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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 271 records · Page 15Linked to original sources
PubMed1993

Effect of gluten-free diet on bone mineral content in growing patients with celiac disease.

Osteoporosis is a complication of celiac disease in adulthood, but little is known about the influence of the disease on bone mineralization in children. In the present study we evaluated radial bone mineral content (BMC) in celiac children and adolescents at diagnosis and after they consumed a gluten-free diet (GFD). The BMC values of 33 celiac patients at diagnosis were significantly lower than those of 255 control subjects (P < 0.001). There was no difference between diabetic and non-diabetic celiac patients. In 14 patients the BMC increased significantly (P < 0.05, ANCOVA) after 1.28 y of GFD. In these patients the mean annual BMC increment was 0.07 g/cm, significantly greater (P < 0.05) than the increment of normal growing children (0.05 g.cm-1.y-1). Our data indicate that although osteoporosis complicates celiac disease during childhood and adolescence, GFD alone is able to remarkably improve bone mineralization.

Bone Density↗
PubMed1993

Exclusion of FAU as the multiple endocrine neoplasia type 1 (MEN1) gene.

The FAU gene (FBR-MuSV associated ubiquitously expressed gene) encodes the ribosomal protein S30 fused with a Ubiquitin-like molecule. The FAU gene is expressed in a wide range of tissues, is evolutionarily conserved, and has putative tumour suppressor activity in vitro. The human FAU gene maps to the long arm of chromosome 11 band q13, close to the PYGM locus. This locus is tightly linked to the Multiple Endocrine Neoplasia type 1 (MEN1) locus. The FAU gene properties, together with its chromosomal localisation on 11q13, make it a candidate gene for MEN1. To test this hypothesis we screened 33 unrelated patients with MEN1 for constitutional genetic alterations in the FAU gene by Southern blot analysis, denaturing gradient gel electrophoresis (DGGE) and in two cases complemented by DNA sequencing to confirm the DGGE data. Furthermore, 10 parathyroid and pancreatic tumours from MEN1 patients and 15 each of sporadic parathyroid and pituitary tumours were similarly examined. In addition, we studied the expression of the FAU gene at the RNA level in 9 MEN1-associated tumours by Northern blot analysis. No FAU gene anomalies could be demonstrated by any of these techniques. We conclude that FAU is not likely to be the MEN1 tumour suppressor gene.

Base Sequence↗
PubMed1993

Use of sensitized fluorescence for the study of the exchange of subunits in protein aggregates.

The exchange of subunits between oligomer protein particles depends upon a cycle of dissociations and associations. To examine the dynamics of these cycles we have employed two methods based on the transfer of excitation energy between fluorochromes attached to different subunits of protein oligomers, at various temperatures and pressures. In the heterotransfer method, identical solutions independently labeled with two different fluorophores, donor D and acceptor A, are mixed. The fluorescence spectrum permits the determination of the subunit exchange by the increase in A and decrease in D fluorescence as mixed AD oligomers are formed. In the homotransfer method the aggregates are labeled with fluorescein to the extent that, ideally, each subunit carries a fluorophore. The emission is strongly depolarized because sufficiently often it takes place after a transfer to a fluorophore oriented differently from the one originally excited. Both dissociation and subunit exchange with unlabeled material result in an increase in polarization and can be independently determined by the homotransfer method. Both homo- and heterotransfer have been employed in the study of the effect of temperature on the stability of the aggregates and the relation between the rate of dissociation and the rate of exchange when dissociation of oligomers is induced by hydrostatic pressure.

Animals↗
PubMed1993

Distribution of lipid and raised lesions in aortas of young people of different geographic origins (WHO-ISFC PBDAY Study). World Health Organization-International Society and Federation of Cardiology. Pathobiological Determinants of Atherosclerosis in Youth.

At the Morphometric Reference Center of the World Health Organization-International Society and Federation of Cardiology PBDAY (Pathobiological Determinants of Atherosclerosis in Youth) project, we studied left hemiaortas of 5- through 34-year-old male and female healthy subjects who died of traumatic injury. The subjects were either of European, American, Asian, or African origin. Three hundred fifty-five thoracic and 343 abdominal left hemiaortas, stained and photographed at the Malmö, Sweden, World Health Organization Reference Center, were studied. Lipid and raised lesion extent was evaluated by using computerized techniques. Probability-of-occurrence maps of lipid and raised lesion distribution were obtained by image processing. Our data have shown that the distributions of atherosclerotic lesions in the aortic intimal surface, which were similar in the different ethnic groups, also prevailed in branching regions, where low-blood flow shear stress and turbulence occur. The areas involved by raised lesions and by lipid lesions only partially overlapped. Lipid lesion extent, which was different among the ethnic groups, continuously increased with age in males but not in females, in whom the increase ceased at an age range from 15 through 24 years. This suggests that ethnic and dietary factors influence the extent but not the distribution of atherosclerotic lesions in the human aorta. Probability-of-occurrence maps also provided evidence that not every fatty streak will develop into a raised lesion, or will not develop quickly.

