PubMed Health⌕ Search

Biomedical subjects

G J Johnson

Publications and source records attributed to G J Johnson.

At least 19 recordsLinked to original sources
PubMed1996

Specificity of G alpha q and G alpha 11 gene expression in platelets and erythrocytes. Expressions of cellular differentiation and species differences.

G alpha q and G alpha 11, members of the Gq family of G-proteins, transduce signals from receptors to the beta isoenzymes of phosphatidyl-inositol-specific phospholipase C (PI-PLC). The receptor specificity of these alpha subunits is unknown. G alpha q and G alpha 11 are ubiquitously expressed in tissues; however, there have been conflicting reports of the presence or absence of G alpha 11 protein in haematopoietic cells. Platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors activate PI-PLC via G alpha q, but the role of G alpha 11 is uncertain. To define their roles in platelet activation we studied G alpha q and G alpha 11 gene expression by immunotransfer blotting and by reverse transcription of mRNA followed by PCR (RT-PCR) and direct sequencing. An antiserum specific for mouse G alpha 11 failed to identify G alpha 11 in dog or human platelets or in dog liver, a tissue known to contain G alpha 11. RT-PCR performed with gene-specific primers demonstrated G alpha q mRNA, but not G alpha 11 mRNA, in normal human and mouse platelets and in thromboxane-sensitive and thromboxane-insensitive dog platelets. Studies of mouse and dog liver and human retina confirmed that the cDNA, primers and probes used could amplify and recognize G alpha 11 in other tissues. However, species-specific oligonucleotide primers and probes were essential to demonstrate G alpha 11, but not G alpha q, mRNA. Compared with mouse cDNA, dog and human G alpha 11 cDNA had twice as many nucleotide substitutions (approx. 12% compared with approx. 6%) as G alpha q, G alpha q mRNA was also found in mature erythrocytes but G alpha 11 mRNA was not identified, whereas both G alpha q and G alpha 11 mRNAs were found in bone marrow stem cells. Therefore G alpha 11 gene expression in haematopoietic cells is linked with cellular differentiation. The lack of G alpha 11 indicates that signal transduction from platelet TXA2/PGH2 receptors to PI-PLC occurs via G alpha q, and that G alpha 11 deficiency is not responsible for defective activation of PI-PLC in thromboxane-insensitive dog platelets. Despite the high degree of similarity that exists between G alpha q and G alpha 11, significantly greater species-specific variation in nucleotide sequence is present in G alpha 11 than in G alpha q. Cellular specificity and species specificity are important characteristics of these Gq family G-proteins.

Amino Acid Sequence↗
PubMed1996

Glaucoma in Mongolia. A population-based survey in Hövsgöl province, northern Mongolia.

OBJECTIVES: To determine the prevalence of glaucoma and suspect glaucoma, and to classify the cases detected according to mechanism. DESIGN: A population-based prevalence study. SETTING: Rural and urban locations in Hövsgöl province, northern Mongolia. PARTICIPANTS: Nine hundred forty-two (94.2%) of 1000 individuals 40 years of age and older were examined. MAIN OUTCOME MEASURE: Primary angle-closure glaucoma was diagnosed in subjects with previous acute or intermittent symptoms of angle closure and in individuals with an occludable angle and an intraocular pressure greater than 19 mm Hg or a glaucomatous visual field. RESULTS: The prevalence of manifest primary angle-closure glaucoma was 1.4% (14 subjects). The prevalence of gonioscopically occludable angles was 6.4% (64 subjects, including those with glaucoma). Primary open-angle glaucoma was diagnosed in 5 subjects (prevalence, 0.5%). As all these subjects were older than 60 years, the prevalence became 2.1% for this age group. Three cases (prevalence, 0.3%) of secondary open-angle glaucoma were detected. No cases of secondary angle-closure glaucoma were diagnosed. The prevalence of blindness was 1.2% (12 subjects), and primary glaucoma accounted for one third of these cases (4 subjects). CONCLUSIONS: We confirmed glaucoma as a major public health problem in northern Mongolia. Primary angle-closure glaucoma is more prevalent than primary open-angle glaucoma, supporting clinic-based data from other east Asian countries. Among the subjects examined, 97 (9.7%) had either manifest, latent, or suspect glaucoma. Neighboring populations may be similarly affected owing to a shared genetic heritage.

Adult↗
PubMed1996

Perceived overqualification and psychological well-being.

