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Biomedical subjects

J H Johnson

Publications and source records attributed to J H Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Cloning of the alpha 1 subunit of a voltage-dependent calcium channel expressed in pancreatic beta cells.

The isoforms of the alpha 1 subunits of voltage-dependent Ca2+ channels expressed in human pancreatic islets were identified by using a pair of degenerate oligonucleotide primers and the polymerase chain reaction (PCR) to amplify mRNAs encoding alpha 1 subunit-like sequences. The sequences of the PCR products indicate that islets express the heart-type alpha 1 subunit as well as a second isoform whose complete sequence has not been previously reported. The sequences of cloned cDNAs encoding the human beta-cell, or neuroendocrine-type, alpha 1 subunit indicate that it is composed of 2181 amino acids. It shares 68%, 64%, and 41% identity with the sequences of the alpha 1 subunits of rabbit heart, skeletal muscle, and brain, respectively, and is predicted to have a similar structure including four homologous domains composed of six membrane-spanning segments each. RNA blotting studies indicate that the beta-cell-type alpha 1 subunit is also expressed in brain as well as in the insulin-producing cell lines RINm5F and beta TC-3; however, it could not be detected by RNA blotting in a third cell line, HIT-T15. In situ hybridization studies revealed expression of beta-cell-type alpha 1 subunit mRNA in beta cells of rat pancreatic islets, implying that this protein may play a role in the regulation of insulin secretion.

Amino Acid Sequence↗
PubMed1992

Engineering of glucose-stimulated insulin secretion and biosynthesis in non-islet cells.

The high-capacity glucose transporter known as GLUT-2 and the glucose phosphorylating enzyme glucokinase are thought to be key components of the "glucose-sensing apparatus" that regulates insulin release from the beta cells of the islets of Langerhans in response to changes in external glucose concentration. AtT-20ins cells are derived from anterior pituitary cells and are like beta cells in that they express glucokinase and have been engineered to secrete correctly processed insulin in response to analogs of cAMP, but, unlike beta cells, they fail to respond to glucose and lack GLUT-2 expression. Herein we demonstrate that stable transfection of AtT-20ins cells with the GLUT-2 cDNA confers glucose-stimulated insulin secretion and glucose regulation of insulin biosynthesis and also results in glucose potentiation of the secretory response to non-glucose secretagogues. This work represents a first step toward creation of a genetically engineered "artificial beta cell."

Adrenocorticotropic Hormone↗
PubMed1992

Bronchovascular mucormycosis in the diabetic: an urgent surgical problem.

This report reviews the successful surgical experience with a diabetic patient with bronchial obstruction due to Mucorales infection. A review of the reported medical and surgical experience is included. The danger of a lethal pulmonary hemorrhage makes early surgical intervention mandatory.

Airway Obstruction↗
PubMed1992

Child temperament, maternal adjustment, and changes in family life style.

Child temperament has been implicated as a relevant factor in understanding parental adjustment. In a study of 77 mothers of 3- and 4-year-old children, difficult child temperament was found to be directly related to maternal distress, discomfort in the role of parent, poor spousal relationships, and negative changes in way of life. Quality and intensity of the child's mood were most predictive of these difficulties.

Adaptation, Psychological↗
PubMed1992

Pharmacokinetics and inflammatory fluid penetration of sparfloxacin.

A single 400-mg oral dose of sparfloxacin was given to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 52 h. The mean peak concentration in plasma of 1.6 micrograms/ml was attained at a mean time of 2.7 h postdose. The mean peak concentration in inflammatory fluid of 1.3 micrograms/ml was attained at a mean time of 5 h postdose. The mean elimination half-life in plasma was 17.6 h, and that in inflammatory fluid was 19.7 h. The overall penetration into inflammatory fluid was 117%. Urinary recovery within the first 52 h postdose was 8.8% of the administered dose. Our results indicate that a once-daily dosage of sparfloxacin should be adequate to treat systemic infections caused by most common bacterial pathogens.

Administration, Oral↗
PubMed1992

Roles of insulin resistance and beta-cell dysfunction in dexamethasone-induced diabetes.

