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J H Johnson

Publications and source records attributed to J H Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1990

The high Km glucose transporter of islets of Langerhans is functionally similar to the low affinity transporter of liver and has an identical primary sequence.

The liver has been shown to contain a facilitated diffusion glucose transporter with high Km for glucose that is structurally distinct from the low Km glucose transporters found in most other tissues. We find that 3-O-methyl glucose is greater than 90% equilibrated across dispersed islet cells within 60 s, consistent with a facilitated diffusion transport mechanism. L-Glucose uptake was minimal throughout the time course, indicating stereospecificity. Measurement of glucose transport over a range of 3-O-methyl glucose concentrations from 0.05 to 60 mM revealed the presence of a component of glucose transport with an apparent Km of 17 mM, a value essentially identical to that previously reported for liver. Interestingly, a second component of glucose transport was also observed with an apparent Km of 1.4 mM, as has been reported for other tissues such as erythrocytes that are known to contain the "HepG2" or "erythroid/brain" type glucose transporter. Further evidence for the existence of two transport components is provided by the observation that a low concentration of cytochalasin B (0.4 microM) completely inhibits the low Km transport activity but has no effect on the high Km transporter. The kinetic similarity of high Km glucose transport in liver and islets is readily understood in light of our structural analysis. Sequence analysis of cDNA clones indicates that the liver and islet glucose transporters have identical sequences and, thus, are the products of the same gene.

3-O-Methylglucose↗
PubMed1990

Inhibition of glucose transport into rat islet cells by immunoglobulins from patients with new-onset insulin-dependent diabetes mellitus.

Because glucose-stimulated insulin secretion is selectively impaired during the development of insulin-dependent diabetes mellitus (IDDM), we tested the possibility that the glucose transporter of pancreatic islet beta cells is a target of the autoimmune process in patients with IDDM. We measured the uptake of 3-O-methyl-beta-D-glucose by dispersed islet cells from rats after a 15-minute incubation with purified IgG from 27 patients with newly diagnosed IDDM, 28 normal subjects, and 5 patients with non-insulin-dependent diabetes mellitus (NIDDM). The IgG fractions from 26 of the 27 patients with IDDM (96 percent), but from none of the 5 patients with NIDDM, reduced the initial rates of 3-O-methyl-beta-D-glucose uptake to at least 1 SD below the mean of the rates observed in the presence of IgG fractions from normal subjects (P less than 0.001). In contrast, the uptake of L-leucine by islet cells was not affected by any of the IgG fractions. The inhibitory activity of IgG from the patients with IDDM was abolished by preincubation with islet cells and membranes from hepatocytes, which contain the same glucose transporter as beta cells, but not with erythrocytes, which do not contain this transporter. We conclude that IgG from patients with IDDM of recent onset, but not from those with NIDDM, inhibits glucose uptake by rat islet cells. The results are consistent with the presence of an antibody against a protein involved in glucose transport by beta cells that would thereby impair glucose-stimulated insulin secretion.

3-O-Methylglucose↗
PubMed1990

Clinical safety of flurbiprofen.

Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid arthritis, osteoarthritis, and other painful musculoskeletal conditions. In these studies serious upper gastrointestinal ADRs occurred in flurbiprofen-treated patients at less than one half the rate seen in aspirin-treated patients. The incidence of serious urinary tract ADRs was lower with flurbiprofen than with aspirin. The flurbiprofen group had no serious clinical ADRs related to the hemic/lymphatic system. The most common laboratory abnormality was a decrease in hematocrit, which occurred less often than in the aspirin group. We also evaluated serious flurbiprofen-related ADRs in 4370 patients in a variety of other studies and reviewed published reports of flurbiprofen clinical trials and case reports. These reviews showed no additional, unanticipated patterns of intolerance. These clinical safety data indicate that in the doses studied, flurbiprofen is a well tolerated agent for patients requiring nonsteroidal antiinflammatory drug therapy.

Adult↗
PubMed1990

Regulation of beta-cell glucose transporter gene expression.

It has been postulated that a glucose transporter of beta cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, we subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated beta-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia (glucose at 29 +/- 5 mg/dl), GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days (blood glucose at 57 +/- 7 mg/dl vs. 120 +/- 10 mg/dl in saline-infused control rats), GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively (P = 0.001). After 12 days (glucose at 54 +/- 8 mg/dl), GLUT-2 mRNA signal density was undetectable whereas proinsulin mRNA was reduced by 51%. After 12 days of hypoglycemia, the Km for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high Km glucose transporter in beta cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, we also infused animals with 50% (wt/vol) glucose for 5 days (glucose at 200 +/- 50 mg/dl). Hyperglycemic clamping increased GLUT-2 mRNA by 46% (P = 0.001) whereas proinsulin mRNA doubled (P = 0.001). We conclude that GLUT-2 expression in beta cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis.

Animals↗
PubMed1990

Evidence that down-regulation of beta-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia.