The relationship between perceived overqualification and psychological well-being was explored within the framework of stress-illness models, using multiple regression analysis. Data were collected from 179 male and 109 female members of a local midwestern chapter of the American Postal Workers Union. As expected, there was a significant, positive relationship between perceived overqualification and psychological well-being: The greater the perceived overqualification, the greater the psychological distress. The interaction between perceived overqualification and gender was not significant.

Adult↗
PubMed1996

A statewide, population-based time-series analysis of the outcome of ruptured abdominal aortic aneurysm.

OBJECTIVES: The purpose of this study was to perform the first statewide, population-based, time-series analysis of the frequency of ruptured abdominal aortic aneurysm (RAAA), to determine the outcomes of RAAA, and to assess the association of patient, physician, and hospital factors with survival after RAAA. The hypotheses of the study were as follows: 1) the rate of RAAA would increase over time and 2) patient, surgeon, and hospital factors would be associated with survival. BACKGROUND: Ruptured abdominal aortic aneurysm is a life-threatening emergency that presents the surgeon with a technically demanding challenge that must be met and surmounted in a short time if the patient is to survive. METHODS: Data were obtained from the following four separate data sources: 1) the North Carolina Hospital Discharge database, 2) the North Carolina American Hospital Association database, 3) the North Carolina State Medical Examiner's database, and 4) the Area Resource File. All patients with the diagnosis of an abdominal aortic aneurysm (AAA) were selected for initial assessment. Patients were grouped into those with and those without rupture of the abdominal aneurysm. RESULTS: During the 6 years of the study, 14,138 patients were admitted with a diagnosis of AAA. Of these, 1480 (10%) had an RAAA. The yearly number of patients with elective AAAs increased 33% from 1889 in 1988 to 2518 in 1993. The yearly number of RAAAs increased 27% from 203 to 258. The mortality rate for AAA was 5%, as compared with 54% in RAAA patients. The patient's age was found to be the most powerful predictor of survival. Univariate logistic regression analyses demonstrated an association of the surgeon's experience with RAAA and patient survival after RAAA. Analysis of the survival rates of board-certified and nonboard-certified surgeons demonstrated that patients with RAAAs who were treated by board-certified surgeons had significantly better survival. When the survival was compared in small (less than 100 beds) and large (more than 100 beds) hospitals, survival was significantly better in the larger hospitals. CONCLUSIONS: Ruptured abdominal aortic aneurysm remains a highly lethal lesion, even in the best of hands. Despite the many improvements in the care of seriously ill patients, there was no significant improvement in the survival of RAAA during this study. This suggests that early diagnosis is the best hope of survival in these patients. The study demonstrated that survival after RAAA was related most strongly to patient age at the time of the RAAA. The physician's and the hospital's experience with RAAA, the physician's background as measured by board certification, and the type of hospital at which the operation was performed (small vs. large) also may be associated with survival. These findings may have important implications for the regionalization of care and the education and credentialling of physicians. Given the lack of recent progress of improving the outcome of RAAA, aggressive efforts to treat patients before rupture are appropriate.

Age Distribution↗
PubMed1995

The effects of union membership on multiple work commitments among female public sector employees.

The effects of union membership on union, organizational, and dual commitment among 245 clerical employees at a midwestern state university represented by a Local of the American Federation of State, County, and Municipal Employees (AFSCME) were investigated. Based on the similarity hypothesis of the social identity theory, it was hypothesized that union membership would be positively related to union and dual commitment and negatively related to organizational commitment. The results of the regression analyses supported the similarity hypothesis, and union membership explained a significant amount of variance in union and dual commitment but not in organizational commitment. These findings are discussed in the context of applying social psychological approaches to understand attitudes toward unionization; industrial conflict; and union, organizational, and dual commitment.

Adult↗
PubMed1994

Efficacy and safety of enoxaparin to prevent deep venous thrombosis after hip replacement surgery. Enoxaparin Clinical Trial Group.