Adolescent↗
PubMed1993

Familial isolated hyperparathyroidism: a distinct genetic entity with an increased risk of parathyroid cancer.

Familial isolated hyperparathyroidism (FIHP) is a rare heritable disorder characterized by hypercalcemia, inappropriately high PTH levels, and isolated parathyroid tumors with no evidence of hyperfunction of any other endocrine tissues. To establish whether FIHP exists as a distinct disease entity or represents a variant of any of the known multiple endocrine neoplasia (MEN) syndromes, we tested 19 members of a large, well characterized family with FIHP in which the disease is transmitted through 4 generations in an autosomal dominant fashion. Fourteen DNA markers at 10 polymorphic loci closely linked to the MEN1 locus on the long arm of chromosome 11 and 5 markers close to the MEN2A gene on chromosome 10 were tested using Southern blot analysis and polymerase chain reaction-based techniques. Additionally, two polymorphic markers (Mir1 and Mir2) within the prepro-PTH gene on the short arm of chromosome 11 were analyzed using denaturant gradient gel electrophoresis. Linkage was clearly excluded between FIHP and the MEN1 and MEN2A loci as well as to the PTH gene. Comparison of constitutional and tumor genotypes showed that constitutional heterozygosity was retained for markers in the MEN1 and MEN2A regions as well as to the PTH gene in 4 tumors from 3 affected members. In 1 individual, a parathyroid carcinoma was found after recurrence of hypercalcemia. We, therefore, propose that autosomal dominant FIHP can occur as a genetically and clinically distinct entity with an increased risk of malignant transformation of parathyroid tumors.

Adolescent↗
PubMed1993

Patient identifiers: stumbling blocks or cornerstones for CPRs (computer-based patient records)?

As the computer-based patient record, or CPR, moves closer to reality, patient identification issues remain unresolved. A mechanism already in place would be the Social Security number, or SSN. But legal questions surround its use for specific identification purposes. And not everyone has one. Healthcare Informatics asked several people closely involved with computerizing patient records about alternatives to social security numbers. Their responses may prove enlightening.

Computer Security↗
PubMed1993

Structure and chromosomal localization of human insulin-like growth factor-binding protein genes.

The insulin-like growth factor binding proteins (IGFBPs) constitute a structurally related protein family with six known members. We have mapped and regionally localized the genes coding for human IGFBP1, 2, 3, and 4, by in situ hybridization and somatic cell hybrid analysis. The IGFBP2 gene maps to chromosomal region 2q33-q34 whereas the genes for IGFBP1 and 3 are localized in a tail-to-tail fashion on chromosome 7 region p14-p12. The IGFBP4 gene is located in the chromosomal region 17q12-21.1. Structural characterization of the genes coding for IGFBP-1, 2, 3, and 5 showed that the translated parts are divided into four exons. The exons are similar both in size and sequence in all studied genes.

Amino Acid Sequence↗
PubMed1993

Homozygotes for the autosomal dominant neoplasia syndrome (MEN1).

Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, we had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development.

Adrenal Cortex Neoplasms↗
PubMed1993

[A new model fo the evaluation of measurements of the neurocranium].

A simple and user-friendly model for trigonometric description of the neurocranium based on newly defined points of measurement is presented. This model not only provides individual description, but also allows for an evaluation of developmental and phylogenetic aspects.

Animals↗
PubMed1993

Hematologic and biochemical profiles of selectively bred WHHL rabbits.

In Watanabe heritable hyperlipidemic (WHHL) rabbits, hypercholesterolemia and hypertriglyceridemia develop from birth, because of a deficiency of low-density lipoprotein receptors, and are followed by a consequent early development of aortic atherosclerosis. This closely resembles human familial hypercholesterolemia. Starting in 1984, we have developed a closed colony by breeding two male and two female homozygous WHHL rabbits, obtained from Japan (Dr. Watanabe, Kobe University). In our facility, the application of a selective breeding program, strictly based on mating parents that both have high serum lipid concentrations, has produced markedly elevated cholesterol (701 +/- 172 mg/dl, mean +/- SD) and triglyceride (780 +/- 325 mg/dl) concentrations in weaning rabbits. Clinical chemical analysis revealed no kidney or liver function abnormalities even in animals with extremely high lipid concentrations, and hematologic profiles were very similar in WHHL and age-matched New Zealand White rabbits, with the exception of platelet count, which was significantly higher in WHHL rabbits. Platelet aggregation induced by collagen and platelet-activating factor was significantly reduced in WHHL rabbits, whereas thrombin and prothrombin times appeared normal when compared with those in New Zealand White rabbits.

Animal Husbandry↗
PubMed1993

Tiazofurin decreases Ras-GTP complex in K562 cells.