The roles of insulin resistance and beta-cell dysfunction in glucocorticoid-induced diabetes were determined in Wistar and Zucker (fa/fa) rats. All Wistar rats treated with 5 mg/kg per d of dexamethasone for 24 d exhibited increased beta-cell mass and basal and arginine-stimulated insulin secretion, indicating insulin resistance, but only 16% became diabetic. The insulin response to 20 mM glucose was normal in the perfused pancreas of all normoglycemic dexamethasone-treated rats but absent in every diabetic rat. Immunostainable high Km beta-cell transporter, GLUT-2, was present in approximately 100% of beta-cells of normoglycemic rats, but in only 25% of beta cells of diabetic rats. GLUT-2 mRNA was not reduced. All Zucker (fa/fa) rats treated with 0.2-0.4 mg/kg per d of dexamethasone for 24 d became diabetic and glucose-stimulated insulin secretion was absent in all. High Km glucose transport in islets was 50% below nondiabetic controls. Only 25% of beta cells of diabetic rats were GLUT-2-positive compared with approximately 100% in controls. Total pancreatic GLUT-2 mRNA was increased twofold suggesting a posttranscriptional abnormality. We conclude that dexamethasone induces insulin resistance, whether or not it induces hyperglycemia. Whenever hyperglycemia is present, GLUT-2-positive beta cells are reduced, high Km glucose transport into beta cells is attenuated and the insulin response to glucose is absent.

Animals↗
PubMed1992

The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia.

Tumor necrosis factor (TNF) is a protein hormone implicated in the development of septic shock and other pathologic states. However, complexities inherent in detecting TNF synthesis by individual tissues have left the precise origins of this protein undefined. In addition, the possibility that localized TNF production may contribute to the pathogenesis of organ-specific diseases such as type I diabetes has not been explored in vivo. We have developed a transgenic mouse line bearing a reporter gene construct in which the TNF coding sequence and introns are replaced by a chloramphenicol acetyltransferase (CAT) coding sequence. In normal transgenic animals, CAT activity is expressed only in the thymus. When endotoxin is administered to the animals, CAT activity is also evident in kidney, heart, islets of Langerhans, spleen, lung, fallopian tubes, and uterus, but not in other organs. The biosynthesis of CAT in vivo correlated with tissue capacity to secrete TNF in vitro. Thus, TNF was secreted by all the tissues that expressed CAT, including lung, spleen, thymus, uterus/fallopian tubes, pancreatic islets, renal glomeruli, and cultured cardiac cells after exposure to endotoxin.

Animals↗
PubMed1992

Applicability of the Impact on Family Scale for assessing families with behaviorally difficult children.

The present paper reports a series of studies on the potential usefulness of the Stein and Riessman Impact on Family Scale for assessing the effects of behaviorally difficult children on their families. Subjects were parents of 54 clinic and 76 nonclinic children who completed a child behavior or child temperament questionnaire in addition to the Impact on Family Scale. Findings suggest that, while the scale was developed for assessing the influence of a physically ill child on the family, this general assessment approach may also have value in assessing family-related changes associated with having a child who is difficult to look after.

Adaptation, Psychological↗
PubMed1992

Lanomycin and glucolanomycin, antifungal agents produced by Pycnidiophora dispersa. II. Structure elucidation.

Two novel antifungal agents, lanomycin and glucolanomycin, as well as a biologically inactive degradation product, lanomycinol, were isolated from liquid fermentations of Pycnidiophora dispersa. All three compounds share an E,E,E-triene appended to a pyran ring. Lanomycin contains a glycine ester and glucolanomycin possesses a glucose unit attached to the glycine nitrogen. The structures, including absolute stereochemistry, were determined by spectroscopic analysis and partial chemical degradation. Both of the glycine containing compounds show activity against several pathogenic fungi in vitro.

Aminoglycosides↗
PubMed1992

Risk factors for heterotopic ossification in children and adolescents with severe traumatic brain injury.

Previous reports on the incidence of heterotopic ossification (HO) in children and adolescents with traumatic brain injury (TBI) have ranged from 3% to 20%. These studies mention HO briefly or address patient cohorts with coma more than three months. We reviewed the medical records of 90 children younger than 19 years old, who were comatose more than 24 hours after TBI. Mean followup was 33.1 months (range = 2 to 128 months). Incidence of HO was 14.4% (n = 13). One to five sites were involved, with hip and knee most frequent, followed by shoulder, elbow, and nonjoint sites. Children with HO were older than 11 years (relative risk [RR] = 18.85, confidence interval [CI] = 3.7, 95.7), had a greater length of coma (RR = 7.22, CI = 1.4, 37.1), and had a greater associated risk for poor functional outcome (RR = 2.89, CI = 1.02, 7.9) compared to those without RO. Multiple limb fractures showed a trend toward association with increased incidence of HO. Other factors, including gender, history of skull fracture, brain CAT scan findings, and presence of spasticity, were not predictive of HO. Eleven children were treated with etidronate, four with nonsteroidal antiinflammatory drugs, and one with surgery. Only three children had residual functional impairments attributed to the presence of HO.

