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Biomedical subjects

S Nielsen

Publications and source records attributed to S Nielsen.

At least 289 records · Page 16Linked to original sources
PubMed1991

Membrane traffic after inhibition of endocytosis in renal proximal tubules.

This study was performed to examine quantitatively the cellular organelles involved in membrane recycling after inhibition of luminal endocytosis in renal proximal tubules. Paraffin oil was microinfused into rat renal proximal convoluted tubules to prevent luminal endocytosis. After 1-2 hr the kidneys were fixed by perfusion and prepared for electron microscopy. Segment 1 proximal tubules infused with paraffin oil and control tubules from the same kidney were studied. In addition we examined proximal tubules from kidneys fixed by immersion 30 sec after removal of the kidney. In the oil-infused tubules the large endocytic vacuoles (greater than 0.5 micron) disappeared, the amount of small endocytic vacuoles (less than 0.5 micron) was reduced to about 10%, and the amount of dense apical tubules was significantly increased. The dense apical tubules were very seldom seen connected to the apical plasma membrane in controls but this was occasionally observed in tubules fixed by immersion and relatively often in oil-infused tubules. An ultrastructural morphometric analysis substantiated and extended the qualitative observations and provided quantitative estimates of volumes and surface areas for large endocytic vacuoles, lysosomes, mitochondria, small endocytic vacuoles, and dense apical tubules in control and experimental tubules. The results strongly support the suggestion that the dense apical tubules located in the apical cytoplasm represent the vehicle for the recycling of membrane from endocytic vacuoles back to the plasma membrane, and show that in renal proximal tubule cells small and large endocytic vacuoles are transformed into dense apical tubules when endocytosis is stopped.

Animals↗
PubMed1991

Peptide YY luminal processing and axial heterogeneity of basolateral binding in renal proximal tubules.

This study investigates the definite location of peptide YY (PYY) binding sites on the basolateral membranes in proximal tubules. S1, S2, and S3 segments were dissected, perfused in vitro, and exposed to [125I-Tyr36]monoiodo-PYY either in the bath fluid or in the perfusate. S1 segments exposed to [125I-Tyr36]PYY in the bath fluid were fixed and prepared for electron microscope autoradiography. The results demonstrated a high degree of axial heterogeneity of basolateral binding of PYY, since only S1 bound PYY, 0.59 +/- 0.09 pg/mm after 15 min; 89.1% could be displaced with unlabeled PYY. PYY was not internalized, 90% of the grains were associated with the basolateral membranes, and no accumulation of grains was observed over the vacuolar apparatus. After luminal perfusion with PYY, 79.3 +/- 7.2% was processed, 61.7 +/- 6.3% was degraded at the brush border, and no tubular accumulation was detected. Thus PYY is not taken up by endocytosis. Unexpectedly, a very large fraction of processed PYY was transported from lumen to bath as trichloroacetic acid (TCA)-precipitable label constituting 41.6 +/- 4.7%. There was no axial heterogeneity in the luminal handling of PYY. In conclusion, this study reveals a high density of PYY binding sites at the basolateral membranes from S1 segments, indicating a selective function of S1 segments on stimulation with PYY. In contrast to other proteins PYY was not internalized from the basolateral membranes.

Animals↗
PubMed1991

Anterolateral instability in the anterior cruciate ligament deficient knee. A cadaver study.

Knee instability was evaluated in 13 normal osteoligamentous knee preparations after transection of the anterior cruciate ligament. Abduction-adduction rotation, coupled tibial translatory movement, and coupled tibial axial rotation were recorded continuously and simultaneously during flexion or extension while applying a well defined valgus directed moment and during extension while applying an anterior tibial force. As a result of the valgus-directed moment, an increase was found in abduction rotation, in coupled anterior tibial translation, and in coupled internal tibial axial rotation. Coupled rotatory and translatory instabilities were larger, and maximum instability was observed at a smaller knee angle during the extension movement than during the flexion movement. The pattern of the instability, excited as a result of the valgus moment, was different from the instability excited as a result of an anterior tibial force.

Aged↗
PubMed1990

A simple calf muscle ergometer for use in a standard whole-body MR scanner.

