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Biomedical subjects

P Weber

Publications and source records attributed to P Weber.

At least 109 records · Page 6Linked to original sources
PubMed1997

Lipoprotein (a): its role in childhood thromboembolism.

PURPOSE: Elevated lipoprotein (a) [LP (a)] concentrations are independent risk factors of coronary heart disease or stroke in young adults. To clarify its role in childhood thromboembolism, Lp (a) was measured in 72 children with thromboembolism. METHODS: In addition to Lp (a), defects of the protein C anticoagulant system, antithrombin, and antiphospholipid antibodies were investigated in children with arterial (n = 36) or venous (n = 36) thrombosis. RESULTS: Enhanced Lp (a) >50 mg/dL was diagnosed in 8 out of 36 children with arterial and 5 out of 36 patients with venous thrombosis. Of the 72 children, 25 showed the factor V Leiden mutation, 10 showed protein C deficiency, 2 showed antithrombin deficiency, and 4 showed primary antiphospholipid syndrome. Three children with increased Lp (a) were heterozygous for the factor V Leiden mutation, and 1 girl showed additional protein C deficiency. CONCLUSIONS: Data of this study indicate that increased concentrations of Lp (a) play an important role in childhood thrombosis.

Adolescent↗
PubMed1997

The impact of a comprehensive, hospital-focused intervention to increase organ donation.

In this article the results of a 2-year intervention designed to increase rates of organ donation while improving services to bereaved families of potential donors are described. The project focused on improving key elements of the organ donation process. The intervention was implemented in 50 hospitals within the service areas of three organ procurement organizations. Results show an increase in identification, referral, and asking rates. The overall donation rate increased significantly, from 33% to 43%. However, consent rates remained unchanged. Future efforts should focus on improving the request process by systematically incorporating practices that are associated with higher consent rates. This should enable hospital and organ procurement organization staff to appropriately and effectively offer families the option of organ donation; further increases in organ donation should follow.

Bereavement↗
PubMed1997

Autoimmune hepatitis in inflammatory bowel disease: report of two unusual cases.

Elevated transaminases occur in up to 17% in patients with inflammatory bowel disease. Primary sclerosing cholangitis (PSC) is an important cause for elevated liver enzymes in these patients whereas autoimmune hepatitis is rare. Both diseases can overlap. We report two patients with an autoimmune hepatitis. One patient had Crohn's disease and arthritis with morphological liver changes typical for autoimmune hepatitis but without the characteristic autoantibody pattern. The other patient suffered from ulcerative colitis. He had antinuclear and antiactin antibodies as in autoimmune hepatitis type I. however, histological examination of the liver showed bile duct changes. Transaminases declined significantly in both patients after onset of steroid treatment. Therefore, the diagnosis of autoimmune hepatitis in patients with inflammatory bowel disease must not be missed, as immunosuppressive therapy improves the prognosis of the illness.

Adolescent↗
PubMed1997

[A rare breast tumor: mammary fibromatosis. Two case reports and a review of the literature].

Aggressive fibromatosis of the breast is an uncommon benign disease. The clinical and X-Ray findings can simulate breast cancer. The diagnosis relies on histology. The typical feature of this disease is a locally aggressive but non metastasizing lesion with high recurrence rate. Treatment consists in wide excision. The role of radiation and drug therapy including antiestrogens has not been clearly established. Colonoscopy is indicated to research for an association with Gardner syndrome.

Adult↗
PubMed1997

Management of osteoporosis: is there a role for vitamin K?

Vitamin K is required for the biological activity of several coagulation factors, which is considered as the classical function of vitamin K. Recent research, however, suggests a role of vitamin K in bone metabolism. The metabolic role of vitamin K is to facilitate the carboxylation of glutamyl to gamma-carboxyglutamyl residues. Besides the hepatic tissue, in which the clotting factors are produced gamma-carboxyglutamyl-containing proteins are also abundantly available in bone tissue. Osteocalcin accounts for up to 80% of the total gamma-carboxyglutamyl content of mature bone. Human carboxylated osteocalcin contains 3 gamma-carboxyglutamyl residues which confer a highly specific affinity to the calcium ion of the hydroxyapatite molecule. Besides the gamma-carboxylation of osteocalcin vitamin K may also affect other parameters of bone metabolism, such as calcium hemostasis, and prostaglandin E2 and interleukin 6 production. Evidence from observational studies and first intervention trials indicate that vitamin K intakes much higher than the current recommendations improved biochemical markers of bone formation as well as bone density. In conclusion, the mechanistic data as well as the observational data and the results of the first controlled clinical trials in humans point to a beneficial effect of additional intakes of vitamin K in bone health.