OBJECTIVE: To determine the most effective and safe dose of enoxaparin to prevent deep venous thrombosis in high-risk surgical patients. DESIGN: A double-blind, randomized, multicenter clinical trial. SETTING: Private, university, and government hospitals in the United States. PATIENTS: 572 patients having elective hip replacement surgery, 568 of whom received study medication and had efficacy data available for evaluation. INTERVENTIONS: Patients were randomly assigned to one of three subcutaneous enoxaparin regimens: 10 mg once daily (161 patients); 40 mg once daily (199 patients); and 30 mg every 12 hours (208 patients). Treatment was initiated within 24 hours after surgery and continued for as long as 7 days. Treatment with 10 mg enoxaparin once daily was discontinued prematurely after an interim analysis showed an increased deep venous thrombosis incidence in this treatment group. MEASUREMENTS: Efficacy was determined by bilateral lower extremity venography, noninvasive vascular imaging methods, or clinical evidence on day 7 of treatment or earlier if clinically indicated. RESULTS: Deep venous thrombosis occurred in 25% (40 of 161) of the patients who received 10 mg of enoxaparin once daily; in 14% (27 of 199) of those receiving 40 mg of enoxaparin once daily; and in 11% (22 of 208) in those receiving 30 mg of enoxaparin every 12 hours. The incidence of deep venous thrombosis was significantly higher in patients who received 10 mg of enoxaparin once daily compared with those who received 40 mg of enoxaparin once daily (P = 0.02) or those who received 30 mg of enoxaparin every 12 hours (P < 0.001). The difference between the patients who received 40 mg once daily and those who received 30 mg every 12 hours was not significant. Only two cases of pulmonary embolism were diagnosed, one in patients receiving 40 mg of enoxaparin and one in those receiving 10 mg once daily. The incidence of hemorrhagic complications differed significantly between patients who received 10 mg of enoxaparin once daily (5%, 8 of 161 patients) and those who received 30 mg of enoxaparin every 12 hours (13%, 26 of 208; P < 0.05). CONCLUSIONS: After surgery, enoxaparin, 40 mg once daily or 30 mg every 12 hours, is more effective than a regimen of 10 mg once daily to prevent deep venous thrombosis in patients having elective hip replacement surgery. The regimens of 40 mg once daily and 30 mg every 12 hours provided prophylaxis similar to the most effective drug treatments previously reported. The incidence of hemorrhagic episodes with the regimens of 40 mg once daily and 30 mg twice daily was higher than that observed with 10 mg once daily; however, major hemorrhage occurred in only 4% to 5% of patients receiving the higher-dose regimens. The risk-to-benefit ratio supports the use of enoxaparin as a therapeutic agent to prevent deep venous thrombosis in these patients.

Aged↗
PubMed1994

The relationship between cataract and climatic droplet keratopathy in Mongolia.

This study evaluated the association between cataract, the commonest single blinding disorder worldwide, and climatic droplet keratopathy which was taken as an indicator of high exposure to ultraviolet sunlight. A sample of 4344 persons from rural Mongolia (1991-92) provided 8634 eyes for analysis of the relationship between cataract and climatic droplet keratopathy. Right and left eyes were combined (paired into matched sets), and analysed using a random-effects regression model. The results indicated an inverse association between cataract and climatic droplet keratopathy in person aged 55 years or older, whereby eyes with more advanced climatic droplet keratopathy had lower prevalence of cataract (age-adjusted odds ratio 0.53, p = 0.047). In the younger group of persons aged 40-54 years, the reverse was found, whereby cataract prevalence was higher in eyes that have climatic droplet keratopathy (age-adjusted odds ratio 13.19, p = 0.046). However, only a small proportion (4%) of all the cataracts occurred in this younger age stratum where the prevalence of cataract was 0.5%, compared to prevalence of 17% in eyes of persons aged 55 years or older. These findings cast further doubts upon the current thesis that lifetime exposure to high levels of ultraviolet sunlight is a major cause of cataract in developing countries.

Adult↗
PubMed1994

Solar ultraviolet radiation and ocular disease: a review of the epidemiological and experimental evidence.

Exposure to solar ultraviolet radiation has been linked, at some point, with more than a dozen eye diseases. Some of these associations are based solely on anecdotes, while others have been subjected to epidemiological investigations. For each eye disease, the evidence for an association with ultraviolet radiation is presented and evaluated. The only eye disease for which there is sufficient evidence of a causal association in humans is photokeratitis. For several eye diseases (climatic droplet keratopathy, pterygium, cataract) there is limited evidence for an association, while for other diseases (uveal melanoma, macular degeneration) there is either little support for an association or inadequate data on which to base an assessment.

Animals↗
PubMed1994

Prevalence and causes of blindness and visual impairment in Mongolia: a survey of populations aged 40 years and older.

