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Biomedical subjects

H Peters

Publications and source records attributed to H Peters.

At least 19 recordsLinked to original sources
PubMed2006

Reinfection after successful eradication of Helicobacter pylori: a 2-year prospective study in Alaska Natives.

BACKGROUND: Limited information exists regarding risk factors for reinfection after cure of Helicobacter pylori infection. AIM: To determine the 2-year reinfection rate of H. pylori in a cohort of urban Alaska Natives. METHODS: Participants over 18 years of age undergoing oesophagogastroduodenoscopy had (13)C urea breath test, culture, CLOtest and histology performed. Those diagnosed with H. pylori who tested urea breath test-negative at 8 weeks after treatment were followed prospectively at 4 months, 6 months, 1 year and 2 years. Subjects experiencing H. pylori reinfection as defined by a positive urea breath test were compared with those who did not become reinfected using univariable and multivariable analysis. Risk of reinfection over time was estimated by the Kaplan-Meier method. RESULTS: Helicobacter pylori reinfection occurred in 14 of 98 subjects successfully treated. The cumulative reinfection rate was 5.1% (95% CI: 0.7%-9.5%) at 4 months, 7.2% (2.0-12.3%) at 6 months, 10.3% (4.2-16.3%) at 1-year and 14.5% (7.5-21.6%) at 2 years. In multivariable analysis, a history of previous peptic ulcer disease or presence of ulcer at time of study oesophagogastroduodenoscopy were the only risk factors associated with reinfection (P = 0.01). CONCLUSIONS: Based on the findings from our study, subjects with a history of or current peptic ulcer disease should be followed, after successful treatment for H. pylori, with periodic urea breath test to detect reinfection, as reinfection would put them at high risk for ulcer recurrence.

Adult↗
PubMed2006

VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis.

We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false-negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2006

Online measurement of oxygen consumption by goat bone marrow stromal cells in a combined cell-seeding and proliferation perfusion bioreactor.

In an effort to produce clinically useful volumes of tissue engineered bone products, a direct perfusion bioreactor system was developed. Perfusion flow rate, flow direction, and the position of the bioreactor are factors that influenced the amounts and homogeneity of the cells seeded on the scaffold surface. Goat bone marrow stromal cells (GBMSCs) were dynamically seeded and proliferated in this system in relevant volumes (10 cm(3)) of small-sized macroporous biphasic calcium phosphate (BCP) scaffolds (2-6 mm). Cell load and cell distribution were shown using Methylene Blue block staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining was used to demonstrate the viability of the cells. Although cells were not distributed homogenously after cell seeding, the scaffolds were covered with a viable, homogeneous cell layer after 25 days of cultivation. The hybrid structures became interconnected, and a dense layer of extracellular matrix formed on and in the scaffolds. Online oxygen measurements during cultivation were correlated with proliferating GBMSCs. It was shown that the oxygen consumption could possibly be used to estimate GBMSC population doubling times during growth in this bioreactor system. On the basis of our results, we conclude that a direct perfusion bioreactor system is capable of seeding and proliferating GBMSCs on BCP ceramic scaffolds that can be monitored online during cultivation.

Animals↗
PubMed2006

[Genetic aspects of cherubism].

INTRODUCTION: Cherubism is an extensive kystic process of the mandibula. The diagnosis is often established in children presented swelling of the jaws. The familial determinism of cherubism is well-known, and recently autosomal dominant cases have been described with detection of the exon 9 - SH3BP2 mutation. OBSERVATION: We describe the case of a 14-year-old boy with grade I cherubism diagnosed late. The familial genomic analyze conducted in Berlin was negative for the recently identified candidate gene. DISCUSSION: Apart from dominant cases cherubism sometimes occurs sporadically, some of the cases resulting from a neomutation of the candidate gene. The present case with familial bone homeostasis and dental disorders is an argument for the recessive transmission hypothesis or for another candidate gene.

Adaptor Proteins, Signal Transducing↗
PubMed2005

[Bisphosphonates and osteonecrosis of the jaw].

