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Biomedical subjects

H Koch

Publications and source records attributed to H Koch.

At least 163 records · Page 9Linked to original sources
PubMed2000

Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform.

Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3). With the exception of a ubiquitously expressed Munc13-2 splice variant, Munc13 proteins are brain-specific. Munc13-1 has a central priming function in synaptic vesicle exocytosis from glutamatergic synapses. In order to identify Munc13-like proteins that may regulate secretory processes in non-glutamatergic neurons or non-neuronal cells, we developed protein profiles for two Munc13-homology-domains (MHDs). MHDs are present in a wide variety of proteins, some of which have previously been implicated in membrane trafficking reactions. Taking advantage of partial sequences in the human expressed sequence tag (EST) database, we characterized a novel, ubiquitously expressed, rat protein (Munc13-4) that belongs to a subfamily of Munc13-like molecules, in which the typical Munc13-like domain structure is conserved. Munc13-4 is predominantly expressed in lung where it is localized to goblet cells of the bronchial epithelium and to alveolar type II cells, both of which are cell types with secretory function. In the present study we identify a group of novel proteins, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD profiles described in the present study are useful tools for the identification of Munc13-like proteins, that would otherwise have remained undetected.

Alternative Splicing↗
PubMed2000

[Outpatient treatment of patients with cardiovascular diseases].

In Germany, cardiovascular disturbances belong to the diseases most frequently treated in the offices of general practitioners and internal specialists. With comprehensive monitoring and the taking of adequate therapeutic measures, the average mortality age of the majority of the 18 million patients suffering from circulatory diseases lies at 79.4 years. In the age group of over 70 years, 70 to 80% of the patients receive treatment against cardiovascular disturbances, most of them against hypertension. One of the most important goals of monitoring and intervention in the outpatient sector is the treatment of hypertension, especially in connection with measures taken against disturbances in lipometabolism in order to prevent secondary diseases. The success of treatment is shown by the decreasing age standardized rate of cardiac infarctions, especially among men, and the decreasing mortality rate of patients below 65. The increasing treatment in the outpatient sector is accompanied by additional interventions, especially by bypass surgery in the hospital sector. The concerted actions in both the outpatient and the inpatient sector result in a higher service provision to come to a higher quality of life in the patients and to prevent early death.

Adult↗
PubMed2000

[The professional profile of the oromaxillofacial surgeon in the clinic].

The German Society of Oral and Maxillofacial Surgery (Die Deutsche Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie) is celebrating its 50th birthday--an occasion to highlight the current professional and political situation and future perspectives in the clinics devoted to this specialty. To this end, structural data from 71 major clinics (or divisions) are analyzed. The clinics have 2,300 beds, 32 on average, with a variance width of 10:64. This corresponds to one clinic bed for approximately 35,000 inhabitants. The neighborhood of the clinics and thus the working conditions and personnel situation have changed markedly in the past few years. Working conditions are evident from the doctor-bed proportion with its resulting burden on the medical team. There are 244 assistants currently studying for their specialty; 107 others are striving for the additional title of "Plastic operations". Plans for positions are based less on the planned number of beds than on the number of cases, productivity, and treatment spectrum of the clinic, sometimes with a bonus for research and teaching. The outpatient sector, which plays a major role, is not considered. Health-care politics continue to stress budgeting and rationalization, i.e., further cuts for positions and beds, including for maxillofacial clinics. While the professional and political concerns of the clinic doctors increase, health insurances are increasingly exerting influence on medical services and the financing of hospitals. This can prove life threatening for the clinics. The administrative structure of the clinics is also being questioned and is to be replaced by a collegial system. But the survival of the clinics and their personnel structure depend specifically on qualified management, clearly set goals, the ability to integrate, and openness to innovation. The advanced education of young oral and maxillary facial surgeons should be reconsidered, and more unlimited positions for medical specialists should be created. If the high standard of our specialty and the quality of education can be strengthened and extended, the perspectives for the future of clinical oral and maxillofacial surgery can be considered to be propitious, in spite of aggravated conditions.

Dental Clinics↗
PubMed2000

Effect of irrigating solution and irrigation temperature on the cornea and pupil during phacoemulsification.