Non-insulin-dependent diabetes mellitus (NIDDM) is attributed to a failure of pancreatic beta cells to maintain insulin secretion at a level sufficient to compensate for underlying insulin resistance. In the ZDF rat, a model of NIDDM that closely resembles the human syndrome, we have previously reported profound underexpression of GLUT-2, the high-Km facilitative glucose transporter expressed by beta cells of normal animals. Here we report that islets of diabetic rats exhibit a marked decrease in the volume of GLUT-2-positive beta cells and a reduction at the electron-microscopic level in the number of GLUT-2-immunoreactive sites per unit of beta-cell plasma membrane. The deficiency of GLUT-2 cannot be induced in normal beta cells by in vivo or in vitro exposure to high levels of glucose nor can it be prevented in beta cells of prediabetic ZDF rats by elimination of hyperglycemia. We conclude that this dearth of immunodetectable GLUT-2 in NIDDM is not secondary to hyperglycemia and therefore that it may well play a causal role in the development of hyperglycemia.

Animals↗
PubMed1990

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. I. Taxonomy, fermentation, isolation, physico-chemical and biological characterization.

Janthinocins A, B and C are novel antibacterial agents produced by Janthinobacterium lividum. They were isolated from fermentation broths and characterized by UV, IR, NMR and mass spectroscopy. They are cyclic decapeptide lactones with marked activity against aerobic and anaerobic Gram-positive bacteria and are 2 to 4 times more potent in vitro than vancomycin. Janthinocins A and B were also found to be effective in a Staphylococcus aureus systemic infection in mice.

Animals↗
PubMed1990

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. II. Structure elucidation.

The structures of janthinocins A, B and C, three novel macrocyclic peptide lactone antibiotics isolated from fermentations of Janthinobacterium lividum, were determined. The janthinocins are of particular interest because they contain three amino acid residues that have not previously been reported in natural products: Each contains erythro-beta-hydroxy-D-leucine while janthinocins A and B also contain beta-hydroxytryptophan and beta-ketotryptophan, respectively.

Amino Acid Sequence↗
PubMed1990

The context of migration: the example of Ireland in the nineteenth century.

"A classic case where out-migration interacted with many other geographical phenomena is provided by rural Ireland in the nineteenth century. The apparent turning point was the Great Famine of the 1840s, but the areas with the greatest suffering from starvation did not necessarily show the greatest population decline, suggesting that other forces were active. Considerable economic and social changes were already taking place before the Famine: fertility was being reduced, later marriage was becoming established and considerable emigration was already taking place. Immediately after the Famine those areas which had been hardest hit often reverted to pre-Famine conditions and did not show strong population decline until the 1870s. The Famine was a most serious event, but the modernization of Irish rural life, which linked emigration with changes in family structure, agriculture and population numbers, was more important in bringing about geographical change."

Conservation of Natural Resources↗
PubMed1990

Daily stress and recurrence of genital herpes simplex.

It is widely believed that emotional stress triggers recurrences of both oral and genital herpes simplex virus. On a daily basis, we studied 64 subjects prospectively for 1 to 3 months; all subjects had at least one culture-proved recurrence of genital herpes simplex virus type 2 before or during the study. All subjects filled out a questionnaire that measured psychological/emotional stress in six areas: physical health, relations with friends, relations with family, relations with sex partner(s), financial, and vocation/education. These questionnaires were mailed back to us daily. Data were analyzed by General Linear Models analysis of variance to compare stress reported on each of the 6 days before a recurrence with that on days during or after a recurrence, as well as days not temporally related to recurrence. Under these conditions, in which retrospective bias was minimized, there was no significant increase in psychological/emotional stress on any day in any area preceding a recurrence of genital herpes simplex virus.

Adult↗
PubMed1989

Increases in Na+,K+-ATPase activity of erythrocytes and skeletal muscle after chronic ethanol consumption: evidence for reduced efficiency of the enzyme.

Increased Na+,K+-ATPase activity observed after chronic ethanol consumption has been examined to determine whether the increase is due to changes in the kinetic properties of the enzyme or increases in the amount of enzyme in the membranes examined. In skeletal muscle and erythrocyte ghosts from rat, as well as from humans, increased Na+,K+-ATPase activity in ethanol-consuming individuals was not accompanied by an increase in the number of ouabain binding sites. In studies with intact human erythrocytes, similar ouabain-sensitive 22Na+ and 86Rb+ pumping rates were observed between normal and ethanol-consuming individuals and the Na+ to Rb+ pumping ratio was found to be 1.5 in all cases. However, ouabain-sensitive lactate plus Pi formation was increased in cells from alcoholic individuals. Thus these data suggest that increased enzyme activity may be due to a kinetic alteration of the Na+,K+-ATPase and that the enzyme may be less efficient in coupling ion pumping to ATP hydrolysis than the enzyme in normal cells.

Adult↗
PubMed1989

Growth hormone (GH) secretion in the pituitary-grafted male rat: in vivo effects of GH-releasing hormone and isoproterenol and in vitro release by individual somatotropes.

