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T Pfeiffer

Publications and source records attributed to T Pfeiffer.

49 records · Page 3Linked to original sources

Design, synthesis and biological activity of novel rigid amidino-phenylalanine derivatives as inhibitors of thrombin.

(3S)-(Naphthalene-2-sulfonylamino)-1-[2R-(4-amidinophenyl)-1- piperidinocarbonylethyl]-2-pyrrolidinone (1a) is a potent inhibitor of thrombin with an IC50 value by 112 times lower than that of NAPAP (racemate). The selectivity versus trypsin can be improved by incorporation of substituents on the naphthyl ring. The mode of binding of the compound was determined by X-ray crystallography.

Animals↗

[The effect of obesity on outcome of kidney transplantation].

BACKGROUND AND AIM: Obesity is a risk factor for postoperative complications in surgery. In a retrospective study we investigated the course of body weight during the waiting period and the first postoperative year and the influence of obesity on graft function. PATIENTS AND METHOD: The medical records of 334 adult patients undergoing cadaveric kidney transplantation between 1986 and 1992 were reviewed. Immunosuppression was performed with cyclosporine and prednisone. For all patients the Broca index was calculated with the relative body weight by the formula: body weight/Broca index x 100 (% BI). Obesity was defined as relative body weight > or = 120% BI. RESULTS: At the time of the indication for kidney transplantation 15.3% of the patients were obese. Only 12 of these 51 obese patients reduced their body weight below 120% BI until transplantation, whereas 25 patients increased weight in excess of 120% BI. Thus the number of obese patients raised to 19.2% by the time of transplantation. The graft survival in the obese group was significantly lower than in the nonobese group. This difference appeared already in the first half year after transplantation being constant in the following time. The resulting 1-year graft survival was 82.8% and 91.4% respectively (p < 0.05). During the first year 59 patients more became obese, the percentage of obese raised up to 36.0%. One year after transplantation there was no longer significant difference of graft survival rate in the further follow-up between obese and nonobese patients. CONCLUSION: Our findings show, that obesity is an important risk factor for early graft loss. Therefore all participating physicians assume a great responsibility for the pre-operative treatment during the waiting time.

Adult↗

[Computerized tomography measurement of torsion angle of the lower extremities].

The precise evaluation of post-traumatic deformities is indispensable when planning a corrective osteotomy. Torsional angles of the lower extremities of 186 patients were measured using CT. The mean age of the studied population was 34 years (18-80). It consisted of 131 men and 55 women. All patients had sustained a fracture of at least one of the leg's bony segments. The normal femoral (n = 293) inward torsion measured 23.47 degrees +/- 17.16 degrees (mean +/- 2 SD). Normal tibia (n = 263) outward torsion was 34.03 degrees +/- 17.22 degrees. The intraindividual torsional differences were not normally distributed. Normal femoral (n = 103) intraindividual torsional difference measured 11 degrees (95% percentile) and 15 degrees (99% percentile), with a median of 4 degrees. The tibiae (n = 76) showed a normal intraindividual torsional difference of 12 degrees (95% percentile) and 15 degrees (99% percentile). Right tibiae showed a statistically significant greater outward rotation when compared to their left counterpart (P < 0.001). No correlation to sex could be established. Preoperative planning of a corrective osteotomy should include the geometric evaluation of all four bony segments of the leg. Intraindividual torsional differences must be considered. A corrective osteotomy appears to be unnecessary with a torsional difference smaller than 15 degrees in the femora and smaller than 15 degrees in the tibiae.

Adolescent↗

The ecology of Cryptococcus neoformans.

Environmental isolations have established that Cryptococcus neoformans var. gattii serotype B appears to have a specific ecological association with Eucalyptus camaldulensis. The global distribution of the tree appears to correspond to the epidemiologic distribution of cryptococcosis caused by C. neoformans var. gattii. The epidemiology of cryptococcosis can primarily be explained by exposure to an infective aerosolized inoculum, such as basidiospores released from specific host plants and/or desiccated blastoconidia (yeast cells) disseminated from accumulations of dried pigeon dung. The ecology of C. neoformans still remains largely unresolved, studies on the host-parasite interaction between serotype B and E. camaldulensis are still in progress, and extensive environmental searches are now underway to determine the natural habitats of serotypes A, C and D.

Animals↗

Retained in vitro infectivity and cytopathogenicity of HIV-1 despite truncation of the C-terminal tail of the env gene product.

