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Biomedical subjects

R Lehmann

Publications and source records attributed to R Lehmann.

At least 145 records · Page 8Linked to original sources

Impact of physical activity on cardiovascular risk factors in IDDM.

OBJECTIVE: To study the impact of physical activity on glycemic control and plasma lipids [HDL cholesterol (HDL-C), HDL-C subfractions, triglycerides, lipoprotein(a)], blood pressure, weight, and abdominal fat and to determine the necessary short-term adaptations in diabetes management during intensive endurance training in patients with IDDM. RESEARCH DESIGN AND METHODS: Well-controlled subjects with IDDM (n = 20; HbA1c = 7.6%) engaged in a regular exercise program over a period of 3 months involving endurance sports such as biking, long-distance running, or hiking. Subjects were instructed to exercise at least 135 min per week. If baseline activity exceeded this level, subjects were to increase further their physical activity as much as possible and record the type and time of such activity. RESULTS: During the 3-month intervention, physical activity increased from 195 +/- 176 to 356 +/- 164 min (mean +/- SD) per week (P < 0.001). Physical fitness as assessed by VO2max increased from 2,914 +/- 924 to 3,092 +/- 905 ml/min (P < 0.001), and insulin sensitivity increased significantly (steady-state plasma glucose [SSPG] decreased from 10.5 +/- 4.8 to 7.0 +/- 3.3 mmol/l; P < 0.01). Subsequently, LDL cholesterol decreased by 14% (P < 0.05), and HDL and HDL3-C subfraction increased by 10 (P < 0.05) and 16% (P < 0.05), respectively. Systolic and diastolic blood pressure decreased significantly from 127 +/- 9 to 124 +/- 8 (P < 0.05) and from 80 +/- 5 to 77 +/- 5 mmHg (P < 0.01), respectively. Resting heart rate decreased from 63 +/- 6 to 59 +/- 7 bpm (P < 0.01). Waist-to-hip circumference ratio decreased from 0.882 +/- 0.055 to 0.858 +/- 0.053 (P < 0.001), body weight decreased from 70.7 +/- 10.4 to 68.7 +/- 10.2 kg (P = 0.003), with a consequent decrease in body fat from 21.9 +/- 8.2 to 18.0 +/- 6.3% (P < 0.001) and an increase in lean body mass from 54.9 +/- 12.2 to 56.8 +/- 11.0 kg. These effects occurred independently of glycemic control. The overall frequency of severe hypoglycemic episodes was reduced from 0.14 to 0.10 per patient-year during the study period. CONCLUSIONS: This study shows that increasing physical activity is safe and does not result in more hypoglycemic episodes and that there is a linear dose-response between increased physical activity and loss of abdominal fat and a decrease in blood pressure and lipid-related cardiovascular risk factors, with a preferential increase in the HDL3-C subfraction.

Adult↗

Small bowel transplantation in children.

Small bowel transplantation has become a life-saving procedure for selected adults and children with intestinal failure who are intolerant to parental nutrition. There are few pediatric data available on the results of this procedure. In this article we review the background of intestinal transplantation, present the results from the University of Western Ontario in London, Ontario and the University of Miami in Miami, Florida, and discuss some future directions. The majority of successful transplants are fully functional, and these children are able to assume a normal diet.

Child↗

Neuropsychological and neurophysiological consequences of partial callosotomy.

Sixty-five patients with lesions affecting the third ventricle (54 patients) or the corpus callosum itself (11 patients) underwent partial callosotomy or a circumscribed callosal resection. Before the surgery 20 patients were studied using the battery of cognitive, affective and behavioural tests which was repeated 10 and 100 days after surgery. No disconnection syndrome was over observed after the partial commissurotomy. Transcranial magnetic stimulation over the sensorimotor cortex was performed in 10 patients to determine conduction time of callosal fibres by measuring inhibition of tonic voluntary electromyographic activity in muscle's ipsilateral to the activated hemisphere. It was found that this inhibition was absent in patients with lesions of the trunk of the corpus callosum and present in patients with lesions of the genu or splenium. In addition magnetic resonance imaging measurements of the corpus callosum were performed in 40 normal subjects to establish a classification system for corpus callosal area. The results showed a wide variability of the cross-sectional area of the corpus callosum. The comparison of the shape of the corpus callosum lead to a categorisation according to the presence and location of depressions on its surface.

