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C Fischer

Publications and source records attributed to C Fischer.

At least 199 records · Page 11Linked to original sources
PubMed1994

Double crossover in the human Xp/Yp pseudoautosomal region and its bearing on interference.

Most models on crossover and crossover interference have assumed that the intensity of interference depends inversely on the physical distance separating the respective intervals. The possibility, however, also exists that interference depends on genetic rather than on physical distance. As the human pseudoautosomal region (PAR) on Xp/Yp is physically small, yet genetically a hot spot of recombination in male meiosis, studies on the existence of multiple crossover events may be particularly useful in addressing the question of interference. Our results demonstrate for the first time a double crossover during male meiosis in the human PAR on Xp/Yp. The occurrence of a single obligatory recombination event in this region can, therefore, no longer be taken as a dogma. However, double crossover events seem to remain exceptional and, thus, the model originally suggested by Burgoyne remains globally correct. As both recombination events can be localized within a narrow range of physical distance, theories describing interference due to steric hindrance may have to be reconsidered. This finding may, therefore, have general implications for our understanding of the mechanism of positive and negative crossover interference in mammalian genomes and may be interesting especially for linkage mapping where double recombinations in small intervals tend to be considered as genotyping errors.

Base Sequence↗
PubMed1994

Loss of protein kinase-catalyzed phosphorylation of HPr, a phosphocarrier protein of the phosphotransferase system, by mutation of the ptsH gene confers catabolite repression resistance to several catabolic genes of Bacillus subtilis.

In gram-positive bacteria, HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), is phosphorylated by an ATP-dependent, metabolite-activated protein kinase on seryl residue 46. In a Bacillus subtilis mutant strain in which Ser-46 of HPr was replaced with a nonphosphorylatable alanyl residue (ptsH1 mutation), synthesis of gluconate kinase, glucitol dehydrogenase, mannitol-1-P dehydrogenase and the mannitol-specific PTS permease was completely relieved from repression by glucose, fructose, or mannitol, whereas synthesis of inositol dehydrogenase was partially relieved from catabolite repression and synthesis of alpha-glucosidase and glycerol kinase was still subject to catabolite repression. When the S46A mutation in HPr was reverted to give S46 wild-type HPr, expression of gluconate kinase and glucitol dehydrogenase regained full sensitivity to repression by PTS sugars. These results suggest that phosphorylation of HPr at Ser-46 is directly or indirectly involved in catabolite repression. A strain deleted for the ptsGHI genes was transformed with plasmids expressing either the wild-type ptsH gene or various S46 mutant ptsH genes (S46A or S46D). Expression of the gene encoding S46D HPr, having a structure similar to that of P-ser-HPr according to nuclear magnetic resonance data, caused significant reduction of gluconate kinase activity, whereas expression of the genes encoding wild-type or S46A HPr had no effect on this enzyme activity. When the promoterless lacZ gene was put under the control of the gnt promoter and was subsequently incorporated into the amyE gene on the B. subtilis chromosome, expression of beta-galactosidase was inducible by gluconate and repressed by glucose. However, we observed no repression of beta-galactosidase activity in a strain carrying the ptsH1 mutation. Additionally, we investigated a ccpA mutant strain and observed that all of the enzymes which we found to be relieved from carbon catabolite repression in the ptsH1 mutant strain were also insensitive to catabolite repression in the ccpA mutant. Enzymes that were repressed in the ptsH1 mutant were also repressed in the ccpA mutant.

Bacillus subtilis↗
PubMed1994

A modified technique for nerve-sparing retroperitoneal lymph node dissection in stage II nonseminomatous germ cell tumors using intraoperative measurement of bladder neck pressure alterations following sympathetic nerve fiber electrostimulation.

