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Biomedical subjects

U Keller

Publications and source records attributed to U Keller.

At least 91 records · Page 5Linked to original sources
PubMed1998

Erbium:YAG laser application in caries therapy. Evaluation of patient perception and acceptance.

OBJECTIVES: In previous studies it has been demonstrated that the Er:YAG laser can be used to prepare cavities efficiently and without thermal damage to the adjacent dental hard and soft tissues. To investigate the patients' response to Er:YAG laser preparation of teeth, a prospective clinical study was performed in five dental hospitals. METHODS: To evaluate patients' perception and response to cavity preparation a direct comparison was made between conventional mechanical preparation and Er:YAG laser preparation of caries in dental hard tissues. Half of the preparations were completed by the laser alone with standardized parameters, with the other half being mechanically prepared. The sequential order of treatment was randomized, and clinical parameters such as depth and location of the cavities were carefully balanced. A three-score evaluation scheme of patient responses was used: comfortable, uncomfortable, very uncomfortable. In addition the patients were asked to decide which was the more uncomfortable form of treatment and the preferred treatment for future caries therapy. RESULTS: The study included 103 patients with 206 preparations distributed amongst 194 teeth. All teeth gave vital responses (ice test) before and after both types of treatment. The laser treatment was found to be more comfortable than the mechanical treatment, with high statistical significance. During treatment, the need for local anaesthesia was 11% for mechanical preparation compared to 6% during laser application. It was found that 80% of the patients rated the conventional preparation as more uncomfortable than the laser treatment and 82% of the patients indicated that they would prefer the Er:YAG laser preparation for further caries treatment. CONCLUSIONS: The application of the Er:YAG laser system is a more comfortable alternative or adjunctive method to conventional mechanical cavity preparation.

Adult↗
PubMed1998

Molecular analysis of a gene encoding a cell-bound esterase from Streptomyces chrysomallus.

A gene (estA) encoding a 42-kDa cell-bound esterase, EstA, was found to be located 75 bp upstream of the cyclophilin A gene (cypA) of Streptomyces chrysomallus. Western blot analysis revealed the presence of EstA (42 kDa) in cell extracts of S. chrysomallus X2 and Streptomyces lividans. EstA specifically hydrolyzes short-chain p-nitrophenyl esters. EstA formation starts at the end of growth phase, and its activity level remains constant throughout stationary phase. Expression of estA from the melanin (mel) promoter in plasmid pIJ702 led to a substantial increase of total esterase activity in streptomycetes.

Amino Acid Sequence↗
PubMed1998

Molecular cloning of the actinomycin synthetase gene cluster from Streptomyces chrysomallus and functional heterologous expression of the gene encoding actinomycin synthetase II.

The actinomycin synthetases ACMS I, II, and III catalyze the assembly of the acyl peptide lactone precursor of actinomycin by a nonribosomal mechanism. We have cloned the genes of ACMS I (acmA) and ACMS II (acmB) by hybridization screening of a cosmid library of Streptomyces chrysomallus DNA with synthetic oligonucleotides derived from peptide sequences of the two enzymes. Their genes were found to be closely linked and are arranged in opposite orientations. Hybridization mapping and partial sequence analyses indicate that the gene of an additional peptide synthetase, most likely the gene of ACMS III (acmC), is located immediately downstream of acmB in the same orientation. The protein sequence of ACMS II, deduced from acmB, shows that the enzyme contains two amino acid activation domains, which are characteristic of peptide synthetases, and an additional epimerization domain. Heterologous expression of acmB from the mel promoter of plasmid PIJ702 in Streptomyces lividans yielded a functional 280-kDa peptide synthetase which activates threonine and valine as enzyme-bound thioesters. It also catalyzes the dipeptide formation of threonyl-L-valine, which is epimerized to threonyl-D-valine. Both of these dipeptides are enzyme bound as thioesters. This catalytic activity is identical to the in vitro activity of ACMS II from S. chrysomallus.

Bacterial Proteins↗
PubMed1998

Effects of glucagon-like peptide 1 (7-36 amide) on glucose kinetics during somatostatin-induced suppression of insulin secretion in healthy men.

