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Biomedical subjects

O Johnson

Publications and source records attributed to O Johnson.

At least 19 recordsLinked to original sources
PubMed2001

Transsexual limb transplants in fiddler crabs and expression of novel sensory capabilities.

We used transsexual limb transplants in fiddler crabs to examine how peripheral sensory structures interact with the central nervous system (CNS) to produce a sexually dimorphic behavior. Female and male chemosensory feeding claws were transplanted onto male hosts in place of nonfeeding, nonchemosensory claws. Successfully transplanted claws retain donor morphologies and contain chemosensory neurons. Neurons in successfully transplanted female feeding claws express the enhanced sensitivity to chemical cues seen in female, but not male, neurons in claws of normal animals. When chemically stimulated, the transplanted claws evoke feeding behavior not observed in normal males, even though the sensory neurons in the transplanted limb project to the host's sexually dimorphic neuropil not known to receive chemosensory input. Behavioral sensitivity is directly related to the sensitivity of peripheral neurons in the transplanted feeding claw. Thus, the interactions between peripheral neurons and their targets may restructure the CNS so that novel sensory capabilities are expressed, and this can produce sexually dimorphic behaviors.

Action Potentials↗
PubMed2001

Growth inhibitory effect of p21 and p53 containing adenoviruses on transitional cell carcinoma cell lines in vitro and in vivo.

Altered p53 expression has been demonstrated in the majority of advanced transitional cell carcinoma (TCC) of the bladder tumors. The objective of this investigation was to examine the effect of the introduction of a p53 or p21((WAF1/CIP1)) adenovirus on the proliferation and apoptosis of various human TCC cell lines in vitro and in vivo. Proliferation was measured by 3H-thymidine incorporation. Apoptosis was measured by DNA fragmentation and bax expression. We also examined the effect of ex vivo introduction of the p21((WAF1/CIP1)) or the p53 gene on growth of the T24 TCC cells and UMUC-3 TCC cells introduced subcutaneously into athymic nude mice. We found that although the effect of the p21-adenovirus on the proliferation of various TCC lines varied with each individual cell line, there was a substantial growth inhibition observed (greater than 80% growth inhibition) in seven of the eight TCC cell lines at the highest viral dosage. In contrast, after 24 h, the highest dosage of the p53-adenovirus produced only a heterogeneous decrease in proliferation compared to the highest dose of the p21((WAF1/CIP1))-adenovirus (40-90%). In ex vivo experiments, no tumors were found in nude mice injected subcutaneously with either TCC cell line exposed in vitro to the AdSCMV-p21((WAF1/CIP1)) or AdSCMV-p53 viruses before three weeks. There was a threefold decrease in tumor square area at week 5 in the Ad5CMV-p21((WAF1/CIP1)) or Ad5CMV-p53 TCC cells injected mice (p<0.001, p<0.009) compared to either mock or Ad5CMVLacZ TCC bladder tumor cells. These data suggest that significant portion of the effect of altered p53 on TCC phenotype may be mediated through the p21((WAF1/CIP1)) pathway. Thus, the restoration of p21((WAF1/CIP1)) function in this tumor system may be a beneficial therapeutic strategy.

Journal Article↗
PubMed2001

A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity.

OBJECTIVE: In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated. RESULTS: After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were negatively associated with leptin in men with low waist circumference (r=-0.59, P<0.01). The following factors were associated with leptin in a multivariate model: low levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women. CONCLUSION: We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results we suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels. International Journal of Obesity (2001) 25, 98-105

Adipose Tissue↗
PubMed2001

Tissue-specific dysregulation of cortisol metabolism in human obesity.

