PubMed Health⌕ Search

Biomedical subjects

M Goetz

Publications and source records attributed to M Goetz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chemical synthesis of yeast mitochondrial ATP synthase membranous subunit 8.

Chemical synthesis of highly hydrophobic peptides and proteins remains a challenging problem. Strong interchain associations within the peptide-resin matrix have to be overcome. A synthetic strategy for solid phase peptide synthesis is proposed, mainly based on prolonged coupling time using aprotic polar solvent mixtures. A tailored chromatographic purification was required to obtain a sample sufficiently pure for structural analysis. In this work, the total chemical synthesis of the membrane-embedded yeast mitochondrial ATP synthase subunit 8 is described. The quality of the synthetic protein was checked by electrospray mass spectrometry, its tendency to adopt alpha-helical secondary structure is evidenced by circular dichroism spectroscopy.

Amino Acid Sequence↗
PubMed1999

Assessment of serum myeloperoxidase in children with bronchial asthma.

BACKGROUND: The role of neutrophils and myeloperoxidase (MPO) - assumed to be a marker of neutrophil activation - in bronchial asthma is still unclear, and the literature is controversial. METHODS: To investigate the participation of neutrophils and their products in childhood asthma, we assessed neutrophil counts and serum MPO in 175 children with bronchial asthma. Ninety of them were asymptomatic, and 85 of them were symptomatic within the last 2 weeks before examination. Bacterial infection of the lower respiratory tract (LRTI) was present in 34 and viral infection in 49 patients. As controls, 45 patients with cystic fibrosis, 23 patients with bacterial LRTI, and 87 healthy children were recruited. RESULTS: Median neutrophil counts (3135 cells/microl) and serum MPO levels (352 microg/l) were not different in children with bronchial asthma from healthy controls (2220 cells/microl and 401 microg/l, respectively), whereas in patients with cystic fibrosis and bacterial LRTI, neutrophil counts and MPO levels were increased. Asthmatic children with bacterial infection had significantly higher serum MPO and neutrophil counts then asthmatic children with viral infection or without infection. In addition, a significant correlation was found between serum MPO and neutrophil counts and C-reactive protein (CRP), and between neutrophil counts and CRP, but no relationship was detected for serum MPO and disease activity or lung function. CONCLUSIONS: Our data indicate that serum MPO - a marker of neutrophil activation - does not contribute to the assessment of the inflammatory process in childhood asthma. In addition, measurement of serum MPO appears not to be useful in assessing the participation of the neutrophil in asthmatic children. However, assessment of MPO may be useful to distinguish between bacterial and viral infection.

Adolescent↗
PubMed1999

The different pH optima and substrate specificities of extracellular and vacuolar invertases from plants are determined by a single amino-acid substitution.

Different plant invertase isoenzymes are characterized by a single amino-acid difference in a conserved sequence, the WEC-P/V-D box. A proline residue is present in this sequence motif of extracellular invertase sequences, whereas a valine is found at the same position of vacuolar invertase sequences. The role of this distinct difference was studied by substituting the proline residue of extracellular invertase CIN1 from Chenopodium rubrum with a valine residue, by site-directed mutagenesis. The mutated gene was heterologously expressed in an invertase-deficient Saccharomyces cerevisiae strain. The single amino-acid difference was shown to be the molecular basis for two enzymatic properties of invertase isoenzymes, for both the pH optimum and the substrate specificity. A proline in the WEC-P/V-D box determines the more acidic pH optimum and the higher cleavage rate of raffinose of extracellular invertases, compared to vacuolar invertases that have a valine residue at this position.

Amino Acid Sequence↗
PubMed1999

Isolation and characterization of novel human immunodeficiency virus integrase inhibitors from fungal metabolites.

We have identified a series of novel inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase by randomly screening natural product extracts using an in vitro biochemical assay designed to identify inhibitors of integrase-catalysed strand transfer. Equisetin recovered from the fungus Fusarium heterosporum and a novel enantiomeric homologue of equisetin from Phoma sp. were isolated as inhibitors of HIV-1 integrase in vitro. Two additional analogues, a novel decalin derivative, integric acid, and oteromycin were also discovered to be inhibitors of integrase. Equisetin and related compounds inhibit 3' end-processing and strand transfer as well as disintegration catalysed by either the full-length enzyme or the truncated integrase core domain (amino acids 50-212). These compounds also inhibit strand transfer reactions catalysed by stable complexes assembled in vitro and integration reactions catalysed by pre-integration complexes isolated from HIV-1-infected cells. The compounds described in this report are structurally novel and mechanistically distinct from many previously described inhibitors of HIV-1 integrase. These results demonstrate the utility of using an appropriately configured assay to identify compounds that are effective post-assembly and the potential of isolating novel integrase inhibitors from complex natural product extracts.

Base Sequence↗
PubMed1999

Production of a family of kinase-inhibiting lactones from fungal fermentations.

