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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 145 records · Page 8Linked to original sources
PubMed1997

Changing trends in frequency and antimicrobial resistance of urinary pathogens in outpatient clinics and a hospital in Southern Israel, 1991-1995.

In order to monitor changes in the frequency and antimicrobial resistance of urinary pathogens over several years, urinary cultures received from outpatient clinics and from a hospital during a period of one month each in 1991 and 1995 were analyzed at a clinical microbiology laboratory. In 1991 and 1995, 1366 and 1534 significant monomicrobic cultures respectively were reviewed. The frequency of Escherichia coli dropped significantly in the outpatient clinics from 70.5% to 61.2% (p < 0.0001). The frequency of Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa and other gram-negative bacteria also decreased, but the frequency of Klebsiella spp. and Enterobacter spp. increased from 2.6% to 5.8% (p < 0.0001). In the hospital, the frequency of Enterobacter spp. (p < 0.04), Escherichia coli and Morganella morganii declined from 1991 to 1995, whereas the frequency of Pseudomonas aeruginosa (p = 0.001), Acinetobacter spp. (p < 0.05), Klebsiella spp., Proteus mirabilis and other gram-negative rods increased considerably. The frequency of gram-positive aerobic bacteria rose markedly in outpatient specimens from 6.1% to 13.5% (p < 0.0001), while a decline from 14.4% to 9.3% was noted in hospital specimens (p < 0.02). A significant rise in the resistance of Escherichia coli to gentamicin and ciprofloxacin (p < 0.0001) was detected in outpatient isolates. In the hospital, gram-negative urinary pathogens demonstrated increased resistance to ampicillin (p = 0.042), cefuroxime (p = 0.005), gentamicin (p = 0.002) and ciprofloxacin (p < 0.0001) during the study period. The changing etiology of urinary tract infections and the increasing resistance of organisms indicate that periodic monitoring and possibly also modification of empirical therapy are required.

Ambulatory Care Facilities↗
PubMed1997

Septic arthritis due to bacteroides fragilis after pilonidal sinus resection in a patient with rheumatoid arthritis.

Bacteroides fragilis is a rare cause of septic arthritis. Most patients with B. fragilis septic arthritis have a chronic joint disease, particularly rheumatoid arthritis, and sources of infection are lesions of the gastrointestinal tract and the skin. We report a 69-year-old male, who developed B. fragilis septic arthritis after pilonidal sinus resection. High level of suspicion of development B. fragilis septic arthritis must be present in patients with chronic joint disease in whom gastrointestinal or skin surgery was previously performed.

Aged↗
PubMed1997

Exclusion of the phosphoinositide-specific phospholipase C beta 3 (PLCB3) gene as a candidate for multiple endocrine neoplasia type 1.

The predisposing genetic defect in multiple endocrine neoplasia type 1 has been assigned to chromosomal region 11q13. Our previous attempts to identify the MEN1 gene have resulted in the isolation of the phospholipase C beta 3 gene from the actual region. PLCB3 plays an important role in signal transduction and, moreover, shows loss of expression in some endocrine tumors, in accordance with a putative tumor suppressor gene function, and thus appears to be an excellent candidate for MEN1. We have therefore undertaken screening for constitutional mutations in individuals from MEN1 families. Several sequence alterations have been discovered, none of them however fulfilling the criteria for a disease-related mutation. We can now exclude PLCB3 from candidacy as the MEN1 gene.

Chromosome Mapping↗
PubMed1997

Mapping of the gene encoding the B56 beta subunit of protein phosphatase 2A (PPP2R5B) to a 0.5-Mb region of chromosome 11q13 and its exclusion as a candidate gene for multiple endocrine neoplasia type 1 (MEN1).

The multiple endocrine neoplasia type 1 (MEN1) locus has been previously localised to 11q13 by combined tumour deletion mapping and recombination studies, and a 0.5-Mb region, flanked by PYGM and D11S449, has been defined. In the course of constructing a conting, we have identified the location of the gene encoding the B56 beta subunit of protein phosphatase 2A (PP2A), which is involved in cell signal transduction pathways and thus represents a candidate gene for MEN1. We have searched for mutations in the PP2A-B56 beta coding region, together with the 5' and 3' untranslated regions in six MEN1 patients. DNA sequence abnormalities were not identified and thus the PP2A-B56 beta gene is excluded as the candidate gene for MEN1. However, our precise localisation of PP2A-B56 beta to this region of 11q13 may help in elucidating the basis for other disease genes mapping to this generich region.