The survey was conducted in 3 out of the 18 administrative regions (aimaks); 4345 people aged > or = 40 years were examined, which represented 95.7% of the proposed sample. The prevalences of blindness and low vision in the sample were 1.5% (95% CI, 0.8-2.3%) and 8.1% (95% CI, 5.5-10.7%), respectively, from which the prevalences of blindness and low vision in the Mongolian population aged 40 years and older were estimated to be 1.4% and 7.7%, respectively. The prevalence of climatic droplet keratopathy was high (ranging from 15% to 50%) in this population, which included a large number of semi-nomadic cattle breeders, and was responsible for 7.2% of the blindness and 19.3% of the low vision. Cataract and glaucoma were the commonest blinding disorders, each accounting for around 35% of the blindness. Trauma accounts for a high proportion of those monocularly blind. Trachoma and xerophthalmia were not found.

Adult↗
PubMed1993

Beta-lactam antibiotics inhibit agonist-stimulated platelet calcium influx.

beta-lactam antibiotics cause platelet dysfunction with reversible agonist-receptor inhibition, irreversible [14C]-penicillin binding, and inhibition of agonist-stimulated elevation in cytosolic Ca2+ ([Ca2+]i), occurring after 24 h exposure in vitro and after in vivo treatment. We investigated beta-lactam antibiotic-induced inhibition of rises in [Ca2+]i stimulated by thrombin, sodium arachidonate or A23187 to determine whether Ca2+ influx or intracellular release was primarily affected. The mean rise in [Ca2+]i, measured with fura-2-AM, was inhibited 43.7-84.1% by penicillin when the extracellular Ca2+ concentration ([Ca2+]e) was 1 mM, but was significantly less inhibited when [Ca2+]e was < 1 microM. NiCl2 (2 mM), that blocks Ca2+ influx, caused inhibition comparable to penicillin. MnCl2 (1 mM), that quenches the intracellular fura-2 signal, significantly decreased the rise in 1 mM [Ca2+]i when [Ca2+]e was 1 mM, but did not increase the inhibition caused by penicillin. Penicillin did not inhibit the rise in [Ca2+]i stimulated by inositol-1,4,5-trisphosphate or GTP gamma S. Therefore, beta-lactam antibiotics inhibit agonist-induced elevations of [Ca2+]i primarily through inhibition of Ca2+ influx, which probably accounts for the irreversible inhibition of platelet function seen after prolonged in vitro or in vivo treatment.

Ampicillin↗
PubMed1993

Thromboxane-insensitive dog platelets have impaired activation of phospholipase C due to receptor-linked G protein dysfunction.

Human platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors are linked to phosphoinositide-specific phospholipase C (PI-PLC) via a G protein tentatively identified as a member of the Gq class. In contrast, platelet thrombin receptors appear to activate PI-PLC via other unidentified G proteins. Platelets from most dogs are TXA2 insensitive (TXA2-); i.e., they do not aggregate irreversibly or secrete although they bind TXA2, but they respond normally to thrombin. In contrast, a minority of dogs have TXA2-sensitive (TXA2+) platelets that are responsive to TXA2. To determine the mechanism responsible for TXA2- platelets, we evaluated receptor activation of PI-PLC. Equilibrium binding of TXA2/PGH2 receptor agonists, [125I]BOP and [3H]U46619, and antagonist, [3H]SQ29,548, revealed comparable high-affinity binding to TXA2-, TXA2+, and human platelets. U46619-induced PI-PLC activation was impaired in TXA2- platelets as evidenced by reduced (a) phosphorylation of the 47-kD substrate of protein kinase C, (b) phosphatidic acid (PA) formation, (c) rise in cytosolic calcium concentration, and (d) inositol 1,4,5 trisphosphate (IP3) formation, while thrombin-induced PI-PLC activation was not impaired. GTPase activity stimulated by U46619, but not by thrombin, was markedly reduced in TXA2- platelets. Antisera to Gq class alpha subunits abolished U46619-induced GTPase activity in TXA2-, TXA2+, and human platelets. Direct G protein stimulation by GTP gamma S yielded significantly less PA and IP3 in TXA2- platelets. Immunotransfer blotting revealed comparable quantities of Gq class alpha-subunits in all three platelet types. Thus, TXA2- dog platelets have impaired PI-PLC activation in response to TXA2/PGH2 receptor agonists secondary to G protein dysfunction, presumably involving a member of the Gq class.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Mortality and cataract: findings from a population-based longitudinal study.

