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G Weber

Publications and source records attributed to G Weber.

At least 109 records · Page 6Linked to original sources
PubMed1998

Recent developments in preparative free flow isoelectric focusing.

Continuous flow electrophoresis (CFE) is a promising method for preparative fractionation of a variety of biological species, ranging from peptides and proteins to subcellular particles and cells. The high separation efficiency of FFE may be deteriorated by hydrodynamic distortion of zones due to the omnipresent parabolic laminar flow profile. We show in this paper that the detrimental hydrodynamic distortion of separated proteins zones can be reduced, with resultant enhancement of separation efficiency, by employing continuous isoelectric focusing in pH gradients as the actual working regime in an advanced instrumentation. Newly developed media for fast generation of narrow- or broad-range pH gradients under CFE conditions are described. The separation efficiency of these pH gradients is comparable to that of the gradients formed with the aid of synthetic carrier ampholytes. The new media are defined mixtures of nontoxic chemicals, and thus they are compatible with the requirements of human medicine. Experimental data are given showing that the new media offer fractionation of isoforms of proteins, that they offer resolution of proteins differing in isoelectric point (pI) by less than 0.05 pH units, and that these media inhibit proteins precipitation in experiments with human serum proteins.

Humans↗
PubMed1998

Interval isotachophoresis for purification and isolation of ionogenic species.

A new preparative electrophoretic method in free solution is described, consisting of three consecutive steps: (i) filling the separation chamber with a suitable electrolyte system and sample in parallel streams by laminar hydrodynamic flow, (ii) applying the voltage across the chamber with isotachophoretic separation for a definite time interval operating in the direction perpendicular to that of filling, (iii) reapplying a hydrodynamic flow (without voltage) and collecting the separated species via an array of outlets. This approach completely eliminates the main drawback of the continuous flow electrophoresis (CFE), i.e., the electrohydrodynamic distortion of zones. This method utilizes the instrumentation devised for CFE and enables the isolation of large amounts of individual sample species comparable to that of CFE, with a resolution comparable to that of capillary isotachophoresis. The precise timing of the consecutive steps in the procedure as well as the stability of the operational parameters are of key importance for reproducibility. By using cationic isotachophoresis with 3 synthetic pI markers as model sample species, the reproducibility, stability and the separation power of the newly presented method are demonstrated. The sample throughput corresponds to micromoles per hour.

Electrophoresis↗
PubMed1998

Stability of continuous flow electrophoresis.

The stability of continuous flow electrophoresis (CFE) was tested by performing uninterrupted continuous flow cationic isotachophoresis for 15 h, using a mixture of two synthetic isoelectric point (pI) markers as the model sample. This sample as well as the other operational electrolytes were continuously pumped into the CFE separation chamber via 10 individual inlets. The operational electrolyte system and the arrangement of the electrolyte streams were selected in accord with previously published results, providing a stable electrophoretic regime. The chamber had 96 individual outlets and here 96 individual fractions were collected in microwell plates in regular time intervals and scanned photometrically. The scanned photometric patterns proved that CFE is sufficiently stable for an overnight operation.

Electrophoresis↗
PubMed1998

Urinary markers of bone turnover in healthy children and adolescents: age-related changes and effect of puberty.

During growth, bones change their dimensions rapidly with the changes involving both formation and resorption processes. Small cross-linked peptides coming from type I collagen molecules are excreted in urine when bone is resorbed. To date, conflicting results have been presented concerning the age- and puberty-related changes of urinary markers. The purpose of the present study was to verify the effect of age, gender, and puberty on the urinary excretion of type I collagen degradation products in healthy children and adolescents. Timed spot urines from 176 children (4-20 years old) and 50 young adults were analyzed. The concentrations of N-telopeptides of type I collagen (NTx), pyridinolines (Pyr), and deoxypyridinolines (Dpyr) were measured, and the results were normalized to creatinine. Age-related changes in cross-links excretion were observed. The levels decreased with age, and a peak of excretion was shown at the beginning of adolescence. Prepubertal levels of all the markers were four- to five-fold higher than in adults, and they decreased towards adult levels in late puberty. Girls had significantly higher levels of all biochemical markers than boys at pubertal stage 2. We also observed a remarkable effect of puberty on the levels of bone degradation products that was independent of age and gender. Our results indicate that bone resorption is high in children relative to that in adults, and that urinary levels of NTx, Pyr, and Dpyr change as a function of age, gender, and puberty.

Adolescent↗
PubMed1998

Expression and chromosomal localization of the Requiem gene.

