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Biomedical subjects

V Peters

Publications and source records attributed to V Peters.

At least 19 recordsLinked to original sources
PubMed2005

Measurement of bile acid CoA esters by high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS).

The novel and rapid assay presented here combines high-performance liquid chromatography and electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS) to directly measure and quantify the CoA esters of 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid (THCA and DHCA). The latter are converted inside peroxisomes to the primary bile acids, cholic and chenodeoxycholic acids, respectively. Prior to MS/MS, esters were separated by reversed-phase HPLC on a C(18) column using an isocratic mobile phase (acetonitrile/water/2-propanol) and subsequently detected by multiple reaction monitoring. For quantification, the CoA ester of deuterium-labelled 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-oic acid (d(4)-CA) was used as internal standard. To complete an assay took less than 8 min. To verify the validity of the assay, the effect of peroxisomal proteins on the efficacy of extraction of the CoA esters was tested. To this end, variable amounts of the CoA esters were spiked with a fixed amount of either intact peroxisomes or peroxisomal matrix proteins and then extracted using a solid-phase extraction system. The CoA esters could be reproducibly recovered in the range of 0.1-4 micromol l(-1) (linear correlation coefficient R(2) > 0.99), with a detection limit of 0.1 micromol l(-1). In summary, electrospray ionization tandem mass spectrometry combined with HPLC as described here proved to be a rapid and versatile technique for the determination of bile acid CoA esters in a mixture with peroxisomal proteins. This suggests this technique to become a valuable tool in studies dealing with the multi-step biosynthesis of bile acids and its disturbances in disorders like the Zellweger syndrome.

Acyl Coenzyme A↗
PubMed2005

Intravenous glycine after cecal ligation and puncture has no effect on impaired hepatic microperfusion, leukocyte adhesion, and mortality in septic rats.

Recent studies indicated that prefeeding of a glycine supplemented diet reduces the hepatic inflammatory response and liver damage in sepsis. We investigated the effect of a glycine-enriched infusion on hepatic microcirculatory disturbances and mortality in a rat model of sepsis after the onset of the disease. Male Wistar rats (240 +/- 13 g) underwent cecal ligation and puncture (CLP) or laparotomy (LAP). A glycine (CLP + Gly, n = 24), valine (CLP + Val, n = 24), or sodium chlorid (CLP + Sc, n = 24) infusion was started 2 h after CLP. The LAP group received sodium chloride intravenously (LAP + Sc, n = 18 ). Five hours, 10 h, and 20 h after CLP or LAP intravital microscopy (IVM) was performed to investigate leukocyte-endothelial interaction (LEI) and mean erythrocyte velocity in liver sinusoids (sMEV) and postsinosoidal venules (vMEV). The portal blood flow (PBF), hepatic enzyme liberation, and glycine values in blood were measured. Immunohistochemical staining for ICAM-1 in liver tissue was performed and survival was observed. Glycine values were significantly elevated in the CLP + Gly vs. the CLP + Val and the CLP + Sc group at every timepoint of investigation. Glycine infusion had no beneficial effects on sMEV, vMEV, LEI, hepatic enzyme liberation, and survival. Heart rate and mean arterial pressure remained stable but PBF decreased significantly in all groups 20 h after CLP. Although glycine reduces the hepatic inflammatory response and liver damage in pretreatment of septic rats, there was no effect of intravenous glycine after the onset of sepsis in our experiments. Our animal model does not support the use of glycine in patients.

Animals↗
PubMed2004

Improvement of CDG diagnosis by combined examination of several glycoproteins.