Glucagon-like peptide 1 (GLP-1) is known to stimulate insulin secretion and biosynthesis, but has also been shown to decrease insulin requirements in type 1 diabetic subjects suggesting insulin-independent effects. To assess whether GLP-1 exerts also direct effects on whole-body glucose metabolism, 6,6-D2-glucose kinetics were measured in 8 healthy volunteers receiving once GLP-1, once saline during hyperglycemic glucose clamping, while somatostatin with replacement amounts of insulin, glucagon and growth hormone was infused. Even though endogenous insulin secretion could not be blocked completely (increased plasma concentrations of C-peptide and proinsulin), somatostatin infusion resulted in stable insulin and glucagon plasma levels in both protocols (GLP-1 vs. placebo: NS). After 3 h of GLP-1 infusion, peripheral glucose disappearance significantly increased compared to placebo (p < 0.03) despite of somatostatin-induced suppression of insulin and glucagon secretion. Thus, GLP-1 infusion seems to have direct stimulatory effects on peripheral glucose metabolism in man.

Adult↗
PubMed1998

VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100.

Mutations in the apolipoprotein (apo) B, E (LDL) receptor gene and in the apolipoprotein B-100 gene are the cause of familial hypercholesterolemia (FH) and of familial defective apo B-100 (FDB), respectively. Whether these abnormalities lead to altered production or uptake of very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) has not been established previously. Therefore VLDL and IDL apo B-100 kinetics were measured in seven subjects with FH, in six subjects with FDB, and in five normocholesterolemic controls using primed-constant infusions of [1-13C]leucine. Absolute production rates (APR) of VLDL apoB were higher in FH than in controls (27.1+/-1.9 vs. 17.9+/-2.1 mg/kg/day P < 0.03). VLDL APR in FDB were between those of FH and controls (24.3+/-4.8 mg/kg/day), and demonstrated a relatively large inter-individual variability. The increase in VLDL APR in FH resulted in higher fasting serum triglyceride concentrations than in controls (P < 0.05), whereas in FDB triglycerides were between those observed in FH and in controls. A significant correlation was observed between VLDL apoB APR and serum triglycerides in FH and in FDB; the correlation coefficient for all subjects was r = 0.84 (P < 0.0001), indicating that the major determinant of serum triglyceride concentrations was VLDL apoB APR. IDL apoB APR was lower in FH and in FDB compared to controls (P < 0.03 P < 0.02, respectively): and its fractional catabolic rate (FCR) was slightly lower in FH and in FDB, resulting in similar plasma IDL apoB concentrations in all three groups of subjects. IDL apoB APR in FH were negatively correlated with LDL cholesterol concentrations (r = -0.89; P < 0.001); LDL cholesterol concentrations correlated positively with the part of VLDL that did not appear in IDL (r = 0.82 P < 0.02), by-passing therefore the delipidation cascade. In conclusion the data demonstrate increased VLDL apoB production rates in FH. VLDL and IDL kinetics differ when LDL concentrations are elevated either due to a LDL receptor defect or due to defective apolipoprotein B-100.

Adult↗
PubMed1997

[Clinical value of C-peptide determination].

The classification of newly diagnosed diabetic patients as type I (insulin-dependent) or type II (non-insulin-dependent) diabetes and the implied therapeutical consequences there of are based on clinical observations and laboratory tests. In case differential diagnosis is difficult, the measurement of the c-peptide secretion to assess beta-cell capacity can be helpful. For adequate control especially after long-standing diabetes in obese patients it is important to identify patients with potential secondary drug failure. Poor compliance with diet is thought to be a major reason for poor response to treatment. On the other hand, diabetics with poor control because of deterioration of beta-cell function must be distinguished. In these situations the measurement of c-peptide concentrations may contribute to identify the need for insulin treatment. As a result the development of diabetic complications can be retarded and beta-cell function can be preserved by adequate insulin therapy, whereas the consequences of hyperinsulinaemia in insulin treated patients not needing insulin can be avoided. In our opinion the c-peptide/glucose-quotient serves as simple, cost-effective and non-invasive method in the assessment of beta-cell capacity. Insulin therapy is indispensable in the case of inadequate insulin secretion.