Chromosome Mapping↗
PubMed1997

Molecular mechanisms in the antiproliferative action of quercetin.

A single treatment with quercetin (5.5 microM), a plant flavonoid, activated both apoptosis and differentiation programs in K562 human leukemia cells. K562 cells expressed commitment to apoptosis after 1 h exposure, however, at least 12 h of drug exposure was needed to induce differentiation. Early (1 h) down-regulation of the c-myc and Ki-ras oncogenes and rapid reduction of inositol-1,4,5-trisphosphate (IP3) concentration (IC50 = 9 microM, 1 h incubation) are part of the antiproliferative action of quercetin and appear to relate to induction of differentiation and/or apoptotic program of K562 leukemia cells treated with quercetin.

Apoptosis↗
PubMed1997

Regulation of the signal transduction program by drugs.

The purpose of this paper was to clarify critical aspects of the behavior of signal transduction activity in normal and cancer cells. 1. Signal transduction activity in the conversion of phosphatidylinositol through PI and PIP kinases and PLC to IP3 is regulated at multiple sites. In liver, hepatomas and human carcinomas PIP kinase is the rate limiting enzyme and PLC activity is present in great excess. 2. The steady-state signal transduction activity as measured by the three enzyme activities and IP3 concentration was markedly up-regulated in rat hepatomas of different growth rates. The steady-state specific activities of the three signal transduction enzymes were elevated in ovarian carcinomas as compared to normal ovary. Increased enzyme activities were also observed in human breast carcinoma cells as compared to normal human breast parenchymal cells. In breast, ovarian and rat hepatoma cells as they go through lag, log and plateau phases, IP3 concentration in the early lag phase increased 4.5- to 20-fold and PI and PIP kinase activities peaked in mid-log phase. These events returned to baseline levels in the plateau phase. PLC activity did not change. 3. The bone marrow PI and PIP kinase activities in 3-day starvation were decreased to 13% and IP3 concentration was reduced to 24%; at 1-day refeeding they returned to normal. PLC activity changed little. These alterations are in line with the rapid t1/2 degradation rates (12 min) of PI and PIP kinases observed in studies with cycloheximide. By contrast, PLC has a long half-life. 4. The molecular action of tiazofurin entails inhibition of IMP DH activity, decrease in GTP and IP3 concentrations, reduction of ras and myc oncogene expression, and signal transduction enzyme activities. These events are followed by induced differentiation and apoptosis. There are also decreases in enzyme activities which have rapid turnover, including TdR kinase, dTMP synthase, and GPRT. In vitro studies indicated that these events are abrogated by addition of guanine which restores GTP concentrations. Therefore, most or all these events were brought about by the reduced GTP concentration in the tiazofurin target cells. 5. Quercetin and genistein are able to inhibit PI and PIP kinase activities and reduce IP3 concentration in vivo and in tissue culture systems. These flavonoids are also inhibitors of cell proliferation and clonogenic ability in rat hepatoma 3924A and in human OVCAR-5 and MDA-MB-435 cells. Quercetin down-regulated the expression of c-myc and Ki-ras oncogenes and led to induced differentiation and apoptosis in K562 cells. Genistein reduced IP3 concentration in vivo and in the tissue culture system. Genistein is antiproliferative and has cytototoxicity in human carcinoma cells. All three drugs, tiazofurin, quercetin and genistein, act, in part at least, through depression of cellular IP3 concentration although the mechanisms may not be identical. 6. Quercetin and genistein, which attack different targets and different phases of the cell cycle, proved to be synergistic in OVCAR-5 cells. The impact of tiazofurin, genistein and quercetin is of interest because the drugs crucially inhibit the display of the neoplastic program of cells and lead to induced differentiation and apoptosis.