Cortisol has been implicated as a pathophysiological mediator in idiopathic obesity, but circulating cortisol concentrations are not consistently elevated. The tissue-specific responses to cortisol may be influenced as much by local prereceptor metabolism as by circulating concentrations. For example, in liver and adipose tissue cortisol is regenerated from inactive cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). In obese Zucker rats 11beta-HSD1 activity is reduced in liver but enhanced in adipose tissue. This study addressed whether the same tissue-specific disruption of cortisol metabolism occurs in human obesity. 34 men were recruited from the MONICA population study in Northern Sweden to represent a wide range of body composition and insulin insensitivity. Plasma cortisol was measured at 0830h and 1230h, after overnight low-dose dexamethasone suppression, after intravenous corticotropin releasing hormone (CRH), and after oral cortisone administration. Urinary cortisol metabolites were measured in a 24 h sample. A subcutaneous fat biopsy was obtained from 16 participants to measure cortisol metabolism in vitro. Higher body mass index was associated with increased total cortisol metabolite excretion (r = 0.47, p < 0.01), but lower plasma cortisol at 1230 h and after dexamethasone, and no difference in response to CRH. Obese men excreted a greater proportion of glucocorticoid as metabolites of cortisone rather than cortisol (r = 0.43, p < 0.02), and converted less cortisone to cortisol after oral administration (r = 0.49, p < 0.01), suggesting impaired hepatic 11beta-HSD1 activity. By contrast, in vitro 11beta-HSD1 activity in subcutaneous adipose tissue was markedly enhanced in obese men (r = 0.66, p < 0.01). We conclude that in obesity, reactivation of cortisone to cortisol by 11beta-HSD1 in liver is impaired, so that plasma cortisol levels tend to fall, and there may be a compensatory increase in cortisol secretion mediated by a normally functioning hypothalamic-pituitary-adrenal axis. However, changes in 11beta-HSD1 are tissue-specific: strikingly enhanced reactivation of cortisone to cortisol in subcutaneous adipose tissue may exacerbate obesity; and it may be beneficial to inhibit this enzyme in adipose tissue in obese patients.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men.

OBJECTIVE: To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake. RESEARCH DESIGN AND METHODS: From a population-based study, 35 men were recruited, representing a wide spectrum of insulin sensitivity and body weight. Each subject underwent a hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured. RESULTS: Insulin resistance was associated with impaired GIP and GLP-1 responses to a mixed meal. The total area under the curve (AUC) of the GIP response after the mixed meal was associated with insulin sensitivity (r = 0.54, P < 0.01). There was a significant difference between the highest and the lowest tertile of insulin sensitivity (P < 0.05). GLP-1 levels 15 min after food intake were significantly lower in the most insulin-resistant tertile compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.47, P < 0.01). Multiple linear regression analysis showed that insulin resistance, but not obesity, was an independent predictor of these decreased incretin responses. CONCLUSIONS: In insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and are related to the degree of insulin resistance. Decreased incretin responsiveness may be of importance for the development of impaired glucose tolerance.

Adult↗
PubMed2001

Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis.

OBJECTIVE: To measure the extent of atherosclerosis in patients with rheumatoid arthritis (RA) with a disease duration of considerable length, and in age and sex matched individuals. METHODS: Thirty-nine patients with RA (30 women, 9 men) with disease onset occurring between 1974 and 1978, and less than 65 years of age at the time of investigation, were enrolled together with 39 sex and age matched controls. Quantitative measurement of intima-media thickness (IMT) and semiquantitative assessment of the presence of plaque were undertaken by B-mode ultrasound of the common carotid artery (CCA-IMT) and the common femoral artery on the right-hand side. Echo Doppler cardiography was performed with an Accuson Aspen. The results were related to disease activity variables and accumulated disease activity, to lipid levels [i.e., cholesterol, high density lipoproteins, low density lipoproteins, triglycerides (TG)], to hemostatic factors [tissue plasminogen activator antigen (tPAag), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF)], and to soluble adhesion molecules (sICAM-1 and sE-selectin). RESULTS: Patients with RA had higher maximal and mean IMT values compared with controls. The difference concerning mean CCA-IMT reached statistical significance in patients with RA and correlated significantly with lipids (cholesterol, LDL, LDL/HDL ratio, TG) and tPAag. The prevalence of plaques, as well as of aortic cusp sclerosis, was higher in RA but only the difference in aortic cusp sclerosis was statistically significant. Patients with plaques had significantly higher levels of lipids (cholesterol, LDL, LDL/HDL ratio) than patients without plaques, while patients with cusp sclerosis had significantly higher cholesterol and TG levels. sICAM-1 was significantly higher both in patients with plaques and in those with aortic cusp sclerosis compared to patients without. CONCLUSION: Our results suggest an accelerated atherosclerosis in patients with RA that is related mainly to lipid levels.

Adult↗
PubMed2000

First Light Measurements of Capella with the Low-Energy Transmission Grating Spectrometer aboard the Chandra X-Ray Observatory.