We present a simplified method for nerve-sparing retroperitoneal lymph node dissection in patients with nonseminomatous testicular cancer. The sympathetic fibers involved in antegrade ejaculation are identified by intraoperative electrostimulation, resulting in an increase of bladder neck closure pressure. This increase is demonstrated by intraoperative monitoring of both the intravesical pressure and the pressure within the bladder neck by a two-channel microtip measuring catheter. 4 patients with stage I and 6 patients with stage II nonseminomatous testicular cancer were operated on with this modified technique. Ejaculation was preserved in all cases. Semen volume ranged from 2.2 to 4.0 ml. Sperm cell count ranged from 2 to 22 x 10(6)/ml with 20-50% motile spermatozoa, except for 2 of the 3 patients who initially presented with preoperative azoospermia following chemotherapy. In 1 of these 3 patients, postoperative semen analyses revealed a recovery of germ cell function demonstrated by oligoasthenozoospermia.

Adrenergic Fibers↗
PubMed1994

Auditory early- and middle-latency evoked potentials in patients with quadrigeminal plate tumors.

Both early auditory evoked potentials (BAEPs) and middle-latency auditory evoked potentials (MLAEPs), were recorded in nine patients suffering from a quadrigeminal plate tumor. These recordings were performed before surgery in six cases and after surgery in three cases. The results of these examinations were correlated with impairments of the midbrain auditory pathways as shown by magnetic resonance imaging. BAEPs and MLAEPs were abnormal in five of nine cases and eight of nine cases, respectively. The two examinations yielded normal results in only one case. These data show that the functional evaluation of the midbrain should not be limited to the recording of BAEPs, routinely performed for brain stem functional evaluation, but should also include recording of MLAEPs, although the technique is a little more delicate. In the five patients with abnormal BAEPs, I-V conduction time was increased unilaterally (three patients) and bilaterally (two patients), and the I/V amplitude ratio was abnormal in two patients. In one of these two patients, isolated destruction of the right inferior colliculus was responsible for an abnormality affecting Wave V of the BAEP that was visible only after left ear stimulation. The most frequently observed MLAEP abnormality was a delay in the peaking of the Pa component, assumed to be of cortical origin. Therefore, a limited impairment of the midbrain may delay the peaking latency of Pa. Unilateral hypovoltage of Na-Pa was also observed. In only one case were Na and Pa components unilaterally abolished, in a patient suffering from a postoperative lesion extending from the right inferior colliculus to the right medial geniculate body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Lung metastasectomy in patients with soft tissue sarcoma.

Metastases develop in 50-60% of patients with high grade soft tissue sarcomas despite primary treatment. Between 1970 and 1990, 189 patients with soft tissue sarcoma referred to the Royal Marsden Hospital Sarcoma Unit developed lung metastases as the sole first site of disseminated disease. 44 of these 189 cases have been treated by pulmonary metastasectomy. In an attempt to determine which patients benefit from this surgery the medical records, radiology and pathology of these cases have been reviewed. Both the overall 5 year survival (70% vs 19%) and the subsequent survival from the time lung metastases developed (52% vs 7.5%) of those selected for thoracotomy were better than in the 145 patients not undergoing surgery. On multivariate analysis, survival and control of lung disease following resection were not related to the number of metastases resected, completeness of excision, use of adjuvant chemotherapy or presence of bilateral disease. The most important factor was the use of lung resection itself as treatment, for which the risk of death was 0.2 compared with those not having metastasectomy. Age less than 40 years and primary tumour in a lower limb site were also factors associated with a reduced risk of death. Pulmonary metastasectomy should be considered in selected patients with soft tissue sarcoma after primary local cure. However, without collection of prospective data on all patients developing lung metastases or a randomized trial the true role of lung metatasectomy will never be clarified.

Adult↗
PubMed1994

Protoplasts from Phaseolus coccineus L. pulvinar motor cells show circadian volume oscillations.

