Search PubMed⌕ Search

Biomedical subjects

A Koch

Publications and source records attributed to A Koch.

At least 163 records · Page 9Linked to original sources
PubMed1998

Expression of the ATM gene is significantly reduced in sporadic breast carcinomas.

The gene mutated in ataxia telangiectasia (A-T) patients (ATM) is located on chromosome 11q22-23, a region frequently altered in mammary tumors. Patients homozygous for ATM mutations are prone to develop a variety of different neoplasms. Female heterozygotes have been reported to carry a 5- to 8-fold increased risk of breast cancer. However, germline mutations in the ATM gene are rare in women with sporadic breast carcinomas. Most of the alterations described in A-T patients result in a functionally inactive ATM protein. Moreover, it has been suggested that mutations of the ATM gene in A-T patients influence the amount of ATM mRNA and that this may affect the severity of the disease. In the present study, we have analyzed ATM transcripts in a series of 39 breast carcinomas, 14 benign breast lesions and 12 normal breast tissue samples. ATM mRNA levels were determined by semiquantitative competitive RT-PCR. Competitor RNA molecules for the ATM gene and the housekeeping gene beta-2-microglobulin (B2M) were generated by PCR mutagenesis. Low concentrations of ATM transcripts were detected in breast carcinomas, intermediate levels in benign lesions and highest levels in normal breast tissue specimens (F-test, p = 0.0013). Our results indicate that reduced expression of the ATM gene may contribute to the development and/or malignant progression of breast carcinomas.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1998

Comparison of the lysogeny modules from the temperate Streptococcus thermophilus bacteriophages TP-J34 and Sfi21: implications for the modular theory of phage evolution.

A 7.6-kb DNA segment covering the putative lysogeny module of the pac-site-containing temperate Streptococcus thermophilus bacteriophage TP-J34 was sequenced. Sequence alignment with the lysogeny module from the cos-site-containing S. thermophilus bacteriophage phiSfi21 revealed areas of high sequence conservation (e.g., over the int gene), interspersed with regions of low or no sequence similarity (e.g., over the cro gene). Four of the six sharp transition zones from high to low sequence conservation were found within open reading frames coding for the CI repressor, the Anti-repressor, the Immunity protein, and a protein of unknown function. The transition points in the cI and ant genes appear to separate gene segments coding for distinct functional domains of these proteins. In addition, these two transition points were located at or near the deletion sites observed in spontaneous phage phiSfi21 deletion mutants, thus suggesting these transition points as recombinational hotspots. Furthermore, the sequence at the transition point in the cI gene resembles the attachment site of the phage, suggesting the involvement of the phage integrase in at least some of the exchange reactions. Contrary to the initial formulation of the modular theory of phage evolution the unit of the evolutionary exchange in streptococcal phages is not a group of functional genes, but can be as small as a single gene. Exchange reactions can also occur within genes, possibly between gene segments encoding distinct protein domains.

Amino Acid Sequence↗
PubMed1998

[Botulinum toxin treatment of neurogenic dislocation of the temporomandibular joint].

Botulinum toxin leads to paresis of the skeletal muscle lasting 2-4 months via an inhibition of acetylcholine release at the neuromuscular junction. Since 1995, botulinum toxin injections have been used in the treatment of recurrent dislocation of the temporomandibular joint (TMJ). The chemical denervation of the external pterygoid muscle restricts the angle of mouth opening, thus helping to prevent dislocation. TMJ dislocations that occur as a result of increased tone in the protracted masticatory muscles were recently defined as neurogenic dislocations of the TMJ. We conducted a clinical study to investigate the efficacy of botulinum toxin injections into the external pterygoid muscle in five patients with recurrent neurogenic dislocations of the TMJ. In the 3 months prior to the first treatment, the patients had suffered a total of 19 dislocations. In the 3-month period following the initial treatment, only one woman experienced a dislocation. We performed the treatment a total of 25 times. Five dislocations occurred during the 6- to 36-month observation period. In the meantime, two patients remain recurrence-free 1 year after receiving treatment. All the patients had a restricted ability to open their mouths as a side effect of the weakening of the external pterygoid muscle that was completely reversible over the course of 3-4 months. All other side effects were equally well-tolerated by the patients and fully reversible after 3 weeks at the most. In the two patients who remain recurrence-free without any further treatment, the increased tone of the muscles serving the jaw normalised spontaneously over the course of the underlying neurological disease. Our results show that, in the treatment of recurrent neurogenic dislocations of the TMJ, botulinum toxin injections represent a therapeutic alternative that has few side effects.