Bone Density↗
PubMed1996

Organization of the 5'-End of the porcine gamma-glutamyl transpeptidase gene and identification of three different mRNAs in the kidney.

Three different mRNAs coding for the porcine gamma-glutamyl transpeptidase (GGT) in the kidney were identified by 5'-RACE-PCR. These differ in their 5'-noncoding region. Genomic Southern blot analysis has demonstrated the existence of a single GGT gene in the porcine genome. Thus, the existence of multiple mRNAs can only be explained by the use of different promoters or alternative splicing. Four GGT-specific genomic clones containing the complete 5'-end of the gene were isolated and characterized, revealing six exons common to all three mRNAs. Four of these exons were located in the coding region comprising the codons for amino acids 1 to 138. Two exons and an intervening sequence were identified upstream from these six common exons representing the unique 5'-ends of the three mRNAs. The coding exons show a significant sequence homology to mouse, rat, and human GGT cDNA, whereas exons 1 and 3 display no homology.

Animals↗
PubMed1996

Analysis of the ATM protein in wild-type and ataxia telangiectasia cells.

Ataxia telangiectasia (A-T) is a human disorder that results in a number of clinical symptoms, including cerebellar degeneration and increased cancer predisposition. Recently the gene that is defective in A-T has been cloned and designated ATM. Here, we describe the production of antisera raised against the approximately 350 kDa ATM protein. Antisera specificity is confirmed by them recognising a approximately 350 kDa polypeptide in wild-type cells but not in A-T cells containing mutations that truncate ATM upstream of the antibody binding sites. We show that ATM is almost exclusively nuclear and is expressed in all cell lines and tissues analysed. However, ATM levels are not regulated in response to u.v. or ionising radiation. These data are consistent with ATM being a component of the DNA damage detection apparatus rather than being an inducible downstream effector of the DNA damage response. In addition, we analyse ATM protein expression in a variety of A-T patients. Strikingly, ATM expression is reduced drastically or absent in all patients analysed, including those predicted to express proteins that should be detected by our antisera. Thus, the A-T phenotype may result not only from mutations that disrupt functional domains of ATM, but also from mutations that destabilise the ATM mRNA or protein. Finally, we report that a group of patients displaying an intermediate A-T phenotype express low levels of apparently full-length ATM. This suggests that the ATM pathway is partially active in these individuals and that there is a correlation between levels of residual ATM expression and disease severity.

3T3 Cells↗
PubMed1996

Ebselen-binding equilibria between plasma and target proteins.

The antiinflammatory drug ebselen (2-phenyl-1,2-benzisoselenazo-3(2H)-one) is known to bind covalently to thiols to form seleno disulfides that, directly or indirectly, are responsible for its pharmacological effects. Due to its reactive thiol group and high plasma concentration, albumin is a preferred target of ebselen, which it binds covalently. Ebselen should not, then, be available for intracellular actions at other target proteins. We have addressed this question, and show by difference spectroscopy that the interaction of ebselen with albumin occurs stoichiometrically under ring opening, but is readily reversible in the presence of glutathione. With intact human polymorphonuclear leukocytes (PMN), a similar stoichiometric reaction with distinct spectral features was observed with ebselen that was completely abolished by pretreatment of PMN with N-ethylmaleimide, but not by selective depletion of cellular glutathione. Human platelets, again, exhibited different spectral changes upon addition of ebselen. In agreement with results reported in the literature, we show that 14C-ebselen is in dynamic equilibrium with all accessible thiol groups and, hence, despite mostly being bound covalently to albumin, it will exchange rapidly with other target proteins in PMN or platelets.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Binding of contactin/F11 to the fibronectin type III domains 5 and 6 of tenascin is inhibited by heparin.

The structural basis for the interaction between tenascin-C and the neuronal cell adhesion molecule, contactin/F11, was investigated using plasmon surface resonance technology. The binding site on tenascin-C for contactin/F11 is shown to span the two fibronectin type III homology domains 5 and 6. Either domain alone is insufficient for binding. Heparin, heparan sulfate and dermatan sulfate inhibit this interaction through binding to a conserved heparin-binding site on domain 5. In contrast, chondroitin sulfates A and C have no such effect.

Animals↗
PubMed1996

Purification and characterization of cysteine-S-conjugate N-acetyltransferase from pig kidney.