Congenital disorders of glycosylation (CDG) represent a family of genetic diseases with broad clinical presentation. Initial diagnosis is currently mainly based on the identification of hyposialylated serum transferrin (TF) by isoelectric focusing (IEF). To improve the diagnosis of known CDG types and to identify so far unknown CDG cases, additional glycoproteins, alpha1-antitrypsin titrypsin (alpha1-AT) and alpha1-antichymotrypsin (alpha1-ACT), were studied. According to the patterns of transferrin, enzyme assays and mutation analysis, 16 patients with various clinical symptoms suspicious for CDG were divided into three groups: group A (n = 6) with confirmed CDG; group B (n = 4) with clear abnormal TF-IEF patterns of unknown origin (all known CDG types were excluded) and group C (n = 6) with borderline TF-IEF patterns; 164 samples served as a control group. Automated IEF of TF, alpha1-AT and alpha1-ACT was carried out using a PhastSystem. CDG patients with glycosylation defects of known origin (group A) and patients with abnormal TF-IEF patterns due to glycosylation defects of as yet unknown origin (group B) showed abnormal IEF patterns of all three glycoproteins. These results confirmed generalized defects of glycosylation. Furthermore, the IEF pattern of alpha1-ACT seems to allow a differentiation between CDG Ia and CDG Ic. However, patients with borderline TF-IEF pattern (group C) showed a normal alpha1-AT-IEF pattern. Four of these six patients also showed a normal alpha1-ACT-IEF pattern; this constellation suggests that CDG can most likely be excluded. In the two remaining patients of group C with a borderline TF-IEF pattern an abnormal pattern of alpha1-ACT-IEF was obtained which needs further investigations. We conclude that the combined investigation of three glycoproteins provides additional information in the diagnostic work-up of patients with possible CDG. The suspicion of CDG in patients with apparent glycosylation defects of unknown origin or borderline TF-IEF pattern can be either substantiated or weakened.

Adolescent↗
PubMed2003

Towards quality assurance in the determination of lysosomal enzymes: a two-centre study.

The definitive diagnosis of lysosomal storage disorders depends on the determination of enzymatic activities in cells, tissues or body fluids. At present, neither an evaluation of the different methods nor an interlaboratory quality assurance scheme is available. We have therefore determined the activities of total hexosaminidase, hexosaminidase A and beta-galactosidase in the same samples (n = 15) at two metabolic centres in Germany. Three different enzymatic methods were employed, two of which were based on leukocytes as enzyme source and one on dried blood spots. The results obtained by the two different methods using leukocytes proved comparable. In contrast, assays with dried blood spots showed poor correlation with results from leukocytes, possibly because enzymatic activity in dried blood is mainly derived from soluble plasma proteins. Nevertheless, accurate detection of a true enzyme deficiency was also possible in dried blood spots. All enzymes were highly stable when mailed frozen (recovery 98-120%). Enzymatic activities in dried blood samples were also stable at room temperature and were not affected even by exposure to elevated temperatures (50 degrees C for 3 h). Dried blood seems to be especially well suited for mailing from distant healthcare facilities, although more accurate results can be expected from leukocytes. In summary, comparability and pitfalls within a lysosomal quality assurance programme were evaluated.

Adult↗
PubMed2002

[CDG (congenital disorders of glycosylation). Differential hereditary ataxia in adulthood diagnosis].

Congenital disorders of glycosylation (CDG) are a group of hereditary multisystem diseases due to different defects of enzymes or transport molecules involved in the synthesis of glycoproteins. CDG-la is the most common subtype, with cerebellar ataxia as the main neurological symptom. Currently there is little information about CDG-la manifestation in adulthood. Here we present two sisters in whom the diagnosis of CDG-la was made in the fourth decade of life and who to our knowledge are the oldest known patients with the disorder in Germany. The clinical course of the disease was typical, although less severe than previously described. The carbohydrate-deficient transferrin (CDT) level was increased but lower than in other CDG patients. Isoelectric focusing of transferrin revealed changes typical of CDG, whereas those of alpha 1-antitrypsin were only moderately pathologic. This might be due to the milder manifestation of the disease in our patients or it could be indicative of a stabilization of the disease after puberty. The CDG should be included in the differential diagnostic workup of hereditary cerebellar ataxia in adults.

Adult↗
PubMed2002

A new case of CDG-x with stereotyped dystonic hand movements and optic atrophy.