Apoptosis in murine myeloid cell lines requires the expression of the Requiem gene, which encodes a putative zinc finger protein. We detected the protein in both cytoplasmic and nuclear subcellular fractions of murine myeloid cells and human K562 leukemia cells, which suggests that the protein might have a function distinct from a transcription factor. This distribution did not alter upon apoptosis induction by IL-3 deprivation. As an approach to investigate its role in development, we determined the spatio-temporal expression pattern in the mouse. Expression was detected in various tissues in earlier gestational age; however, confined to testes, spleen, thymus, and part of the hippocampus in the adult mouse. The expression profile is consistent with a functional role during rapid growth and cell turnover, and in agreement with a regulatory function for hematopoietic cells. The human cDNA clone sequenced showed high homology to its murine counterpart and extended the open reading frame by 20 codons upstream. The gene is located in the proximal region of mouse Chromosome (Chr) 19. In the homologous human region at 11q13, it is located at about 150 kb centromeric from MLK3.

Amino Acid Sequence↗
PubMed1998

[Reactive arthritis after cat bit: a rare manifestation of cat scratch disease--case report and overview].

Cat scratch disease (CSD) is a rarely recognized infectious disease in Germany. Only a few years ago the causative agent, Bartonella henselae, could be isolated. The typical clinical manifestations of CSD consist of skin changes at the inoculation site and a benign lymphadenopathy; other manifestations are rare. We report the case of a 47 year old woman, who developed a reactive spondylarthropathy with synovitis of finger joints, polyarthralgias of large- and medium-sized joints, and inflammatory spinal pain after a cat bite. The rheumatic manifestations resolved after 10 months by treatment with non-steroidal antirheumatic drugs. Only a few cases of rheumatic manifestations associated with CSD have been described in the literature. Because the prevalence of Bartonella henselae infection of cats is high in Europe, rheumatic manifestations might be more frequent. Diagnosis of CSD is now improved by the development of serological tests. We provide an overview of the clinical manifestations and the diagnostic criteria.

Animals↗
PubMed1998

Synergistic action of tiazofurin and genistein on growth inhibition and differentiation of K-562 human leukemic cells.

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193), an oncolytic drug, inhibits IMP DH (inosine 5'-monophosphate dehydrogenase, EC 1.1.1.205), reduces signal transduction activity and IP3 (inositol 1,4,5-trisphosphate) concentration and arrests the cell cycle chiefly in S phase. Genistein (4',5,7-trihydroxyisoflavone), an inhibitor of PIP kinase (1-phosphatidylinositol 4-phosphate 5-kinase, EC 2.7.1.68), tyrosine kinase and topoisomerase-II, induces arrest in G2 and/or early M phase in most carcinoma cells. Both drugs, as single agents, induce differentiation. Since tiazofurin and genistein attack different enzymic targets and arrest the cell cycle at different phases and they each induce differentiation, we tested the hypothesis that tiazofurin might be synergistic with genistein in inducing differentiation. Human leukemic K-562 cells were grown in suspension culture and were seeded in 24-well culture plates. In growth inhibition assays for tiazofurin and genistein IC50s (drug concentration that inhibits 50% of cell proliferation) were 7 and 37 microM, respectively. For tiazofurin and genistein the concentrations of drug that induce differentiation in 50% of the cells were 35 and 45 microM, respectively. Various combinations of these two drugs were tested. Since tiazofurin decreased GTP concentration in cells by 50% at 12 hr after administration, genistein (10 to 30 microM) was added 12 hr after tiazofurin (5 to 15 microM). Synergistic action on differentiation was obtained from all tiazofurin and genistein combinations and in most combinations on growth inhibition. The percent of differentiating cells induced by genistein (10 microM) and tiazofurin (10 microM) as single agents increased 1.1- and 2.8-fold, respectively, of the control values. The two drugs together caused 5.9-fold elevation in inducing differentiation. Similar action was observed on inhibition of proliferation.

Anticarcinogenic Agents↗
PubMed1998

The remarkable influence of steroid A/B-ring junction on the Wittig olefination reaction of the 11-oxo group: towards the synthesis of 5 alpha- and 5 beta-oriented delta 3-isomers of desogestrel.

The 5 alpha- and 5 beta-oriented delta 3-double bond isomers 8, 9 of the widely used progestin desogestrel (7) were synthesized. Wittig olefination reaction of the 5 alpha-intermediate 12 showed a dramatically reduced reaction rate compared with the olefination of the 5 beta-intermediate 13. Computational studies suggest that different energies of the intermediary 1,2-oxaphosphetanes may, at least partially, have been the reason for this phenomenon.

Alkenes↗
PubMed1998

Evaluation of different transvaginal sonographic diagnostic parameters in women with postmenopausal bleeding.

