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Biomedical subjects

T Jensen

Publications and source records attributed to T Jensen.

At least 109 records · Page 6Linked to original sources

Regulation of CFTR expression and function during differentiation of intestinal epithelial cells.

CFTR, the protein defective in cystic fibrosis is regulated during differentiation of intestinal epithelial cells. The undifferentiated cells (Caco-2 and HT-29) show a lower level of CFTR mRNA, while a 10-fold increase is seen in differentiated cells. These differences correlate well with those of other intestinal-specific genes, including sucrase-isomaltase, villin and alpha 1-antitrypsin, indicating that the regulation is cell specific. In Caco-2 cells the increase in CFTR mRNA cannot be accounted for by increased transcription of the gene. These data indicate that CFTR mRNA stabilizing factor(s) might be present in differentiated cells. The higher levels of CFTR mRNA in differentiated cells are accompanied by decreased protein levels, indicating, as well, involvement of translational control in the regulation of CFTR in these cells. Finally, fully differentiated cells show lowered levels of cyclic AMP-activated C1- transport, the characteristic function of CFTR. Thus, CFTR function in differentiated cells is modulated by a complex interaction of regulatory elements. Caco-2 and HT-29 cells provide a suitable in vitro system in which to study the mechanism of regulation of CFTR.

Blotting, Western↗

Urinary excretion of retinol-binding protein in type 1 (insulin-dependent) diabetic patients with microalbuminuria and clinical diabetic nephropathy.

The urinary excretion of retinol-binding protein (RBP) was studied in 101 insulin-dependent diabetic patients allocated to three groups according to 24-h urinary albumin excretion rate (UAE) (median of three urine collections): group 1 (n = 45), normal UAE less than 30 mg/24 h; group 2 (n = 27), microalbuminuria (UAE 30-300 mg/24 h); and group 3 (n = 29), clinical diabetic nephropathy (UAE greater than 300 mg/24 h). We used 23 healthy subjects as controls. Fractional clearance of RBP (FC-RBP) and its 24-h urinary excretion rate (URBP) were higher in each diabetic group than in healthy subjects, the highest values being found in group 3. Groups 1 and 2 did not differ in URBP and FC-RBP. There was a correlation between FC-RBP and haemoglobin A1c in both the total diabetic cohort (P less than 0.001) and in diabetic patients in groups 1 and 2 with a glomerular filtration rate of more than 90 ml/min (P less than 0.05). No correlation was found between FC-RBP and UAE and/or duration of diabetes in any of the diabetic groups. We conclude that the increased urinary excretion of RBP, indicating proximal tubular dysfunction, is already present in normoalbuminuric insulin-dependent diabetic patients and correlates with metabolic control. Further deterioration in proximal tubular function was not observed in microalbuminuric patients, but is a late event in clinical diabetic nephropathy.

Adult↗

The importance of sculpin (Myoxocephalus scorpius) as intermediate host and transmitter of the sealworm Pseudoterranova decipiens.

A total of 186 sculpins (Myoxocephalus scorpius) were caught at Vega, Nordland, Norway, and examined for sealworm larvae (Pseudoterranova decipiens). Over 80% of the fish were infected. Very high infections were found with a maximum of nearly 300 larvae in one sculpin. Infections of this magnitude have so far not been reported from sculpins or any other fish species of this size. The importance of the sculpin in the life cycle and in the transmission of P. decipiens to seals or other fish species is briefly discussed.

Animals↗

Increments in glucose, glucagon and insulin after morphine in rats, and naloxone blocking of this effect.

In awake rats adapted to experimental conditions and allowed food ad libitum, hyperglycemia was induced by the administration of morphine 10 mg/kg through indwelling catheters in the external jugular vein. High glucose values were measured at 5, 15 and 25 min. Glucagon values were high at 5 and 15 min, and again at basal level at 25 min. Insulin was increased after morphine both at 5, 15 and 25 min, whereas somatostatin levels did not change after morphine. When morphine was administered together with naloxone after an initial 10 min period of naloxone administration, there was no increment in glucose, insulin or somatostatin values; neither at 5, 15 or 25 min. There was a remarkable glucagon decrease after naloxone and morphine remaining from 5 to 25 min. Then, one of the possible mechanisms for the hyperglycemic response after morphine may be an opioid effect on pancreas, stimulating glucagon and thereby causing hepatic glucose output.

Animals↗

Micro-albuminuria and large vessel disease in diabetes.