PURPOSE: To evaluate the effect of irrigation solution and temperature on pupil diameter, corneal endothelium, and corneal pachymetry during and after phacoemulsification. SETTING: Klinik Dardenne, Bonn, Germany. METHODS: Eighty patients who had cataract surgery by phacoemulsification were assigned to 1 of 4 cross-classified groups and had intraoperative irrigation with room-temperature or refrigerated fortified balanced salt solution (BSS Plus) or modified Ringer's solution. Pupil diameters were recorded at different stages during the surgery. Epithelial cell counts and pachymetry were determined before and 1 day after surgery. RESULTS: The solution temperature did not affect any parameter. The type of solution did not influence endothelial cell loss; however, the solution had a significant effect on corneal pachymetry 1 day postoperatively. The corneas irrigated with BSS Plus were less swollen than the corneas irrigated with Ringer's solution. By day 14, corneal thickness was equal among all groups. CONCLUSION: Long-term results were equally favorable in all 4 groups. However BSS Plus induced less short-term corneal swelling than Ringer's solution. From these findings, it appears that BSS Plus may decrease corneal risk in cases with compromised corneas or prolonged surgery.

Adult↗
PubMed2000

[Diagnostic spectrum and treatment requirements of general practice clients. Results of the ADT Panel of the Central Institute of National Health Insurance Management].

Results of the ADT-Panel of the Central Research Institute of ambulatory health care in Germany. The ADT-Panel of the Central Research Institute contains the remuneration data that are quarterly collected by office-based physicians and transmitted in anonymous form. These data can be classified according to the status of the insured patient, the diagnoses made or the treatment provided. The Patient Panel does therefore represent an important instrument which allows a rapid scientific analysis (3 to 4 weeks after the end of a quarter) about how patients are treated by different specialists. It might also be used to forecast trends. The Patient Panel does as well allow the demonstration of specialty-related statistics on diagnoses and disease-related treatment provision. The complete publication and some exemplary tables can be found in the DGN Internet (www.dgn.de; Deutsches Gesundheitsnetz). A short summary is available on the home page of the Central Research Institute (www/zi-koeln.de).

Ambulatory Care↗
PubMed1999

A presynaptic role for the ADP ribosylation factor (ARF)-specific GDP/GTP exchange factor msec7-1.

ADP ribosylation factors (ARFs) represent a family of small monomeric G proteins that switch from an inactive, GDP-bound state to an active, GTP-bound state. One member of this family, ARF6, translocates on activation from intracellular compartments to the plasma membrane and has been implicated in regulated exocytosis in neuroendocrine cells. Because GDP release in vivo is rather slow, ARF activation is facilitated by specific guanine nucleotide exchange factors like cytohesin-1 or ARNO. Here we show that msec7-1, a rat homologue of cytohesin-1, translocates ARF6 to the plasma membrane in living cells. Overexpression of msec7-1 leads to an increase in basal synaptic transmission at the Xenopus neuromuscular junction. msec7-1-containing synapses have a 5-fold higher frequency of spontaneous synaptic currents than control synapses. On stimulation, the amplitudes of the resulting evoked postsynaptic currents of msec7-1-overexpressing neurons are increased as well. However, further stimulation leads to a decline in amplitudes approaching the values of control synapses. This transient effect on amplitude is strongly reduced on overexpression of msec7-1E157K, a mutant incapable of translocating ARFs. Our results provide evidence that small G proteins of the ARF family and activating factors like msec7-1 play an important role in synaptic transmission, most likely by making more vesicles available for fusion at the plasma membrane.

ADP-Ribosylation Factors↗
PubMed1999

Association between monoamine oxidase A activity in human male skin fibroblasts and genotype of the MAOA promoter-associated variable number tandem repeat.