The circadian movement of the lamina of the primary leaf of Phaseolus coccineus is mediated by circadian volume changes of the extensor and flexor cells in the upper and lower half of the laminar pulvinus. Isolated protoplasts from the extensor, flexor, and flank cells of the pulvinus showed a circadian volume rhythm with a period longer than 24 h. In the case of the flexor protoplasts, we found a period length of 28 h, which is similar to that of the pulvinar cells in situ. In the extensor protoplasts, the volume rhythm was synchronized with 14-h light/10-h dark cycles. The larger volume was correlated with the early hours in the light period and the smaller volume with the dark period, as would be expected from the behavior of the extensor cells in situ.

Circadian Rhythm↗
PubMed1994

Dexfenfluramine and serotonin neurotoxicity: further preclinical evidence that clinical caution is indicated.

Dexfenfluramine, a drug used as an appetite suppressant in Europe, is currently under evaluation for approval in the United States. Studies in animals indicate that dexfenfluramine damages brain serotonin neurons, but have been challenged by some because of questions regarding their relevance to humans. The present studies were designed to address the three most salient questions regarding the applicability of preclinical dexfenfluramine neurotoxicity data to humans. Specifically, the present studies sought to determine: 1) whether dexfenfluramine's effects on brain serotonin neurons are transient and related to its therapeutic actions; 2) whether the p.o. route of administration affords protection against dexfenfluramine neurotoxicity; and 3) whether the mouse, an animal thought to best approximate the human with regard to dexfenfluramine metabolism, is sensitive to dexfenfluramine's neurotoxic action. Results from the present study indicate that monkeys continue to show large serotonergic deficits as long as 12 to 17 months after dexfenfluramine treatment, suggesting that dexfenfluramine's effects in nonhuman primates are persistent and unlikely to be related to its therapeutic actions. Furthermore, the present results indicate that the p.o. route of administration affords little or no protection against dexfenfluramine neurotoxicity. Finally, mice, like all other animals tested to date, were found to be susceptible to dexfenfluramine neurotoxicity. Taken together, these findings indicate that concern over possible dexfenfluramine neurotoxicity in humans is warranted, and that physicians and patients alike need to be aware of dexfenfluramine's toxic potential toward brain serotonin neurons.

Animals↗
PubMed1994

Preparation and sequence analysis of Taenia crassiceps metacestode recombinant antigens with potential for specific immunodiagnosis of human cerebral cysticercosis.

A Taenia crassiceps metacestode cDNA expression library in lambda gt 11 was screened with rabbit antisera to metacestodal T. solium and T. saginata crude extract. Primary clones (121) were identified, and after rescreening and lysogenization in Escherichia coli Y 1089, were tested in Western blot for reactivity with the same antisera. In addition, analyses were performed with rabbit antisera directed towards T. crassiceps and Echinococcus granulosus metacestode crude extract, sera from humans with neurocysticercosis (Mexico) and other important helminth diseases, mice and calves with experimental T. crassiceps and T. saginata infections and normal sera. Of those tested, 22 clones expressing beta-galactosidase fusion proteins (approximately 118-132 kDa) were reactive with IgG antibodies of cysticercotic patients and T. crassiceps infected mice. Of these clones, 11 were also sero-positive with calf-IgG antibodies against T. saginata larvae. None of the 22 clones reacted with IgG antibodies due to human cystic and alveolar echinococcosis, intestinal/hepatic or urinary schistosomiasis, African onchocerciasis or with sera from uninfected controls (man, rabbit, calf and mouse). Of these 22 clones, 15 have been subcloned into the plasmid vectors pGEX-2T (modified) and pT7T3 alpha 19. Expressed glutathione-S-transferase fusion proteins were again tested for sensitivity and specificity by Western blot, and concentrated by affinity chromatography. The nucleotide sequence of the cDNA inserts of 9 clones has been determined in pT7T3 alpha 19 and revealed identity in 4 and 5 clones, respectively.

Amino Acid Sequence↗
PubMed1994

[Clinical and electroencephalographic manifestations during the Wada test using intracarotid injection of methohexital (Brietal)].

