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Biomedical subjects

J Köhler

Publications and source records attributed to J Köhler.

At least 55 records · Page 3Linked to original sources

Vesicoureteral reflux diagnosed in adulthood. Incidence of urinary tract infections, hypertension, proteinuria, back pain and renal calculi.

STUDY PURPOSE: To determine the incidence of urinary tract infections, hypertension, back pain, and renal calculi in adult patients with vesicoureteral reflux and reflux nephropathy. METHODS: A group of 115 patients (16-60 years of age, median 28 years) with vesicoureteral reflux, combined with reflux nephropathy in 101 patients, first detected between 1967 and 1984, was studied retrospectively. The group comprised 99 women and 16 men. RESULTS: Symptoms and findings associated with the urinary tract preceded the diagnosis of vesicoureteral reflux by median 14 years (1-60 years). Intravenous pyelography preceded investigation with micturating cystography in 99 patients. Fifteen patients had no urinary tract infections, 17 patients had only lower urinary tract infections, and 83 patients had upper with or without lower urinary tract infections. Females had 12 times more lower and seven times more upper urinary tract infections than males, whereas males had impairment of renal function and proteinuria more often than females. Hypertension was present in 39 patients (34%) and five times more frequent in patients with bilateral than in those with unilateral reflux nephropathy. The median age at the first recording of hypertension was 33 years (16-60 years). Malignant hypertension was uncommon and occurred in two patients. An older group (> 45 years of age at presentation) of 19 patients showed a 90% incidence of hypertension compared with 23% in 96 patients in the younger group (< or = 45 years of age at presentation). Back pain of varying type and severity was present in 48 patients (42%). A total of 38 renal calculi was found in 21 (18%) patients, of whom 14 were completely asymptomatic. CONCLUSIONS: The natural history of vesicoureteral reflux first detected in adulthood has shown a strikingly high incidence of urinary tract infections, arterial hypertension, back pain, and renal calculi.

Adolescent↗

Related enhancers in the intron of the beta1 tubulin gene of Drosophila melanogaster are essential for maternal and CNS-specific expression during embryogenesis.

Expression of the beta1 tubulin gene of Drosophila melanogaster is under complex developmental control. For high levels of transcription in the embryonic central nervous system (CNS) different modules dispersed over 3 kb have to co-operate. Combination of a core promoter with either far upstream localized enhancer elements or, alternatively, with an enhancer from the intron results in expression limited to only a few neuronal cells. Cooperation of all three modules, however, leads to high level expression in most neuronal cells of the CNS. In the intron, we identified a 6 bp core element which is essential for transcription in the CNS, as well as an 8 bp element required for maternal expression. Interestingly, both motifs are quite similar, with CAAAAT as the CNS core and CAAAAAT as the maternal enhancer core. Specific binding of proteins from nuclear extracts to the CNS-specific element could be demonstrated. We suggest that the beta1 tubulin gene represents an ideal marker gene to elucidate connections between pro-neural or neurogenic genes and downstream target genes throughout the CNS.

Animals↗

Germline mosaicism in 4q35 facioscapulohumeral muscular dystrophy (FSHD1A) occurring predominantly in oogenesis.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominantly inherited neuromuscular disorder affecting facial and shoulder girdle muscles with subsequent progression to the pelvic girdle and lower extremities. The major gene involved has been localized to chromosome 4q35 (FSHD1A). The 4q35 DNA marker p13E-11 (D4F104S1) detects a de novo EcoRI DNA rearrangement of < 30 kb in isolated and familial cases. The intrafamilial size of the fragment is constant, inversely correlated with the severity, and directly correlated with the age of onset of the condition. There has been evidence of parental mosaicism in FSHD1A for the D4F104S1 locus. Four female and three male clinically unaffected parents have been described to be carriers of EcoRI fragments of the same size as their affected offspring, but with a markedly less intensive hybridization signal (semi-quantitative evidence). In our total sample of 42 FSHD1A families, we found semi-quantitative evidence of parental D4F104S1 mosaicism in 11 families (EcoRI fragment size range: 12-27 kb). On analysis with adjacent 4q35 probes (D4S163, D4S139), additional qualitative evidence of germline mosaicism could be obtained in two families. In our mosaic families and in the families reported in the literature, a female predominance of mosaicism carriers (13 females versus 5 males) could be noted. In our sample, mosaicism was observed in multigeneration families, in families with isolated cases, and in families with two and three affected children from seemingly unaffected parents. A short EcoRI fragment once having emerged in a mosaicism carrier was found to be transmitted autosomal dominantly to subsequent generations. Of all reported sporadic patients, 19% have a mosaic parent. Finding evidence of parental mosaicism in all our families with more than one affected child of seemingly unaffected parents suggests that there is no autosomal recessively inherited form of FSHD1A.

