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Biomedical subjects

Peter Simon

Publications and source records attributed to Peter Simon.

At least 19 recordsLinked to original sources
PubMed2006

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.

Base Sequence↗
PubMed2006

A statewide assessment of tuberculin skin testing of preschool children enrolled in medicaid managed care.

OBJECTIVES: This study examined tuberculosis screening among preschool children enrolled in a statewide Medicaid managed care program. METHODS: A random sample of 2,000 was selected from 19 to 35 month old children who were continuously enrolled in Rhode Island's Medicaid managed care program for 1 year. Sociodemographic data were obtained from computerized administrative databases. Medical record audits were performed to obtain the dates and results of tuberculosis tests. RESULTS: Data from the medical record audits were available for 1,988 of the study children. For 1,215 of the study children (1,215/1,988 = 61%) a tuberculin skin test had been performed, but a reading was only documented for 736 children (60% of children who received a tuberculin skin test) and only one child tested positive (0.1%). CONCLUSIONS: A majority of preschool children in this population in which the prevalence of risk factors for tuberculosis is likely to be relatively high did have a tuberculosis test performed. However, in many cases the tuberculin skin test was either not read or the results not documented. The low rate of positivity is consistent with current AAP guidelines for selective tuberculin skin testing.

Child Health Services↗
PubMed2006

Germline mutations and gene polymorphism associated with human pancreatitis.

A wide range of mutations and polymorphisms in genes that relate to pancreatic function seem to be involved in the development of pancreatitis. Some of these genetic alterations lead to disease phenotypes with unequivocal mendelian inheritance patterns, whereas others seem to act as modifier genes in conjunction with environ-mental or, as yet unidentified, genetic cofactors. This article reviews germline changes in the genes for trypsin, pancreatic secretory trypsin inhibitor, the cystic fibrosis conductance regulator, lipid metabolism proteins, inflammatory mediators for cytokines, and cathepsin B.

Carrier Proteins↗
PubMed2006

Endocrine tumors of the pancreas.

Neuroendocrine tumors of the pancreas are rare neoplasms of the heterogeneous group of neuroendocrine gastroenteropancreatic tumors that originate from totipotential stem cells or preexisting endocrine cells within the pancreas. Most neuroendocrine tumors of the pancreas are benign or show an indolent course of disease.A subset of them shows a very aggressive behavior, becomes highly malignant, and metastasizes early with life-limiting consequences. An effective disease-management includes the diagnostic approach with hormonal testing and localization and surgical treatment with histologic classification in combination with biotherapy, chemotherapy, or therapy with radionucleotides, de-pending on the individual behavior of the tumor. The primary goal is the improvement of symptoms leading to an acceptable quality of life in the individual patient.

Biomarkers, Tumor↗
PubMed2006

A randomized, community-based trial of home visiting to reduce blood lead levels in children.

OBJECTIVE: The objective of this study was to measure the effectiveness of intensive case management to reduce blood lead levels (BLLs) in children. Lead poisoning remains a common, preventable pediatric condition despite advances in reducing children's BLLs in the United States. Substantial evidence implicates lead paint-contaminated house dust as the most common high-dose source of lead in children's environments. Housekeeping and parental supervision also may contribute to risk for lead exposure. METHODS: We conducted a community-based, randomized trial of comprehensive education and home visiting for families of children with BLLs 15 to 19 microg/dL. BLLs after 1 year of follow-up were compared for intervention group children, whose families received individualized education that was designed to address specific risks factors in a child's environment, and comparison group children, whose families received customary care, usually 1 or 2 educational visits. Environmental samples were collected at baseline and after 1 year of follow-up for intervention group children and compared with those of comparison group children, collected only at the end of study. RESULTS: During the follow-up period, parents of intervention group children (n = 92) successfully decreased dust lead levels and significantly improved parent-child interaction and family housekeeping practices compared with comparison group children (n = 83). Overall geometric mean BLLs declined by 47%, and the difference in BLL by group was not significant (9 vs 8.3 microg/dL for intervention versus comparison group children, respectively.) After 1 year, nearly half of enrolled children had BLLs > or = 10 microg/dL. CONCLUSIONS: Until a reservoir of lead-safe housing is created, programs that educate families to reduce environmental exposure are needed. Although providing families with quantitative information regarding lead contamination may have a role in short-term efforts to prevent lead exposure, these null findings suggest that it has little benefit once BLLs are elevated.

Child↗
PubMed2005

Evaluation of oxidation stability of lignite humic substances by DSC induction period measurement.