Among fifteen male skin fibroblast cultures from eleven donors ranging in age from less than 1 year to 90 years old, the specific activity of monoamine oxidase A (MAO-A) differed 515-fold. Each culture had one of the two most common alleles (three or four 30-bp repeats) at the variable number tandem repeat locus positioned 1.2 kb upstream from MAOA exon 1 (uVNTR). The mean MAO-A activity in cultures with three uVNTR repeats was significantly lower than that in cultures with four repeats (1.6 +/- 1.1 and 13 +/- 12 nmol/h per milligram, respectively; P=0.032). MAO-A expression was confined to a cell sub-population varying from 0.5% to 90% of cells in different cultures. The mean specific activity in MAO-A+ cells (whole culture specific activity divided by the proportion of immunopositive cells) was lower for cultures with three repeats than for those with four (7.2 +/- 3.1 and 23.9 +/- 9.5 nmol/h per milligram protein, respectively; P=0.0013), with no overlap in activity between genotypes. Finding lower MAO-A activity in cultures with three uVNTR repeats compared to those with four is consistent with published evidence that MAO-A promoter constructs bearing three repeats have lower transcriptional activity in transfected neuroblastoma and choriocarcinoma cells. The uVNTR genotype may be a common genetic determinant of significant individual differences in oxidizing capacity for critical MAO-A substrates, which include serotonin, norepinephrine, and tyramine.

Adolescent↗
PubMed1999

Prevalence of risk factors of coronary heart disease in Turks living in Germany: The Giessen Study.

Turkish people represent the majority of immigrants in Germany. Even though a high proportion of Turks has been living in Germany since about 20 years, little is known about risk factors of coronary heart disease (CHD) in this population. In this study a sample of 325 male and 155 female Turks are investigated, who voluntarily underwent a health check-up in Germany. Data about the presence of CHD, risk factors and blood parameters were collected. Mean residence time was 21 and 17 years (males/females). A low percentage of female participants was observed compared to the general Turkish population in Germany. Age adjusted prevalence of CHD reached 9.5% in males and 6.7% in females, respectively. Dyslipoproteinemia (DLP) showed the highest prevalence of all risk factors investigated in both genders. Total cholesterol (TC) levels were comparable to those of other western countries and remarkably higher than reported for the population in Turkey. Besides this, low high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) levels could be found in the majority of the sample. The highest odds ratios for CHD were estimated for stress and hypertension in males and obesity in females. It is concluded that Turkish immigrants in Germany showed an assimilation of lipid pattern to western populations. However, reasons for low HDL-C levels remain unclear. Changes in the lipid metabolism chiefly seem to contribute to the risk factor pattern of Turkish immigrants in Germany.

Adolescent↗
PubMed1999

Familial clustering of infantile cirrhosis in Northern Germany: A clue to the etiology of idiopathic copper toxicosis.

Two cases of infantile liver cirrhosis of unknown origin occurred in a circumscribed rural area of Northern Germany. Both children had increased dietary copper exposure. The search for additional cases of what appeared to be idiopathic copper toxicosis (ICT) revealed a cluster of affected infants in this region, raising questions about the relative importance of genetic and environmental factors that are considered to be etiologic. We gathered clinical and pathologic data concerning the patients, analyzed the pedigrees of affected families, and searched for possible environmental factors contributing to the pathologic process. We encountered 8 cases of infantile liver cirrhosis in 5 families in Emsland, a circumscribed and predominantly rural area of Northern Germany; ICT was definitely proven in 2 cases. Clinical presentation and liver pathology in 6 additional cases were consistent with the diagnosis of ICT. Pedigrees of affected families revealed complex relationships with occasional consanguinity of parents, suggesting autosomal recessive inheritance. The households were served by private wells with water of low pH flowing through copper pipes, suggesting the possibility of increased alimentary copper exposure. These findings support earlier conclusions that ICT develops when an infant with a genetic predisposition is exposed to a copper-enriched diet.

Age of Onset↗
PubMed1999

Direct interaction between the ARF-specific guanine nucleotide exchange factor msec7-1 and presynaptic Munc13-1.

Msec7-1, a mammalian homologue of yeast sec7p, is a specific GDP/GTP exchange factor for small G-proteins of the ARF family. Overexpression of msec7-1 in Xenopus neuromuscular junctions leads to an increase in synaptic transmitter release that is most likely caused by an increase in the pool of readily releasable vesicles. However, the molecular mechanisms by which msec7-1 is targeted to presynaptic compartments and enhances neurotransmitter release are not known. In the present study, we demonstrate that msec7-1 interacts directly with Munc13-1, a phorbol ester-dependent enhancer of neurotransmitter release that is specifically localized to presynaptic transmitter release zones. Given that Munc13-1 and msec7-1 participate in very similar presynaptic processes and because Munc13-1 is specifically targeted to presynaptic active zones, we suggest that the msec7-1/Munc13-1 interaction serves to colocalize the two proteins at the active zone, a subcellular compartment with extremely high membrane turnover.