A calf muscle ergometer, designed for use in a standard whole-body MR scanner, is described. The instrument allows isotonic or isometric calf muscle exercise over a continuous range of work loads from 0 to individual maximum work output. Work output may be recorded on a strip chart recorder. A sound encoding provides an effective guidance for the subject tested to accurately reproduce his performance in each contraction cycle at a given work load. The FID recording may be triggered from the ergometer at any point during the contraction cycle. Nonmetal materials are used for the instrument construction in order to eliminate potentially disturbing eddy currents. The force resistance of the ergometer is obtained by a combined hydraulic-pneumatic system, which is loaded by coupling to an outside source of compressed air equipped with a suitable pressure regulator. When varying the time of data sampling within a repeated 6-s contraction cycle it was found that the recorded Pi/PCr ratio remained essentially constant at low and moderate work loads. However, at work loads at or above 70% of individual Vmax a pronounced dependence of the time of sampling with the contraction cycle was observed.

Equipment Design↗
PubMed1990

Long-term bone loss in insulin-dependent diabetes mellitus.

The bone mineral content (BMC) in patients with insulin-dependent diabetes is reduced by 10% early in the disease, but due to a lack of long-term longitudinal studies it is unknown whether this diabetic osteopenia develops further through life. Over a time period of 11 years we examined the BMC in a group of seven adult insulin-dependent diabetics, in whom physiological and pathological factors affecting bone metabolism had been excluded; the patients were well regulated without diabetic complications. The BMC was not significantly decreased at the initial examination. The longitudinal study revealed a small but statistically significant fall in BMC, mainly in trabecular bone. The narrow (95%) confidence interval of median end value (93.3-99.0% of initial BMC) indicates that the annual decrease in BMC in such patients is of the order of 0.5%, a reduction that is probably clinically insignificant.

Adult↗
PubMed1990

Reversible somatotropin deficiency (psychosocial dwarfism) presenting as conduct disorder and growth hormone deficiency.

The syndrome of reversible somatotropin deficiency (psychosocial dwarfism) is characterized by environment-related impairment of stature and mental growth and growth-hormone secretion. The syndrome is well illustrated by this case report of an eight-year-old boy with psychosocial dwarfism since the third year of life. It was undetected for four years, despite his having been in regular contact with a number of health workers. After he was removed from the deleterious environment, both his growth and behaviour improved markedly, and at follow-up he had maintained this progress.

Child↗
PubMed1990

The epidemiology of anorexia nervosa in Denmark from 1973 to 1987: a nationwide register study of psychiatric admission.

A nationwide register study of psychiatric admission for anorexia nervosa in Denmark yielded average incidence rates of 1.9 per 100,000 per year for females and 0.17 per 100,000 per year for males. The prevalence was 6.7 per 100,000 per year for females and 0.6 per 100,000 per year for males. The female-male ratio for first admissions was 11.8:1. The incidence of anorexia nervosa showed no trend in the general population, but an increase was found among psychiatric inpatients. This increase was explained by a reduction by one third in all psychiatric first admissions and in available psychiatric beds and augmented by an increase in readmissions of anorectic patients. Males were younger than females at first admission. Females were older at first admission from 1973 to 1977 than in later periods. Of males readmitted for non-eating disorders, more were psychotics and fewer psychopaths than among females. Age-period and age-cohort analysis of the 10- to 24-year-old females showed that only age exerted a significant independent influence on first-admission rates, whereas all 3 factors exerted significant independent influence on readmission rates. This might reflect changes in admission policy, greater diagnostic vigilance and changes in attitude towards weight, shape and fitness.

Adolescent↗
PubMed1990

Distal humeral migration as a component of multidirectional shoulder instability. An anatomical study in autopsy specimens.

The object of the present study of autopsy specimens was to evaluate distal humeral migration during abduction allowed by sequential severance of capsular and ligamentous structures stabilizing the shoulder joint. A kinesiologic testing device continuously registered distal humeral migration, abduction angle, rotation, and flexion-extension. No distally directed force was applied to the humerus except the weight of the apparatus. Significant distal migration was recorded in the entire range of abduction (0 degrees -60 degrees) after solitary severance of the coracohumeral ligament as well as the proximal part of the anterior joint capsule. Further sectioning of the proximal part of the posterior capsule did not significantly increase distal humeral migration. Maximum distal migration (25 mm) was measured at 20 degrees of abduction. Applying an internal torque to the humerus significantly prevented distal migration as long as the posterior capsule was kept intact. Clinical testing for distal humeral migration should be performed with the shoulder joint at 20 degrees of abduction and neutral rotation. Furthermore, distal humeral migration can be significantly reduced by internal rotation of the humerus when the posterior joint capsule is intact.