Adult↗
PubMed1998

Development of a homologous transformation system for the human pathogenic fungus Aspergillus fumigatus based on the pyrG gene encoding orotidine 5'-monophosphate decarboxylase.

A homologous transformation system for the opportunistic fungal pathogen Aspergillus fumigatus was developed. It is based on the A. fumigatus pyrG gene, encoding orotidine 5'-monophosphate decarboxylase, which was cloned and sequenced. Transformation of both Aspergillus (Emericella) nidulans and A. fumigatus pyrG mutant strains by the use of protoplasts or electroporation established the functionality of the cloned gene. DNA sequencing of the A. fumigatus pyrG1 mutant allele revealed that it encodes a truncated, non-functional, PyrG protein. Transformation of an A. fumigatus pyrG1 mutant with a plasmid carrying the novel pyrG2 allele constructed by in vitro mutagenesis yielded prototrophic transformants following recombination between both mutation sites. Analysis of transformants carrying the entire plasmid showed that up to 45% of integration had occurred at the pyrG locus. This provides a tool to target defined genetic constructs at a specific locus in the A. fumigatus genome in order to study gene regulation and function.

Amino Acid Sequence↗
PubMed1998

Is image selection a useful strategy to decrease the transmission time in teleradiology? A study using 100 emergency cranial CTs.

This study examines the suitability of working with a selection of images in a teleradiology consulting system in neurological or neurosurgical emergency situations. The teleradiology system was based on IBM-compatible personal computers, video digitization for data acquisition, and data transmission by Integrated System Digital Network. Forty normal and 60 abnormal emergency cranial computed tomograms were shown to a radiologist on call who presented all cases he regarded as pathologic to a neuroradiologic expert by teleradiology. To reduce transmission time, only a selection of images from the CT study was presented (up to four images per case). For each case the on-call radiologist's diagnosis (D(on-call)), the expert's diagnosis on the teleradiology screen (D(monitor)), and the expert's diagnosis on the original film (D(original)) was documented, together with an estimation of the agreement between those diagnoses. There was clinically relevant disagreement between the on-call radiologist's diagnosis and the neuroradiologist's diagnosis based on the image selection on the teleradiology monitor in 23% of cases. A clinically important discrepancy between the neuroradiologist's diagnosis based on the image selection and his diagnosis using the original films was found in 30% of cases. This was due to the presence of clinically relevant information on images not transferred by the on-call radiologist. Image quality of the transferred images was sufficient in all cases. Drastic selection of images from a complete CT study leads to a high rate of incorrect diagnoses and is not appropriate to reduce transmission time in teleradiology.

Humans↗
PubMed1998

[Echocardiography diagnosis of a partial anomalous pulmonary vein anastomosis in 2 patients with Ullrich-Turner syndrome].

We report on 2 infants with Ullrich-Turner syndrome in whom partial anomalous pulmonary venous drainage was diagnosed noninvasively by color-coded Doppler sonography. Several patients with the combination of anomalous drainage of one or more pulmonary veins and Ullrich-Turner syndrome have been described in the literature. However, in the majority of those previously reported cases the diagnosis of partial anomalous pulmonary venous drainage was established by angiography during cardiac catheterization performed for confirmation of other cardiovascular malformations. Our patients show that partial anomalous pulmonary venous drainage can be diagnosed easily in neonates and young infants, as long as this anomaly is taken into consideration.

Aortic Coarctation↗
PubMed1998

Radiocontrast-induced natriuresis associated with increased urinary urodilatin excretion.

OBJECTIVE: Intravascular radiocontrast agents induce a pronounced diuresis. The aim of the present study was to investigate the (patho-)physiological mechanisms of the radiocontrast-induced diuresis. DESIGN: The fractional excretion of sodium, the urinary excretion of the renal natriuretic peptide urodilatin and the plasma concentration of atrial natriuretic peptide were measured in 42 unselected patients immediately before and after intravascular radiocontrast administration during coronary angiography. SETTING: Cardiac catheterization laboratory of a university hospital. RESULTS: After angiography both the plasma concentration of atrial natriuretic peptide (median post-pre difference: 3.9 pmol L(-1), quartiles -1.2; 7.0) and the urinary excretion of urodilatin (median post-pre difference: 67.0 nmol urodilatin/mol creatinine, quartiles 39.7; 152.1) were increased. The urinary urodilatin excretion was correlated with an increase in the fractional excretion of sodium (median post-pre difference: 1.7%, quartiles 0.6; 3.1). There was no correlation between the serum concentration of atrial natriuretic peptide and urinary sodium excretion. For the radiocontrast-induced increase in both urodilatin and sodium excretion there was no indication for differences between patients without (31) and with (11) intravenous saline infusion. CONCLUSION: The radiocontrast-induced diuresis is a natriuresis which is associated with an increased urinary excretion of urodilatin. The association between natriuresis and urinary urodilatin excretion irrespective of baseline volume status corroborates the hypothesis that urodilatin contributes to the sodium excretion after radiocontrast administration in a paracrine manner. This finding has pathophysiological and potentially therapeutic implications in radiocontrast-induced nephropathy.

