cristae surface area only in convalescent samples from glucose-treated animals. Serum free fatty acid (FFA) levels were considerably higher in the glucose-treated animals during fasting before influenza and also after feeding during convalescence. Serum triglyceride (TG) levels were also high during convalescence in the glucose-treated group. Adipose tissue lipoprotein lipase activities were similar between groups, but hormone-sensitive lipase activity was twelvefold higher in glucose-treated ferrets before and after influenza B. These findings indicate that for a given stimulus, glucose-treated ferrets would mobilize more FFA than untreated ferrets. The total capacity for beta-oxidation of FA by the mitochondrial pathway was identical in all groups of animals. Total carnitine palmitoyl transferase (CPT) activity was the same in both control groups, but was significantly diminished in glucose-treated animals during convalescence. As CPT regulates the entry of FA into the mitochondrial matrix, its reduction in response to higher insulin concentrations would limit the oxidation of FA and stimulate TG accumulation. Therefore, the accumulation of lipid in the liver in this model is regarded to have been caused by the simultaneous occurrence of increased lipolysis and increased hepatic TG synthesis owing, in part, to diversion of activated FA by CPT, which is reduced in activity due to the regulatory action of insulin. These findings may have pathophysiologic relevance for the lipid changes that occur in Reye's syndrome and to fatty liver formation in hyperinsulinemic states.

Adipose Tissue↗
PubMed1990

The influence of physician specialty on housecalls.

Despite growing numbers of frail elderly, physicians make housecalls infrequently. We surveyed 1000 primary care physicians from Virginia regarding their attitudes and knowledge about housecalls, and 389 completed questionnaires (response rate, 52%): 185 family physicians, 36 general practitioners, 101 general internists, and 63 subspecialists. Despite similar proportions of homebound patients and practice demographics, family physicians (69%) and general practitioners (63%) were significantly more likely than either internists (53%) or subspecialists (37%) to make routine housecalls. Although all four groups thought the fee was rarely a motivation, internists and subspecialists suggested larger increases. Also, internists and subspecialists were less likely than family physicians or general practitioners to increase housecalls with increased payment. Internists and subspecialists also were more likely than family physicians or general practitioners to report that housecalls were often unnecessary, not "enjoyable," "inefficient," and unimportant. While improved reimbursement may lead to increased housecalls by family physicians, future strategies should include efforts to change internists' attitudes.

Aged↗
PubMed1990

Contrast echocardiography: a method to visualize changes in regional myocardial perfusion in the dog model for CABG surgery.

The ability of contrast echocardiography to assess regional myocardial perfusion during cardiopulmonary bypass in a dog model for coronary artery bypass surgery was evaluated. Sonicated Renograffin-76 microbubbles (meglumin diatrigoate and sodium diatrigoate) were injected into an aortic root proximal to an aortic occlusion clamp root while dogs were on cardiopulmonary bypass, with the heart arrested in diastole. Echocardiographic contrast-enhanced regions of myocardial perfusion were easily visualized. Differences in contrast-enhanced myocardial regions depended on coronary artery occlusion or patency. The contrast-enhanced images of myocardial perfusion showed that, for a given myocardial segment of the supplying vessel, the presence or absence of contrast effect reliably predicted vessel occlusion or patency (P less than .01). In the future contrast echocardiography may allow the direct assessment of regional myocardial perfusion in the operating room.

Animals↗
PubMed1989

Processing and presentation of insulin. II. Evidence for intracellular, plasma membrane-associated and extracellular degradation of human insulin by antigen-presenting B cells.

