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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 91 records · Page 5Linked to original sources
PubMed2001

Antidepressive response to sleep deprivation in unipolar depression is not associated with dopamine D3 receptor genotype.

The psychostimulant theory of antidepressive sleep deprivation (SD) proposes a contribution of dopamine D3 receptors (DRD3) in the limbic system to the antidepressant effects of SD. Neuroendocrinological studies suggest a positive correlation of clinical response to SD and cortisol secretion. We hypothesized that the clinical response to SD and amount of cortisol secretion upon SD is associated with the 1-1 genotype of the Bal1 polymorphism of DRD3 on exon 1. In this study, aiming at evaluating the feasibility of screening large patient samples, 52 inpatients (19 males/33 females) with unipolar depression and a score of 18 or more on the 21-item Hamilton Depression Rating Scale were treated with 1 night of total SD. We found that 31% of our patients responded to SD. There was no association between response to SD and the genotype of the DRD3 Bal1 polymorphism (p < 0.879). There was also no association between increase in cortisol secretion after SD and DRD3 genotypes (p < 1.000) in a subgroup of patients. Statistical power analysis ruled out a major effect of the DRD3 Bal1 polymorphism on clinical response to SD. These results suggest that the DRD3 Bal1 polymorphism is not a promising lead to be followed up in larger patient samples.

Adult↗
PubMed2001

Biosynthesis of N-acetylneuraminic acid in cells lacking UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase.

The first two steps in mammalian biosynthesis of N-acetylneuraminic acid, an important carbohydrate moiety in biological recognition systems, are performed by the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. A subclone of the human B lymphoma cell line BJA-B K20, lacking UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase mRNA as well as epimerase activity, displayed hyposialylated, functionally impaired cell surface glycoconjugates. Here we show that this cell line surprisingly still retains N-acetylmannosamine kinase activity. A gel filtration analysis of BJA-B K88 control cells, which express UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, revealed two N-acetylmannosamine kinase activity peaks, one co-eluting with UDP-N-acetylglucosamine 2-epimerase activity and one co-eluting with N-acetylglucosamine kinase. For this enzyme previous studies already showed a ManNAc kinase activity in vitro. In contrast, the hyposialylated BJA-B K20 subclone displayed only the N-acetylmannosamine kinase peak, co-migrating with N-acetylglucosamine kinase. The CMP-N-acetylneuraminic acid content of both K88 and K20 cells and the sialylation of cell surface glycoconjugates of K20 cells could be significantly increased by supplementing the medium with N-acetylmannosamine. This N-acetylmannosamine-induced increase was drastically reduced by co-supplementation with N-acetylglucosamine only in K20 cells. We therefore propose the phosphorylation of N-acetylmannosamine as a hitherto unrecognized role of N-acetylglucosamine kinase in living cells.

Acetylgalactosamine↗
PubMed2001

Unchanged incidence of lower-limb amputations in a German City, 1990-1998.

OBJECTIVE: A reduction of diabetes-related amputations by at least one-half within 5 years was declared a primary objective for Europe (St. Vincent Declaration, 1989). We collected data about incidence rates of amputations in one German city (Leverkusen, with a population of approximately 160,000 inhabitants) between 1990 and 1998 to ascertain a potential change in rates of incidence. RESEARCH DESIGN AND METHODS: From all three hospitals in Leverkusen, we obtained complete lists of lower-limb amputations. From each patient record, diabetic status was determined. Only the first observed amputation was counted for the analysis. We estimated incidence rates of amputations in the entire population, the diabetic population, and the nondiabetic population. To test for time trend, we fitted Poisson regression models, adjusting for age and sex. RESULTS: During, the defined period (the years 1990, 1991, and 1994-1998), 339 patients (all residents of Leverkusen) without previous amputations had nontraumatic lower-limb amputations. Of all subjects. 46% were female. Moreover, 76% of the subjects were known to have diabetes. Mean age was 71.3 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population, per 100,000 person-years) were as follows: 1990, 549; 1991, 356; 1994, 544; 1995, 386; 1996, 426; 1997, 433; and 1998, 463. The Poisson models showed no significant change of incident amputations over time in the diabetic population or in the nondiabetic population. CONCLUSIONS: Beyond random variation, no change of incidence rates could be observed over the past 9 years. More specific interventions are needed to achieve a substantial reduction of diabetes-related amputations.