The study was carried out in a rural population in central India. A random sample of 11 village communities provided 1020 persons aged 40-64 years, who were examined in 1982 and again reassessed in 1986. Statistical analysis, based on the Mantel-Haenszel method for stratified data, showed increased mortality in persons who had central lens opacities, compared with those who had trivial or no central lens opacities. The significant age-adjusted death ratio was just over 2 (2.2), as were the age/sex-adjusted and age/vision-adjusted estimates, which indicate doubling of mortality in the cataract cohort. Multiple regression analysis using the Cox proportional-hazards model gave very similar results. Statistical tests for homogeneity of death ratios across the various age/sex/vision strata were carried out, and the observed association between cataract and mortality was found to be consistent, both in males and in females, in the youngest and oldest age groups, and among those with adequate vision of 6/18 or better as well as among persons with serious visual impairment. There were no known diabetics in the study sample, which came from what could reasonably be regarded as a non-diabetic population.

Adult↗
PubMed1991

Thromboxane responsiveness of dog platelets is inherited as an autosomal recessive trait.

Most mongrel dogs have platelets that form thromboxane A2 (TXA2) from exogenous arachidonate, but they fail to aggregate or secrete in response to it. In contrast to these TXA2 insensitive (TXA2-) platelets, some dogs have TXA2 sensitive (TXA2+) platelets that aggregate and secrete when stirred with arachidonate. To evaluate the possible genetic basis for this difference, we carried out seven matings of mongrel dogs that yielded 48 viable offspring. Four matings of dogs with TXA2- platelets (presumed genotype TT) including 2 back-crosses, produced 32 pups with TXA2- (TT) platelets and 0 pups with TXA2+ platelets. A cross between a male with TXA2+ platelets (presumed genotype tt) and a female with TXA2+ (tt) platelets yielded 9 offspring with TXA2+ (tt) platelets and 0 with TXA2- platelets. Crossing a male presumed homozygous (TT) for TXA2- platelets with a female with TXA2+ (tt) platelets produced 2 pups with TXA2- (Tt) platelets and 0 pups with TXA2+ (tt) platelets. The same female with TXA2+ platelets crossed with a male presumed to be heterozygous (Tt) for TXA2- platelets yielded 2 pups with TXA2+ (tt) platelets and 3 pups with TXA2- (Tt) platelets. Segregation analysis of these data supports the hypothesis that the ability of dog platelets to aggregate and secrete in response to TXA2 is inherited as an autosomal recessive trait.

Aging↗
PubMed1990

Adenosine potentiates the inhibitory effects of calcium channel antagonists on human platelet aggregation induced by thromboxane A2 or U46619.

Calcium channel antagonists inhibit platelet function in vitro and ex vivo, but the mechanism responsible has not been clearly defined. The concentrations of these agents required to inhibit platelet aggregation in vitro are several fold higher than those attained in vivo. Adenosine, a known inhibitor of platelet function, is produced in large quantities in ischemic myocardium. In order to test the hypothesis that adenosine may potentiate the platelet-inhibitory effects of calcium channel antagonists, we studied the effect of adenosine plus nifedipine, verapamil or diltiazem on human platelet aggregation induced by thromboxane A2 or the stable endoperoxide/thromboxane A2 mimic, U46619 +/- epinephrine. Adenosine, in concentrations achieved in the plasma during myocardial ischemia (0.01-0.1 microM), enhanced the inhibitory effects of nifedipine, verapamil and diltiazem on platelet aggregation 5-100 fold. The same concentrations of adenosine alone did not inhibit platelet aggregation. In the presence of non-inhibitory concentrations of adenosine, nifedipine, in concentrations approaching those attained in vivo following standard therapeutic doses (as low as 0.29 microM), significantly inhibited thromboxane A2-induced platelet aggregation. Therefore, adenosine potentiates the in vitro inhibitory effects of calcium channel antagonists on platelet aggregation induced by thromboxane A2 or thromboxane A2 plus epinephrine. These results suggest that adenosine production by ischemic myocardium may augment the inhibitory effect of calcium channel antagonists on platelets.

Adenosine↗
PubMed1990

Beta-lactam antibiotic-induced platelet dysfunction: evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin.

beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