BACKGROUND: Atherosclerosis is a major cause of morbidity and mortality in insulin-dependent diabetes mellitus. Recent studies have shown that albuminuria is a predictor of cardiovascular disease in these patients and there is a particularly high incidence of coronary heart disease in the early stages of albuminuria. AVAILABLE EVIDENCE: A number of established cardiovascular risk factors, such as elevated blood pressure, atherogenic changes in the plasma concentrations of lipids and lipoproteins, elevated plasma levels of fibrinogen and, probably, hyper-reactivity of platelets are present in patients with diabetic nephropathy. Further, albuminuria may be a marker of generalized disease in the vascular wall of small and large blood vessels. Findings of an elevated rate of transcapillary albumin escape, an elevated plasma concentration of von Willebrand's factor and impaired fibrinolytic capacity in early diabetic nephropathy support this hypothesis. CONCLUSION: The initial pathophysiological mechanisms involved in diabetic nephropathy are still hypothetical and largely unknown.

Albuminuria↗

The prevalence of hypercholesterolaemia and its relationship with albuminuria in insulin-dependent diabetic patients: an epidemiological study.

To assess the prevalence of hypercholesterolaemia and its relationship with metabolic control and urinary albumin excretion in Type 1 diabetic patients, all 1577 insulin-dependent patients attending the outpatient clinic at the Steno Memorial Hospital were studied. None had previously received lipid-lowering drugs. Hypercholesterolaemia, defined as plasma concentration of cholesterol above 6.4 mmol l-1 was found in 156 patients (10%) (95%) confidence intervals (CI) 8.4-11.5%) compared with 11% in the Danish background population. Compared with the normolipidaemic diabetic patients, the hyperlipidaemic patients were older (42 vs 37 years: p less than 0.001, 95% CI for difference in means 3-7 years), they had a higher glycosylated HbA1C (9.2 vs 8.6%, p less than 0.001, 95% CI for difference in means 0.4-1.3%) and their urinary albumin excretion was 32 vs 12 mg 24 h-1, p less than 0.001. Of the 1577 diabetic patients, 1084 patients (73%) had normal urinary albumin excretion (UAE less than 30 mg 24 h-1), 255 (17%) had microalbuminuria (UAE 30-300 mg 24 h-1) and 136 (9%) had overt clinical nephropathy (UAE greater than 300 mg 24 h-1). The plasma concentration of cholesterol rose significantly with increasing urinary albumin excretion; normoalbuminuric 4.78 mmol l-1 +/- 1.06 (mean +/- SD); microalbuminuric: 5.12 mmol l-1 +/- 1.23 and macroalbuminuric: 4.89 mmol l-1 +/- 1.38 (p less than 0.001). The influence of metabolic control on the plasma level of cholesterol was of only minor clinical importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Localization of an immunodominant domain on baculovirus-produced parvovirus B19 capsids: correlation to a major surface region on the native virus particle.

An immunodominant region on baculovirus-produced parvovirus B19 VP2 capsids was localized between amino acids 259 and 426 by mapping the binding sites of a panel of monoclonal antibodies which recognize determinants on the particles. The binding sites of three monoclonal antibodies were fine-mapped within this antigenic domain. Six VP2-specific monoclonal antibodies recognized determinants common to both the empty capsids and native parvovirus. The defined antigenic region is most probably exposed on the native B19 virion and corresponds to part of the threefold spike on the surface of canine parvovirus particles.

Amino Acid Sequence↗

Microalbuminuria. Implications for micro- and macrovascular disease.

Microalbuminuria is diagnosed when the UAER is greater than 20 but less than 200 micrograms/min. The prevalence of microalbuminuria among diabetic patients is 15-20%. Persistent microalbuminuria in diabetic patients is a risk marker not only of renal disease, but also of proliferative retinopathy and cardiovascular morbidity and mortality. Even among nondiabetic individuals, those with microalbuminuria tend to have an increased cardiovascular morbidity. The established cardiovascular risk factors, such as smoking, elevated plasma cholesterol, fibrinogen, and hypertension, are seen more frequently in diabetic patients with persistent microalbuminuria than in normoalbuminuric diabetic patients of similar age, sex, and diabetes duration. However, these risk factors cannot by themselves explain the cardiovascular overmortality in these patients. In addition, insulin resistance or genetic disposition to hypertension or cardiovascular disease fails to be the missing link. Accumulating evidence suggests a common pathogenetic mechanism for microalbuminuria and premature atherosclerosis (i.e., qualitative alterations of the extracellular matrix, including decreased density and sulfation of HS-PG). Decreased density of HS in the glomeruli may lead to albuminuria and mesangial proliferation. In the intima of large vessel walls, decreased density and/or sulfation of HS may enhance several of the processes involved in premature atherosclerosis. Diabetes affects the composition and structure of the extracellular matrix in many ways and leads to decreased density and sulfation of HS-PG by several mechanisms. Genetic differences in the sulfation of HS and/or genetic defects in the coordinated biosynthesis of HS-PG might contribute to decreased concentration and sulfation of HS-PG in susceptible individuals. It is hoped that susceptibility genes can be identified soon, thereby making prevention of severe late diabetic complications more successful.