Aged↗
PubMed1997

[Bilateral glomus tumors with a blood pressure regulation disorder due to baroreceptor dysfunction].

HISTORY AND CLINICAL FINDINGS: A 73-year-old woman was admitted because of vertigo of recent onset with a tendency to fall down and progressive hearing impairment with tinnitus over the last 2 years. Neurological examination also revealed right recurrent nerve paresis, facial hemispasm and lingual atrophy, pointing to a lesion involving cranial nerves VII, VIII, IX, X and XII. She was found to have spontaneous nystagmus to the left, due to peripheral vestibular function deficit, without otoscopic abnormalities. She was in atrial fibrillation with a blood pressure of 140/80 mm Hg. The suspected cause was a hormonally active glomus jugulare tumour with intermittent hypertension and involvement of several cranial nerves. INVESTIGATIONS: Repeatedly measured plasma and urinary catecholamine concentration was normal. Neuroradiology showed a contrast-rich lesion close to the jugular vein and the hypoglossal nerve, as well as a tumour in the left retromandibular fossa with displacement of the left internal carotid artery. The suspected cause of these findings was a neurologically asymptomatic left carotid body tumour with multiple cranial nerve deficits (VII, VIII, IX and XII) due to their compression at the base of the skull. No abnormal catecholamine activity could be demonstrated. TREATMENT AND COURSE: After complete excision of the right carotid body there were no further hypertensive crises. Later on the left carotid body tumour was embolised because it had continued to grow. CONCLUSION: The repeated hypertensive crises were probably caused by absent blood pressure regulation, the result of destruction of the afferent fibres. This destruction was due to compression of the hypoglossal nerve by the right jugular glomus, at the same time as the contralateral carotid body had been destroyed by tumour.

Aged↗
PubMed1997

Effects of Er:YAG laser in caries treatment: a clinical pilot study.

BACKGROUND AND OBJECTIVE: Various lasers have been suggested for cavity preparation. Pain reduction is expected as a potential benefit of laser usage. Among the systems studied in vitro, the Er:YAG laser offers a distinct combination of high ablation efficiency and low thermal side effects. Animal studies demonstrated that pulp damage can be avoided when appropriate laser parameters are used. STUDY DESIGN/MATERIAL AND METHODS: The present prospective clinical study was intended to test the practical applicability of the system and to investigate the patient's response. The study population consisted of 67 teeth on 33 subjects. Patient's reaction to pain was documented in four categories: no pain, little pain (like a brief pressure to the tooth), medium pain (like needle sticks), and strong pain (like a thermal shock test). RESULTS: For superficial cavities 200 pulses (SD: 114) were needed. At a pulse repetition rate of 2 Hz, the preparation time was 1.6 min (SD: 2.1 min). Deeper cavities required 391 pulses (SD: 251), or approximately 3.3 min (SD: 2.1 min). No loss in pulp vitality was observed. In 36% of the laser-treated teeth, no pain was felt, and in 57%, little pain was reported. With one exception, no local anesthesia was needed. CONCLUSION: On the basis of this study, we suggest that the Er:YAG: laser can provide caries removal and cavity preparation in an adequate preparation time with minimal patient discomfort.

Adult↗
PubMed1997

Comparison of bezafibrate and simvastatin in the treatment of dyslipidaemia in patients with NIDDM.

Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia. However, these two groups of drugs have not been compared in diabetic patients in a randomized controlled trial. Therefore, a multicentre study was performed in 73 subjects with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and combined hyperlipidaemia (serum cholesterol 6.2-10.0 mmol l(-1), serum triglycerides 2.3-10.0 mmol l(-1)), comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion. Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin (-41% vs -22%, p < 0.001) and increased HDL cholesterol more (bezafibrate: + 17% vs simvastatin: + 9%, p < 0.05). LDL cholesterol levels decreased by 14% (p < 0.001) during simvastatin and increased by 21% (p < 0.01) during bezafibrate. This increase in LDL cholesterol was positively correlated with fasting serum triglycerides (p < 0.001) and was associated with a reduction of the serum apolipoprotein B concentration, suggesting an increase in LDL particle size. Metabolic control of diabetes (fasting glycaemia; HbA1c) and insulin secretion (C-peptide levels) were unaffected by both treatments. The incidence of side-effects during treatment was similar for both drugs. Thus, 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides.