1-Phosphatidylinositol 4-Kinase↗
PubMed1997

Bone turnover in neonates: changes of urinary excretion rate of collagen type I cross-linked peptides during the first days of life and influence of gestational age.

New markers have been used to monitor the changes of bone turnover occurring during growth. Data on bone turnover rate during the perinatal period are, however, very scarce. In the present study we evaluated bone turnover rate, assessed by the measurement of urinary N-terminal telopeptide of type I collagen (NTx) concentrations, at different gestational ages, and we documented the trend of bone turnover rate occurring in the first days after birth. Urine samples were obtained from 83 healthy full term newborn infants, 16 preterm, and 17 infants of diabetic mothers (IDMs). The first miction after birth was collected. Urine samples were also collected 24 and 48 h after birth. NTx was measured by an enzyme-linked immunosorbent assay (Osteomark, Ostex International, Inc. Seattle, WA). The relationship between NTx at birth and all the other variables has been evaluated using multiple regression analysis. The changes of NTx excretion over time and the effect of the groups were studied by multivariate analysis of variance (MANOVA) for repeated measures. We found a remarkable association between gestational age and NTx concentrations at birth (R = 0.56; p < 0.00001). NTx concentrations showed a progressive decrement, reaching a nadir between the 38th and the 42nd week of gestation. The NTx concentrations changed significantly during the first 48 h of life in the three groups. Moreover, preterm infants had NTx excretion values at birth significantly higher than full term infants (p < 0.001), whereas NTx excretion rates of IDMs were not different from those of the other two groups of subjects. In conclusion, gestational age seems to be the major determinant of bone turnover in neonates; NTx excretion rate is higher before term, it slows in proximity of delivery, and it increases significantly during the first 48 h of life. Preterm infants have higher bone turnover rate than full term infants. NTx excretion rate of IDMs was comparable with those of the control subjects.

Biomarkers↗
PubMed1997

Expression of LAZ3/BCL6 in follicular center (FC) B cells of reactive lymph nodes and FC-derived non-Hodgkin lymphomas.

Chromosomal translocation resulting in abnormal expression of the LAZ3/BCL6 gene in B cells has been implicated in the tumorigenesis of non-Hodgkin lymphoma (NHL). Therefore we studied the expression pattern of LAZ3/BCL6 by in situ hybridization with synthetic oligonucleotide probes in frozen tissue sections from five reactive lymph nodes and 38 B cell and non-B NHL. In addition, we investigated the expression of LAZ3/BCL6 by Northern blot analysis on multiple human tissues. The LAZ3/BCL6 transcript was found in a variety of tissues, including skeletal muscle, peripheral blood leukocytes, and weakly in normal lymph nodes. In the tumor samples, expression of LAZ3/BCL6 was observed in 68% of all B cell NHL and none of the non-B lymphomas. All cases of follicular, mixed small and large cell lymphomas showed LAZ3/BCL6 expression confined to the neoplastic follicles. A follicular expression pattern was also found in all non-malignant reactive lymph nodes. Hence, the expression of LAZ3/BCL6 does not correlate to malignancy, but reflects the origin of B cells from the germinal centers.

B-Lymphocytes↗
PubMed1997

Application of transvaginal and abdominal three-dimensional ultrasound for the detection or exclusion of malformations of the fetal face.