We present the first X-ray spectrum obtained by the Low-Energy Transmission Grating Spectrometer (LETGS) aboard the Chandra X-Ray Observatory. The spectrum is of Capella and covers a wavelength range of 5-175 Å (2.5-0.07 keV). The measured wavelength resolution, which is in good agreement with ground calibration, is Deltalambda approximately 0.06 Å (FWHM). Although in-flight calibration of the LETGS is in progress, the high spectral resolution and unique wavelength coverage of the LETGS are well demonstrated by the results from Capella, a coronal source rich in spectral emission lines. While the primary purpose of this Letter is to demonstrate the spectroscopic potential of the LETGS, we also briefly present some preliminary astrophysical results. We discuss plasma parameters derived from line ratios in narrow spectral bands, such as the electron density diagnostics of the He-like triplets of carbon, nitrogen, and oxygen, as well as resonance scattering of the strong Fe xvii line at 15.014 Å.

Journal Article↗
PubMed2000

Clathrin plays a novel role in the regulation of cell polarity, pseudopod formation, uropod stability and motility in Dictyostelium.

Although the traditional role of clathrin has been in vesicle trafficking and the internalization of receptors, a novel role in cytokinesis was recently revealed in an analysis of a clathrin-minus Dictyostelium mutant (chc(-)). chc(-) cells grown in suspension were demonstrated to be defective in assembling myosin II into a normal contractile ring. To test whether this defect reflected a more general one of cytoskeletal dysfunction, chc(-) cells were analyzed for cell polarity, pseudopod formation, uropod stability, cell locomotion, chemotaxis, cytoskeletal organization and vesicle movement. chc(-) cells crawled, chemotaxed, localized F-actin in pseudopods, organized their microtubule cytoskeleton in a relatively normal fashion and exhibited normal vesicle dynamics. Although chc(-) cells extended pseudopods from the anterior half of the cell with the same frequency as normal chc(+) cells, they extended pseudopods at twice the normal frequency from the posterior half of the cell. The uropods of chc(-) cells also exhibited spatial instability. These defects resulted in an increase in roundness, a reduction in polarity, a reduction in velocity, a dramatic increase in turning, a high frequency of 180 degrees direction reversals and a decrease in the efficiency of chemotaxis. All defects were reversed in a rescued strain. These results are the first to suggest a novel role for clathrin in cell polarity, pseudopod formation, uropod stability and locomotion. It is hypothesized that clathrin functions to suppress pseudopod formation and to stabilize the uropod in the posterior half of a crawling cell, two behavioral characteristics that are essential for the maintenance of cellular polarity, efficient locomotion and efficient chemotaxis.

Actins↗
PubMed2000

Gastric carcinoma at Tikur Anbessa Hospital, Addis Ababa.

OBJECTIVE: To provide a baseline epidemiologic information on gastric cancer from Ethiopia based on hospital data. DESIGN: Prospective study. SETTING: Department of Surgery, Tikur Anbessa Hospital, Faculty of Medicine, Addis Ababa University, Addis Ababa. SUBJECT: Ninety six patients treated for gastric cancer from 1992-1996. INTERVENTIONS: Data including demographic and clinical features, pathology of the disease and treatment outcome were analysed on 96 of 125 cases of gastric cancer. MAIN OUTCOME MEASURES: Duration of symptoms, diagnosis and stage of disease at the time of definitive diagnosis, and postoperative mortality. RESULTS: Sixty eight patients were males and 28 females. The mean age was 48.2 +/- 12.7 (range 20-73) years. The histopathology was adenocarcinoma with a Laurence intestinal type in 89 cases. Majority of the cases (90%) had advanced (stage III-IV) tumours. More than forty four per cent of cases had resectable lesions. Postoperative mortality rate was 18.6%. Twenty seven of the 70 cases operated on (57 survived the operations) could be followed up only for less than one year. CONCLUSION: This study, although based on the relative frequency in a hospital material, indicates that gastric cancer is not rare in Ethiopia. Patients appear to present late with advanced cancers.

Adenocarcinoma↗
PubMed2000

Gastrointestinal tract cancer: a five year study in a teaching central referral hospital, Ethiopia.