BACKGROUND: Since 2003, reports have been published on necrosis of the jaw bones possibly being associated with the administration of bisphosphonates. Bisphosphonates are highly active inhibitors of osteoclasts which have been used prophylactically or symptomatically in the treatment of plasmocytoma, bone metastasis of malignant disease, tumor-associated hypercalcaemia and in the treatment of osteoporosis. Due to the importance of this side effect of bisphosphonates, we report six cases. CASE REPORTS: Six patients (two women and four men) with a median age of 69 years (range 55-37) were diagnosed with osteonecrosis of the maxilla and/or mandible. These osteonecroses did not react adequately to local treatment and systemic therapy with antibiotics. Four patients suffered from plasmocytoma and two patients had a history of metastasising breast cancer. Besides cytostatic chemotherapies, all patients received bisphosphonates over an extended period. DISCUSSION: Bisphosphonates are considered an important standard in the treatment of plasmocytoma and bone metastasis due to malignancies. Since 2003, several reports have been published describing patients in whom therapy resistant osteonecrosis of jaw bones occurred either after dental extractions or spontaneously. Until then, unknown side effects of bisphosphonate therapy had been suspected. Since patients with malignant diseases receive cytostatic therapy and a range of other drugs, including bisphosphonates, enhancement of the side effects may be presumed. CONCLUSIONS: The probable association of the therapeutic use of bisphosphonates and the occurence of jaw bone necrosis has to be studied in further investigations. Patients receiving bisphosphonates should be followed-up regularly to avoid the occurrence of extended osteonecrotic lesions, which should be diagnosed early and treated adequately.

Adult↗
PubMed2005

Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage.

Embryonic stem cells (ESCs) are capable of extended self-renewal and maintenance of pluripotency even after many population doublings. This is supported by high levels of telomerase activity and enhanced antioxidant protection in ESCs, both of which are downregulated during differentiation. To examine the role of telomerase for ESC self-renewal and differentiation, we overexpressed the reverse transcriptase subunit (Tert) of murine telomerase in ESCs. Increased telomerase activity enhances the self-renewal ability of the Tert-overexpressing ESCs, improves their resistance to apoptosis, and increases their proliferation. The differentiated progeny of wild-type ESCs express little Tert and show shortening of telomeric overhangs. In contrast, the progeny of Tert-overexpressing ESCs maintain high telomerase activity, as well as the length of G-rich overhangs. In addition, these cells accumulate lower concentrations of peroxides than wild-type cells, implying greater resistance to oxidative stress. Finally, differentiation toward hematopoietic lineages is more efficient as a result of the continued expression of Tert. Microarray analysis revealed that overexpression of Tert altered expression of a variety of genes required for extended self-renewal and lifespan. Our results suggest that telomerase functions as a "survival enzyme" in ESCs and its differentiated progeny by protecting the telomere cap and by influencing the expression patterns of stress response and defense genes. This results in improved proliferation of ESCs and more efficient differentiation, and these results might have profound consequences for stem cell-replacement therapies.

Animals↗
PubMed2004

FTY720: early clinical experience.

FTY720 is the first in a new class of immunomodulators--sphingosine 1-phosphate receptor (S1P-R) agonists. It is highly effective in prolonging allograft survival in preclinical models of transplantation. Furthermore, FTY720 acts synergistically with calcineurin inhibitors and proliferation inhibitors in these models, suggesting that use of FTY720 in combination with classical immunosuppressants may be a promising new option for transplant patients. Phase I studies conducted in stable renal transplant patients maintained on a cyclosporine (CsA)-based regimen have revealed a tolerable profile of FTY720 for transplant pharmacotherapy. The pharmacokinetics of FTY720 is characterized by linear dose-proportional exposure over a wide range of doses, only moderate interpatient variability, and a prolonged elimination half-life (t(1/2) 89 to 157 hours). These factors suggest that FTY720 can be administered according to a simple once-daily schedule, without the need for blood-level monitoring or dose titration. The pharmacodynamics of FTY720 in humans are characterized by a significant reduction in peripheral blood count by up to 85%. In contrast to the nonspecific myelosuppressive effects of other immunosuppressants, this effect of FTY720 is specific for lymphocytes, with no effect observed on monocytes or granulocytes. In combination with CsA, FTY720 was well tolerated following single or multiple dosing, without any evidence of additional toxicities, indicating that FTY720 may be useful in the future design of more effective and less toxic regimens for prevention of graft rejection.

Animals↗
PubMed2004

Artificial in vivo biofiltration: slow continuous intravenous plasmafiltration (SCIP) and artificial organ support.

An intravenous plasmafiltration (SCIP) catheter has been developed and is proposed for clinical investigation into the alleviation of acute fluid overload by SCUF of the extracted plasma. The system utilizes a unique backflushing technique, high intravenous shear flow rates and biocompatible polymers to minimize protein and platelet aggregation along the filter surfaces. The absence of platelets from the extracted plasma promotes the longevity of ultrafiltration cartridges, thus theoretically minimizing attendant labor associated with continuous renal replacement therapies. Clinical studies are currently being planned for the near future. Plasma SCUF is envisioned as a predecessor technology to future applications in therapeutic apheresis, tissue engineering, therapeutic sorbent technologies. Further, with improved longevity profiles, intravenous SCUF or dialysis and implantable or wearable artificial organs based upon artificial in vivo biofiltration are possible.