We report the clinical findings and the diagnostic work-up of a 17-month-old girl with CDG-x. Predominant clinical signs were, besides psychomotor retardation and truncal hypotonia, stereotyped dystonic hand movements and ophthalmological abnormalities such as optic atrophy, nystagmus and strabismus. Other symptoms that are often found in patients with CDG were not present, such as seizures, microcephaly, cerebellar hypoplasia, dysmorphic features, hepatointestinal disease, coagulopathy or multiorgan involvement. Isoelectric focusing (IEF) of the patient's serum showed a marked elevation of disialotransferrin, thus confirming an IEF type 1 pattern. A generalized glycosylation defect was confirmed also by IEF of a further glycoprotein (alpha1-antitrypsin), an increased carbohydrate deficient transferrin (CDT) serum concentration and an increased CDT/transferrin ratio. All known types of CDG-I, secondary glycosylation abnormalities and variants of amino acid sequence were excluded.

Dystonia↗
PubMed2002

Congenital disorder of glycosylation IId (CDG-IId) -- a new entity: clinical presentation with Dandy-Walker malformation and myopathy.

A 1.5-year-old boy with macrocephaly due to a Dandy-Walker malformation presented with progressive hydrocephalus, extensive muscular hypotonia, transient cholestatic syndrome, extensive coagulation abnormalities and elevated creatine kinase indicating myopathy. Diagnostic work-up indicated a congenital disorder of glycosylation (CDG, formerly carbohydrate deficient glycoprotein syndrome). The serum transferrin pattern obtained by automated isoelectric focusing (IEF) showed an hitherto unreported pattern with strongly elevated tri-, di-, mono- and asialotransferrin bands, increasing in this order together with markedly decreased tetrasialotransferrin. Investigation of two additional glycoproteins, alpha(1)-antitrypsin and alpha(1)-antichymotrypsin, confirmed a generalised defect of glycosylation. All known glycosylation defects could be ruled out by enzymatic analyses in either leukocytes or fibroblasts or by the results obtained by IEF. SDS-electrophoresis demonstrated a marked difference in the molecular weight of transferrin, suggesting the lack of parts or of all oligosaccharide chains. The defect could be delineated to a deficiency of beta-1,4-galactosyltransferase (E.C.2.4.1.38) due to a homozygous insertion (1031 - 1032 insC). Details of the biochemical and molecular findings will be described elsewhere.

Adolescent↗
PubMed2001

A new subtype of a congenital disorder of glycosylation (CDG) with mild clinical manifestations.

A boy with an unspecific symptomatology consisting of mental retardation, strabismus, hypotonia and mild ataxia was diagnosed with a congenital disorder of glycosylation (CDG). Neither cerebellar atrophy nor dysmorphic features were present. The serum transferrin band pattern obtained by isoelectric focusing(IEF) showed a strongly elevated disialotransferrin band together with only slightly elevated asialotransferrin, thus a type I pattern. This is a new CDG classified CDG-x since CDG-la, -b, -c, -d and -e were excluded. Quantitative differences to the type 1 pattern of a CDG-la patient with a moderate to severe course were confirmed by densitometric evaluation of the gels and by SDS gel electrophoresis. Liver biopsy showed lysosomal inclusions suggesting a pre-Golgi defect. This patient's case supports the approach to include isoelectric focusing of serum transferrin in the diagnostic work-up of patients with unexplained symptoms.

Asialoglycoproteins↗
PubMed2000

Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children < or = 5 years of age, Pediatric Spectrum of HIV Disease project (PSD), USA.

BACKGROUND: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. METHODS: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. RESULTS: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classified in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. CONCLUSION: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Investigations into an unknown organism on the martian meteorite Allan Hills 84001.

Examination of fracture surfaces near the fusion crust of the martian meteorite Allan Hills (ALH) 84001 have been conducted using scanning electron microscopy (SEM) and atomic force microscopy (AFM) and has revealed structures strongly resembling mycelium. These structures were compared with similar structures found in Antarctic cryptoendolithic communities. On morphology alone, we conclude that these features are not only terrestrial in origin but probably belong to a member of the Actinomycetales, which we consider was introduced during the Antarctic residency of this meteorite. If true, this is the first documented account of terrestrial microbial activity within a meteorite from the Antarctic blue ice fields. These structures, however, do not bear any resemblance to those postulated to be martian biota, although they are a probable source of the organic contaminants previously reported in this meteorite.