In this retrospective study we report our 12 years' experience of the Wada test (intra-carotid injection of short half-life barbiturates) using Methohexital. The clinical manifestations induced by Methohexital were similar to those observed with Amobarbital. The inocuity of the test is attested by the finding that no incident or accident has been reported in 126 injections, the risk being the same as for arteriography. The two main advantages of Methohexital over Amobarbital are: 1) short hemispheric narcosis, which makes it possible to explore the two carotid arteries territories during the same session and limits the risk of drug diffusion to the two hemispheres; 2) the rare occurrence of vigilance troubles such as drowsiness or falling-asleep, which are frequently observed during Amytal Wada test. Intracarotid Methohexital injections are effective to determine the hemispheric lateralization of language and useful to evaluate the role of each hemisphere in memory, especially before the surgical treatment of drug-resistant focal epilepsies.

Brain Diseases↗
PubMed1994

[HIV infection and AIDS in urology].

Up to December 1993, a total of 10858 AIDS cases were reported to the central AIDS registry at the Federal Health Office. Human immunodeficiency virus is acquired through needle sharing (i.v. drug users), contaminated blood transfusions, intercourse with infected persons and transplacentally by fetuses. In Germany, about seven people a day are estimated to acquire the HIV infection. Half the patients will develop systemic manifestations of AIDS within 12-13 years. Only a small percentage of these patients suffer from urological manifestations, e.g. urinary tract infection, prostatism or HIV-associated nephropathy. Nevertheless, knowledge of genitourinary pathology caused by HIV makes early diagnosis of AIDS possible.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Initial experiences with combined balloon angioplasty and rtPA thrombolysis in dialysis shunt failure].

The 23 interventions performed by us on 18 patients had a very high success rate both in intraarterial lysis therapy of obstructed haemodialysis shunts and in balloon angioplasty (19/23). Shunt failure had to be primarily treated by surgery in 3 cases only. The complications were confined to a rupture of a vessel that required surgical care. 14 shunts were found to be patent in a total of 18 patients (18 being of course as small patient group). Our experience leads us to believe that patients suffering from shunt insufficiency should always be primarily treated endoluminally if angiography confirms that intervention is possible. Surgical intervention is always advisable even if the result may occasionally be negative in a few rare cases.

Adult↗
PubMed1993

Simultaneous assessment of the intravenous and oral disposition of the enantiomers of racemic nimodipine by chiral stationary-phase high-performance liquid chromatography and gas chromatography/mass spectroscopy combined with a stable isotope technique.

An enantioselective method of high specificity and sensitivity for the determination of the enantiomers of two racemic 1,4-dihydropyridine compounds after simultaneous oral (po) and intravenous (iv) administration is reported. The method is suitable for the simultaneous administration by two different routes of a racemic drug labeled with stable isotopes and unlabeled racemate. For workup, an internal racemic standard labeled with a different number of stable isotopes is added. After separation of the enantiomers by chiral stationary-phase high-performance liquid chromatography and subsequent analysis by gas chromatography/mass spectroscopy (GC/MS) with selected ion detection, the R and S enantiomer concentrations arising from i.v. and p.o. administration can be precisely measured because of their mass difference. This method has been applied to assess the disposition of the R and S enantiomers of nimodipine and nitrendipine after simultaneous i.v. and p.o. administration. The assay is highly specific and sensitive, with a limit of quantification per enantiomer of 0.1 ng/mL after extraction of 0.5 mL of human serum samples and monitoring the M- ions in the electron capture, negative ion chemical ionization mode. The calibration curve was linear in the range 0.1-100 ng/mL. Within- and between-day precision were satisfactory (coefficient of variation, < 10%). Enantiomeric excess in the range 0-100% could be accurately determined. Comparison of the enantioselective method with the achiral method (GC/MS only) gave good agreement.