Aged↗
PubMed1989

Cachectin/tumor necrosis factor and interleukin-1 show different modes of combined effect on lipoprotein lipase activity and intracellular lipolysis in 3T3-L1 cells.

Cachectin/tumor necrosis factor (cachectin/TNF) and interleukin-1 (IL-1) share many effects in various tissues and cells, including suppression of lipoprotein lipase (LPL) activity and enhancement of intracellular lipolysis. A possible interaction between cachectin/TNF and IL-1 in these lipase systems was studied in 3T3-L1 adipocytes. The two cytokines showed marked synergy in their suppression of LPL activity in these adipocytes. The least effective dose of cachectin/TNF or IL-1 was at around 5 x 10(-11) or 2.5 x 10(-12) M, respectively. However, when present in combination in amounts as small as 1/20 or 1/100 of the minimum effective dose for either cytokine alone (2.5 x 10(-12) M cachectin/TNF and 2.5 x 10(-14) M IL-1), the cytokines showed marked suppression of LPL activity. In marked contrast, such synergism was not seen for enhancement of intracellular lipolysis. This discrepancy in the combined effects of the two monokines on the two different enzyme systems in the same cells suggests that synergism between cachectin/TNF and IL-1 is unlikely at the level of their receptors on the surface of 3T3-L1 cells. Because the two monokines are considered to be secreted from macrophages under similar conditions, their effect on LPL suppression in many pathophysiological situations would be much greater than that of either monokine alone.

Adipose Tissue↗
PubMed1989

Validity of rapid estimation of erythrocyte volume in the diagnosis of polycytemia vera.

In the diagnosis of polycytemia vera, estimation of erythrocyte volume (EV) from plasma volume (PV) and venous hematocrit (Hctv) is usually thought unadvisable, because the ratio of whole body hematocrit to venous hematocrit (f ratio) is higher in patients with splenomegaly than in normal subjects, and varies considerably between individuals. We determined the mean f ratio in 232 consecutive patients suspected of polycytemia vera (f = 0.967; SD 0.048) and used it with each patient's PV and Hctv to calculate an estimated normalised EVn. With measured EV as a reference value, EVn was investigated as a diagnostic test. By means of two cut off levels the EVn values could be divided into EVn elevated, EVn not elevated (both with high predictive values), and an EVn borderline group. The size of the borderline EVn group ranged from 5% to 46% depending on position of the cut off levels, i.e. with the efficiency demanded from the diagnostic test. EV can safely and rapidly be estimated from PV and Hctv, if f is determined from the relevant population, and if the results in an easily defineable borderline range of EVn values are supplemented by direct EV determination.

Adult↗
PubMed1989

Cortisol and treatment of depression: predictive value of spontaneous and suppressed cortisol levels and course of spontaneous plasma cortisol.

In 72 consecutive depressed hospitalized patients afternoon plasma cortisol was measured in three ways before treatment with antidepressants: 1) Spontaneous (n = 72), 2) 2h after oxazepam suppression (45 mg, n = 28; 60 mg, n = 37) and 3) 16 h after dexamethasone suppression (2 mg, n = 71). In addition, spontaneous cortisol was measured after 3 weeks' treatment (n = 55) and 5 weeks' treatment (n = 36). Both spontaneous and suppressed cortisol levels seemed to have a predictive value in the endogenously depressed patients: complete responders had significantly lower pretreatment cortisol levels compared to poor responders. However, other covarying factors such as distress and age may as well account for the differences in treatment effect. During treatment a significant decrease of spontaneous cortisol was found from about 400 nM in poor responders and 325 nM in complete responders to about 300 nM in all groups. There was a positive correlation between pre- and post-treatment cortisol levels and between pretreatment levels and per cent fall in spontaneous cortisol levels.

Adult↗
PubMed1989

Insulin absorption in renal proximal tubules: a quantitative immunocytochemical study.

