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Biomedical subjects

P Schroth

Publications and source records attributed to P Schroth.

At least 19 recordsLinked to original sources
PubMed2006

Thymus and myasthenia gravis: antigen processing in the human thymus and the consequences for the generation of autoreactive T cells.

Peptides displayed by antigen presenting cells in the thymus shape the T cell repertoire. We investigated the antigen processing machinery of the MHC class II presentation pathway and describe the differential expression of lysosomal proteases in compartments of the thymus and the peripheral lymphoid tissue. Overexpression of certain proteases found in the thymus and thymoma associated with myasthenia gravis is likely to affect tolerance induction and may promote the generation autoreactive CD4(+) T helper cells.

Antigen-Presenting Cells↗
PubMed1999

Insect-based BioFETs with improved signal characteristics.

Insect-based BioFETs (biologically sensitive field-effect transistors) with improved signal characteristics have been developed. These BioFETs require a specifically adapted signal interfacing between a FET as signal transducer and an intact insect antenna as biocomponent. Therefore, different field-effect transistors have been fabricated in order to study the signal transfer at the bioelectronic interface. As relevant features of the BioFET, its current-voltage characteristics, the transconductance and the signal-to-noise ratio have been investigated as affected by the choice of gate insulator materials and gate dimensions (width-to-length ratio, thickness of the dielectric layers). The performance of the improved FET arrangement in the isolated-antenna BioFET was validated by employing dilution series of the plant odour component Z-3-hexen-1-ol.

Animals↗
PubMed1999

Pharmacokinetics of recombinant factor VIII (recombinate) using one-stage clotting and chromogenic factor VIII assay.

In a study designed to demonstrate the safety and pharmacokinetics of a recombinant factor VIII (Recombinate) manufactured in Andover, MA and Thousand Oaks, CA, two different methods of factor VIII assay (one-stage clotting and Chromogenic substrate) were compared in vivo. The study was performed in four centres in the UK: London, Oxford, Cardiff and Manchester. Two pharmacokinetic studies, at least one week apart, were performed in 30 patients with severe haemophilia A (VIII:C < 2 IU/dl). A dose of 50 IU/kg was administered with sampling pre-infusion, and +0.25, 0.5, 1, 3, 6, 9, 12 and 24 h post-infusion. The aggregate 60 pharmacokinetic study showed a half-life of 12.7 and 13.0 h (p = 0.28) and recovery of 127 and 161 IU/dl (p = 0.0001) using one-stage clotting or chromogenic substrate respectively. In a supplementary experiment, 20 post-infusion samples were re-assayed by 1-stage and chromogenic assay using two plasma (20th British plasma standard and an "in-house" pooled normal plasma) and two concentrate standards, derived from the same type, but different batch of infused concentrate (Recombinate) and pre-diluted in either individual pre-infusion sample or in pooled commercial haemophilic plasma. The use of the Recombinate concentrate standard overcame the significant difference in FVIII levels between 1-stage and chromogenic assay methods when a plasma standard was used (p <0.0001). It is concluded that where potency dosing designation is carried out by an assay system different to that used in the clinical situation, the use of the recombinant concentrate as a standard in post-infusion plasma samples is likely to give more reliable and reproducible results.

Biological Assay↗
PubMed1992

1-C-glucuronidation of N-nitrosodiethylamine and N-nitrosomethyl-n-pentylamine in vivo and in primary hepatocytes from rats pretreated with inducers.

The organ specificity of the carcinogenic action of nitrosamines is partly explained by organ specific activation. The specificity might also be determined by conjugation of reactive intermediates in e.g. the liver. 14C-Labeled N-nitrosodiethylamine (NDEA) a liver carcinogen and N-nitrosomethyl-n-pentylamine (NMPentA) which induces esophageal and nasal tumors were administered to rats or incubated with primary cells. Urine and cell extracts were separated by HPLC after addition of synthetic marker glucuronides and these were quantified by liquid scintillation counting. In urine of rats treated with NDEA 0.03% of administered nitrosamine was recovered as the O-glucuronide derived from N-nitroso-1-hydroxyethylethylamine. In rats treated with NMPentA 2.86% was metabolized to the glucuronide at the methyl group. In hepatocytes of untreated rats 0.03% of the added NDEA was conjugated to the glucuronide, phenobarbital pretreatment induced this conjugation reaction 5-fold. Hepatocytes from untreated rats metabolized 1.2% of NMPentA to the primary glucuronide; after phenobarbital pretreatment this value increased to 1.6%. In hepatocytes from 3-methylcholanthrene-pretreated rats, 0.04% of NMPentA was metabolized to the glucuronide derived from N-nitroso-1-hydroxy-n-pentyl-methylamine, while 0.85% was derived from N-nitroso-hydroxymethyl-n-pentylamine. In hepatocytes from Aroclor-pretreated rats, 0.09% were pentyl conjugates and 1.1% methyl conjugates. The induction pattern and organ specificity of glucuronidation indicate that all three 1-hydroxy nitrosamines are conjugated by group II phenobarbital inducible UDP-glucuronosyltransferase activity. The lipophilicity of a nitrosamine seems to determine the extent of glucuronidation in hepatocytes and in vivo. No glucuronides derived from either NDEA or NMPentA were detectable in incubations with kidney cells, nor was the glucuronide of NDEA found in incubations with whole bladders.