Adult↗

Structure/function studies on the pH-dependent actin-binding protein hisactophilin in Dictyostelium mutants.

Our previous studies have shown that the actin-binding protein hisactophilin from Dictyostelium discoideum is a candidate for organizing the actin cytoskeleton at the plasma membrane in a pH-dependent manner. To further characterize this interaction we isolated hisactophilin overexpression (hisII+) and hisactophilin minus (his-) mutants. D. discoideum contains two hisactophilin isoforms; both genes are independently transcribed and carry a short intron at the same position of the coding region. The deduced amino acid sequence of hisactophilin II showed a characteristic high content of 35 histidine residues out of a total 118 amino acids. After transformation of Dictyostelium AX2 wild-type cells with a genomic fragment designed to inactivate the hisactophilin I gene we obtained hisactophilin II overexpressing mutants (hisII+). Multiple integration of the vector led to strong overexpression of hisactophilin II which even outnumbered the actin concentration by a factor of two. Hisactophilin II protein showed the same biochemical properties as hisactophilin I during purification and in its pH-dependent binding to F-actin; as shown by mass spectrometry the hisactophilin II fraction was almost completely myristoylated despite of this high overexpression. The inactivation of both hisactophilin genes was achieved by gene replacement with a vector construct encompassing parts of gene I and gene II connected by a geneticin cassette. The properties of the hisII+ and his- cells with regard to growth in shaking culture and on Klebsiella plates, development, chemotaxis and morphology were not affected under normal conditions. However, the hisII+ transformants revealed a significant difference to wild-type cells and his- cells when the cytoplasmic pH was lowered by diethylstilbestrol (DES), a proton pump inhibitor. HisII+ cells were more resistant to the acidification; in contrast to AX2 wild-type cells and his- cells they did not form plasma membrane protrusions, showed an increase in F-actin content, and contained large clusters of F-actin. Lowering the internal pH caused an accumulation of hisactophilin below the plasma membrane. The fact that cells deficient in hisactophilin again lose resistance to acidification is in good agreement with the hypothesis that hisactophilin functions as a pH sensor at the plasma membrane by reversibly connecting the membrane with the actin cortical network upon local changes of the proton concentration.

Actins↗

Heterogeneity of bromodeoxyuridine sensitivity of cultured cells from melanoma metastases.

Continuously growing cell cultures, testing positive for tyrosine activity, were derived from two brain and three lymph-node metastases of five patients with malignant melanoma. These cell cultures were analyzed regarding their proliferation rate with continuous bromodeoxyuridine (BrdUrd) labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry. Melanoma cell cultures are more sensitive toward BrdUrd in comparison to human diploid fibroblast cultures: 50% growth inhibition at 360 +/- 130 microM BrdUrd (range: 130-520; n = 11) vs. 650 +/- 50 microM BrdUrd (n = 3) for fibroblasts. Moreover, BrdUrd sensitivity in melanoma cells is oxygen dependent: 50% growth inhibition at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs. 360 +/- 130 microM BrdUrd for 5% oxygen. The cell cycle kinetic mechanisms of BrdUrd-induced growth inhibition is accumulation of cells in the G2 phase. Cultures from a single metastasis showed up to a 3-fold variation in BrdUrd sensitivity. In one of the brain metastases two populations of different ploidy level (pseudotriploid vs. pseudotetraploid) and BrdUrd sensitivity could be resolved. Thus, continuous BrdUrd labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry is a powerful tool to detect heterogeneity in proliferative capacity and drug sensitivity of cell populations within one tumor biopsy.

Bisbenzimidazole↗

DNA polymorphisms in strains of Legionella pneumophila serogroups 3 and 4 detected by macrorestriction analysis and their use for epidemiological investigation of nosocomial legionellosis.

Genomic DNAs of clinical and environmental isolates of Legionella pneumophila belonging to serogroups 3 and 4 were analyzed by macrorestriction analysis by pulsed-field gel electrophoresis. The restriction enzymes SfiI and NotI allowed easy visual separation of epidemiologically unrelated serogroup 3 strains. Three unrelated serogroup 3 strains that were isolated from different locations were identical by this genome mapping technique. Five unrelated serogroup 4 strains were separable by this technique. The electrophoretic patterns obtained after SfiI or NotI cleavage of the DNA of strains isolated from four patients with hospital-acquired legionellosis were identical to the patterns of strains isolated from the hot water supply systems of the buildings in which the patients were hospitalized. In conclusion, macrorestriction analysis is a valuable tool for epidemiological studies of infections caused by L. pneumophila serogroups 3 and 4.