OBJECTIVE: To determine whether the accuracy of transvaginal sonography to detect endometrial pathology is enhanced by assessing endometrial morphology and the regularity of the endometrial border in addition to measurement of endometrial thickness in women with postmenopausal bleeding. DESIGN AND METHODS: A total of 159 women with postmenopausal bleeding were included in a prospective study performed at the Clinic of Obstetrics and Gynecology, University of Mainz. The results obtained on transvaginal sonographic assessment of the endometrium were compared with the histological evaluation of the operative endometrial specimen. RESULTS: A cut-off level for endometrial thickness of 5 mm had a sensitivity of 94%, specificity of 48% and positive and negative predictive values of 69% and 87%, respectively for the presence of endometrial pathology. Assessment of the regularity of the endometrial border showed a sensitivity of 75%, specificity of 66% and positive and negative predictive values of 73% and 69%, respectively. For the third sonographic parameter, endometrial morphology, the sensitivity was 82%, specificity 64%, the positive predictive value 73% and the negative predictive value 74%. The combined consideration of the three sonographic parameters showed a sensitivity of 97%, specificity of 65%, and positive and negative predictive values of 80% and 94%, respectively. CONCLUSION: The combined evaluation of endometrial thickness, endometrial morphology and the endometrial border enhances the accuracy of transvaginal sonography to detect endometrial pathology in women with postmenopausal bleeding, thus facilitating the decision regarding further diagnostic and therapeutic measures.

Endometrial Neoplasms↗
PubMed1998

A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis.

The presence of germline and somatic mutations in the RET proto-oncogene (RET) in patients with hereditary and sporadic medullary thyroid carcinoma (MTC) may have important ramifications for patient management. It has been suggested that the presence of the mutation ATG-->ACG at codon 918 in sporadic MTC is associated with a worse prognosis, and hence the need for more aggressive surgical, or other, treatment. Since fine-needle aspiration biopsy (FNAB) is an important component of the preoperative management of patients with thyroid tumors, we developed a rapid (20-min) method that enables extraction of DNA from FNABs for RET mutation analysis. The method allows preoperative genetic analysis to aid in management of patients with MTC, and may be applied to other tumor types where a preoperative mutation analysis based on polymerase chain reaction amplification is desired.

Biopsy, Needle↗
PubMed1998

A new sonomorphologic scoring system (Mainz Score) for the assessment of ovarian tumors using transvaginal ultrasonography. Part I: A comparison between the scoring-system and the assessment by an experienced sonographer.

OBJECTIVE: The problem of an accurate sonographic assessment of ovarian tumor status has not yet been solved. To what extent can the preoperative assessment of adnexal tumors be improved on the basis of a maximum number of sonographic tumor parameters included in the newly developed sonomorphologic Mainz Score? MATERIALS AND METHODS: In a prospective study 314 premenopausal patients with adnexal tumor underwent a transvaginal sonographic examination performed by an experienced sonographer. In parallel to the sonographic examination a new score including 10 different sonographic parameters was used to predict adnexal tumor status: 1. Total tumor structure, 2. tumor border, 3. wall thickness, 4. inner echos in cystic component, 5. septa, 6. shape of echo complex or of the completely solid tumor, 7. echogenicity of the echo complex or of the completely solid tumor, 8. acuostic phenomena behind tumor, 9. ascites, 10. detection of liver metastases/peritoneal carcinosis Depending on the respective degree of expression, the individual characteristics were rated on a scale from 0 to 2. The total score obtained following addition of the points recorded for each parameters served to confirm the validity of the sonographic tumor status assessment. The first sonographer assessed the tumor status based on his experience and in the knowledge of all clinical parameters. The second sonographer evaluated the tumor status based on the score. All preoperative ultrasonographic findings were compared with the postoperative histologic analysis. RESULTS: A maximum number of 20 points may be obtained using the Mainz Score. Tumors with a total score of below 9 were rated as benign and those with a score of above 9 as malignant. This resulted in a sensitivity of 96.4%, a specificity of 80.7%, a positive predictive value of 47.4%, and a negative predictive value of 99.6%. The predictive value of the scoring-system was diminished by the presence of 30 false-positive cases, which were identified as inflammatory conglomerate tumors, teratomas, endometrial cysts, cystadenomas and hemorrhagic cysts. The experienced sonographer assessed 233 cases as benign and 24 cases as malignant. The findings were confirmed by the histological examination in 252 of 257 cases. No conclusive prediction of tumor status could be made in 57 tumors. However, the application of the Mainz Score enabled an accurate prediction of the tumor status in 44 of the 57 cases. With the exception of septal thickness all assessment criteria of the score showed a statistically significant correlation between the assigned score and the histologic findings, (p < 0.05). CONCLUSIONS: The use of the Mainz Score enables even less experienced sonographers to assess the status of premenopausal adnexal tumors with a high degree of accuracy. The score provides the experienced sonographer with a refined and improved method for the prediction of tumor status, especially in the presence of not readily assessable findings.