Actinomycetales↗
PubMed2000

Improved hepatitis B vaccination rates in ESRD patients in California.

According to the Centers for Disease Control (CDC) Survey of Dialysis Associated Diseases, California, which includes Network 17 and 18, had one of the lowest hepatitis B vaccination rates in the country for 1994, 1995, and 1996. With 3 outbreaks of hepatitis B (HBV) in California in 1994, hepatitis B vaccination was chosen as a quality improvement project in both Network 17 and 18. With input from both Medical Review Boards and HCFA Region X, a project was formulated which focused on the improvement of the number of facilities which had hepatitis B vaccination rates which are greater than 50%. The overall purpose of both projects was to: (1) achieve access to preventative services for end-stage renal disease (ESRD) Medicare beneficiaries; (2) increase the number of ESRD patients in California who are vaccinated for HBV; (3) eliminate dialysis in California as an independent risk factor for contracting HBV; (4) decrease the number of ESRD facilities with HBV vaccination rates of 0%; and (5) increase the number of ESRD facilities with HBV vaccination rates greater than 50%. In 1998, both Network 17 and 18 denominators were adjusted to reflect the population which is eligible for vaccination. Because of historically low vaccination rate in California, the 1998 data collection sought to ascertain precise numbers for the ESRD patient population. Data were used from the 1996 and 1997 CDC Survey of Dialysis Associated Diseases from baseline measurements of HBV vaccination rates for all facilities in both Network 17 and 18. The CDC did not conduct a survey in 1998, however, Network 17 and 18 conducted a survey of dialysis associated diseases for all of California ESRD facilities. A data collection tool was designed to gather information on processes and outcomes in each facility. This allowed a continuous quality improvement (CQI)-based approach to analyze the problem, where tools like cause/effect and Pareto diagrams provided information on factors and issues affecting low HBV vaccination rates. Interventions were designed to target those specific factors. Interventions included creation of the "Hepatitis Booklet" (Network 18) and the "Hepatitis Resource Guide" (Network 17); mailing of the resource material to all providers (Network 18), and with vaccination rates less than 50% (Network 17); development of facility specific profiles; and policy statements by both Medical Review Boards on Hepatitis B Vaccination. The number of ESRD patients in California who are vaccinated for HBV increased to 53% or 11,412 patients of 21,617 eligible patients in both Networks. The number of ESRD patients in California who are vaccinated plus those in the process of receiving the series brought the California vaccination rate of 72% or 15,653 for 21,617 eligible patients in both Networks. The number of ESRD facilities in California with HBV vaccination rates of 0% decreased to 10 facilities in 1998, from 75 facilities in 1997, and 135 facilities in 1996. The number of ESRD facilities in California with HBV vaccination rates more than 50% increased to 175 facilities, from 87 facilities in 1997, and 52 in 1996. The number of patients developing antibodies post-vaccine was 62% (Network 18). Facilities in Network 17 with vaccination rates exceeding 50% who did not receive the Hepatitis B Resource Guide vaccinated 44% of all patients vaccinated or in progress in Network 17 in 1998. Facilities in Network 17 with vaccination rates less than 50% who did receive the Hepatitis B Resource Guide vaccinated 57% of all patients vaccinated or in progress in Network 17. For the first time, vaccination rates were collected on peritoneal dialysis (PD) patients. In Network 17, 51% of PD patients are vaccinated versus 59% of hemodialysis patients. In Network 18, 48% of PD patients are vaccinated versus 48% of hemodialysis patients. Resource material and feedback reports developed by both Networks facilitated improvements in Hepatitis B vaccination of ESRD patients in Ca

California↗
PubMed1995

Methanogenic and other strictly anaerobic bacteria in desert soil and other oxic soils.