To study the biochemistry of processing of a soluble protein Ag by an APC, we investigated how 125I-labeled human insulin (HI) is processed in situ by TA3 mouse hybridoma B cells. Fractionation of TA3 cells into their extracellular, plasma membrane-associated and intracellular compartments coupled with the use of HPLC enabled us to analyze several peptides derived from each compartment. One HI peptide found in all three compartments is composed of residues A1-A14 disulfide-linked to B7-B26 (A1-A14/B7-B26). The presence of this peptide in the extracellular compartment likely resulted from digestion of HI by an enzyme(s) released from the APC. Extracellular processing of radiolabeled HI was inhibited completely by unlabeled HI and N-ethylmaleimide, an inhibitor of a previously described insulin-specific protease, partially by lysozyme but not by BSA or OVA. This suggests that the enzyme involved in the extracellular processing of insulin is relatively insulin-specific and gives rise to the A1-A14/B7-B26 peptide. The processing of HI both at the plasma membrane and intracellularly was inhibited by chloroquine, monensin, and NH4Cl, suggesting that both intracellular pH changes and endocytic and exocytic events may be required for these compartments to process insulin. Kinetic analyses revealed that the processing of insulin into the A1-A14/B7-B26 peptide is first detected at the plasma membrane then intracellularly and finally in the extracellular compartment. This unlabeled A1-A14/B7-B26 peptide was purified from the extracellular compartment of TA3 APC by HPLC; when presented by TA3 APC this peptide effectively stimulated pork insulin (PI/I-Ad) specific Th cells to secrete IL-2. These data, taken together with the identification of another processed insulin peptide, A7-A11/B7-B26, have enabled us to elucidate the first steps in the biochemical pathway(s) of processing of insulin as an Ag in a B cell APC.

Animals↗
PubMed1989

Cloning of a polymorphic DNA fragment from the genome of Leishmania donovani.

Recombinant DNA clones, containing highly repetitive DNA sequences, have been isolated from a Leishmania donovani genomic DNA library prepared in the replacement vector lambda gt.WES.lambda B. Two clones, probably telomeric in location, have been characterised and show a restriction fragment size polymorphism. Evidence is presented which suggests that L. donovani is diploid for this cloned genomic locus.

Animals↗
PubMed1989

Translocation and activation of protein kinase C in striatal neurons in primary culture: relationship to phorbol dibutyrate actions on the inositol phosphate generating system and neurotransmitter release.

The actions of the tumor-promoting phorbol ester phorbol dibutyrate were examined, under identical physiological conditions, on three distinct cellular processes in striatal neurons: the distribution of protein kinase C, the carbachol-stimulated generation of [3H]inositol monophosphate, and the KCl-evoked release of gamma-[3H]aminobutyric acid ([3H]GABA). Phorbol dibutyrate induced a rapid (complete in 5 min), dose-dependent, entirely reversible (t0.5 = 15 min) translocation of protein kinase C from cytosol to membrane. On longer exposure to phorbol dibutyrate, membrane-associated protein kinase C returned toward the control level, and total cellular enzyme activity declined markedly. Phorbol dibutyrate also induced the dose-dependent attenuation of carbachol-stimulated [3H]inositol monophosphate production and potentiation of KCl-evoked release of [3H]GABA. The translocation of protein kinase C and the potentiation of KCl-evoked [3H]GABA release were both rapidly reversed following washout of phorbol dibutyrate. In addition, for both processes, the effect of a 1-h exposure to phorbol dibutyrate was markedly less than that observed following a 5-min exposure to the agent. In direct contrast, inhibition of carbachol-stimulated [3H]inositol monophosphate production was not rapidly reversed following washout of phorbol dibutyrate and was actually more pronounced following a 1-h exposure, compared with a 5-min exposure. These findings indicate that some, but not all, of the actions of phorbol dibutyrate are closely associated with the translocation of protein kinase C in striatal neurons in primary culture.

Animals↗
PubMed1989

Retrovirus vectors containing an internal attachment site: evidence that circles are not intermediates to murine retrovirus integration.

Murine cells were infected with a retrovirus vector containing a defective native attachment (att) site, an internal att site, and a neo gene. Analysis of the proviruses by virus rescue and Southern blots demonstrated that internal att sites were not utilized for integration and could not complement defects in the native site. These data suggest that murine retroviruses do not integrate in vivo through tandem long terminal repeat circular DNA intermediates.

Animals↗
PubMed1989

Gene targeting with retroviral vectors: recombination by gene conversion into regions of nonhomology.

We have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418r cell per 3 x 10(6) infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

Animals↗
PubMed1989

Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.