Artificial Organs↗
PubMed2003

[Clinical and molecular genetic observations on families with cherubism over three generations].

BACKGROUND: Cherubism is a rare fibro-osseous disorder that almost exclusively affects the maxilla and mandible. CASE REPORT: We report on three affected males in three generations in family A, and ten affected patients in family B. The youngest affected relative in family A also had craniosynostosis. His father and grandfather had cherubism and clubbed fingers. RESULTS AND DISCUSSION: Cherubism was mapped to region 4p16.3. Because of the associated craniosynostosis, we excluded the FGFR3 gene as a candidate gene for cherubism. The inheritance pattern is autosomal dominant with variable expression. The penetrance is 100% in males and 50-70% in females. We found incomplete penetrance in males, which does not conform with all publications.

Adolescent↗
PubMed2003

Laser capture microdissection and real-time PCR for analysis of glomerular endothelin-1 gene expression in mesangiolysis of rat anti-Thy 1.1 and murine Habu Snake Venom glomerulonephritis.

Molecular analysis of pathologic changes in glomeruli requires methods allowing rapid and exact detection of alterations in gene expression. Here, we analyzed endothelin-1 (ET-1) mRNA expression in mesangiolytic glomeruli during the course of a rat and murine model of mesangioproliferative glomerulonephritis (GN). A novel method combining laser capture microdissection (LCM), which permits the precise removal of selected mesangiolytic glomeruli, with a highly sensitive real-time RT-PCR technique was used. Anti-Thy 1.1. GN was introduced in male Sprague-Dawley rats (1.0 mg/kg body weight of OX-7 IV) and Habu Snake Venom GN was introduced in C57BL6 mice (habu snake venom toxin 6 mg/kg body weight IV). The degree of mesangiolysis during both GNs was analyzed using a semiquantitative scoring system. Mesangiolytic glomeruli were microdissected at different days of the diseases (day 2, 6, and 12 in anti-Thy 1.1 GN and days 1, 3, 7, and 14 in Habu Snake Venom GN) and from normal control animals. After RNA extraction and cDNA synthesis, ET-1 gene expression was measured by real-time RT-PCR. In parallel, in anti-Thy 1.1. GN ET-1 mRNA expression was analyzed using semiquantitative nonradioactive in situ hybridization; ET-1 protein expression was investigated by immunohistochemistry. Mesangiolysis peaked at day 6 in anti-Thy1.1 GN and at day 1 in Habu Snake Venom GN. Mesangiolytic glomeruli were easily microdissected on cryostat sections in both models; quantification of mRNA with RT-PCR was reliable and reproducible. Glomerular ET-1 mRNA expression increased during the course of anti-Thy 1.1 GN and Habu Snake Venom GN peaked when mesangiolysis was most pronounced. This was seen by RT-PCR after glomerular LCM and by in situ hybridization; in parallel, glomerular ET-1 protein expression was increased. Combination of LCM and RT-PCR is a reliable method for quantification of localized gene expression in isolated renal structures. The above data argue for an important role of ET-1 in pathogenesis and/or repair of mesangiolysis in experimental mesangioproliferative GN.

Animals↗
PubMed2002

Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HLCS) deficiency (HLCSD) is a rare autosomal recessive disorder of biotin metabolism. HLCS catalyzes the biotinylation of the four human biotin-dependent carboxylases. Using the newly available human genomic sequence, we report the map of HLCS genomic structure and the predicted exon/intron boundaries. Moreover, the molecular studies of four patients (two Italians, one Iranian, and one Australian) affected by HLCS deficiency are here reported. The clinical findings, the age of onset, and response to biotin treatment differed between our patients. The diagnosis was made by organic acid analysis and confirmed by enzymatic analysis in three patients. Six mutations in the HLCS gene were identified, including two novel (N511K and G582R) and four known missense mutations (L216R, R508W, V550M, and G581S). Five of the mutations are localized within the HLCS biotin-binding domain, whereas the L216R amino acid change is located in the N-terminal region outside of the putative biotin-binding domain. This mutation, previously reported in a heterozygous state, was detected for the first time in a patient with homozygous status. The patient's severe clinical phenotype and partial responsiveness to biotin support a genotype-phenotype correlation through the involvement of residues of the N-terminal region in a substrate specificity recognition or regulation of the HLCS enzyme.