Brain Neoplasms↗

The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins.

Translation of hunchback(mat) (hb[mat]) mRNA must be repressed in the posterior of the pre-blastoderm Drosophila embryo to permit formation of abdominal segments. This translational repression requires two copies of the Nanos Response Element (NRE), a 16-nt sequence in the hb[mat] 3' untranslated region. Translational repression also requires the action of two proteins: Pumilio (PUM), a sequence-specific RNA-binding protein; and Nanos, a protein that determines the location of repression. Binding of PUM to the NRE is thought to target hb(mat) mRNA for repression. Here, we show the RNA-binding domain of PUM to be an evolutionarily conserved, 334-amino acid region at the carboxy-terminus of the approximately 158-kDa PUM protein. This contiguous region of PUM retains the RNA-binding specificity of full-length PUM protein. Proteins with sequences homologous to the PUM RNA-binding domain are found in animals, plants, and fungi. The high degree of sequence conservation of the PUM RNA-binding domain in other far-flung species suggests that the domain is an ancient protein motif, and we show that conservation of sequence reflects conservation of function: that is, the homologous region from a human protein binds RNA with sequence specificity related to but distinct from Drosophila PUM.

Amino Acid Sequence↗

Germ plasm assembly and germ cell migration in Drosophila.

Many aspects of germ cell behavior, migration, and gonad formation are shared between vertebrate and invertebrate species. For example, a specialized germ plasm has been observed in many species including Caenorhabditis elegans and Xenopus. Furthermore, the fact that Vasa marks germ cells in many species suggests that even certain molecular aspects of germ cells may be common between different organisms. In most organisms, germ cells initially form at a location away from their target mesodermal tissues and have to migrate to reach the mesoderm. Further genetic studies will reveal the extent to which molecular aspects of germ cell migration and gonad formation are conserved.

Animals↗

Screening and identification of familial defective apolipoprotein B-100 in clinical samples by capillary gel electrophoresis.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder. It is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor, as a consequence of a substitution of adenine by guanine in exon 26 of the apolipoprotein B-100 gene, coding for the putative LDL receptor-binding domain of the mature protein. This disorder is associated with a strikingly high incidence of arteriosclerosis and tends to cause disease and premature death. In this communication we describe a rapid capillary gel electrophoretic method in combination with molecular biology techniques to facilitate the diagnosis of FDB. Mutation screening for FDB is performed by an allele-specific amplification followed by capillary gel electrophoresis (CGE). For the combined polymerase chain reaction (PCR)-CGE method, a total analysis time of only 3 h is needed, a period that is normally necessary for the run and for staining of the gel only, not including the time for PCR, gel casting, etc. In our pilot study 4 of 43 hypercholesterolemic patients were found to have the predominant apoB 3500 codon mutation. The verification is demonstrated by DNA-sequencing. This pilot study will be followed by a large cohort analysis of the south-west German population to determine the frequency of FDB in this area. The PCR-CGE method on the Dionex capillary electrophoresis system (CES I) allows rapid, fully automated detection of the mutation resulting in the unequivocal diagnosis of FDB.

Adult↗

Identification of cis-acting sequences that control nanos RNA localization.

The generation of anterior-posterior polarity during development in Drosophila requires the localization of determinant molecules to the anterior and posterior poles of the embryo. Localization of the maternally synthesized nanos RNA to the posterior pole of the embryo is essential to provide a source for a gradient of Nanos protein that directs abdomen formation. nanos RNA localization occurs during oogenesis and requires the function of at least nine genes. cis-acting sequences that direct nanos RNA localization lie within the nanos 3'UTR. In this analysis, we have used nanos 3'UTR deletion mutants to define the localization signal more precisely. Our results indicate that the nanos RNA localization signal is large and complex and that targeting of nanos RNA may be achieved by the combined effects of multiple, partially independent sequences. This idea is supported by evolutionary conservation, both in sequence and in function, of the nanos 3'UTRs of Drosophila melanogaster and Drosophila virilis.

Animals↗

Characterization of natural peptides from bovine tissue using capillary electrophoresis, high performance liquid chromatography, matrix-assisted laser desorption ionization, and Edman degradation.