Adolescent↗
PubMed2001

Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study.

BACKGROUND: Over recent years, the use of antidepressants for the symptomatic treatment of insomnia has grown substantially, but controlled studies are still lacking. Our study is the first investigation to prove objective efficacy and tolerability of low doses of a sedating antidepressant in a randomized, double-blind, and placebo-controlled manner in patients with primary insomnia. METHOD: Forty-seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean +/- SD duration of complaints = 11.2+/-9.7 years) received either 25-50 mg of the tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polysomnography at baseline and the first night of application, at 4 weeks of treatment and the first to third night of withdrawal, and after 2 weeks of withdrawal. RESULTS: In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p < or = .001) and subchronic (night 28, p < or = .05) intake compared with the patients who received placebo (N = 20, 47.4+/-16.8 years of age). Latency to sleep onset was not affected since the patients had normal baseline sleep latencies. Investigators found doxepin to cause significantly (p < or = .05) better global improvement at the first day of treatment. Patients rated sleep quality (p < or = .001) and working ability (p < or = .005) to be significantly improved by doxepin during the whole treatment period. Overall rebound in sleep parameters was not observed, but patients with severe rebound insomnia were significantly more frequent in the doxepin group (night 29, p < .01, night 30, p < or = .01; night 31, p < or = .05). No significant group differences in side effects were found, but 2 doxepin-treated patients dropped out of the study due to specific side effects (increased liver enzymes, leukopenia, and thrombopenia). CONCLUSION: The results support the effectiveness of low doses of doxepin to improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound insomnia and specific side effects have to be considered.

Antidepressive Agents, Tricyclic↗
PubMed2001

Association of ARF and Rabs with complement receptor type-1 storage vesicles in human neutrophils.

During neutrophil activation, the properties of the cell are rapidly altered by increases in the surface expression of functionally important receptors and adherence molecules. At the same time, endocytic and phagocytic activities increase. These alterations require precise regulation of membrane and protein movement, which is achieved, at least in part, by bidirectional movement of small transport vesicles. GTP-binding proteins, including Rabs and ADP-ribosylation factors (ARFs), play critical roles in regulating vesicle trafficking in other types of cells. The ability to immunoisolate the "secretory" vesicle subpopulation in which complement receptor type 1 (CR1) is stored allowed us to determine which types of low-molecular-weight GTP-binding proteins interact with these vesicles and under what conditions. CR1-containing vesicles from resting human neutrophils constitutively copurify with Rabs 3a, 4, and 5a, and reversibly bind an ARF, likely ARF1. ARF binding is dependent on free Mg(2+) and is enhanced by GTPgammaS. Mg(2+) at 0.4 microM is necessary for half-maximal binding of ARFs to CR1 storage vesicles. Artificial phospholipid vesicles and primary and secondary granules from human neutrophils do not bind ARFs themselves and do not compete for recruitment of ARFs to CR1 vesicles, suggesting that specific membrane environments and/or proteins on these vesicles stabilize the ARF-GTP-Mg(2+) complex. Free Ca(2+) at 300 nM does not inhibit ARF binding to CR1 storage vesicles, but 10 mM Ca(2+) does reduce such binding. These findings suggest that ARF-GTP specifically and reversibly interacts with CR1 storage vesicles in human polymorphonuclear leukocytes and may play a role in regulating their transport.

ADP-Ribosylation Factor 1↗
PubMed2001

[Orthodontic correction of a complex malocclusion of the canine teeth of dento-alveolar and skeletal origin using a model cast device in the upper jaw of the dog].

Malocclusion of the canines, which in dogs is frequent and often has a congenital pattern, remains a challenge to treat. Steeply positioned lower jaw canines are corrected by means of a specifically designed orthodontic intervention. The case at hand was characterized by a combination of a slight skeletal distal bite and compensatory distal tilt of the entire premaxilla (retrusion, caudal tilt) with a mesial tilt of the canines in the upper jaw (rostral and anterior tilt). An individual solution was found which resulted in a functional adjustment of both upper and lower jaws. A model cast device which included both appropriately tilted areas and screws to ensure distal adjustment solved the problem.

Animals↗
PubMed2001

[Progressive correction of an ulnar clubhand secondary to post-traumatic epiphysiodesis of the distal ulna].