ADP-Ribosylation Factors↗
PubMed1999

Effects of cannabinoids on dopamine release in the corpus striatum and the nucleus accumbens in vitro.

Cannabinoid receptors are widely distributed in the nuclei of the extrapyramidal motor and mesolimbic reward systems; their exact functions are, however, not known. The aim of the present study was to characterize the effects of cannabinoids on the electrically evoked release of endogenous dopamine in the corpus striatum and the nucleus accumbens. In rat brain slices dopamine release elicited by single electrical pulses was determined by fast cyclic voltammetry. Dopamine release was markedly inhibited by the OP2 opioid receptor agonist U-50488 and the D2/D3 dopamine receptor agonist quinpirole, indicating that our method is suitable for studying presynaptic modulation of dopamine release. In contrast, the CB1/CB2 cannabinoid receptor agonists WIN55212-2 (10(-6) M) and CP55940 (10(-6)-10(-5) M) and the CB1 cannabinoid receptor antagonist SR141716A (10(-6) M) had no effect on the electrically evoked dopamine release in the corpus striatum and the nucleus accumbens. The lack of a presynaptic effect on terminals of nigrostriatal and mesolimbic dopaminergic neurons is in accord with the anatomical distribution of cannabinoid receptors: The perikarya of these neurons in the substantia nigra and the ventral tegmental area do not synthesize mRNA, and hence protein, for CB1 and CB2 cannabinoid receptors. It is therefore unlikely that presynaptic modulation of dopamine release in the corpus striatum and the nucleus accumbens plays a role in the extrapyramidal motor and rewarding effects of cannabinoids.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Pantoprazole lacks induction of CYP1A2 activity in man.

OBJECTIVE: This drug-drug interaction study investigated the potential influence of the proton pump inhibitor pantoprazole on the CYP1A2 activity as assessed by urinary excretion of caffeine metabolites. SUBJECTS, MATERIALS AND METHODS: 12 healthy, non-smoking volunteers underwent two treatment periods of 7 days each in randomized order with once-daily oral intake of 40 mg pantoprazole (test) or placebo (reference). On days 6 and 7 of both periods, 200 mg caffeine was administered two hours after pantoprazole intake, i.e. at the expected t(max) of pantoprazole serum concentrations. Urinary excretion of the caffeine metabolites 1X, 1U, AFMU, 17U was measured up to 8 hours after caffeine intake. In accordance with recent guidelines on drug-drug interactions, lack of interaction was handled as an equivalence problem. RESULTS: Point estimate and 90% confidence intervals (CI) of the respective ratios test/reference were 0.91 (0.81, 1.03) for (1X + 1U + AFMU)/17U, indicative for CYP1A2 activity, 1.03 (0.94, 1.13) for AFMU/1X (N-acetyl transferase activity) and 1.01 (0.94, 1.09) for 1U/1X (xanthine oxidase activity). CONCLUSION: Pantoprazole does not induce CYP1A2 activity, consistent with previous findings following theophylline administration, nor does it have any influence on N-acetyl-transferase or xanthine oxidase activity.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Spontaneous secretion of interleukin 1 receptor antagonist (IL-1ra) by cells isolated from herniated lumbar discal tissue after discectomy.

In the study presented, cells of a herniated lumbar disc were cultivated in vitro and analysed for interleukin 1beta (IL-1beta) and interleukin 1 receptor antagonist (IL-1Ra) production. The objective of this study was the detection of IL-1beta and IL-1Ra secreted by herniated lumbar discal cells after discectomy. The involvement of cytokines in the degeneration of intervertebral discs and in the pathophysiology of radiculopathy is established. Antagonizing proteins, e.g. IL-1Ra are thought to have considerable therapeutic potential. In the present study, a 51-year-old male with massive sequestrated lumbar disc herniation at L5/S1 was treated by microsurgical discectomy. Discal cells were isolated, cultures and culture supernatants immunochemically analysed for IL-1beta and IL-1Ra secretion. Spontaneous secretion of IL-1Ra was found. IL-1beta was not detected. Our findings might contradict recent studies on the role of IL-1beta and IL-1Ra. A possible therapeutic role of exogenous IL-1Ra in disc degeneration needs further research.

Cells, Cultured↗