Atrial Natriuretic Factor↗
PubMed1998

A rapid and sensitive protocol for competitive reverse transcriptase (cRT) PCR analysis of cellular genes.

The specific analysis of gene transcripts is of increasing importance for studies in molecular pathology. Competitive RT-PCR with mutagenized exogenous competitor templates has evolved as an attractive approach to quantify individual mRNA levels. The generation of exogenous competitor RNAs usually requires mutagenesis and cloning of the mutant fragment into plasmids followed by in vitro transcription. In contrast to primer directed mutagenesis and in vitro transcription, preparation of the mutant fragments is a time consuming procedure. Here we report on a modified semi-quantitative RT-PCR protocol to circumvent the laborious cloning of mutant exogenous competitors. Templates for the in vitro transcription are generated in a single PCR reaction with simultaneous addition of a promoter sequence 5'of the forward primer and deletion of 10-20 nucleotides at the opposite end just ahead of the reverse primer binding site. The product of this PCR step serves as template for in vitro transcription to yield exogenous competitor RNA of equal quality and amount as conventional cloning strategies. Total RNA amounts are corrected for by analyzing the expression of different housekeeping genes in the same manner. One of the primers used in the following competitive RT-PCR reaction is labeled with a fluorescent dye for the analysis of target and exogenous competitor product on an semiautomated sequencer. In the present study, this protocol was employed to analyze the expression of the PTCH, Fas-receptor, NF-1, beta2-microglobulin and GAPD genes in human brain tumors. It will, however, be widely applicable to studies on cellular transcripts in biological specimens.

Binding, Competitive↗
PubMed1998

Processing of the Borna disease virus glycoprotein gp94 by the subtilisin-like endoprotease furin.

Open reading frame IV (ORF-IV) of Borna disease virus (BDV) encodes a protein with a calculated molecular mass of ca. 57 kDa (p57), which increases after N glycosylation to 94 kDa (gp94). The unglycosylated and glycosylated proteins are proteolytically cleaved by the subtilisin-like protease furin. Furin most likely recognizes one of three potential cleavage sites, namely, an arginine at position 249 of the ORF-IV gene product. The furin inhibitor decRVKRcmk decreases the production of infectious BDV significantly, indicating that proteolytic cleavage of the gp94 precursor molecule is necessary for the full biological activity of the BDV glycoprotein.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Impact of early risk stratification on the length of hospitalization in patients with acute Q-wave myocardial infarction. 'The 60-minutes myocardial infarction project'.

UNLABELLED: An assessment of individual risk factors may identify a subgroup of postinfarction patients at low risk, i.e. patients appropriate for early discharge. Using a large unselected population of the national registry, 'The 60-Minutes Myocardial Infarction Project', we (1) attempted to provide a retrospective analysis of clinical factors and in-hospital mortality in a population living on the 6th hospital day following admission to define a low-risk patient group with a residual in-hospital mortality of less than 1% eligible for early discharge, and (2) to analyze the current impact of risk stratification based on these clinical factors on the length of hospitalization. The study group consisted of 12,045 survivors on the 6th day after admission out of 14,980 patients of the registry with proven Q-wave myocardial infarction. Risk modeling was performed with multiple logistic regression. RESULTS: A total of 873 patients (7.3%) died after day 6 in hospital. The most important prognostic factors were cardiopulmonary resuscitation prior to admission (odds ratio, OR: 7.2, confidence interval, CI: 5.11-10.22), thrombolysis complicated by severe bleedings (OR: 6.2, CI: 1.2-31. 2) and age >70 years (OR 4.7, CI 3.51-6.39). The other more significant independent predictors of increased mortality were end-stage renal disease, age between 56 and 70 years, systolic blood pressure <95 mm Hg on admission, history of trauma </=2 months, cancer and left-bundle-branch block. Summarizing these nine groups of patients with the strongest association to in-hospital mortality, we defined a high-risk group comprising 79% of the AMI patients with a residual in-hospital mortality of 8.8%. On the other hand, by excluding these nine high-risk patient groups, a low-risk group of 21% of all AMI patients seems to be appropriate for early discharge (residual in-hospital mortality = 1.07%). However, in the current practice, there was no difference regarding the median length of hospital stay between the two risk groups. The low-risk patients were hospitalized 20 days compared to 22 days in the high-risk patients. CONCLUSION: Using a simple logistic regression model, which considers clinical factors of the early hospital phase, one fifth of the infarction patients can be stratified to be at low risk, and might be eligible for early hospital discharge. Currently, an individual risk stratification has no impact on the length of hospital stay in Germany.