Although the pituitary-grafted rat is a classic model of chronic PRL excess, the presence of somatotropes in grafted pituitary tissue indicates a potential for GH secretion. The current study was designed to investigate GH-releasing hormone (GRH)-induced GH secretion and beta-adrenergic inhibition of GH release in animals bearing ectopic pituitary tissue free from hypothalamic control. Positive findings with regard to these in vivo experiments led us to an initial determination of GH secretion by individual somatotropes from transplanted pituitary tissue. In litters of 10 30-day-old Fisher rats, 2 male animals received subcapsular renal grafts of 3 littermate pituitary glands each. Thirty-five days after grafting, 1 group received saline (SAL) followed by GRH, and the other received the beta-adrenergic agonist isoproterenol (ISO) followed by GRH. Blood samples were taken before and after SAL or ISO treatment, GRH was then infused, and sampling was continued. Plasma was assayed for GH and PRL, and the reverse hemolytic plaque assay was used to determine GH release by individual somatotropes from transplanted pituitary tissue. Plasma PRL was clearly elevated in pituitary-grafted compared to muscle-grafted animals, but there was no difference in either body weight gain or basal GH levels between the groups. As shown previously, ISO itself induced a brief release of GH due to its direct effect on the pituitary gland. The GH response to GRH was greater in pituitary-grafted animals than in muscle-grafted controls after both SAL and ISO. GRH-induced GH release was suppressed by ISO pretreatment in muscle-grafted animals, but not in pituitary-grafted animals. The reverse hemolytic plaque assay unequivocally showed that transplanted pituitary tissue was capable of tonic as well as GRH-stimulated GH release. These results demonstrate that despite similar basal GH levels, animals bearing pituitary grafts release significantly greater amounts of GH in response to GRH. The evidence for GH secretion by individual somatotropes from transplanted pituitary tissue directly shows the grafted tissue to be a source of GRH-stimulated GH. The lack of beta-adrenergic inhibition of GRH-induced GH release in pituitary-grafted animals is consistent with the hypothesis that beta-adrenergic inhibition of GRH-induced GH secretion is mediated by an effect on the hypothalamus.

Animals↗
PubMed1989

Stability of esmolol hydrochloride and sodium nitroprusside in intravenous admixtures.

The stability of esmolol hydrochloride and sodium nitroprusside in an admixture containing both drugs was studied. Solutions containing sodium nitroprusside in a final concentration of approximately 200 micrograms/mL and esmolol hydrochloride in a final concentration of 10 mg/mL in 5% dextrose injection were prepared in a 250-mL volumetric flask. The flask was wrapped with a light-protective cover, stored at ambient room temperature (15-30 degrees C), and protected from light. All experiments were conducted in triplicate with samples taken at 0, 2, 4, 8, and 24 hours. Testing included measurement of pH and absorbance at 400 and 600 nm. High-performance liquid chromatography was used to measure esmolol hydrochloride and sodium nitroprusside concentrations. No changes were observed in the physical appearance, pH, or absorbance of the admixtures. Neither the esmolol hydrochloride nor the sodium nitroprusside concentrations varied by more than 4% during the study. Under the conditions studied, esmolol hydrochloride is compatible with sodium nitroprusside in an admixture containing both drugs.

Adrenergic beta-Antagonists↗
PubMed1988

Differences in the performances of baccalaureate, associate degree, and diploma nurses: a meta-analysis.

The findings of 139 studies of nurses educated in one of three basic nursing education programs (associate degree, diploma, and baccalaureate degree) were synthesized using meta-analysis. The results indicated significant differences between professional (BSN) and technical (AD and diploma) nurses on measures of nurse performance. Measures resulting in larger effects for professional nurses included communication skills, knowledge, problem-solving, and professional role. No differences resulted from studies of nurses from the two technical programs, AD and diploma. Further analyses indicated that the effects could not be solely attributed to substantive and methodological features of the studies. However, the hospital setting where a study was conducted and years of nursing experience decreased the size of the effect. The results of the meta-analysis have implications for policy development about educational preparation and for service expectations of professional and technical nurses.

Clinical Competence↗
PubMed1988

Beta-adrenergic stimulation of growth hormone (GH) release in vivo, and subsequent inhibition of GH-releasing factor-induced GH secretion.

In vivo and in vitro studies of beta-adrenergic influences on GH secretion have produced apparently conflicting data in which the in vivo effect seems to be inhibitory and the in vitro effect to be stimulatory. The present studies were designed to observe the in vivo effect of isoproterenol (ISO), a beta-adrenergic agonist, on 1) GH release during a brief interval after intraatrial infusion, and 2) GH release in response to GRF infused 10 min after ISO. ISO was found to stimulate GH release in both intact and hypothalamus-lesioned animals within 2 min after infusion, but GH returned to control levels within 10 min. ISO also profoundly inhibited the release of GH in response to GRF. Pretreatment of animals with somatostatin (SRIF) antiserum prevented the inhibitory action of ISO on GRF-induced GH release. No change in peripheral levels of SRIF was detected. Also, there was no suppression of GRF-induced GH release by ISO when the treatments were applied in vitro to dispersed perifused pituitary cells. These data show that beta-adrenergic systems can stimulate a rapid but brief release of GH in vivo, and that the subsequent inhibitory action on GRF-induced GH release might be by means of SRIF release.

Adrenergic beta-Agonists↗