Albuminuria↗

Diabetic retinopathy, nephropathy and neuropathy. Generalized vascular damage in insulin-dependent diabetic patients.

The most serious complication of diabetes mellitus is clinical nephropathy. The development of persistent proteinuria (urinary excretion of more than 300 mg albumin/24 hours) implies an extremely high risk of early death. Renal failure is the most frequent cause of death but the mortality of cardiovascular diseases is also increased. Besides the link between albuminuria (nephropathy) and atherosclerosis in coronary arteries, albuminuria is also a predictor of microangiopathy in other organs than the kidneys. The annual incidence of proliferative retinopathy in early nephropathy is 10-15% compared to only 1% in patients without nephropathy. Also signs of cardiomyopathy have been demonstrated in early nephropathy. Further we have described markers of universal endothelial damage in these patients, and we hypothesize that albuminuria not only is a predictor of renal disease but also of widespread vascular disease. Long-term improvement of metabolic control by use of insulin infusion pumps and early antihypertensive treatment seem to stop the further progression of early diabetic nephropathy and to significantly improve the prognosis of clinical nephropathy.

Albuminuria↗

Effects of isradipine in Type 1 (insulin-dependent) diabetic patients with albuminuria and normal blood pressure.

The effects of the calcium channel blocker, isradipine, on BP, urinary albumin excretion, plasma lipoproteins and natriuresis in albuminuric Type 1 (insulin-dependent) diabetic patients were assessed. Fifteen Type 1 diabetic patients aged 22-52 years were studied. All had elevated urinary albumin excretion (more than 30 mg/24h) based on several 24 h urine collections, and BP was normal (below 140/90 mmHg). After a placebo treatment period of eight weeks the patients were randomly assigned to two groups for a double-blind crossover study. Each patient received either 2.5 mg isradipine twice daily or placebo for eight weeks. Then, after 4 weeks (the wash-out period), each patient received the drug he or she had not taken before for another 8 weeks. Systolic blood pressure was lowered by 8 mmHg from 127 (114-139) mmHg (P less than 0.01) and diastolic by 5 mmHg from 81 (70-87) mmHg (P less than 0.03) during isradipine treatment. The 24 h urinary sodium excretion increased and no signs of volume expansion were observed during treatment with isradipine. Urinary albumin excretion and total body exchangeable sodium remained unchanged. During isradipine treatment the plasma concentrations of VLDL cholesterol and triglyceride decreased significantly (P less than 0.01) and the level of HDL cholesterol increased, but not significantly (P = 0.08). In conclusion, treatment of Type 1 diabetic patients, at risk of progressive clinical nephropathy, with the calcium channel blocker, isradipine, had beneficial effects on plasma lipoprotein levels and resulted in a reduction in BP. We did not find any effect of isradipine on urinary albumin excretion.

Albuminuria↗

Mucosal immunity to Pseudomonas aeruginosa alginate in cystic fibrosis.

Patients with cystic fibrosis commonly acquire chronic pulmonary infection with alginate-producing Pseudomonas aeruginosa. The infection remains localized at the mucosal surfaces of the airways. Using enzyme-linked immunosorbent assays immunoglobulin concentrations and titers of specific antibodies to purified P. aeruginosa alginate and to P. aeruginosa sonicated antigens were measured in tears, saliva, sputum and serum. CF patients had significantly higher concentrations of IgG, IgA and SIgA in serum and saliva than controls. They also had significantly higher levels of specific antibodies to alginate and sonicated antigen in secretions and serum. Local production of IgA, IgG and IgM antibodies to P. aeruginosa was demonstrated. Only a minor proportion of specific IgA antibodies were present as secretory IgA in tears, saliva and sputum. The ratio of alginate-specific SIgA to specific monomeric IgA in sputum was significantly lower than the similar ratio in saliva, whereas the same ratio for specific P. aeruginosa sonicate antigens was found in saliva and sputum.

Adolescent↗