Aged↗
PubMed1998

Die Rolle der Randomisation in klinischen Studien.

The Place of Randomisation in Clinical TrialsRandomised clinical trials are nowadays the accepted gold standard for treatment comparisons. However, controversies still exist concerning the possibility to perform randomised trials or the adequacy and the ethical appropriateness of randomisation. Randomisation is sometimes credited with advantages it does not possess, and an extremely negative view or even a categorical rejection of non-randomised trials is found. This attitude may be comprehensible from a historical, pragmatic or educational viewpoint, but is not well-founded on epistemological grounds. This article argues that non-randomised clinical trials are needed, clarifies the role of randomisation in clinical trials and analyses the arguments raised against the validity of results from observational studies. It is shown that it has not been demonstrated up to now that well-designed and analysed observational studies would have yielded results that are distinct or even qualitatively different from results of similar randomised clinical trials. Although one is well advised to randomise whenever possible, there is still room for a considerable improvement of observational studies: Randomisation itself should be the only difference between observational studies and randomised clinical trials.

Journal Article↗
PubMed1998

Respiratory tract infections in Greenlandic children: a prospective cohort study.

Respiratory tract infections in children, measured in terms of both morbidity and mortality, represent a major health problem in Greenland. In particular, otitis media is highly prevalent, and is characterized by early onset and a high degree of chronicity. There is, however, little knowledge about the epidemiology of respiratory tract infections in Greenland. In the spring of 1996, a prospective study of such infections in infants and children was initiated in Sisimiut, West Greenland. The main objectives of the study are to describe the epidemiology of respiratory tract infections in children under four years of age, to estimate the impact of these diseases on short- and long-term morbidity, and to identify risk factors for transmission and clinical severity. An open cohort of children in Sisimiut will be formed, including all resident children below three years of age at the beginning of the study, as well as all children born in the following two-year period: in total approximately 600 children. During two years, these children will be followed closely, including registration of episodes of respiratory tract infections. Furthermore, growth will be measured and microbiological samples obtained.

Child, Preschool↗
PubMed1998

[Abdomino-thoracoscopic esophagus resection--an animal experiment study].

Based on animal trials the presented study results describe a method of abdomino-thoracoscopic oesophagectomy for the treatment of oesophageal carcinoma of the middle and lower third. Technical details and the advantages of the surgical procedure, including the avoidance of thoracotomy and the practicability of the thoracoscopic dissection of the oesophagus are shown. Problems exist in the salvage of the specimen, especially in the transcervical passage of the tumorbearing oesophageal part. A final evaluation of the importance of the minimally invasive techniques in oesophageal surgery should not be given until the results of clinical studies are available.

Anastomosis, Surgical↗
PubMed1998

[Indications for surgical therapy of gallstones].

4675 patients which underwent a cholecystectomy because of gallstone disease were included in a prospective multi-institutional study from 01/09/1994 to 31/08/1995 at 29 east-german hospitals. 3,207 (68.6%) patients had done a laparoscopic cholecystectomy (LCE). 1,468 (31.4%) patients received a primary open cholecystectomy (KCE). A conversion rate of 7.7% (n = 247) was seen. In 32.8% of LCE and in 39.5% of KCE diagnostic procedures of the common bile duct were not performed at all. The rate of open revision of the common bile duct was 4.5% (n = 211). The highest postoperative morbidity and operative mortality were found in KCE with revision of the common bile dutct.

Cholecystectomy↗
PubMed1998

[Laparoscopy-assisted harvesting of free small intestine transplants for reconstruction of voice and deglutition after total laryngopharyngectomy--an animal experiment study].

Based on animal trials the presented study results describe a laparoscopic assisted removal of an extra-long free jejunal graft to reconstruct voice and swallowing after a total laryngo-pharyngectomy in cases with advanced malignancies of the larynx including invasion in the upper oesophagus. With a microvascular anastomosed small bowel segment, we have been able to reconstruct parts of the pharynx and to create a speaking syphon as devised by Ehrenberger in an one-stage procedure. The concept of avoidance of an extensive laparotomy may result in an decreased morbidity of this surgical procedure. Therefore it represents a challenging single indication of minimally invasive surgery of the oesophagus. A well established interdisciplinary teamwork is the key for success in this extensive procedure.

Animals↗