Microsomal cysteine-S-conjugate N-acetyltransferase catalyses the N-acetylation of various S-substituted cysteines in liver and kidney. We describe here the purification and more detailed characterization of this enzyme catalysing the final reaction of mercapturic acid biosynthesis, and thus playing a crucial role in the detoxicating metabolism of many xenobiotics. The solubilization of cysteine-S-conjugate N-acetyltransferase by deoxy-BIGCHAP [N,N'-bis-(3-D-gluconamidopropyl)deoxycholamide] was the prerequisite for partial purification by means of anion-exchange chromatography. The molecular mass of the enzyme was determined by gel filtration. A polyclonal antiserum was raised against the excised protein band from SDS/PAGE and purified antibodies were used for the complete purification of native cysteine-S-conjugate N-acetyltransferase by immuno-affinity chromatography. A dimeric form of the enzyme was sometimes detected on SDS/PAGE, depending on the degree of purification. For further characterization of cysteine-S-conjugate N-acetyltransferase, the stability of catalytic activity, the pH optimum and K(m) values were determined. The inhibitory effects of various agents were tested, revealing a substantial, yet not complete, loss of cysteine-S-conjugate N-acetyltransferase activity after treatment with cysteine proteinase inhibitors or probenecid under various conditions.

Acetyltransferases↗
PubMed1996

[Solar retinopathy. Rare cause of acute loss of vision].

HISTORY AND CLINICAL FINDINGS: A 15-year-old girl was admitted to hospital for acute bilateral visual deterioration and central scotoma of two days' duration. It became known on the third day that she had looked into the sun on several occasions, for several minutes at a time. INVESTIGATIONS: In addition to the scotoma there was a visual loss to 0.05 in the right and 0.1 in the left eye. Neurological examination and imaging of the head were unremarkable. At first the visual evoked potential was prolonged (122 ms on right, 130 ms on left), but all other electrophysiological tests were normal. Fundoscopy at first showed macular oedema and pigment changes in the macula. TREATMENT AND COURSE: Local application of prednisolone (0.5 mg five times daily) gradually improved the vision and it returned to normal after 8 weeks. The initially prolonged visual evoked potential restored to normal either. No pathophysiological reason for this was found. CONCLUSION: In case of acute loss of vision in the absence of other neurological findings, external factors should be considered in the differential diagnosis.

Adolescent↗
PubMed1996

Surface thiols of human lymphocytes and their changes after in vitro and in vivo activation.

Cellular thiols have long been known to play a role in cell activation and proliferation; however, the differential expression of surface thiols on the lymphoid subsets had not been described. Neither was it known whether alteration of surface thiols occurs after exposure to mitogens or infectious agents. Herein, an impermeant thiol-specific fluorescent probe was employed for flow cytometric analysis of surface thiols. Quantification of surface thiols on resting lymphocytes revealed that some subsets expressed different concentrations of surface thiols (CD19+ > CD8+ > CD4+). Furthermore, surface thiols increased on all subsets by 8 h after mitogenic activation. This increase was blocked by cycloheximide or monensin but not by actinomycin D or inhibition of glutathione synthesis by buthionine sulfoximine. In addition, bacitracin, an inhibitor of protein disulfide isomerase, inhibited the increase in surface thiols and DNA synthesis. Lymphocytes from HIV-infected individuals displayed increased surface thiols on CD19+ and CD4+ cells but not CD8+ cells. Although cellular thiols in general have been believed to play a role in protection against oxidants, signaling associated with cell growth, and apoptosis, there is now evidence that changes in exofacial thiols appear to be involved in some of these critical cell reactivities. Thus, quantitative and possibly qualitative differences in surface thiols correlate with membrane differences between lymphoid subsets and with their differential sensitivities to oxidative stress, which suggests that the mechanisms by which surface thiols are maintained and modified after activation are important cellular functions that need to be further evaluated.

Antigens, CD19↗
PubMed1996

Alteration of interleukin-1 alpha production and interleukin-1 alpha binding sites in mouse brain during rabies infection.

We have evaluated the effect of rabies virus infection on interleukin-1 alpha (IL-1 alpha) production and its receptors in mouse brain. Study of virus dissemination in the central nervous system (CNS) showed a massive infection of main brain structures from day 4 post infection (p.i.) up to the agony stage on day 6 p.i. At the same time, IL-1 alpha concentrations increased in cortical and hippocampal homogenates, whereas no change was detected in serum. In non-infected mice, IL-1 alpha binding sites were observed in the dentate gyrus, the cortex, the choroid plexus, the meninges and the anterior pituitary. During rabies virus infection, a striking decrease in IL-1 alpha binding sites was observed on day 4 p.i. with a complete disappearance on day 6 p.i., except in the pituitary gland where they remained at control level. In conclusion, concomitantly with the early rabid pathological signs, brain IL-1 alpha production and IL-1 alpha binding sites are specifically and significantly altered by brain viral proliferation. These results indicate that IL-1 alpha could be involved in the brain response to viral infection as a mediator and could participate in the genesis of the rabies pathogeny.