During the course of our screening for natural products from fungi, extracts of several cultures were found to make a family of related resorcylic acid lactone compounds, which are potent inhibitors of MEK kinase. Comparative and empirical studies of fermentation conditions improved the titers of the compounds of interest. Striking changes in the ratios and amounts of the major and minor compounds in some cases were achieved by manipulations of media composition.

Culture Media↗
PubMed1997

Prophylaxis and treatment of bladder dysfunction after Wertheim-Meigs operation: the positive effect of early postoperative detrusor stimulation using the cholinergic drug betanecholchloride.

The efficacy of betanecholchloride in the postoperative treatment of bladder dysfunction is controversial. We therefore performed a comparative study on the effect of this therapy for the prophylaxis of detrusor hypotonia after Wertheim-Meigs operation. Forty patients with cervical cancer FIGO stage Ib/IIa were divided into two study groups. The control group (24 patients) only received betanecholchloride if the residual urine persisted above 50 ml after the 10th postoperative day. The study group (16 patients) received 50 mg betanecholchloride three times a day from the 3rd postoperative day onward. In this group postoperative catheter treatment, and consequently hospital stay, were significantly shorter (9.6 versus 13.3 days and 15.5 versus 18.6 days). The residual urinary volume normalized faster (8.0 versus 13.0 days) and the rate of cystitis was lower (18.8 versus 25%). According to our study, a prophylactic application of the parasympathomimetic drug betanecholchloride diminishes postoperative complications associated with bladder dysfunction after Wertheim-Meigs operation.

Adult↗
PubMed1997

Antigenic variability of an immunodominant region (239-261) of the surface glycoprotein of HTLV-I.

In the 239-261 region of the surface glycoprotein of HTLV-I, we delineated five epitopes recognized by antibodies present in sera from HTLV-I infected patients. Three epitopes are located between the amino acids 252 and 261, one is of a linear type and the two others of a conformational type. One epitope is comprised between amino acids 244 and 249. The last epitope described lies between the amino acids 244 and 257 and strictly requires the presence of a serine at position 250 for its recognition. When patients are infected by viral isolates presenting a substitution of the serine at position 250 by a proline, no antibodies recognizing the 244-257 region could be found. Altogether, our data demonstrate that the immunodominant 239-261 region is complex and is subject to antigenic variability.

Amino Acid Sequence↗
PubMed1997

False elevation of CA 19-9 levels in a patient with a history of pancreatic cancer.

CA 19-9 is the most sensitive and specific marker currently used in the diagnosis of pancreatic cancer. Its interpretation, however, can be limited in the presence of certain nonmalignant diseases that have been correlated with elevated serum levels of CA 19-9. We report an unusual case of falsely elevated CA 19-9 levels in a patient with a history of resected pancreatic cancer. This patient presented 4 yr after resection with painless jaundice and markedly elevated CA 19-9 levels (2327 U/ml). Although it was initially suspected that the patient had recurrent cancer, further evaluation proved that her jaundice and increased CA 19-9 value were due to a benign stricture that led to cholestatic jaundice and concomitant cholangitis. No previous cases of falsely elevated CA 19-9 levels have been reported in the context of a known history of pancreatic cancer. Physicians should be aware of the perturbations that extrahepatic cholestasis and certain inflammatory diseases of the pancreas and hepatobiliary system may impose on CA 19-9 levels. Furthermore, this case demonstrates that even markedly elevated CA 19-9 levels in patients being assessed for recurrence of pancreatic cancer need to be carefully interpreted in the context of other clinical findings.

Adenocarcinoma↗
PubMed1996

Development of quantitative Doppler indices for uteroplacental and fetal blood flow during the third trimester.

The aim of our study was to describe the development of uteroplacental and fetal blood flow during the third trimester. Doppler examination was carried out on 393 uncomplicated pregnancies with uncomplicated term delivery. Using a pulsed color Doppler, we calculated the maximum systolic, mean and maximum end-diastolic velocity after correcting the angle of insonation. Patients under tocolysis or other medication influencing blood flow parameters were excluded from this cross-sectional study. Summarizing the results gained by Doppler ultrasound investigation of the uteroplacental and fetal blood vessels, we created quantiles as quantitative Doppler indices for the maximum systolic, mean (TAMX = time averaged maximum velocity) and maximum end-diastolic velocity. The following conclusions could be drawn: (1) resistance to the blood flow in the maternal portion of the placenta does not change during the third trimester; (2) resistance to the blood flow on the fetal side of the placenta decreases up to week 42 of gestation; (3) cerebral vascular resistance decreases constantly up to gestational week 42; and (4) vascular resistance to the blood flow of the kidney decreases only slightly during the third trimester. This study offers clinically important values for quantitative Doppler flow velocimetry for the first time. We hope that our findings improve the usefulness of Doppler ultrasound as a diagnostic tool in obstetrical management.

Blood Flow Velocity↗
PubMed1996

Hemodynamic study of the anterior communicating artery.