The stability of lignite humic acids and four regenerated humic acids was estimated by employing differential scanning calorimetry. Induction period for the oxidative decomposition of humic matter was calculated from non-isothermal measurements at six different rates of heating. To simulate the gradual evolution history of humic acids, different intensities of oxidation attack by nitric acid on the original lignite was used. Experimental data showed higher stability of natural humic acids in the temperature range where the decomposition step occurred. On the other hand, extrapolation to lower temperatures and calculated kinetic parameters did not correspond to the order observed at higher temperatures. An oscillating trend of calculated parameters of the two proposed parts of stability was observed, which agreed with data concerning regenerated humic acids production. The approach applied in this work represents a rapid and useful method for evaluation of organic matter stability.

Calorimetry, Differential Scanning↗
PubMed2005

Independent risk factors for gallstone formation in a region with high cholelithiasis prevalence.

BACKGROUND/AIMS: Cholelithiasis is a common disorder in north-eastern Germany. Analyses of risk factors for gallstone formation in this population may have high explanatory power. Gender-specific risk factors for gallstone formation and their interactions were investigated by using data of the population-based Study of Health in Pomerania (SHIP). METHODS: Data of 4,202 persons aged 20-79 years were available. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on abdominal ultrasound. Multivariable analyses were performed to identify independent risk factors for gallstone formation. RESULTS: There were 468 persons (11.1%) with previous cholecystectomy and 423 persons (10.1%) with sonographic evidence of gallstones. Women had a twofold higher risk for cholelithiasis compared to men. Age, body mass index and low serum HDL cholesterol levels were independently associated with cholelithiasis in both men and women. In the male population, low alcohol and high coffee consumption and in the female population, low physical activity, were further independently related to gallstone formation. Additionally, sex-specific interactions between risk factors were found. CONCLUSIONS: Female sex, age and being overweight are major risk factors for gallstone formation in this region where cholelithiasis is a frequent disorder. Additional factors and interactions contribute to a gender-specific gallstone risk.

Adult↗
PubMed2004

New screening method for the determination of stability of pharmaceuticals.

A rapid method for obtaining the parameters describing the lengths of oxidation induction periods from non-isothermal differential scanning calorimetry measurements, based on the dependence of onset temperature of the oxidation peak on heating rate, is presented. The method has been applied for screening the stability of a set of three pharmaceuticals. The order of stabilities of the compounds obtained by the method coincides with the order determined by classical stability tests.

Calorimetry, Differential Scanning↗
PubMed2004

Medical treatment of acute pancreatitis.

Eighty percent of all cases of acute pancreatitis are linked etiologically to gallstone disease or caused by immoderate alcohol consumption. No specific causal treatment for acute pancreatitis exists. Early prognostic factors that indicate severe disease are three or more signs on organ failure scores according to Ranson, Imrie, or Acute Physiology and Chronic Health Evaluation (APACHE) 11, extrapancreatic complications of the disease, or the detection of pancreatic necrosis on CT scans. Elevated CRP levels above 130 mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Moreover, relief of often severe visceral pain is a high priority. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis, or other infectious complications. Enteral nutrition has no adverse effect compared with parenteral nutrition during the course of acute pancreatitis, and is probably beneficial in regard to outcome.

Acute Disease↗
PubMed2004

Clinical and genetic characteristics of hereditary pancreatitis in Europe.

BACKGROUND & AIMS: Hereditary pancreatitis is an autosomal dominant disease that is mostly caused by cationic trypsinogen (PRSS1) gene mutations. The aim was to determine phenotype-genotype correlations of families in Europe. METHODS: Analysis of data obtained by the European Registry of Hereditary Pancreatitis and Pancreatic Cancer was undertaken using multilevel proportional hazards modelling. RESULTS: There were 112 families in 14 countries (418 affected individuals): 58 (52%) families carried the R122H, 24 (21%) the N29I, and 5 (4%) the A16V mutation, 2 had rare mutations, and 21 (19%) had no PRSS1 mutation. The median (95% confidence interval [CI]) time to first symptoms for R122H was 10 (8, 12) years of age, 14 (11, 18) years for N29I, and 14.5 (10, 21) years for mutation negative patients (P = 0.032). The cumulative risk (95% CI) at 50 years of age for exocrine failure was 37.2% (28.5%, 45.8%), 47.6% (37.1%, 58.1%) for endocrine failure, and 17.5% (12.2%, 22.7%) for pancreatic resection for pain. Time to resection was significantly reduced for females (P < 0.001) and those with the N29I mutation (P = 0.014). The cumulative risk (95% CI) of pancreatic cancer was 44.0% (8.0%, 80.0%) at 70 years from symptom onset with a standardized incidence ratio of 67% (50%, 82%). CONCLUSIONS: Symptoms in hereditary pancreatitis start in younger patients and endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher. There is an increasingly high risk of pancreatic cancer after the age of 50 years unrelated to the genotype.

Adult↗
PubMed2003

[Conservative treatment of acute pancreatitis].