A combination of high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) spiking, Edman degradation, amino acid analysis and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) was applied for the analysis of the primary structure of beta-thymosins. CE has been used to resolve peaks which coelute on HPLC, as well as to help establish the identity of tryptic fragments in the peptide mapping experiments of the two highly homologous beta-thymosins.

Amino Acid Sequence↗

Regulated synthesis, transport and assembly of the Drosophila germ plasm.

Germ cells are set aside during early development and, in many organisms (including Drosophila melanogaster, Caenorhabditis elegans and Xenopus laevis), they form in a unique cytoplasm, termed the germ plasm. The germ plasm is synthesized during oogenesis, and the initial polarization of the oocyte is likely to determine where the germ plasm will form within the egg cell. Although we do not know how the fate of germ cells is specified in any organism, recent genetic analysis in Drosophila has identified the TGF-alpha homolog gurken as the signal involved in the initial polarization of the oocyte. These results imply that the limiting steps in the assembly of the germ plasm are localization of the OSK RNA and regulated synthesis of the OSK protein, encoded by oskar, which are components of the germ plasm.

Animals↗

Mapping heavy metals in polluted soil by disjunctive kriging.

The soil of some 50 km(2) around the town of Weinfelden in north-east Switzerland has been sampled and analysed to estimate and map the concentrations of heavy metals before an incinerator for the canton's waste is built. Given that the estimates are subject to error, the probabilities that true values exceed the maximum tolerable concentrations of the Swiss federal guide have also been estimated by disjunctive kriging. These may now be used by the local planners for making decisions. Of the metals examined, lead exceeded the guide value at several sampling points, and a moderate probability of excess of lead is fairly widespread. Copper exceeded the guide value in vineyards and orchards, but also in a few places elsewhere, and the estimated probabilities of excess were not negligible. The other two metals of concern, cadmium (with one exception) and zinc, had concentrations much less than the guide values. The patterns of distribution of the four metals were similar, the product-moment correlations among them are substantial, except in the vineyards and orchards, and it seems likely that they had common sources.

Journal Article↗

Germ cell development in Drosophila.

More than 100 years have passed since Weismann first recognized the role of germ cells in the continuity of a species. Today, it remains unclear how a germ cell is initially set aside from somatic cells and how it chooses its unique developmental path. In this review, we address various aspects of germ cell development in Drosophila, such as germ cell determination, germ cell migration, gonad formation, sex determination, and gametogenesis. Many aspects of germ cell development, including the morphology of germ cells, their migratory behavior, as well as the processes of gonad formation and gametogenesis, show striking similarities among organisms. Considering the conservation of factors that regulate somatic development, it is likely that some aspects of germ cell development are shared not only on a morphological but also on the molecular level between Drosophila and other organisms.

Animals↗

A conserved 90 nucleotide element mediates translational repression of nanos RNA.

Correct formation of the Drosophila body plan requires restriction of nanos activity to the posterior of the embryo. Spatial regulation of nanos is achieved by a combination of RNA localization and localization-dependent translation such that only posteriorly localized nanos RNA is translated. Cis-acting sequences that mediate both RNA localization and translational regulation lie within the nanos 3' untranslated region. We have identified a discrete translational control element within the nanos 3' untranslated region that acts independently of the localization signal to mediate translational repression of unlocalized nanos RNA. Both the translational regulatory function of the nanos 3'UTR and the sequence of the translational control element are conserved between D. melanogaster and D. virilis. Furthermore, we show that the RNA helicase Vasa, which is required for nanos RNA localization, also plays a critical role in promoting nanos translation. Our results specifically exclude models for translational regulation of nanos that rely on changes in polyadenylation.

Animals↗

Evaluation of delayed gastric emptying in diabetic patients with autonomic neuropathy by a new magnetic resonance imaging technique and radio-opaque markers.