Strictly anaerobic bacteria such as methanogenic, sulfate-reducing, and homoacetogenic bacteria could be enriched from all five oxic soils tested. The number of cells was lower than that in typical anoxic habitats. Spores did not always dominate the population of sulfate-reducing bacteria. In all soils, the methanogenic population displayed a long lag phase after anoxic conditions were imposed before methane production began.

Journal Article↗
PubMed1995

Increased expression of activation markers on CD8 lymphocytes in children with human immunodeficiency virus-1 infection.

The aims of the present study were to analyze the impact of perinatal human immunodeficiency virus (HIV)-1 infection on lymphocyte maturation in children, to determine the expression of activation markers on CD8+ cells, and to define predictors of survival in HIV-infected children. Seventy-one children presenting HIV-related symptoms were included in the study; 29 were less than 2 y old and 42 were 2 to 12 y of age. Results were compared with those obtained in normal children of a similar age. In HIV-infected children the proportion of CD4+ and CD8+CD45RA+ cells was significantly decreased, whereas that of CD8+, CD8+CD38+, and CD8+CD45RO+ cells was strikingly increased compared with controls. In children less than 2 y old the absolute number of CD4+ and CD8+CD45RA+ cells decreased, and the number of CD8+CD45RO+ cells increased significantly, whereas the number of CD8+ and CD8+CD38+ cells did not change. The absolute number of CD4+ T cells declined with age both among controls and among HIV-infected children. In contrast, the absolute number of CD8+ cells and CD8 subsets decreased with age only in controls but not in infected children. In HIV-1-infected children the expression of the CD38 and CD45RO markers on CD8+ cells was significantly correlated, indicating that these were activated cells. The survival of less than 2-y-old children with AIDS symptoms was positively correlated with the total number of CD8 cells and CD8+CD38+ cells at time of entry into the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

Common epitope on HIV p24 and human platelets.

Mimicry of human antigen by HIV may underlie the autoreactivity seen in AIDS. A mouse monoclonal antibody (VIC8) raised against HIV p24 cross-reacted with human platelets; binding could be abolished by recombinant p24 antigen. VIC8 bound less well to platelets from patients with HIV than to those from healthy individuals. In the HIV group, binding was not related to p24 antigenaemia, disease stage, or platelet counts. This cross-reactivity is another example of antigenic mimicry by HIV and may be mechanistically important in HIV-associated autoimmune-like thrombocytopenia.

Antibodies, Monoclonal↗
PubMed1993

Mouse monoclonal anti-idiotypic antibodies to HIV p24: immunochemical properties and internal imagery.

Two mouse monoclonal antibodies (VIC5 and VIC6; referred to as Ab1) reacting with the p24 core antigen of HIV-1 were used to produce mouse monoclonal anti-idiotypic antibodies (Ab2). Six anti-idiotypic antibodies were characterized. The five anti-idiotypic antibodies directed against VIC6 partly competed which each other and thus defined a set of overlapping idiotypes on Ab1. All 6 Ab2s inhibited the binding of the corresponding anti-p24 antibody to antigen, although four (W1, Y16, Y6, X14) were markedly more inhibitory than the remaining two (G6, Y11). All six Ab2s were antigen-inhibitable; however the interaction of G6 and Y11 with Ab1 was blocked with considerably less soluble p24 antigen than the remaining four. Correspondingly, G6 and Y11 had lower affinities for Ab1 than did W1, Y6 and X14; the affinity index of Y16 was equivalent to that of Y11. None of the Ab2s reacted with H or L chains of Ab1 after reduction on SDS-gels. Similarly, both Ab1s failed to react with the H or L chains of Ab2. These criteria appeared to define at least four of these Ab2s as internal image antibodies whose image is composed of both H and L chains. The anti-idiotypic antibodies were injected either individually or as a combined preparation of all 6 into syngeneic mice and Porton rats. Despite the presence of anti-anti-idiotypic antibodies (Ab3) in these animals, when used individually no antigen-specific antibodies were found. A small response to p24 antigen was induced in 3 of 6 mice using preparations containing all 6 anti-idiotypes.

Animals↗