Adolescent↗
PubMed1998

A sequence highly similar to PNG is located on chromosome 22q12 in intron 15 of the LIMK-2 gene.

In this report we describe a sequence (PNG22) highly similar to the Phospholipase C beta3 Neighboring Gene (PNG). We also report that PNG22 is located in the q12 region on chromosome 22 between markers D22S1144 and D22S280. This finding explains that PNG probes cross hybridize to sequences on chromosome 22. Fine mapping using our sequence data and the complete sequence of a PAC clone (DJ515N1), located in this region, determined that PNG22 is located in intron 15 of the LIMK-2 gene. PNG22 is 93% homologous to PNG, however it do not have the introns described for the PNG gene, instead matching the cDNA sequence. This leads us to suggest that PNG22 probably represents a PNG pseudogene. In this report we also list the exon intron borders and the genomic structure of LIMK-2 and place it on the Sanger Center chromosome 22 Physical map. It also explains the finding that PNG probes cross hybridize to sequences on chromosome 22.

Base Sequence↗
PubMed1998

Reversal of low bone density with a gluten-free diet in children and adolescents with celiac disease.

Osteoporosis is a common finding in adult celiac disease patients; however, there are still few data regarding children and adolescents. In the present study we measured the bone mineral density (BMD) in children and adolescents at diagnosis of celiac disease and after approximately 1 y of a gluten-free diet. BMD was measured at the lumbar spine and in the whole skeleton by dual-energy X-ray absorptiometry in 44 celiac disease patients aged 2.58-20.42 y at diagnosis. BMD was also measured in a subset of 25 patients after 1.4 +/- 0.04 y of a gluten-free diet. BMD was compared with that of 177 healthy control subjects aged 1.52-20.99 y. Lumbar spine and whole-body BMD values at diagnosis of celiac disease were significantly lower than in control subjects (P = 0.015 and P = 0.0001, respectively) after differences in age and anthropomorphic variables were controlled for. The subjects studied after the gluten-free diet had BMD values not significantly different from those of control subjects. In conclusion, children and adolescents with celiac disease have remarkably reduced lumbar spine and whole-body bone density. A gluten-free diet promotes a rapid increase of BMD that leads to a complete recovery of bone mineralization. These results emphasize the need for an early diagnosis and treatment in patients with celiac disease to obtain an adequate peak bone mass at the end of puberty.

Absorptiometry, Photon↗
PubMed1998

Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies: a phase I trial.

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m2/24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen for metastatic disease. Gallium was administered at a fixed dose of 300 mg/m2/day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m2 was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 microg/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m2 and 225 mg/m2 with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase II dosage is gallium nitrate at 300 mg/m2/day over 120 hours, with paclitaxel at 110 mg/m2 over 24 hours without G-CSF or 225 mg/m2 over 24 hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of this modified regimen for outpatient administration are in progress.

Adult↗
PubMed1998

Imported severe falciparum malaria in Israel.

Malaria remains an overwhelming problem in tropical developing countries, with 300 to 500 million new cases and 1.5 to 3.5 million deaths per year. Malaria is a potentially life-threatening disease for travelers to the tropics. Imported malaria is an important clinical problem in nonendemic areas of the world because of increasing numbers of travelers, overseas workers, and immigrants from endemic areas. According to the World Health Organization's criteria, the recognition of one or more of the following clinical features should raise the suspicion of severe malaria: cerebral malaria (unrousable coma), severe anemia (hemoglobin <5 g/dL), renal failure (serum creatinine >3 mg/dL), pulmonary edema or adult respiratory distress syndrome, hypoglycemia (glucose <40 mg/dL), circulatory collapse or shock, disseminated intravascular coagulation, repeated generalized convulsions, acidosis (pH <7.25), macroscopic hemoglobinuria, hyperparasitemia (>5 percent of the erythrocytes infested by parasites), or jaundice (bilirubin >3 mg/dL). Although only a small proportion of patients with malaria develops severe manifestations, these patients require the most urgent and intensive care. Mortality among patients with cerebral malaria, even when treated in modern intensive care units, exceeds 30%, and when complicated by the adult respiratory distress syndrome, it may approach 80%. Among travelers, mortality remains a serious issue because of failure to obtain and use preventive measures, delay in seeking medical attention, and misdiagnosis.

Adult↗