The in vitro responses of T cells from 13 insulin-nonresistant and 1 immunologically insulin-resistant (IIR) type I diabetes patients to sulfated beef insulin (SBI) were analyzed. Insulin A-loop specific CD4+ T cells from these patients did not respond to SBI. After 1 yr of treatment with SBI the IIR patient's T cell and antibody responses to beef, pork, and human insulin progressed from very high to nondetectable levels. This occurred in parallel to the appearance of her insulin-specific CD8+ T cells, which inhibited the response of her A-loop-specific CD4+ T cells to insulin. A transient increase in her CD8+ anti-insulin antibody activity coincided with a relative lack of her CD8+ T cell activity. CD8+ T cells that regulate T cell responsiveness to insulin are probably present but difficult to detect in most type I diabetes patients. These T cells were identified in only 2 of 13 insulin-nonresistant patients who presented with lipoatrophy and insulin allergy, respectively, and who possessed high-titered, anti-insulin antibodies. Our data demonstrate that CD8+ T cells play an important role in controlling peripheral tolerance to insulin and may abrogate IIR in a diabetic patient treated with SBI.

Adult↗
PubMed1989

The relationship of anxiety to depression in children and adolescents.

The relationship of anxiety to depression in children and adolescents has perplexed and preoccupied researchers and professionals in the field of child and adolescent psychiatry over the last two decades. This article illustrates this as it is demonstrated through epidemiologic, genetic, and biologic issues as well as environmental and developmental considerations and investigated procedures. The relevant literature is reviewed in depth, and the discussion on the inter-relatedness of the various factors, as they influence anxiety and depression, is brought forth.

Adolescent↗
PubMed1989

Gallamine exerts biphasic allosteric effects at muscarinic receptors.

Although gallamine and a number of other compounds have been reported to slow the rate of dissociation of labeled ligands, especially [3H]N-methylscopolamine (NMS), from muscarinic receptors of heart and brain, there has been some dispute as to whether the dissociation of [3H]quinuclidinyl benzilate (QNB) is subject to such allosteric regulation. The present studies were intended to determine whether past discrepancies might be due to differences between tissues. We have found that gallamine modulates the dissociation of [3H]QNB from muscarinic receptors of the heart in a biphasic manner. Low concentrations (micromolar) accelerate the rate of dissociation, whereas higher concentrations (millimolar) slow it; at about 0.1 mM, the two effects cancel each other. Similar results were obtained with muscarinic receptors from the brainstem, but gallamine had only marginal effects on the dissociation of [3H]QNB in the forebrain. On the other hand, verapamil exerts only monophasic effects (slowing) on the dissociation of both [3H]NMS and [3H]QNB from heart receptors and gallamine slows the dissociation of [3H]NMS to a similar extent in all three tissues. Thus, it appears that past discrepancies in the literature can be attributed to the tissues and concentrations of gallamine that were used. Furthermore, the biphasic effects of gallamine suggest that there are multiple allosteric regulatory sites associated with muscarinic receptors.

Allosteric Regulation↗
PubMed1988

T cell autoreactivity to insulin in diabetic and related non-diabetic individuals.

T cell autoreactivity to insulin in type I diabetic and related non-diabetic individuals was analyzed. Peripheral T lymphocytes from both insulin-treated diabetic and untreated non-diabetic members of four families were found to proliferate in vitro in response to human insulin. T cell autoreactivity to insulin therefore does not appear to be diagnostic of the onset of type I diabetes. Highest T cell responses to human insulin were usually detected in insulin-dependent type I diabetes patients treated with a mixture of beef and pork insulin than with self insulin, the greater the dose of animal insulin the higher the T cell response. The T cell repertoires for self insulin appear to be similar in diabetics and non-diabetics based on their patterns of T cell reactivity to beef insulin, port insulin, human insulin, and various peptide of human insulin. The autoreactive T cells analyzed recognize two conformational epitopes of human insulin formed by interactions between A chain and B chain residues. One epitope is associated with the A chain loop and is present in the A1-A14/B1-B16 peptide, and the other epitope consists mainly of B chain residues located in the A16-A21/B10-B25 peptide. These two epitopes are present in amphipathic alpha-helical regions of insulin. HLA-DR (DR3, DR4, and DR5) and HLA-DQ (DQw2/DQw3) Ag can restrict these T cell responses to human insulin epitopes. The ability to detect insulin-specific autoreactive T cells in healthy non-diabetic individuals supports the hypothesis that autoreactive lymphocytes do not necessarily elicit autoimmune disease if present in an environment in which their activity is immunoregulated.