The authors report the correction of an ulnar club-hand in a 16 year-old boy who complained of recurrent wrist pain after a fracture of both bones of his left forearm treated by internal fixation at the age of nine years. Correction was achieved by progressive ulnar lengthening, using Ilizarov's method, without radius osteotomy or bone grafting. Union was achieved 2 months post-operatively. Functional outcome and cosmetic appearance were satisfying.

Adolescent↗
PubMed2000

A role for the polyproline domain of p53 in its regulation by Mdm2.

The p53 protein plays a key role in the cellular response to stress by inducing cell growth arrest or apoptosis. The polyproline region of p53 has been shown to be important for its growth suppression activity. p53 protein lacking the polyproline region has impaired apoptotic activity and altered specificity for certain apoptotic target genes. Here we describe the role of this region in the regulation of p53 by its inhibitor Mdm2. p53 lacking the polyproline region was identified to be more susceptible to inhibition by Mdm2. Furthermore, the absence of this region renders p53 more accessible to ubiquitination, nuclear export, and Mdm2-mediated degradation. This increased sensitivity to Mdm2 results from an enhanced affinity of Mdm2 toward p53 lacking the polyproline region. Our results provide a new explanation for the impaired growth suppression activity of p53 lacking this region. The polyproline region is proposed to be important in the modulation of the inhibitory effects of Mdm2 on p53 activities and stability.

Animals↗
PubMed2000

Universal bases for hybridization, replication and chain termination.

Several unnatural, predominantly hydrophobic nucleobases that pack efficiently in duplex DNA without hydrogen bonding functionalities are reported to circumvent the hydrogen bonding-based specificity, both during oligonucleotide hybridization and enzymatic DNA synthesis. The reported nucleoside analogs are efficient 'universal bases' for hybridization, template directed DNA synthesis and chain termination. Moreover, several of the universal bases function in their biological role, hybridization or replication, with an efficiency not significantly reduced relative to their natural counterparts.

Base Pairing↗
PubMed2000

[Self-treatment instruction of patients with type 1 diabetes. Report from hospitals belonging to Working Group for Structured Diabetes Therapy (ASD) in Germany 1998].

AIM: Intensified insulin therapy is the therapy of choice for patients with diabetes Type I. Intensified insulin therapy includes an basis-bolus insulin injection regimen or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring, self-adaptation of insulin dosages by the patients themselves and a far-reaching liberalization of nutrition. The patients learn self management of diabetes therapy in a structured treatment and teaching program. The effectivity of this program is evaluated in the routine care. PATIENTS AND METHOD: A peer-review quality circle was formed as an official working group of the German Diabetes Association based on the formation of a working group (Arbeitsgemeinschaft für Strukturierte Diabetestherapie [ASD]) of presently 135 general internal medicine departments from city, country and university hospitals throughout the country. The group attempted to document and to improve the quality of structure and process of Type-I diabetes care in its participating institutions by a system of peer supervision. Systematic follow-up examinations of 50 consecutive Type-I diabetic patients 12 to 15 months after participation in the program confirm the outcome quality. The working group meets every year to discuss the results non anonymously. A PC-system (DIQUAL) was developed for collecting, checking and pooling of the outcome data. RESULTS: From 1992 a representative sample of 6.555 patients with Type-I diabetes was examined. At the first time in 1998 the outcome results of 1.789 patients were analyzed depending on the therapeutic goals. In patients with a high initial HbA1c (> or = 8%) an improvement from 9.8 to 8.0% was reached going together with a reduction of severe hypoglycemia from 0.23 to 0.13/patient/year. In patients with an acceptable initial HbA1c (< 8%) the frequency of severe hypoglycemia could be reduced from 0.65 to 0.24/patient/year without any deterioration in metabolic control. Furthermore the incidence of ketoacidosis with hospitalization and the inpatient days were reduced significantly. CONCLUSION: A substantial improvement of HbA1c and reduction of acute complications, especially of severe hypoglycemia in patients with Type-I diabetes were reached by participation in a structured teaching and treatment programme in clinical routine care.

Blood Glucose Self-Monitoring↗
PubMed2000

c-Jun and p53 activity is modulated by SUMO-1 modification.