The purposes of the present study are mainly biological concerning proximal tubular handling of insulin: we will study the intracellular transport to subcellular compartments involved in insulin degradation, the specificity and saturability of the luminal endocytic absorption of insulin, the visualization of transtubular transport, and finally, if possible, the evaluation of the relative distribution (accumulation) of insulin in endocytic vacuoles and lysosomes. The second part is methodological: application of quantitative immunocytochemistry to endocytosis, quantitation of the effect of particle size and antigen density on labeling density on tissue sections, labeling at very low antigen densities, and effect of fish gelatin on background. Isolated renal proximal tubules were perfused with native insulin, 125I-insulin, or [leucineB-25]-insulin (2% receptor-binding ability and full immunoreactivity) or exposed to native insulin from the basolateral membranes. In conclusion, the luminal uptake of insulin is of low specificity, as native and [leucineB-25]-insulin were accumulated to the same extent. Endocytic uptake is of high capacity and the mechanism is saturable. Insulin accumulated in endocytic vacuoles and lysosomes, thus following the classical degradation pathway. No other subcellular compartment is associated with insulin degradation. It was not possible to detect the basolateral uptake, indicating loss of immunoreactivity after binding to its receptor. Absolute quantitative immunocytochemistry is applicable in studying endocytosis. The labeling density increases nonproportionally with antigen density probably caused by steric hindrances. Reduction of the particle size (16 to 6 nm) increased the labeling density 17.6 times.

Animals↗
PubMed1989

Absorption of epidermal growth factor and insulin in rabbit renal proximal tubules.

Epidermal growth factor (EGF), which stimulates the growth of a variety of tissues, was originally isolated from mouse submandibular glands. Human EGF (hEGF) has been isolated from the urine, and cDNA encoding for EGF has been isolated from the human kidney. Thus the kidney may represent an alternate source of EGF. Another potential explanation for the urinary content of EGF is a limited reabsorption of filtered EGF and/or a transtubular transport of EGF from the peritubular compartment to the lumen. Therefore, we exposed isolated and perfused rabbit proximal tubules to 125I-hEGF either in the perfusate or in the bath fluid. Luminal uptake of hEGF was compared with uptake of 125I-porcine insulin, which is known to be taken up with large efficiency. The results demonstrate that only 4% of the perfused 125I-hEGF load was taken up per millimeter of tubule length compared with 73% for insulin. Furthermore, hEGF is subject to a small transtubular transport from bath to lumen. Renal clearance of endogenous rabbit EGF was also measured and was comparable with that of creatinine. Thus in conclusion this study strongly suggests that filtered EGF to a large extent remains in the ultrafiltrate, unlike insulin, which is removed within the first few millimeters of proximal tubule. In addition filtered EGF in preurine is probably supplied by EGF transported intact across the proximal tubular epithelium.

Absorption↗
PubMed1989

Decrease in membrane-bound G4 form of acetylcholinesterase in postmortem Alzheimer brain.

Samples of left hippocampus, septal nucleus, parietal lobe (area 40), and nucleus basalis of Meynert (NBM) were removed from eight patients with pathologically confirmed Alzheimer's disease (AD), four controls, and three patients with non-Alzheimer's dementia. Extracts of these brain regions were assayed for choline acetyltransferase (ChAT) specific activity, acetylcholinesterase (AChE) specific activity, and AChE molecular form composition. Average specific activities of ChAT from hippocampus, septum, and area 40, but not NBM, were significantly lower (p less than 0.01) in the AD population than in the control group. The average AChE specific activity was significantly less (p less than 0.05) in hippocampus and area 40 when the AD group was compared with controls. The average percentage of total AChE activity represented by the globular tetrameric (G4) molecular form was decreased in all AD brain regions as compared to control or to non-Alzheimer's demented groups. The decrease in G4 was, in all cases, due to a selective decrease in the membrane-bound form of G4. The loss of percent membrane-bound G4 in the AD group was significant for hippocampus (p less than 0.05) and area 40 (p less than 0.001) when compared to controls. The percentages of total AChE present as G4 and as membrane-bound G4 in each brain region were correlated with the ChAT specific activities in that region. The correlations showed that AChE molecular form composition changed significantly only if ChAT activity fell below a certain consistent level. The human data agreed well with data from fornix-lesioned mice which strongly suggest the existence of a soluble factor that regulates production of membrane-bound G4.

Acetyltransferases↗