Aged↗
PubMed1997

Absence of short-term effects of glucagon-like peptide-1 and of hyperglycemia on plasma leptin levels in man.

In rodents, leptin and the incretin glucagon-like peptide-1 (7-36) amide (GLP-1) affect feeding at least in part via interaction with hypothalamic neuropeptide Y (NPY), suggesting that cross talk may exist between GLP-1 and the ob gene product. Besides insulin, acute hyperglycemia has recently been shown to induce ob gene expression. To address the question of whether leptin plasma levels in humans are affected by GLP-1 infusion and/or hyperglycemia, eight healthy volunteers were studied during euglycemia and hyperglycemic clamping with or without GLP-1 administration while insulin levels were kept constant by somatostatin infusion. Under all conditions, leptin plasma levels remained unchanged, demonstrating that in humans leptin plasma concentrations are affected neither by short-term peripheral GLP-1 infusion nor by hyperglycemia, which suggests that postprandial GLP-1 release and hyperglycemia do not modulate secretion of the ob gene product.

Adult↗
PubMed1997

Ethanol exerts acute protein-sparing effects during postabsorptive but not during anabolic conditions in man.

Ethanol abuse is frequently associated with protein malnutrition. To assess the acute effects of ethanol on whole-body protein metabolism, [1-13C]leucine kinetics were measured in eight postabsorptive normal male subjects three times, ie, during administration of two doses of ethanol (dose 1, 0.52 g/kg during 2 hours and 0.3 g/kg during 3 hours; dose 2, 0.69 g/kg during 2 hours and 0.3 g/kg during 3 hours) and during saline (controls). During the last 2 hours of the studies, glucose, insulin, and amino acids were infused to assess the effects of ethanol on protein kinetics under anabolic conditions (euglycemic clamp). The decreases in leucine flux (reflecting whole-body protein breakdown) and nonoxidative leucine disappearance (a parameter of protein synthesis) during saline infusion were abolished in both ethanol protocols (P < .05 or less v saline). The rate of leucine oxidation decreased during the higher dose of ethanol compared with saline (P < .005), indicating an anticatabolic effect. During anabolic conditions (clamp), leucine flux and nonoxidative leucine disappearance were significantly higher in both ethanol studies compared with saline (P < .05). Resting energy expenditure (REE) and oxygen consumption (VO2) during the euglycemic clamp increased to a greater degree during both ethanol studies than during saline (P < .05 or less). Thus, an elevation of blood ethanol concentrations to the levels observed in social drinking results in a net anticatabolic effect (diminished leucine oxidation) when ethanol is administered alone. However, during administration of other nutritional substrates, the anticatabolic effect was not detectable, possibly because ethanol enhanced nutrient-induced thermogenesis.

Adult↗
PubMed1997

Mechanism of alkaloid cyclopeptide synthesis in the ergot fungus Claviceps purpurea.

BACKGROUND: Previous analyses of the biosynthesis of the alkaloid cyclopeptides from the ergot fungus Claviceps purpurea were hampered by a lack of suitable systems for study in vitro, and this led to conflicting results concerning the mechanism of alkaloid cyclopeptide formation. Recently, D-lysergyl peptide synthetase (LPS) of the ergot fungus Claviceps purpurea, which assembles the non-cyclol precursors of the ergopeptines, has been partially purified and shown to consist of two polypeptide chains of 370 kDa (LPS 1) and 140 kDa (LPS 2); these contain all the sites necessary for the assembly of the D-lysergyl peptide backbone. The mechanism of D-lysergyl peptide synthesis remained unclear, however. RESULTS: We have identified the obligatory peptidic intermediates in D-lysergyl peptide synthesis and the sequential order of their formation. The two LPS subunits catalyze the formation of D-lysergyl mono-, di-, and tripeptides as enzyme-thioester intermediates, the formation of which appears to be irreversible. Peptide synthesis starts when D-lysergic acid binds to the LPS 2 subunit, which most probably occurs after the previous round of synthesis has been completed by the release of the end product from the LPS enzyme. CONCLUSIONS: We have shown that the mechanism of D-lysergyl peptide synthesis is an ordered process of successive acyl transfers on a multienzyme complex. This knowledge opens the way for enzymatic and genetic investigations into the formation of novel alkaloid cyclopeptides.