The ubiquitin-related SUMO-1 molecule has been shown recently to modify covalently a number of cellular proteins including IkappaBalpha. SUMO-1 modification was found to antagonize IkappaBalpha ubiquitination and protect it from degradation. Here we identify the transcription factors c-Jun and p53, two well known targets of ubiquitin, as new substrates for SUMO-1 both in vitro and in vivo. In contrast to ubiquitin, SUMO-1 preferentially targets a single lysine residue in c-Jun (Lys-229), and the abrogation of SUMO-1 modification does not compromise its ubiquitination. Activation of Jun NH(2)-terminal kinases, which induces a reduction in c-Jun ubiquitination, similarly decreases SUMO-1 modification. Accordingly, loss of the two major Jun NH(2)-terminal kinase phosphorylation sites in c-Jun, Ser-63 and Ser-73, greatly enhances conjugation by SUMO-1. A SUMO-1- deficient c-JunK229R mutant shows an increased transactivation potential on an AP-1-containing promoter compared with wild-type c-Jun, suggesting that SUMO-1 negatively regulates c-Jun activity. As with c-Jun, SUMO-1 modification of p53 is abrogated by phosphorylation but remains unaltered upon chemical damage to DNA or Mdm2-mediated ubiquitination. The SUMO-1 attachment site in p53 (Lys-386) resides within a region known to regulate the DNA binding activity of the protein. A p53 mutant, defective for SUMO-1 conjugation, shows unaltered ubiquitination but has a slightly impaired apoptotic activity, indicating that modification by SUMO-1 might be important for the full biological activity of p53. Taken together, these data provide a first link between the SUMO-1 conjugation pathway and the regulation of transcription factors.

HeLa Cells↗
PubMed2000

Postprandial hepatic glycogen synthesis in liver transplant recipients.

BACKGROUND: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion. METHODS: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen. RESULTS: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis. CONCLUSIONS: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.

Adult↗
PubMed2000

Polymeric membrane electrodes for monohydrogen phosphate and sulfate.

A zwitterionic bis(guanidinium) ionophore bearing an anionic closo-borane cluster (1) and a dihydrochloride analogue (2) are investigated in polymeric membrane ion-selective electrodes (ISEs). Both compounds have been previously shown to complex and selectively extract oxoanions. By systematic variation of the kind and concentration of the ion-exchanger sites in the membrane, the optimal performance with the so far best sulfate selectivity is found for ISE membranes based on the dihydrochloride, whereas those with the zwitterion analogue are shown to possess a reasonably good selectivity for monohydrogen phosphate.

Hydrogen↗
PubMed2000

[Perspectives and limits in treatment of obesity].

The widely propagated morbidity and mortality risks of obesity appear somewhat exaggerated, except for morbid obesity (BMI > 40 kg/m2) and for high risk obese subgroups concerning diabetes mellitus, hypertension, metabolic syndrome and obstructive sleep apnea syndrome. Non-medical reasons represent a major component of the social pressure that is presently experienced by obese persons in our society. Weight reduction represents the primary therapeutic approach in overweight patients with type 2 diabetes, hypertension, metabolic syndrome and obstructive sleep apnea, and it may be recommended in high-risk individuals for primary prevention of these diseases. Massive obesity is associated with excess mortality, especially in younger, physically inactive men with upper-body-segment obesity. It is widely assumed that weight reduction will lead to a reduction of excess mortality in these individuals; so far, however, there is no proof for this assumption. Non-medicamentous conservative therapeutic approaches to weight reduction have the advantage of safety, even though their long-term efficacy is generally disappointing. There are no randomized, controlled trials to prove a reduction of morbidity or mortality risks and of therapeutic safety for pharmacological, invasive or surgical methods to treat obesity.

Body Mass Index↗
PubMed2000

[The concept of "evidence-based medicine" in psychiatry. A path to a more rational psychiatry?].

Many of the diagnostic and therapeutic procedures in psychiatry and psychotherapy are based on opinion rather than evidence. The concept of evidence-based medicine aims to bridge the gap between clinical research and clinical decision-making by integrating the best available external evidence with personal expertise. In this article, we demonstrate several examples of the non-evidence-based medicine paradigm. Then we show the usefulness and practicability of the new evidence-based medicine paradigm by using a clinical example. Finally, we discuss the consequences, chances, and limitations of this new model. We also examine the role of the individual clinician's viewpoint as well as the need of institutional re-engineering and the possible restructuring of the entire health care system towards evidence-based methods.

Antidepressive Agents, Tricyclic↗