Due to lack of national cancer registry, the pattern and outcome of gastrointestinal tract (GIT) cancer is unknown in Ethiopia. In the period 1992-1996, a prospective study was carried out in 534 patients with GIT malignant tumours admitted to the Tikur Anbessa Hospital Department of Surgery, Addis Ababa. Relevant data were recorded on a prepared proforma for specific disease. Of these, 437 cases (82%), 142 oesophageal, 68 pancereato-biliary, 96 gastric, and 131 lower GIT cancers have been included in this study. The mean age was 52 +/- 13 (range 17-88) years. The male to female ratio was 1.7:1.0. The mean duration of the presenting symptoms was 10 months. One hundred and thirty-six patients were not operated because of poor clinical performance status or advanced metastatic disease in 105 patients and refusal to undergo surgery in 31 patients. In nearly 50% of 301 operated cases, the tumours were resected. Clinical staging was defined in 269 cases. Of these, 224 (83.3%) were advanced and only 45 were early cancers. The histopathology in 371 cases showed a predominance of adeno and squamous cell carcinomas. An overall postoperative in-hospital mortality rate was 20%. Of the 241 operative survivals (80%), only 110 (46%) had a limited follow-up of 3 to 12 months. Few cases were followed longer. The diagnosis was late and the follow-up was poor. A high index of suspicion of GIT cancer in all age groups will result in earlier diagnosis and improved survival.

Adenocarcinoma↗
PubMed1999

Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women.

BACKGROUND: Leptin is a crucial mediator of satiety signals and energy balance, and its circulating levels are increased in obesity. It has recently been shown that plasma leptin levels in humans correlate with circulating insulin and to insulin secretion. This indicates that leptin may be an important link in metabolic consequences of the insulin resistance syndrome. Whether this includes abnormalities in fibrinolysis has not been studied. METHODS AND RESULTS: Healthy subjects (n = 165; 85 men and 80 women) from the Northern Sweden MONICA population were investigated. Anthropometric measurements, oral glucose tolerance tests and sampling for plasma leptin, lipids, fibrinogen and fibrinolytic variables were made. Leptin levels were 342% higher in women than in men and were in both sexes strongly correlated to body mass index (BMI). After adjustments for age and BMI, leptin levels correlated significantly to pre/post glucoseload insulin levels in both sexes. After further adjustment for baseline insulin levels, leptin levels were in males significantly associated with increased waist circumference (P<0.001), low HDL cholesterol (P<0.05), low tPA activity (P<0.01) and high PAI-1 activity (P<0.001). In postmenopausal females, a significant association between leptin and low tPA activity/high PAI-1 activity was seen after adjustment for age and BMI (P<0.05). Conclusions. Circulating levels of leptin are associated with components of the insulin resistance syndrome, including defective fibrinolysis, in men and postmenopausal women. This suggests that leptin may be involved in the mediation of consequences of insulin resistance.

Adult↗
PubMed1999

Leptin is associated with increased risk of myocardial infarction.

OBJECTIVES AND DESIGN: Leptin is involved in the regulation of bodyweight and metabolism in man and might also be involved in the pathophysiology of the insulin resistance syndrome, which is associated with the development of cardiovascular diseases. We tested whether leptin is a risk factor for acute myocardial infarction (AMI) in a nested case-referent study. SUBJECTS AND METHODS: Sixty-two men with first-ever AMI were identified who, prior to AMI, had participated in population-based health surveys in Northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographical region. Blood pressure, body mass index (BMI) and the presence of smoking, diabetes and hypertension were recorded. Total cholesterol, apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B), plasminogen activator inhibitor (PAI-1), insulin, and leptin were analysed in stored samples. Their influences on first-ever AMI were analysed by conditional logistic regression analysis. RESULTS: Men with first-ever AMI had higher BMI, plasma insulin and leptin, and diastolic blood pressure than the referents. Furthermore, they had lower plasma apo A-1 and were more often smokers. Smoking, high leptin, PAI-1 and cholesterol, and low apo A-1 levels were significant risk factors for first-ever AMI in univariate analysis. High leptin (OR 8.97; 95% CI: 1.73-46.5) and cholesterol (OR 5.18; 95% CI: 1.34-20.0) levels remained significant risk factors for AMI in a multivariate model. High apo A-1 was protective (OR = 0.13; 95% CI: 0.03-0.55). The combination of high leptin and low apo A-1 was associated with a particularly pronounced increased risk for AMI. CONCLUSION: Plasma leptin strongly predicts first-ever AMI. Our data support the hypothesis that leptin is an important link in the development of cardiovascular disease in obesity.

Adult↗
PubMed1999

Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort.