Animals↗
PubMed1991

Dietary restriction on serum thyroid hormone levels.

To determine the long term effects of a protein sparing fast on serum thyroid hormone levels, the authors studied 38 obese patients ingesting a diet of 320 kcal for up to 13 weeks. The high baseline serum triiodothyronine (T3) levels decreased significantly by the first week, further decreased by the third week, and this lower level persisted for the duration of the fast until realimentation. Serum free T3 index followed the same general pattern as did serum T3 levels. Serum reverse T3 increased significantly by the first week, but by week three, the reverse T3 level had begun to fall, although still significantly increased above baseline. By week seven, reverse T3 had decreased to almost baseline and remained not significantly changed from the baseline to 13 weeks. Serum thyroxine (T4) increased significantly by the first week in all patients, but by the third week had returned to baseline levels which persisted to 13 weeks. The free T4 index and free T4 concentrations showed the same increment at week one and then returned to baseline levels. There were no significant changes in serum thyroxine-binding globulin (TBG) or thyroid-stimulating hormone (TSH) concentrations. The changes in serum T3 and reverse T3 levels are attributable to alterations in peripheral 5'-monodeiodination of T4 and reverse T3 induced by the protein sparing fast.

Body Weight↗
PubMed1989

Psychometric assessment of first-degree relatives of 62 autistic probands in Utah.

The Wechsler Intelligence Scales, Wide Range Achievement Test, and the Shipley-Hartford Test were administered to 122 parents and 153 siblings of 62 autistic probands in Utah. Scores were distributed as expected within the published normative ranges for each scale. Parents' scores correlated with those of their nonautistic children, but neither parents' nor siblings' scores correlated with the IQ level of the autistic probands. These results do not confirm prior reports from England and the United States of a high rate of cognitive and learning problems in the siblings of autistic individuals, nor the aggregation of such problems in the siblings of probands with high or low levels of cognitive function.

Achievement↗
PubMed1985

Obesity and hypertension: long-term effects of weight reduction on blood pressure.

Long-term follow-up studies were conducted on massively obese hypertensive subjects during and after a successful protein supplemented fast (PSMF) in order to correlate blood pressure changes with caloric intake and body weight. The blood pressures in 43 subjects were compared during rapid weight loss and at identical weights during post-fast weight gain (Study A). Blood pressures and body weights in 50 subjects were compared prior to starting PSMF and prior to restarting the program 21 months later (Study B). One hundred twenty-five compliant subjects were observed after one month of weight maintenance (Study C-1), and 39 subjects were followed during six months of weight maintenance (Study C-2). In Study A, during subsequent weight gain on an unrestricted diet blood pressure was significantly higher than at identical weight during continuous weight loss on PSMF. However, this increase in blood pressure was only approximately 30 percent of the original decrease. In Study B, weight loss and blood pressure reduction were significantly correlated. After one month of weight maintenance following continuous weight loss of 73 lb, there was no increase in blood pressure (Study C-1). A small but significant increase in blood pressure after six months (Study C-2) was associated with similar small weight increment. However, all blood pressures remained well within the normotensive range and significantly lower than control values. In this study, long-term changes in blood pressure correlated with changes in body weight.

Blood Pressure↗
PubMed1984

Study of fenfluramine in outpatients with the syndrome of autism.

Fenfluramine was administered to 14 outpatient children with the syndrome of autism to determine whether previously produced decreases in blood serotonin concentrations and clinical improvements could be reinstituted. A double-blind medication-placebo crossover design was used. Each patient received fenfluramine 1.5 mg/kg daily (0.75 mg/kg twice daily) for 8 months, followed by placebo for 2 months. Blood serotonin levels promptly fell approximately 49% regardless of baseline levels. Clinical improvement returned, and on some scales gains after 8 months exceeded those noted after only 4 months of treatment. Significant correlations emerged among the amount of clinical response, initially high verbal IQs, and low blood serotonin concentrations. Compliance was excellent, and no clinically relevant side effects or weight changes occurred. It appears that fenfluramine is effective in ameliorating specific symptoms in certain autistic patients. The extent and mechanism of its action remain to be discovered.

Adolescent↗