In a total of 618 pregnant women between 9 and 37 weeks' gestation, the fetal face was evaluated by two-dimensional and three-dimensional ultrasound imaging as part of a level III screening evaluation for fetal anomalies. A three-dimensional endovaginal probe (5 MHz) was used for examinations at between 9 and 15 weeks, and an abdominal three-dimensional probe (3.5 MHz) was used after 15 weeks. Three different three-dimensional image display modes were employed: (1) the orthogonal display; (2) the surface display; and (3) the transparent display. When we studied the three-dimensional orthogonal displays in a 125 cases evaluated by abdominal ultrasound, we found that the facial profile shown in the two dimensional image represented the true mid-sagittal profile in only 69.6% of the cases. In the remaining 30.4%, the profile view deviated from a true mid-sagittal section by up to 20 degrees in one or two planes. In a total of 25 facial anomalies detected by abdominal ultrasound, 20 were clearly demonstrated by both two-dimensional and three-dimensional technology. In the remaining five cases, three-dimensional ultrasound revealed or confirmed an additional defect or abnormality: a narrow cleft lip in an unfavorable position of the fetal face (n = 2), a unilateral orbital hypoplasia (n = 1), a cranial ossification defect (n = 1) and a flat profile in the presence of marked oligohydramnios (n = 1). When transvaginal scanning was used, there were cases in which a detailed surface image of the fetal face could be obtained as early as 9 weeks' gestation. Abdominal scanning routinely yielded high-quality surface images by 20 weeks. Three-dimensional ultrasound consistently displayed facial abnormalities with greater accuracy and clarity than conventional two-dimensional imaging. This particularly applied to chromosomal aberrations and syndromes associated with subtle facial abnormalities requiring a detailed evaluation. Not only does three-dimensional ultrasound help in appreciating the severity of a fetal defect, but it can also provide more convincing evidence of a normal fetus than conventional two-dimensional sonograms.

Face↗
PubMed1997

[Transvaginal ultrasound biometry in early pregnancy--a growth model].

PURPOSE: Evaluation of a growth model for the biometric parameters of early pregnancy: Chorionic cavity, yolk sac, amniotic cavity, crown-rump length and biparietal diameter. METHOD: 618 clinically well-dated singleton pregnancies of the first trimester were measured in a prospective cross-sectional study with high-frequency transvaginal ultrasound between 28 and 94 days post menstruation. RESULTS: Normal curves (5th, 50th, 95th percentiles) for all parameters were established using our growth model. The growth curves of chorionic cavity amniotic cavity, and biparietal diameter showed a linear growth whereas the growth curve of the crown-rump-length represented an exponential curve. Linear growth of the yolk sac was found until 8 weeks of gestation and there was no growth alteration after this time. CONCLUSION: With our growth curves of the first trimester it is possible to monitor the embryonic development with several parameters.

Anthropometry↗
PubMed1997

[Ultrasound assessment of ovarian tumors--comparison between transvaginal 3D technique and conventional 2-dimensional vaginal ultrasonography].

DEFINITION: Three-dimensional (3D) ultrasound is capable of visualising all three orthogonal planes simultaneously. With the stored volumetric data, imaging planes can be reconstructed that are not visible when using standard vaginosonographic procedures. AIMS OF THE STUDY: In patients with ovarian tumours, diagnosis and the appropriate therapeutic approach depend to a crucial degree upon the results of sonographic investigations, which therefore need very exact diagnostic data. Two-dimensional (2D) vaginosonography can only yield sagittal and frontal sections of the lesser pelvis; 3D volume scanning, however, visualises all three perpendicular planes simultaneously on a monitor screen. In cystic tumours of the ovary, conspicuous parietal structures can be specifically localised and rendered three-dimensionally in the surface mode. Such imaging capabilities create new perspectives in assessing ovarian tumours. METHOD: Within the framework of a prospective study at the Gynecological Clinic of the University of Mainz, we compared the sonographic findings obtained for 45 patients with ovarian tumours using 2D and 3D vaginosonography. After the transvaginal application of conventional 2D vaginosonography, the tumours were examined by means of 3D sonography. RESULTS: The use of 3D volume scanning was advantageous because we could image specifically targeted planes and reconstruct image planes that cannot be shown using standard vaginosonography. In addition, the volumetric technique allows 3D surface reconstruction of conspicuous parietal structures from a wide variety of different perspectives. These advantages allow one to better assess the grading of tumours especially of those that are cystic. Problems associated with the application of this transvaginal 3D technique module orientation within a given volume, the overlapping of sonographic planes, increase the time required for surface calculations and increased data storage capacity. CONCLUSION: Transvaginal 3D sonography represents a new technique of imaging. Owing to its ability to register all three imaging planes simultaneously as well as to visualise surfaces three-dimensionally, this technique opens up new sonomorphologic possibilities in the evaluation of ovarian tumours.