BACKGROUND AND PURPOSE: Leptin, important for body weight regulation, may be involved in the pathogenesis of the insulin resistance syndrome, associated with cardiovascular disease. We tested to determine whether leptin is a risk marker for first-ever stroke in a nested case-referent study. METHODS: We identified 113 patients with first-ever stroke (94 with ischemic and 19 with hemorrhagic stroke) who, before the stroke, had participated in population-based health surveys in northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographic region. Blood pressure (BP), body mass index (BMI), and presence of smoking, diabetes, and hypertension were recorded. Total cholesterol, insulin, and leptin were analyzed in stored samples. Risk markers for first-ever stroke were analyzed by conditional logistic regression analysis. RESULTS: Patients with hemorrhagic stroke had higher levels of BMI and systolic and diastolic BPs. Leptin levels were 72% and 59% higher in males and females, respectively, with hemorrhagic stroke versus referents. Patients with ischemic stroke more often had hypertension, diabetes mellitus, and higher fasting glucose and insulin levels. A diagnosis of hypertension and elevated systolic and diastolic BPs were significant risk markers for first-ever hemorrhagic stroke in univariate analysis. High leptin (OR=20.55; 95% CI, 1.12 to 376.7) levels together with hypertension (OR=16.28; 95% CI, 1.49 to 177.3) remained as significant risk markers in a multivariate model. The combination of high leptin and high systolic or diastolic BP were associated with a profoundly increased risk for hemorrhagic stroke (OR=22.11; 95% CI, 1.57 to 310.9). Diabetes, hypertension, and obesity (BMI >/=27), together with high levels of insulin, glucose, systolic and diastolic BP, were significant risk markers for first-ever ischemic stroke in univariate analysis. Hypertension (OR=2.10; 95% CI, 1.14 to 3.86) remained as an independent risk marker in a multivariate model. CONCLUSIONS: Plasma leptin is strongly associated with an increased risk for first-ever hemorrhagic stroke, independent of other risk markers for cardiovascular disease. Leptin may be an important link in the development of cardiovascular disease in obesity.

Adult↗
PubMed1998

Perceived health modifies the effect of biomedical risk factors in the prediction of acute myocardial infarction. An incident case-control study from northern Sweden.

OBJECTIVES: To assess the importance of biomedical risk factors, social factors and self-reported health in the prediction of the first event of acute myocardial infarction (AMI) in an apparently healthy middle-aged population. DESIGN: An incident case-control study. SETTING: The study was nested within the Västerbotten Intervention Program and the Northern Sweden MONICA cohorts. SUBJECTS: The study consists of 78 AMI cases with two randomly selected controls per case from the same study cohorts. RESULTS: Significant odds ratios were found for history of diabetes, daily smoking, cholesterol, body-mass index, hypertension, lower education and perceived ill health. In multivariate logistic regression smoking, hypertension and cholesterol of > or =7.8 mmol L(-1) remained significant. An interaction was observed between number of biomedical risk factors and perceived health. CONCLUSIONS: Smoking, hypertension and hypercholesterolaemia explain a major share of incident AMI events in a Swedish middle-aged population. The study further illustrates that perceived ill health negatively modifies the impact of these risk factors.

Case-Control Studies↗
PubMed1998

von Willebrand factor, tissue plasminogen activator, and dehydroepiandrosterone sulphate predict cardiovascular death in a 10 year follow up of survivors of acute myocardial infarction.

BACKGROUND: Haemostasis plays a major part in the process initiating a myocardial infarction. The impact of haemostatic variables on long term prognosis is unknown. OBJECTIVE: To evaluate von Willebrand factor (vWF), tissue plasminogen activator antigen (t-PA) and its activity before and after venous occlusion, plasminogen activator inhibitor (PAI-1), dehydroepian-drosterone sulphate (DHEAS), and established clinical risk factors as long term predictors for reinfarction and mortality. PATIENTS: 123 consecutive survivors of myocardial infarction followed up for 10 years. DESIGN: Study entry took place between 1982 and 1983. Fifty seven patients died (54 of cardiovascular disease) during the mean observation time of 10 years. RESULTS: Cox's univariate regression analysis showed that cardiovascular mortality was significantly associated with age, hypertension, previous history of angina pectoris, DHEAS, mass concentration of t-PA, and vWF. These associations were significant for vWF and mass concentration of t-PA after adjusting for age and hypertension. CONCLUSIONS: A low concentration of DHEAS and high levels of the endothelially derived haemostatic variables vWF and mass concentration of t-PA are predictors of cardiovascular mortality in survivors of myocardial infarction. This association is independent of established clinical risk factors for mass concentration of t-PA and vWF.

Aged↗