Animals↗
PubMed1988

Generation of corticosteroid binder IB from binder II by a sulfhydryl dependent renal cytosolic factor.

It has long been debated whether binder IB represents a unique form of the glucocorticoid receptor or is derived from the larger molecular weight form, binder II, by limited proteolysis. Transformed glucocorticoid receptors in kidney, liver and mixed kidney/liver cytosols were examined using anion exchange and gel filtration chromatography. The transformed receptor in liver cytosols chromatographs as binder II on DEAE-Sephadex A-50 anion exchange columns and has a Stokes radius of approx 6.0 nm. The transformed receptor in kidney cytosols chromatographs as binder IB on DEAE-Sephadex A-50 anion exchange columns and has a Stokes radius of 3.0-4.0 nm (3.2 nm on agarose; 3.0-4.0 nm on Sephadex G-100). Using cytosols prepared from mixed homogenates (2 g kidney plus 8 g liver tissue), our experiments show that binder II is converted to a lower molecular weight form (Rs = 3.2 nm on agarose; Rx = 3.9 nm on Sephadex G-100) that is identical to binder IB in its elution position from DEAE-Sephadex anion exchange resin. Identical results are obtained using kidney/liver/cytosols mixed in vitro in which only the hepatic receptor, binder II, is labelled with [3H]TA. These results support the hypothesis that the renal receptor, binder IB, is a proteolytic fragment of binder II and does not represent a polymorphic form of the glucocorticoid receptor. The renal converting activity is dependent on free-SH for full activity but is insensitive to the protease inhibitors leupeptin, antipain, and PMSF. The conversion of hepatic binder II to binder IB in in vitro mixing experiments can be prevented if kidney cytosol is gel filtered on Sephadex G-25 and the eluted macromolecular fraction is adjusted to 10 mM EGTA (or EDTA) prior to mixing with the [3H]TA labelled hepatic cytosol.

Adrenalectomy↗
PubMed1988

Direct evidence for concomitant release of noradrenaline, adenosine 5'-triphosphate and neuropeptide Y from sympathetic nerve supplying the guinea-pig vas deferens.

Concomitant release of noradrenaline (NA) (using tritium labelling), adenosine 5'-triphosphate (ATP) (using the luciferin-luciferase firefly technique) and neuropeptide Y (using the enzyme-linked immunosorbant assay) during electrical stimulation of the guinea-pig vas deferens has been demonstrated. In addition it has been shown: (1) that release of NA and ATP is unaffected following selective desensitization of the P2 (ATP)-purinoceptor by alpha, beta-methylene ATP and (2) that total block of contractile responses of the vas deferens to nerve stimulation by a combination of prazosin and alpha, beta-methylene ATP does not reduce the release of NA and ATP. These results are consistent with the hypothesis that NA, ATP and neuropeptide Y are released as co-transmitters or modulators in sympathetic nerves supplying the vas deferens.

Adenosine Triphosphate↗
PubMed1988

Characterisation of a simple, highly repetitive DNA sequence from the parasite Leishmania donovani.

Repetitive DNA sequences of the Leishmania donovani genome have been identified by screening a recombinant DNA library made by cloning sheared genomic DNA into the vector pAT153. Bacterial clones containing a highly repetitive DNA sequence have been isolated. DNA sequencing has shown that this sequence is composed of tandem repeats of the sequence 5'-CCCTAA-3'. This sequence is identical to the telomeric repeats found in Trypanosoma brucei and hybridizes to all Leishmania chromosomes. In this study we show that there is considerable heterogeneity in the distribution and copy number of this repeat and associated hybridising sequences throughout the genomes of different Leishmania species.

Animals↗