The ras oncogene product (p21ras, Ras) is a GTP-binding protein and is thought to transduce signals regulating cellular proliferation and differentiation. The active form Ras-GTP is inactivated by hydrolyzing bound GTP to GDP. Tiazofurin, a specific inhibitor of IMP dehydrogenase, decreased cellular GTP pools and downregulated c-ras gene expression, leading to differentiation (Olah, E. et al., Proc. Natl. Acad. Sci. USA 85: 6533-6537, 1988; Weber et al., Cancer Commun. 3:61-66, 1991). To clarify the link between the action of tiazofurin on metabolic alterations and the induction of differentiation, we examined the effect of tiazofurin on the ratio of active Ras-GTP to total Ras in K562 cells in culture. Cells were labeled for 6 h with [32P]Pi in phosphate-free RPMI 1640. Tiazofurin (100 or 200 microM) was added to cells, and samples were taken at 0, 2, 4, 6 and 12 h of incubation. Cell lysates were immunoprecipitated with monoclonal anti-p21 antibody (Y13-259), then developed on thin layer chromatography. GTP and GDP bound to Ras were visualized by autoradiography. Tiazofurin treatment decreased Ras-GTP concentration in a time- and dose-dependent fashion. In the untreated K562 cells the Ras-GTP concentration was 26.3 +/- 1.4, and tiazofurin (200 microM) decreased it at 6 h to 16.6 +/- 2.9 and at 12 h to 10.6 +/- 2.1%. Inhibition of the GTP salvage pathway with hypoxanthine (100 or 200 microM) enhanced the tiazofurin-induced decrease of Ras-GTP, whereas addition of guanosine (100 microM) prevented the Ras-GTP decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗
PubMed1993

Deoxycytidine kinase and thymidine kinase activities in rat brain.

Deoxycytidine (CdR) kinase (E.C. 2.7.1.74) acts as a salvage enzyme in DNA biosynthesis, but little is known about this important nucleoside kinase in the brain. We report that CdR kinase activity in the 100,000 x g cytosolic fraction of normal adult rat brain cortex was 0.89 +/- 0.04 nmol/hr/mg protein which is twice that of the liver enzyme. For brain CdR kinase the apparent Km for CdR, ATP and Mg++ were 0.22, 1.1 and 0.63 mM, respectively. When the cytosolic preparation was incubated at 37 degrees C, CdR kinase activity rapidly decreased (t1/2 = 15 min); CdR (400 microM) protected the enzyme. Addition of DFDC (0 to 100 microM) competitively inhibited brain CdR kinase activity with Ki = 17 microM. DFDC elevated the apparent Km for CdR of brain CdR kinase 3.5-fold, from 0.22 to 0.8 mM. DFDC did not inhibit brain TdR kinase. AZT, which competitively inhibited TdR kinase (Ki = 0.6 microM), did not affect brain CdR kinase activity. These results indicate that the cytosol of rat brain contains CdR kinase which is inhibited by the deoxycytidine analog, DFDC. The enzyme is protected from thermal denaturation by CdR but not by TdR.

Animals↗
PubMed1993

Preliminary morphometric data on lipid lesion distribution in aortas of young people (WHO-ISFC PBDAY study).

As the Morphometric Reference Center of the WHO-ISFC PBDAY Project (Pathobiological Determinants of Atherosclerosis in Youth) we are studying lesion involvement of left hemiaortas of young people from different parts of the world. Gross specimens were stained and photographed at the Malmö reference Center (Dir. Prof. N.H. Sternby). Percentage of lipid lesions were evaluated and probability maps of lipid lesion distribution at the aortic surface were obtained by image processing. In all samples from Italy, Mexico and Sri Lanka, high probability of lipid lesion occurrence was found between the emergences of the intercostal arteries, next to the emergence of the celiac trunk, between the emergence of the superior and inferior lumbar arteries and between the emergence of the 1st and the 2nd mesenteric arteries. Our data reveal that a) lipid lesions are localized in low shear-stress regions or in turbuecent regions; b) our samples taken from groups of different geographical origin present the same lipid lesion distribution at the aortic surface.

Adolescent↗
PubMed1993

Synergistic action of taxol and tiazofurin in human ovarian, pancreatic and lung carcinoma cells.

Since taxol (NSC 125975) and tiazofurin (NSC 286193) attack at two different sites in microtubular synthetic processes, we tested the rationale that the two drugs might be synergistic in human ovarian (OVCAR-5), pancreatic (PANC-1) and lung carcinoma (H-125) cells and in rat hepatoma 3924A cells. In human OVCAR-5, PANC-1, H-125 and rat 3924A cells, for taxol the anti-proliferative IC50 was 0.05, 0.06, 0.03 and 0.04 microM, respectively; for tiazofurin IC50 = 8.3, 2.3, 1.8 and 6.9 microM. Thus, the concentrations for taxol required for IC50 for inhibiting cell proliferation were 166-, 38-, 60- and 173-fold lower than those for tiazofurin. Taxol and tiazofurin proved synergistic in all four cell lines tested. The synergism of taxol with tiazofurin should have implications in the clinical treatment of human solid tumors with particular relevance to ovarian, pancreatic, lung and hepatocellular carcinomas.

Animals↗