Alkaloids↗
PubMed1997

Effects of glucagon-like peptide 1 (7-36 amide) on whole-body protein metabolism in healthy man.

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-13C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO2 production during GLP-1 administration (P < 0.0005). Plasma insulin increased after 3h of GLP-1 infusion to 1486 +/- 145 pmol L(-1) vs. 185 +/- 12 pmol L(-1) for saline (P < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.

Adult↗
PubMed1997

Effects of insulin-like growth factor I combined with growth hormone on glucocorticoid-induced whole-body protein catabolism in man.

Treatment with insulin-like growth factor I (IGF-I) alone failed to affect glucocorticoid-induced protein catabolism in a previous study from our laboratory. To assess the effects of the combination of IGF-I and GH in a similar protocol, 24 normal subjects received (in a double-blind, randomized, placebo-controlled manner) s.c. injections of either GH alone (0.3 IU/kg.day), the combination of IGF-I (80 micrograms/kg.day) and GH (0.3 IU/kg.day), or placebo for a period of 6 days during which they were treated with methylprednisolone (0.5 mg/kg.day). Whole-body protein kinetics measured, using the [1-13C]-leucine infusion technique, demonstrated that leucine flux (a parameter of protein breakdown) increased during administration of glucocorticoids alone (placebo group) and during GH-treatment, whereas the glucocorticoid-induced increase was abolished during IGF-I plus GH (P < 0.03 vs. GH). Leucine oxidation (a parameter of irreversible protein catabolism) increased in the placebo group (+60 +/- 14.5%, P < 0.005, day 7 vs. day 1), remained unchanged in the GH group (+2.5 +/- 10%), and decreased in the combination group (-17.7 +/- 3.3%, P < 0.002, day 7 vs. day 1). Glucose MCR decreased in the group receiving placebo (P < 0.05) and remained unchanged during combined treatment with IGF-I plus GH. It is concluded that glucocorticoid-induced protein, catabolism (leucine oxidation) is abolished during coadministration of GH (anticatabolic effect), whereas treatment with IGF-I and GH results in a net anabolic effect without adverse effects on peripheral glucose clearance.

Adult↗
PubMed1997

Risk factor control and perceptions of risk factors in patients with coronary heart disease.

Treatment of hypertension and hyperlipidaemia improves cardiovascular and overall mortality in patients with coronary heart disease. Adequate awareness of atherogenic risk factors is a key first step that enables patients to address their risk factors. In a recently completed study in coronary heart disease patients at coronary angiography and 18 months later, we found that skewed views about atherogenic risk factors in general were expressed. In addition, awareness of the patients' own hypercholesterolaemia or diabetes mellitus was often inadequate or lacking, in contrast to their awareness of blood pressure or bad smoking habits. Awareness of risk factors had only marginally improved 18 months after the initial investigation. Smoking habits, total cholesterol, and HDL values had improved over 18 months but lipid values were far from reaching target values of accepted guidelines. A majority of our patients remained with at least one treatable and insufficiently controlled atherogenic risk factor, usually hypercholesterolaemia. Interestingly, higher awareness of risk factors correlated with better risk factor control. These observations suggest that systematic interventions are necessary to further ameliorate secondary prevention in coronary heart disease. Successful standardized programmes of high or perhaps medium intensity, that include systematic screening of risk factors, reasoned educational interventions, and methodical management of treatable atherogenic risk factors according to accepted, guidelines, therefore require further attention in daily medical practice.

Coronary Angiography↗