OBJECTIVE: Our objective was to validate a new noninvasive magnetic resonance imaging (MRI) technique for diagnosis of delayed gastric emptying by using radio-opaque markers (ROMs) in diabetic patients with and without cardiovascular autonomic (CAN) and peripheral sensomotoric neuropathy (PSN). RESEARCH DESIGN AND METHODS: Fifteen diabetic outpatients were recruited, eight with CAN and PSN (group A, age 28-61 years, mean diabetes duration 27 years) and seven without CAN (group B, age 28-60 years, mean diabetes duration 16 years). Gastric emptying and motility were assessed with ROMs and MRI in random order. After an overnight fast either a test meal (451 kcal) containing a capsule with 10 ROMs is eaten and a supine plain abdominal X ray is taken after 6 h or 500 ml intralipid 10% (550 kcal) is swallowed for the MRI study, using a 1.5 Tesla Gyroscan ACS II (Philips, Eindohoven, The Netherlands). Computer-assisted segmentation of images was used to measure gastric emptying (T1/2, min) over 125 min, contraction frequency (F, min-1), mean contraction amplitude (CA, % basal), and velocity (V, cm/s). Blood glucose was kept constant at 5.0-8.0 mmol/l. RESULTS: In group A, 6.1 +/- 1.36 ROMs (mean +/- SE) were retained in the stomach after 6 h and 0 ROM in group B, indicating a significant delay of gastric emptying in patients with CAN. The MRI study revealed a significantly longer gastric emptying (P < 0.005) in group A (T1/2 = 124 +/- 10 min) as compared with group B (T1/2 = 85 +/- 18 min). There was no difference in F, CA, and V between the two groups: F 2.9 +/- 0.07 and 2.7 +/- 0.1 (min-1), CA 26.8 +/- 1.2 and 29.6 +/- 1.6 (% basal), V 0.43 +/- 0.02 and 0.40 +/- 0.02 (cm/s), respectively. CONCLUSIONS: MRI offers the possibility of visualizing and examining exactly the mechanisms responsible for gastric emptying and is characterized by a high specificity but a lower sensitivity as compared with ROMs, which proved to be an ideal screening test for diagnosis of gastroparesis in clinical practice.

Adult↗

[Antibody formation after filtered blood cell replacement in hematologic-oncologic patients].

We studied the value of leucocyte depletion of platelet and erythrocyte transfusion by filter for the prevention of alloimmunization. In 109 patients with hematological diseases we detected HLA- and platelet specific antibodies by using lymphocytotoxic and IgG-EIA-Thrombomatch. In 17 of the 109 evaluable patients (16%) HLA-antibodies developed (9 female and 8 male). 16 of the 17 had only HLA-antibodies and 1 patient a platelet specific alloantibody primary immunisation. 15 of 17 with a high-risk of prior immunization induced by pregnancy or other transfusions had a 'secondary alloimmunization'.

Adult↗

[Role of physical activity in the therapy and prevention of Type II diabetes mellitus].

Increased physical activity should be part of the treatment for non insulin-dependent diabetic patients. Increased physical activity delays the onset of non insulin-dependent diabetes mellitus (NIDDM) or even prevents the disease in about 50% of susceptible individuals (positive family history of NIDDM, body-mass index > 25, hypertension or gestational diabetes). Regular exercise has been shown to lower plasma triglyceride and to increase high-density lipoprotein cholesterol levels. Exercise has also beneficial effects on hypertension, body composition and fat distribution. Improved glucose tolerance has been achieved in type II diabetic patients in as little as one week with an exercise program. The beneficial effect of regular exercise on glucose control appears to reflect the cumulative effect of transient improvement in glucose tolerance following each individual bout of exercise. Increased insulin sensitivity is lost after as little as three days of inactivity. Most studies suggest that the maximum benefit from exercise is most likely to occur in patients with mild diabetes in whom insulin resistance and hyperinsulinemia are present (i.e. patients with fasting blood glucose of < 11 mM). The recommended frequency and duration of exercise is three times per week or every other day and, as adjunct for weight reduction, five to seven times per week for 30 to 45 min. at an intensity of 50 to 70% VO2max (or 60 to 80% of maximal the heart rate). Because of the high incidence of ischemic heart disease in type II diabetic patients, patients older than 35 years of age should undergo a graded exercise stress electrocardiogram. Attention should be paid to foot-care and the use of appropriate footwear and diabetic late complications, such as autonomic and peripheral neuropathy. Older obese NIDDM patients can achieve significant metabolic benefits from low-intensity programs, such as daily walking, which can be easily incorporated into daily living. Taking the necessary precautions, most patients with diabetes can take part in a monitored exercise program safely.

Adult↗