Administration, Oral↗
PubMed1993

Genetic map of the human pseudoautosomal region reveals a high rate of recombination in female meiosis at the Xp telomere.

This paper describes the genetic map of the pseudoautosomal region bounded by the telomere of the short arms of the X and Y chromosomes. In males, meiotic exchange on Xp/Yp is confined to this region, leading to highly elevated recombination rates. The map was constructed using 11 pseudoautosomal probes (six of which are new) and typing individuals from 38 CEPH families. All markers have been physically mapped, thus providing the opportunity to compare genetic distance to physical distance through all intervals of the map. This comparison reveals an unexpected high rate of recombination in female meiosis between loci DXYS20 and DXYS78, within 20-80 kb from the telomere. Within this telomere-adjacent region no differences in male and female recombination rates are seen. Furthermore, data from this genetic map support the hypothesis of a linear gradient of recombination across most of the region in male meiosis and provide densely spaced anchor points for linkage studies especially in the telomeric portion of the pseudoautosomal region.

Alleles↗
PubMed1993

[Effect of anesthetics on sensory evoked potentials].

The authors have reviewed the main effects of anaesthetic agents on sensory evoked potentials (EPs) in the auditory, somatosensory and visual modalities. Knowledge of EP changes induced by anesthetic drugs is important to avoid false alarms when monitoring neural structures at risk during surgery. Intraoperative EP monitoring is all the more efficient as the following points are taken into account: 1) whatever the sensory modality considered, EPs are more attenuated by volatile halogenated agents than by intravenous drugs; 2) the cortical components of EPs are more sensitive to anesthetic drugs than the brainstem components; 3) in each modality, the first component of the "primary cortical complex" is less attenuated by anaesthetic agents than the following cortical waves; 4) continuous administration of anaesthetic agents rather than acute administration (bolus) is preferred during EP monitoring. EPs also represent an objective means to assess the depth of surgical anaesthesia, since they may provide a reliable index of cortical depression. Amplitude changes of middle-latency auditory responses (Pa/Nb) seem to be a good marker for estimating depth of anaesthesia with the aid of EPs.

Acoustic Stimulation↗
PubMed1993

Evaluation of the utility of interphase cytogenetics to detect residual cells with a malignant genotype in mixed cell populations: a Burkitt lymphoma model.

Interphase cytogenetics has been used to detect tumor cells in the presence of a large excess of normal cells. Probes for fluorescence in situ hybridization were chosen to reveal a specific hybridization pattern in tumor cell nuclei as well as to provide an internal control for the assessment of the hybridization results. By enumerating mixtures of cytogenetically normal cells and tumor cells from a Burkitt lymphoma cell line, we were able to detect tumor cells at a frequency of one in 500. Normal cells could be differentiated from Burkitt lymphoma cells with a specificity of approximately 99.9%.

Burkitt Lymphoma↗
PubMed1993

Lymphocyte-endothelial interactions in inflamed synovia: involvement of several adhesion molecules and integrin epitopes.

The role of several adhesion molecules for lymphocyte-endothelial interactions in the synovia of rheumatoid arthritis patients was studied using the frozen section assay. Partial inhibition of lymphocyte binding to endothelium of synovial sections could be observed with antibodies against CD44, L-selectin, and beta 1- and beta 2-integrins, pointing to the participation of several adhesion molecules in the regulation of lymphocyte immigration into inflamed synovia rather than the presence of a unique homing receptor. Different degrees of inhibition were found within a series of antibodies against alpha 4- and beta 1-integrins known to have functional effects in other interaction systems. In addition, increased binding to endothelial cells was induced when lymphocytes were pretreated with TS2/16 anti-beta 1 IgG, whereas binding to non-endothelial components of synovia was increased after treatment with HP 2/4 (anti-alpha 4) Fab. The data suggest a multifunctional role of alpha 4/beta 1-integrins in directly mediating adhesion as well as regulating adhesive interactions in the rheumatoid synovia.

Animals↗