Acidosis↗
PubMed2001

Transcriptional response to hypoxia in human tumors.

BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy. To investigate the mechanisms by which cancer cells adapt to hypoxia, we looked for novel hypoxia-induced genes. METHODS: The transcriptional response to hypoxia in human glioblastoma cells was quantified with the use of serial analysis of gene expression. The time course of gene expression in response to hypoxia in a panel of various human tumor cell lines was measured by real-time polymerase chain reaction. Hypoxic regions of human carcinomas were chemically marked with pimonidazole. Immunohistochemistry and in situ hybridization were used to examine gene expression in the tumor's hypoxic regions. RESULTS: From the 24 504 unique transcripts expressed, 10 new hypoxia-regulated genes were detected-all induced, to a greater extent than vascular endothelial growth factor, a hypoxia-induced mitogen that promotes blood vessel growth. These genes also responded to hypoxia in breast and colon cancer cells and were activated by hypoxia-inducible factor 1, a key regulator of hypoxic responses. In tumors, gene expression was limited to hypoxic regions. Induced genes included hexabrachion (an extracellular matrix glycoprotein), stanniocalcin 1 (a calcium homeostasis protein), and an angiopoietin-related gene. CONCLUSIONS: We have identified the genes that are transcriptionally activated within hypoxic malignant cells, a crucial first step in understanding the complex interactions driving hypoxia response. Within our catalogue of hypoxia-responsive genes are novel candidates for hypoxia-driven angiogenesis.

Blotting, Western↗
PubMed2001

Quantitation of the changes in vascularity during arthritis in the knee joint of a mouse with a digital image analysis system.

Many joint and bone diseases are caused by, or associated with vascular changes. Particularly in rheumatoid arthritis, vascular sprouting of synovial vessels plays a major role in the generation of joint pathology. To assess the effects of pharmaceuticals that are designed to inhibit neovascularization, we developed a quantitative procedure to measure vascular changes in cross-sections of the mouse knee joint during arthritic inflammation. Arthritis was induced in the knee joint of C57Black6 mice by a single subpatellar injection of methylated BSA after previous immunization. Total vascularity was visualized with a specific monoclonal rat anti-mouse antibody (9F1). Functional vessels were detected with the fluorescent perfusion marker Hoechst 33342. The localization of Hoechst and the vascular marker 9F1 were analyzed in separate images with an automated digital image processing system. By combining the two images, total vascularity and the perfusion status of the vessels during arthritis could be established. The digital image system measures synovial area (SA), number of all blood vessels (NBV) and the number of perfused blood vessels (NpBV). From these parameters the percentage of perfused vessels (perfusion fraction; PF), the vessel density (VD = NBV/SA) and the density of perfused vessels (VDp = NpBV/SA) can be calculated. The measurements showed that the area of synovial tissue had increased during arthritis. Moreover, both the number of blood vessels (NBV) and the number of perfused vessels (NpBV) in the synovial area had increased significantly on Days 4 and 7 after arthritis induction. This procedure enabled quantitation of total vascularity and of functional blood vessels in cross-sections of synovial tissue. It is expected to be a powerful tool, not only to analyze the effects of anti-angiogenic therapies in animal models of arthritis, but could also be applicable to study vascular and perfusion changes in vascular related diseases of the skeleton.

Animals↗
PubMed2001

Comparative analysis of the genomic organization of Pax9 and its conserved physical association with Nkx2-9 in the human, mouse, and pufferfish genomes.

As a first step towards the identification of cis-regulatory elements of Pax9 by means of comparative genomics, we have analyzed genome regions encompassing the Pax9 gene in three vertebrate species, humans, mice (Mus musculus), and the Japanese pufferfish (Fugu rubripes). We show the genomic organization of Pax9 and its physical association with Nkx2-9 conserved in the three species. We discuss about possible implications of the conserved synteny between Pax9 and Nkx2-9 in a context of vertebrate evolution. This report also includes the first description of the primary structures of Fugu Pax9 and Nkx2-9. Furthermore, we report the identification of a novel upstream exon and putative transcription start sites in mouse Pax9. Our results suggest that transcription of Pax9 may be initiated at two alternative start sites and driven by TATA-less promoters.

Amino Acid Sequence↗
PubMed2001

Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism.

Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism.

Adaptor Proteins, Signal Transducing↗