The incidence of acute pancreatitis per 100,000 population ranges from 10 to 46. The mortality of acute edematous interstitial pancreatitis is < 1%, while patients suffering from hemorrhagic necrotizing pancreatitis die from their disease in 10-24%. 80% of all cases of acute pancreatitis are etiologically correlated to diseases of the biliary tract or an excess alcohol consumption. As of today, no specific and causal treatment for acute pancreatitis has been established. Early prognostic factors for the evaluation of the clinical course of acute eipancreatitis are three or more indicators of organ failure in the Ranson or Imrie score, the development of extrapancreatic complications or the detection of pancreatic necrosis on contrast-enhanced CT scans. Elevated C-reactive protein (CRP) levels > 130 mg/l can predict a severe course of acute pancreatitis with a high sensitivity. The foundation of medical treatment in acute pancreatitis is the substitution of fluids to counteract hypovolemia. Furthermore, the relief of sometimes severe visceral pain has the highest priority. Infusion of procaine has been found to be ineffective for this purpose. The use of antibiotics should be restricted to patients with pancreatic necrosis. Enteral nutrition has no adverse effect compared to parenteral nutrition and is likely to be beneficial to the course of pancreatitis.

APACHE↗
PubMed2002

Optimisation of solid-phase microextraction of volatiles.

The results of a systematic study on the precision and repeatability of measurements of the headspace solid phase micro-extraction (SPME) with open-cap vials in combination with capillary gas chromatography in comparison with septum-sealed vials are reported. Benzene, toluene, ethylbenzene, and xylene isomers (BTEX) were used as the target analytes in the investigation of spiked water samples at concentration levels of 42.5 microg l(-1). The dependence of a sample volume versus peak area showed maximum SPME recovery. The influence of sample volume on the precision and the time of taking the sample on the losses of volatile analytes was examined.

Hydrocarbons↗
PubMed2002

Directional bias during mating type switching in Saccharomyces is independent of chromosomal architecture.

Haploid Saccharomyces cells have the remarkable potential to change mating type as often as every generation, a process accomplished by an intrachromosomal gene conversion between an expressor locus MAT and one of two repositories of mating type information, HML or HMR. The particular locus selected as donor is dictated by the mating type of the cell, a bias that ensures productive mating type interconversion. Here we use green fluorescent protein tagging of the expressor and donor loci on chromosome III to show that this preference for donor locus does not result from a predetermined organization of chromosome III: HML and MAT as well as HMR and MAT remain separated in cells of both mating types. In fact, cells in which the inappropriate donor locus is artificially tethered to MAT still predominantly select the correct donor. We find, though, that initiation of switching leads to a rapid association of the correct donor locus with MAT. Thus, in mating type switching in Saccharomyces, donor preference is imposed at commitment to recombination rather than at physical contact of interacting DNA strands.

Chromosomes, Fungal↗
PubMed2001

Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 --> Cys) that alters autoactivation and autodegradation of cationic trypsinogen.

Hereditary pancreatitis has been found to be associated with germline mutations in the cationic trypsinogen (PRSS1) gene. Here we report a family with hereditary pancreatitis that carries a novel PRSS1 mutation (R122C). This mutation cannot be diagnosed with the conventional screening method using AflIII restriction enzyme digest. We therefore propose a new assay based on restriction enzyme digest with BstUI, a technique that permits detection of the novel R122C mutation in addition to the most common R122H mutation, and even in the presence of a recently reported neutral polymorphism that prevents its detection by the AflIII method. Recombinantly expressed R122C mutant human trypsinogen was found to undergo greatly reduced autoactivation and cathepsin B-induced activation, which is most likely caused by misfolding or disulfide mismatches of the mutant zymogen. The K(m) of R122C trypsin was found to be unchanged, but its k(cat) was reduced to 37% of the wild type. After correction for enterokinase activatable activity, and specifically in the absence of calcium, the R122C mutant was more resistant to autolysis than the wild type and autoactivated more rapidly at pH 8. Molecular modeling of the R122C mutant trypsin predicted an unimpaired active site but an altered stability of the calcium binding loop. This previously unknown trypsinogen mutation is associated with hereditary pancreatitis, requires a novel diagnostic screening method, and, for the first time, raises the question whether a gain or a loss of trypsin function participates in the onset of pancreatitis.

Amino Acid Sequence↗
PubMed1999

Nonlinear effects of electrolyte diodes and transistors in a polymer gel medium.

The polarization curve of an acid-base interface in a hydrogel medium has a diode characteristic. Two of each such electrolyte diodes can be combined to give an electrolyte transistor. When a salt is added to the alkaline or to the acidic part of a reverse biased electrolyte diode, the current response is highly nonlinear. If the salt is added to the acidic side, even bistability can be observed. This bistability can generate complex oscillations in a base-acid-base electrolyte transistor. These nonlinear effects are studied experimentally and theoretically. While the nonlinear salt effect can be explained with the Nernst-Planck equations, to understand the bistable behavior further investigations are necessary. (c) 1999 American Institute of Physics.

Journal Article↗