Adolescent↗
PubMed1997

Brain magnetic resonance imaging in congenital hypothyroid infants at diagnosis.

The aim of our study was to investigate the central nervous system (CNS) morphology and myelination with magnetic resonance imaging (MRI) in congenital hypothyroid (CH) infants detected by neonatal screening before replacement therapy. We studied 11 CH infants, 9 girls and 2 boys, mean age 22 days, 3 with aplasia, 5 with ectopia, 2 with hypoplasia of the thyroid gland, 1 with unknown diagnosis. As normal controls 22 term newborns (38 to 41 weeks of gestational age) were studied. MRI studies were performed with a 1.5-T magnet, extremity coil, T1-weighted and heavily T2-sequences axial sections were obtained. No sedation was needed for the MRI studies. MRI brain examination was normal in all patients compared with controls. In particular, no differences in the myelination patterns of the brain were observed between normal subjects and patients with hypothyroidism. Our study shows no morphological brain abnormalities in CH infants detected by neonatal screening before replacement therapy. Perinatal hypothyroidism seems to have no effect on CNS structures.

Brain↗
PubMed1997

Acute functional iron deficiency in obese subjects during a very-low-energy all-protein diet.

We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 g protein after a 1-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by approximately equal to 50% (P < 0.0001), and despite a small decrease in total-iron-binding capacity, transferrin saturation decreased from 30 +/- 11% to 18 +/- 5% (P < 0.0001). Serum ferritin did not change significantly but serum soluble transferrin receptor (sTfR), an indicator of iron deficiency, increased progressively from 4630 +/- 1110 to 6070 +/- 1390 micrograms/L (P < 0.0001). Changes in sTfR correlated inversely with prior changes in serum iron. Changes in iron metabolism did not translate into changes in erythropoiesis or red cell indexes, but the white blood cell count decreased from 7.3 +/- 1.6 to 6.2 +/- 1.9 x 10(9)/L (P < 0.002). There was no evidence of deficiency for the other trace elements and minerals tested. Daily supplementation with 200 mg Fe in 18 other subjects only partially corrected these observations despite some increase in iron stores. These results indicate that during a 2-wk VLED serum iron is significantly depressed, inducing functional tissue iron deficiency too short in duration to produce alterations in red blood cell indexes. These changes are not mediated by absolute iron deficiency, inflammation, or protein malnutrition but could be related to alterations in the iron storage and release behavior of the reticuloendothelial cell during energy deprivation alone.

Adolescent↗
PubMed1997

Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centromerically by PYGM and telomerically by D11S1783 defined by combined meiotic and tumour deletion mapping studies. Two candidate genes, ZFM1 and PPP2R5B, from this region have been previously excluded, and in order to identify additional candidate genes we used a BAC to isolate cDNAs from a bovine parathyroid cDNA library by direct selection. One of the novel genes that we identified, SCG2, proved to be identical to the recently published MEN1 gene, which is likely to be a tumour suppressor gene. The SCG2 transcript was 2.9 kb in all tissues with an additional 4.2 kb transcript also being present in the pancreas and thymus. Mutational analysis of SCG2 in 10 unrelated MEN1 families identified one polymorphism and nine different heterozygous mutations (one missense, four non-sense, one insertional and three deletional frameshifts) that segregated with the disease, hence providing an independent confirmation for the identification of the MEN1 gene.

Animals↗
PubMed1997

Multiple endocrine neoplasia type 1 and the search for the genetic trigger.

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by primary hyperparathyroidism, endocrine pancreatic-duodenal and anterior pituitary tumors. The diagnosis is challenging and involves the exclusion of other endocrine neoplasia syndromes with overlapping features. The predisposing genetic defect was assigned to chromosomal region 11q13 based on linkage analysis. Combined tumor and pedigree genotype analysis showed that allele losses in pancreatic, parathyroid and pituitary tumors eliminated the wild-type allele at the 11q13 loci, suggesting inactivation of a tumor suppressor gene in this region. A 5-Mb integrated map of the region has been established by the European consortium on MEN-1. Based on this mapping the critical interval was restricted to 2 Mb, a region within which eight candidate genes are located.

Chromosome Mapping↗