Adolescent↗
PubMed1991

Analysis of neurotransmitter receptors mediating changes in LH release induced by electrical stimulation of the dorsal raphe nucleus in the rat.

We report studies of neurotransmitter and receptor species mediating the inhibition of LH release in ovariectomized (OVX) rats and stimulation in OVX estrogen-primed rats induced by electrical stimulation of the dorsal raphe nucleus (DRN). Attempts were made to block effects of stimulation of the DRN in groups of four to nine ovariectomized rats with or without priming with estradiol benzoate (EB) by pretreatment with the 5HT receptor antagonists ketanserin, methysergide, or metergoline; the alpha-adrenergic antagonist phenoxybenzamine; or the opiate antagonist naltrexone. Blood samples were collected via jugular cannulae from the unanesthetized rats at 10-min intervals before and during electrical stimulation of the DRN, and assayed by double antibody radioimmunoassay for LH. To test the effect of stimulation, data from animals in each treatment group were subjected to analysis of variance to obtain the contrast matrix including prestimulation and stimulation time points of interest. The contrast matrix was then used to construct an F ratio and thereby to evaluate the level of significance. In unprimed OVX rats the sustained decrease in plasma LH concentration during stimulation was prevented in rats pretreated with ketanserin or phenoxybenzamine. Methysergide pretreatment delayed the inhibitory effect of DRN electrical stimulation for 30 min, whereas metergoline and naltrexone were ineffective. In EB-primed animals the increase in plasma LH observed during stimulation was prevented in rats pretreated with metergoline, and reversed in those receiving naltrexone. Ketanserin limited the duration of the increase to 10 min, while phenoxybenzamine and methysergide had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Screening of murine monoclonal antibodies against living schistosomula of Schistosoma mansoni by radioimmunoassay.

A radioimmunoassay was developed to screen supernatants of murine monoclonal antibodies against surface antigens of living schistosomula of Schistosoma mansoni. Of 196 clones screened, 10% bound schistosomula. Of these, 74% bound only schistosomula. The remaining molecules also reacted with soluble adult worm antigens and soluble egg antigens as determined by enzyme-linked immunosorbent assay. Immunoblot analysis demonstrated that monoclonal antibody 204-3E4 reacted with a 68 kDa protein, a glycoprotein that induces substantial resistance against S. mansoni infection. Recognition of an 18 kDa antigen by 204-3F1 antibody was stage-specific with the antigen being expressed in cercariae, 3- and 24-h-old parasites but not 4-day, lung stage or adult worms. Monoclonal antibody 204-4E3 reacted with purified S. mansoni paramyosin. These data indicate that radioimmunoassay using living schistosomula is a rapid alternative method to identify murine hybridomas that secrete antibodies which react with surface antigens of S. mansoni.

Animals↗
PubMed1991

Prediction of maximal heart rate during a submaximal work test.

A multiple regression equation was developed utilizing submaximal ratings of perceived exertion and heart rate collected during a treadmill walking test to predict maximal heart rate (MHR). One hundred subjects were administered a modification of the Balke Treadmill test during which time submaximal ratings of perceived exertion (Borg Scale) and heart rate measurements were recorded. Subjects worked until volitional fatigue and maximal heart was recorded. A multiple regression equation was developed which did not require the subject to work at greater than 85% of MHR. The multiple regression equation is MHR = 108.461 + 0.5108 (RPE 15)-0.6570 (8HR) + 0.6075 (10HR)-0.2641 (age in years) with RPE 15 equal to the heart rate at a perceived exertion rating of 15 on the Borg Scale, 8HR equal to the heart rate at 8 minutes and 10HR equal to the heart rate at 10 minutes. It was found that the regression equation significantly improved the ability to predict MHR and represented a 28% improvement in the commonly used equation MHR = 220-age.

Adult↗
PubMed1990

Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes.

The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The beta cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.

3-O-Methylglucose↗
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↗