Animals↗
PubMed1996

Induction of immunoreactive interleukin-1 beta and tumor necrosis factor-alpha in the brains of rabies virus infected rats.

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are important cytokines in the development of brain inflammation during pathological process. During rabies virus infection, the level of these proinflammatory cytokines are enhanced in the brain. In the present study we determined the cellular localization of these two cytokines by immunocytochemistry in brains of rats infected with rabies virus, at different time-intervals of the disease (day 1, 3, 4, 5 and at final stage day 6 post-infection (p.i.)). Cellular identification of IL-1 beta (irIL-1 beta) and TNF alpha (irTNF alpha) immunopositive cells was studied using a polyclonal antibody against these cytokines and against glial fibrillary acidic protein (GFAP) to detect astrocytes and GSA-I-B4 isolectin to detect microglial cells and/or infiltrating macrophages. In brains of control and early infected rats, irIL-1 beta was only detected in fibers located in the hypothalamus, supraoptic and tractus optic nuclei and infundibular nucleus. From day 4 onwards until day 6 p.i., enhanced irIL-1 beta was found and identified either in activated ameboid and/or infiltrated macrophages (amygdala, thalamus, internal capsula, subtantia nigra, septal nuclei and around blood vessels), or in activated ramified cells (hypothalamus and periventricular nucleus, piriformis and cingulate cortex, hippocampus). IrTNF alpha was observed in the brains of rats at a final stage of disease (day 5 and 6 p.i.): in the hypothalamus, the amygdala, the internal capsula, the thalamus, the septal nuclei, the hippocampus, the habenular nuclei and around the blood vessels. Ir-TNF alpha was detected in round cells identified as ameboid microglia and/or infiltrated macrophages. A marked activation of microglial and astroglial cells was observed mainly in the hypothalamus, the thalamus and hippocampus and around the blood vessels, at day 4 p.i. and later, revealing a high central inflammatory reaction in brains of rabies virus infected rats. These results showed that IL-1 beta and TNF alpha are produced in the brain both by local microglial cells and infiltrating macrophages during rabies infection. Thus, these cytokines may play an important role in coordinating the dramatic inflammatory response associated with the rabies-encephalopathy as well as in the neural modification and alteration of brain functions.

Animals↗
PubMed1996

Lipophilicity in molecular modeling.

PURPOSE: The molecular lipophilicity potential (MLP) offers a three-dimensional representation of lipophilicity, a molecular property encoding intermolecular recognition and intramolecular interactions. METHOD: The interest and applications of the MLP in molecular modeling are varied, as illustrated here. RESULTS: The MLP is a major tool to assess the dependence of lipophilicity on conformation. As a matter of fact, the MLP combined with an exploration of the conformational space of a solute reveals its "chameleonic" behavior, i.e. its capacity to adapt to its molecular environment by hydrophobic collapse or hydrophilic folding. Another successful application of the MLP is its concatenation into 3D-QSAR (Comparative Molecular Field Analysis, CoMFA). CONCLUSION: Work is in progress to expand the MLP into a docking tool in the modeling of ligand-receptor interactions.

Chemical Phenomena↗
PubMed1996

Ionizing radiation modulates the spread of an apathogenic rabies virus in mouse brain.

Ionizing radiation has been shown to affect a broad range of viral diseases including neurotropic infections through an immunosuppression mechanism. In the present study we have investigated the effect of ionizing radiation on the characteristics of neurotropic infection by rabies virus, which has the unusual feature of infecting almost exclusively neurons. In order to analyze better the effect produced, the study concerned the spread of an apathogenic rabies virus variant in mouse brain. Irradiation was shown to increase both the intensity and duration of the infection in a reversible and dose-dependent manner and was effective in whole-body irradiation and in head-protected body irradiation, whereas cephalic irradiation had no effect. These results underline the role played by the immune system in the regulation of neurotropic virus infections in the brain and show that phenomena such as viral clearance and time-course of a neurotropic viral infection may be significantly modified by ionizing radiation, even for viruses whose infection involves only neurons.

Animals↗