Biomedical subjects

T Zahn

Publications and source records attributed to T Zahn.

12 recordsLinked to original sources

PubMed1999

Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein.

A pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP) was cloned using a subtractive cDNA expression cloning procedure from mouse insulinoma tissue. Two alternatively spliced variants that differed by the presence or absence of a 118-bp exon (exon IV) were detected in normal balb/c mice, diabetic ob/ob mice, and insulinoma tissue. The longer, 1901-bp full-length cDNA encoded a 355-amino acid protein (molecular weight 40,684) structurally related (50% overall identity) to the liver glucose-6-phosphatase and exhibited similar predicted transmembrane topology, conservation of catalytically important residues, and the presence of an endoplasmic reticulum retention signal. The shorter transcript encoded two possible open reading frames (ORFs), neither of which possessed His174, a residue thought to be the phosphoryl acceptor (Pan CJ, Lei KJ, Annabi B, Hemrika W, Chou JY: Transmembrane topology of glucose-6-phosphatase. J Biol Chem 273:6144-6148, 1998). Northern blot and reverse transcription-polymerase chain reaction analysis showed that the mRNA was highly expressed in pancreatic islets and expressed more in beta-cell lines than in an alpha-cell line. It was notably absent in tissues and cell lines of non-islet neuroendocrine origin, and no other major tissue source of the mRNA was found. During development, it was expressed in parallel with insulin mRNA. The mRNA was efficiently translated and glycosylated in an in vitro translation/membrane translocation system and readily transcribed into COS 1, HIT, and CHO cells using cytomegalovirus or Rous sarcoma virus promoters. Whereas the liver glucose-6-phosphatase showed activity in these transfection systems, the IGRP failed to show glucose phosphotransferase or phosphatase activity with p-nitrophenol phosphate, inorganic pyrophosphate, or a range of sugar phosphates hydrolyzed by the liver enzyme. While the metabolic function of the enzyme is not resolved, its remarkable tissue-specific expression warrants further investigation, as does its transcriptional regulation in conditions where glucose responsiveness of the pancreatic islet is altered.

Alternative Splicing↗

PubMed1996

Cytological and biochemical response of R1 cells and isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) to subacute in vitro exposure to disulfoton.

Ultrastructural, stereological and biochemical alterations in isolated hepatocytes and the permanent fibrocyte-like cell line R1 from rainbow trout (Oncorhynchus mykiss) exposed to 0, 0.2, 2 and 20 mg/l of the phosphorodithioate pesticide disulfoton (Solvirex, O,O-diethyl S-2-ethylthioethyl phosphorodithioate) for up to 5 days were investigated. In both R1 cells and isolated hepatocytes, distinct dose- and time-dependent morphological alterations including diminished amounts of heterochromatin, proliferation of lysosomal elements, dilation and vesiculation of endoplasmic reticulum cisternae, induction of concentric membrane whorls and an increased amount of lipid droplets could be detected at concentrations of > or = 2 mg/l (R1 cells) and > or = 0.2 mg/l disulfoton (hepatocytes). Additional effects in isolated hepatocytes comprised marginalization of heterochromatin, myelin-like structures attached to mitochondrial membranes, formation of ring-shaped mitochondria, proliferation of smooth endoplasmic reticulum, reduction of rough endoplasmic reticulum, induction of ring-shaped Golgi cisternae, glycogen depletion and occurrence of glycogenosomes. Structural changes in isolated hepatocytes could be correlated to suppression of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, alanine aminotransferase, malic enzyme, esterase as well as glutathione S-transferase, but to a stimulation of 7-ethoxycoumarin-O-deethylase and the rate of lipid peroxidation at concentrations > or = 0.01 mg/l disulfoton. Comparison with data from in vivo experiments with rainbow trout indicate the suitability of in vitro techniques for the evaluation of the toxicological potential of a wide range of ecotoxicologically relevant substances.

Animals↗

PubMed1995

Acute and sublethal toxicity of seepage waters from garbage dumps to permanent cell lines and primary cultures of hepatocytes from rainbow trout (Oncorhynchus mykiss): a novel approach to environmental risk assessment for chemicals and chemical mixtures.

In order to evaluate the suitability of cytopathological criteria in isolated fish hepatocytes as endpoints in (eco)toxicological research, liver cells isolated from rainbow trout (Oncorhynchus mykiss) by collagenase perfusion were exposed in vitro for up to 5 days to sublethal dilutions of two seepage water samples collected from garbage dumps. Hepatocytes were analysed with respect to acute (lactate dehydrogenase leakage) and sublethal toxicity (electron microscopy, stereology). In addition, acute toxicity (24 h) was tested in the piscine fibrocytic cell line R1 by means of crystal violet staining and neutral red retention. Acute toxicity in R1 cells and isolated hepatocytes could only be documented for sample I at dilutions of 1:2 and 1:4. This difference in toxicity could be corroborated by cytological alterations in isolated hepatocytes, which could be documented for dilutions of 1:100 and 1:8 in samples I and II, respectively. Ultrastructural changes were time- and dose-dependent and included reduction of hepatocellular volume, disturbance of intracellular compartmentation, modified heterochromatin distribution, transformation of rough endoplasmic reticulum into concentric membrane whorls, proliferation of lysosomes and cytoplasmic vacuoles, as well as reduction of hepatocellular glycogen. Although several hepatocellular reactions were found after exposure to either sample, the syndrome of ultrastructural alterations allowed clear differentiation between the two samples. Results illustrate that cytological effects far below macroscopically detectable damage can be discovered not only in intact fish, but also in fish cell culture systems. On the basis of the data presented, a multi-tiered test procedure for aquatic toxicity assessment exclusively based on tests with fish cell culture systems is proposed: (1) rapid screening for acute toxicity with permanent cell lines; (2) short-term tests with more complex, yet more sensitive systems such as primary hepatocytes with straightforward biochemical endpoints; (3) prolonged exposure of isolated hepatocytes in combination with ultrastructural and biochemical investigations as a sensitive tool to detect adverse effects at environmentally relevant toxicant concentrations.