BACKGROUND AND PURPOSE: The anterior communicating artery (ACoA) is a site of predilection for intracranial saccular aneurysms causing subarachnoid hemorrhage. ACoA aneurysms are frequently associated with an asymmetrical circle of Willis. In such cases, the ACoA is probably exposed to high hemodynamic stress caused by a considerable shunt flow across the ACoA to the distal segment of the contralateral anterior cerebral artery (ACA). In the present study, the flow pattern and flow-induced shear stress in the ACoA complex that may initiate aneurysmal lesions were studied under steady and pulsatile flow conditions. METHODS: Flow visualization was studied with dye injection and birefringent flow visualization in symmetrical and asymmetrical models of various sizes of ACoA. The distribution of wall shear stress was measured using an electrochemical method based on a diffusion-controlled reaction of ferricyanide ion to ferrocyanide ion at a platinum electrode embedded in the wall of the ACoA model. RESULTS: With equal flow rate (Reynolds number 150 to 600), vortical flow was formed in the mouth of the ACoA, and no cross flow through the ACoA was observed. The wall shear stress on the mid-wall of the ACoA was almost zero. However, as soon as the flow rate became unequal, a cross flow through the ACoA was observed. The stagnation point also appeared at the medial junction of the ACoA and ACA. The wall shear stress increased to a very high level at the wall of the ACoA and around the stagnation point. CONCLUSIONS: Geometric changes from the symmetrical to the asymmetrical ACoA develop higher shear stress on the ACoA than critical values and the stagnation point at the ACoA junction. A combination of these hemodynamic factors is considered to play an important role in initiation of aneurysm.

Blood Flow Velocity↗
PubMed1995

Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action.

Tubulin polymerization into microtubules is a dynamic process, with the equilibrium between growth and shrinkage being essential for many cellular processes. The antineoplastic agent taxol hyperstabilizes polymerized microtubules, leading to mitotic arrest and cytotoxicity in proliferating cells. Using a sensitive filtration-calorimetric assay to detect microtubule nucleating activity, we have identified epothilones A and B as compounds that possess all the biological effects of taxol both in vitro and in cultured cells. The epothilones are equipotent and exhibit kinetics similar to taxol in inducing tubulin polymerization into microtubules in vitro (filtration, light scattering, sedimentation, and electron microscopy) and in producing enhanced microtubule stability and bundling in cultured cells. Furthermore, these 16-membered macrolides are competitive inhibitors of [3H]taxol binding, exhibiting a 50% inhibitory concentration almost identical to that of taxol in displacement competition assays. Epothilones also cause cell cycle arrest at the G2-M transition leading to cytotoxicity, similar to taxol. In contrast to taxol, epothilones retain a much greater toxicity against P-glycoprotein-expressing multiple drug resistant cells. Epothilones, therefore, represent a novel structural class of compounds, the first to be described since the original discovery of taxol, which not only mimic the biological effects of taxol but also appear to bind to the same microtubule-binding site as taxol.

Animals↗
PubMed1994

[Puerperium after threatened premature labor--positive effects of infection screening by determination of CRP in pregnancy].

Silent intrauterine infection as cause of preterm labour should be recognised early by measuring C-reactive protein (CRP) levels in the maternal serum. Ensuing antibiotic therapy may not only cause gestational prolongation, but also has a positive effect on pathology during the puerperal period. Consequently, we examined the rate of infectious puerperal complications of 181 patients who suffered from so-called idiopathic preterm labour. 84 patients showed normal CRP-levels at the onset of tocolysis (< 5 mg/l); an elevated level was found in 97 patients (> 5 mg/l). Patients with elevated CRP-levels and supplemented antibiotic therapy during pregnancy (n = 51) showed significantly fewer symptoms of postpartal endometritis than women with similarly elevated CRP-levels but without antibiotics (n = 46). This effect was not produced when preterm labour was associated with normal CRP-levels. Patients with premature contractions and elevated CRP-values at the onset of tocolysis seem to benefit from the antibiotic therapy during pregnancy because they show reduced infectious complications throughout the puerperal period.

Adult↗
PubMed1992

L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease. II. Isolation and structure.

A novel HIV-1 protease inhibitor, L-696,474 (C30H39NO4, 477), was isolated from the fermentations of the fungus Hypoxylon fragiforme (ATCC 20995, MF5511) and purified by silica gel chromatography followed by crystallization. Spectroscopic studies have shown the competitive inhibitor L-696,474 to be a novel cytochalasin. Two related novel cytochalasins were also isolated and had no effect on the enzyme.

Ascomycota↗
PubMed1986

Defensive alkaloid in blood of Mexican bean beetle (Epilachna varivestis).

The blood of the Mexican bean beetle (Epilachna varivestis) contains a homotropane alkaloid, euphococcinine (1). The beetles 'reflex bleed' when disturbed, thereby deploying the alkaloid, which is provenly deterrent to spiders and ants. Newly emerged adults lack the alkaloid, but the compound builds up to deterrent levels in their blood within days. Eggs and larvae of Epilachna are devoid of the compound.

Alkaloids↗