Adult↗

Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog.

A Candida albicans gene (CPH1) was cloned that encodes a protein homologous to Saccharomyces cerevisiae Ste12p, a transcription factor that is the target of the pheromone response mitogen-activated protein kinase cascade. CPH1 complements both the mating defect of ste12 haploids and the filamentous growth defect of ste12/ste12 diploids. Candida albicans strains without a functional CPH1 gene (cph1/cph1) show suppressed hyphal formation on solid medium. However, cph1/cph1 strains can still form hyphae in liquid culture and in response to serum. Thus, filamentous growth may be activated in C. albicans by the same signaling kinase cascade that activates Ste12p in S. cerevisiae; however, alternative pathways may exist in C. albicans.

Amino Acid Sequence↗

Towards a vibrational analysis of spheroidene. Resonance Raman spectroscopy of 13C-labelled spheroidenes in petroleum ether and in the Rhodobacter sphaeroides reaction centre.

We report resonance Raman spectra of the carotenoid spheroidene and its 14'-13C and 15'-13C substituted analogues in petroleum ether and bound to the reaction centre of Rhodobacter sphaeroides R26. The spectra in petroleum ether correspond to planar all-trans spheroidene while those of the reaction centres are consistent with a nonplanar 15,15'-cis spheroidene. The effect of 13C labelling is largest in the carbon-carbon double-bond stretching region. The 15'-13C substitution of the reaction centre bound spheroidene, however, hardly changes the C=C band as compared to that for the natural abundance spheroidene apart from a new weak band at 1508 cm(-1). This observation has been interpreted as a decoupling of the C15=C15' stretch from the other double-bond stretches in combination with a small intrinsic Raman intensity of this local mode for 15,15'-cis spheroidene.

Alkanes↗

Color-coded Doppler imaging of the vena contracta as a basis for quantification of pure mitral regurgitation.

The narrowest central flow region of a jet is defined as the vena contracta. This term is applied also to the contracted zone of the Doppler color flow image of a jet at its passage through an incompetent mitral valve. The clinical applicability of measuring the size of the vena contracta by transthoracic color-coded Doppler echocardiography for estimating the severity of mitral regurgitation (MR) was evaluated. In 78 of 82 patients with angiographically proved MR, a coherent flow image across the valve was visualized. The maximal diameter in the apical long-axis view was considered as a representative value for the size of the vena contracta. In comparison with the maximal left atrial velocity pixel area, this parameter revealed higher correlations to the angiographic degree of MR and to the regurgitant volume (r = 0.94 vs 0.72, and 0.83 vs 0.71, respectively). The highest positive and negative predictive accuracies for differentiating mild-to-moderate from severe MR were determined for a diameter of 6.5 mm (88 and 96%, respectively). Because the vena contracta is directly related to the severity of MR, it is concluded that it is helpful to use this parameter instead of the maximal velocity pixel area for semiquantitative grading.

Adult↗

Performance of indirect embolectomy aided by a new developed flush-suction catheter system. Forty-seven experimental embolectomy procedures in test animals.

Embolectomy by means of the Fogarty catheter is the therapy of choice in the event of acute occlusions of limb arteries. However, less invasive catheter procedures have become established means to perform embolectomies lately. In order to improve the results after using the above mentioned methods, we have developed a new embolectomy procedure. The system applied consists of a flush-suction catheter as well as a high pressure pump. There is a jet-suction unit on the head of the tubular two-lumen catheter to gather thromboembolic material from the circumference of the head, to erode the collected material and evacuate it. The flushing pressure is generated by the pump. For the experimental testing of the system, the flush-suction embolectomy has been performed in 19 pigs after 47 artificial produced extremities embolism. Angiographically and angioscopically it could be proved that even older thrombotic material could be removed completely and without significant trauma of the vessel. At the pathologic investigation of the vessel in which embolectomy had been performed in no case an essential vessel-wall damage could be found. In almost each case the embolic material was removed completely. Only in 5 cases (10.6%) we have distal microembolism. Due to the experimental tests, the system turns out to be reliable as far as the technique is concerned. In addition, in the event of clinical application, the system allows the expectation of a reduction of the time interval between diagnosis and therapy, as well as a percutaneous application.

Angiography↗

Cytogenetic differences between intestinal and diffuse types of human gastric carcinoma.