Five in-frame stop mutations in the HIV-1 env gene, which lead to the production of env gene products truncated within the cytoplasmic C-terminal tail, have been generated and their effects on membrane fusion capacity, glycoprotein incorporation into virus particles, infectivity, and cytopathogenicity were analyzed. The resulting truncated glycoproteins were processed normally, were transported to the cell surface, and were able to induce CD4-dependent membrane fusion. The membrane fusion capacity of one of the mutant glycoproteins with a truncation of 144 amino acids was increased to about double of that induced by wild-type glycoprotein. With a single exception, the truncated viral glycoproteins were incorporated into virus particles which were infectious and cytopathic for permissive MT-4 cells. The infection kinetics with the mutated viruses were, however, delayed to varying degrees in comparison to infection with wild-type virus. Nevertheless, in each case, PCR amplification and direct sequencing of viral DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA. The mutant virus encoding a viral glycoprotein with the longest truncation (144 amino acids), in which only 7 cytoplasmic C-terminal amino acids in gp41 remain, resulted in infection kinetics in MT-4 cells which were only marginally delayed in comparison to those induced by wild-type virus. This means that these C-terminal 144 amino acids of gp41 are not necessary for glycoprotein incorporation into virus particles nor do they significantly contribute to the infectivity nor the cytopathogenicity of HIV-1 in MT-4 cells.

Biological Transport, Active↗

HIV-1-induced cytopathogenicity in cell culture despite very decreased amounts of fusion-competent viral glycoprotein.

In order to examine the potential role of env-induced membrane fusion in the cytopathogenic properties of HIV-1 in cell culture, the effects of mutations within the proteolytic cleavage site of gp160, which result in a reduction but not a complete absence of proteolytic processing have been further studied. Cells expressing the mutant glycoproteins were shown to be severely reduced in their capacity to form syncytia. However, viruses encoding these glycoproteins could infect cell culture cells, albeit with delayed kinetics, and, at late infection time points, resulted in complete cytolysis of the infected culture. Since amplification by polymerase chain reaction and direct sequencing of the DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA, this shows that the amount of fusion competent viral glycoprotein does not influence HIV-1 cytopathogenicity, but rather that other parameters must be involved in inducing cell death.

Cell Line↗

[Therapeutic concepts in treatment of circulatory and heart failure in surgery].

Perioperative circulatory disorders in patients may take the form of a transitory reduction in oxygen transport to the peripheral tissues (pre-shock), manifest circulatory insufficiency in the presence or absence of concomitant heart insufficiency or general congestive heart failure due to the destabilization of an preexisting heart disease. The least problematical stage in this programme of therapy is the treatment of transitory perioperative circulatory insufficiency by manipulation of the oxygen transport system using the following means: comparative volume optimization [according to the central venous pressure (CVP)], positive inotropic support with dobutamine (5-10 micrograms.kg-1.min-1), monitoring of the blood pressure, heart rate and oxygen consumption and, in severe cases, insertion of a Swan-Ganz catheter. In manifest circulatory insufficiency, sepsis or acute congestive heart failure, the Swan-Ganz catheter seems to be obligatory. In such cases, the positive inotropic therapy is based on catecholamines of medium (dobutamine) or high (epinephrine) positive inotropic efficacy, as a normal pattern and functioning of beta-adrenoceptors can be assumed in such cases if there is no history of cardiac insufficiency. The systemic vascular resistance (SVR) is adjusted to 800-1200 n.s.cm-5 to relieve the working capacity of the heart and to maintain sufficient perfusion pressure by means of constrictors (phenylephrine, norepinephrine) or dilators [nifedipine, nitroglycerin or, if necessary, angiotensin-converting-enzyme (ACE) inhibitors].(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗

Preventive effects of acute inflammation on liver cell necrosis and inhibition of heparan sulphate synthesis in hepatocytes.

The hepatocytoprotective effect of acute, turpentine-induced inflammation on experimental liver injury, caused by thioacetamide and D-galactosamine, respectively, was studied in relation to the synthesis of glycosaminoglycans and of heparan sulphate in hepatocytes isolated from livers of treated rats. As judged from biochemical parameters of liver cell lesion in serum (various cytosolic and mitochondrial enzymes, bile acids) the extent of liver damage caused by either noxious agent was greatly attenuated under acute inflammatory conditions. There was an inverse statistical correlation (r = -0.63 to r = -0.84) between the functional concentration of a proteinase inhibitor protein determined with the chromogenic substrate assay for human alpha 2-macroglobulin and the catalytic concentrations of various cell leakage enzymes in serum from liver-injured rats with turpentine-generated inflammation. The strong inhibition of heparan sulphate synthesis in hepatocytes from injured livers (synthesis rate between 0.2 and 0.4 of that in control cell incubations) is abolished in hepatocytes from livers exposed to the noxious agents but with acute inflammation. The latter condition alone caused a 1.8 fold increase in heparan sulphate synthesis of hepatocytes. Heparan sulphate was the only type of glycosaminoglycan synthesized under all conditions. The results are discussed in view of the pathogenetic potential of heparan sulphate for liver cell necrosis.

Animals↗

[A psychophysiological analysis of the cognitive tempo by means of evoked potentials].

A new approach to measure the speed of cognitive behaviour is introduced. The decomposition of reaction time allows to identify different stages: perception, comparison steps and motoric organization. For this reason the additive factor method and the analysis of event-related potentials is used. The results show specific decelerations in elderly subjects and alcoholics. The application of the method in clinical psychodiagnostic and psychopharmacology is discussed.

Adult↗