This study concerns the cytogenetics of 23 gastric carcinomas, classified histologically as intestinal or diffuse types. In carcinomas of the diffuse type, the only numerical changes observed were Y chromosome loss associated with X-chromosome disomy in four of seven male patients. A 46, XX karyotype without recognizable alterations was observed in three of five female patients, and rare structural changes in diffuse carcinomas involved chromosomes 1 and 18. In contrast, intestinal type tumors were exclusively aneuploid, with chromosome modes ranging from 48 to 84. The most consistent change was trisomy 20 in seven of 11 patients, each of which displayed a number of both single and clonal structural aberrations. Frequent structural changes were translocations involving chromosome 13 (including a putative isochromosome 13q in three of 11 patients), and alterations in chromosomes 1, 6 and 12. This study therefore suggests that diffuse and intestinal types of gastric carcinomas do not share a common sequence of genetic changes. The tumor with the worse prognosis (diffuse type) is surprisingly diploid, with uniform X-disomy in both males and females. The clinically less aggressive tumors (intestinal type) show multiple changes, both numerical and structural, of which some are reminiscent of changes seen in tumors of the lower gastrointestinal tract. Cytogenetics may thus be a valuable adjunct in establishing the diagnosis, classification, and prognosis of gastric carcinomas.

Adult↗

A microchromosome derived from chromosome 11 in a patient with the CREST syndrome of scleroderma.

A patient with the CREST syndrome of scleroderma was found to carry a mosaicism for a supernumerary microchromosome. The microchromosome was approximately 1 micron in size and present in over half of the lymphocyte metaphases examined. It bound centromeric proteins specifically recognized by CREST autoimmune sera (including the patient's serum). In situ hybridization with a panel of chromosome-specific alpha-satellite probes showed that the microchromosome was derived from chromosome 11, most or all of its chromatin consisting of the chromosome 11 subset of alpha-satellite DNA. It had no detectable telomeric sequences. Microchromosomes observed by electron microscopy had no visible free ends. The chromatin looked exactly the same as it did in normal chromosomes. Although we have no direct evidence for a circular structure, we conclude that the microchromosome originated by an interstitial deletion including the alpha-satellite DNA sequences and subsequent ring formation. The newly formed chromosomal element proved to be relatively stable somatically and was transmitted through meiosis. Since it possesses at least some structural and functional features of a centromeric region, the microchromosome can be thought of as an isolated centromere.

Centromere↗

[Doppler echocardiography imaging of construction-induced regurgitation of technical heart valve prostheses].

The normal leakage flow in modern technical heart valve prostheses can be visualized by color-coded Doppler-echocardiography, provided that an adequate ultrasonic image quality can be achieved. Sometimes it may be difficult, however, to distinguish such a normal leakage flow from pathological regurgitation. We therefore mounted new specimens of five different types of prostheses (Bjørk-Shiley monostrut, Medtronic-Hall, Omnicarbon, Saint Jude Medical, Duromedics) into an invitro model, where the leakage flows could directly be visualized as emerging water jets. When the system was completely filled, the jets could also be registered by two-dimensional Doppler-echocardiography. For each valve, characteristic patterns for the localization of the principal jets were found. Besides the relative broad central jet in the Medtronic-Hall valve, all other jets arose mainly at the ring. They were detected at the hinges or the basis of the larger struts, respectively, and with asymmetrical mono-disc valves at the side of the smaller opening. The length and the orientation of the jets were found to change significantly with minimal variations of the position of the closing discs. This variability could be confirmed, when in a separate model the overall leakage flows were repeatedly measured. For patient examinations it seems useful to refer mainly to the localization of the jet origins. The comparison with reference values of jet-dimensions in Doppler images will rarely enable the examiner to distinguish between normal and pathological jets.

Echocardiography, Doppler↗

[Comparison of two methods for conscious sedation in maxillofacial surgery with local anesthesia].

A randomised, prospective study was conducted to compare the efficiency and safety of methods for intravenous conscious sedation in patients undergoing oral surgery under local analgesia. 150 systemically healthy patients (ASA Class I and II) participated. Three groups were formed: group 1 received 0.05 mg/kg midazolam; group 2 0.05 mg/kg midazolam, 1.5 mg/kg tramadol, 50 mg alizaprid; group 3 0.05 mg/kg midazolam, 0.2 mg/kg nalbuphine, 50 mg alizaprid. Blood pressure, heart rate and oxygen saturation were measured throughout the procedure. The results confirmed that the use of nalbuphine (group 3) allows a reduction in the mean dosage of midazolam required to produce satisfactory sedation and effected a more rapid recovery time compared to group 12 and 2. With the combination nalbuphine and alizaprid nausea and vomiting could be reduced for the most part compared to group 2.

Procedural Sedation↗