Animals↗

PubMed1994

[Bronchial asthma: use of combination therapy. Anti-obstructive and anti-inflammatory treatment--result of treatment].

On the basis of a single case report, combined antiobstructive and anti-inflammatory treatment of bronchial asthma is described. The anti-obstructive component used was a sustained-release theophylline preparation (Euphylong, 750 mg/day), and as anti-inflammatory drug, the inhalant beclomethasone diproprionate (Viarox, 300 mg/day). During the 4-week treatment period, obvious improvements in lung function parameters (FEV1 from 21 prior to to 31 after treatment; FVC from 2.81 to 3.31) were seen. At a daily dose of 750 mg theophylline, a favorable therapeutic concentration of 16.5 micrograms/ml was achieved. It was found that the combination of sustained-release theophylline and the low-dose glucocorticoid inhalant resulted in an impressive improvement in bronchial asthma.

Adult↗

PubMed1994

[Successful combination therapy in bronchial asthma. Anti-obstructive and anti-inflammatory treatment].

METHOD: In a post-marketing surveillance study, patient data were documented with the aim of assessing the effect of a combination of both anti-inflammatory and bronchodilatory treatment with inhaled beclomethasone dipropionate and a sustained-release theophylline preparation. A total of 2,166 patients with mild-to-moderate bronchial asthma (FEV1 about 60%) were included in the multicenter open study. RESULTS: It was found that treatment with inhaled glucocorticoid and sustained-release theophylline resulted in a clear improvement in symptom scores. More than 90% of the physicians and patients rated the treatment "very good" or "good". Only 4.6% of the participants had side effects. CONCLUSION: It may be concluded that combination therapy with inhaled glucocorticoid and sustained release theophylline is a safe and effective form of treatment of mild-to-moderate asthma.

Administration, Inhalation↗

PubMed1994

Childhood-onset schizophrenia: an NIMH study in progress.

An ongoing study of the phenomenology, genetics, neuropsychology, physiology (eye tracking, autonomic responsivity), neuroimaging, biochemistry, and pharmacology of childhood-onset schizophrenia is described, and pilot data are presented for the first 22 subjects. Differentiation from autism "spectrum" disorders and other poorly defined, severe neurodevelopmental disorders is needed. Eye tracking and autonomic results are similar to patterns seen in later-onset schizophrenia and possibly more striking. Magnetic resonance imaging showed larger left frontal ventricular horn area for the schizophrenia subjects, larger left caudate, and lack of normal caudate asymmetry. Fluorodeoxyglucose positron emission tomography during an auditory continuous performance task revealed decreased right parietal/occipital glucose metabolic rate in the schizophrenia subjects, which may be secondary to poor attentional performance, and increased glucose metabolic rate in three left frontal regions, a left parietal region, and the right putamen. Clozapine has been effective and well tolerated in an open trial with 12 adolescents who responded poorly to typical neuroleptics; 16 subjects have been enrolled in a double-blind comparison of haloperidol and clozapine. Longitudinal study of this narrowly defined and possibly more homogeneous group of very early-onset schizophrenia subjects will be relevant to current neurodevelopmental theories addressing the role of puberty, progression of pathology, and continuity or discontinuity with later-onset schizophrenia.

Adolescent↗

PubMed1991

[Thyroid abscess caused by Salmonella enteritidis].

A 70-year-old diabetic woman with a nodular goitre developed a swelling in the right neck, increasing over two weeks, as well as fever (38.2 degrees C), increased tendency towards sweating, finger tremors and pain on swallowing. Ultrasound examination of the thyroid raised the suspicion of an abscess, 3.5 x 1.5 cm, at the upper pole of the right thyroid lobe. Material obtained by fine-needle puncture grew Salmonella enteritidis. There have been no symptoms of gastroenteritis at any time. Stool and sputum cultures and nasopharyngeal swabs revealed the sites from which haematogenous spread had come. The abscess regressed (as monitored by ultrasound) within four weeks during intravenous treatment with 1,600 mg/d sulphamethoxazole and 320 mg/d trimethoprim (antibiotics determined by drug sensitivity tests) and after several ultrasound-directed needle punctures. Initially manifest hyperthyroidism (fT4: 3.4 ng/dl; basal TSH: 0.03 microU/l) regressed during the treatment without antithyroid treatment. The patient has been symptom-free for 6 months.

Abscess↗

PubMed1991

Recombinant human interferon-alpha in the treatment of angioimmunoblastic lymphadenopathy: results in 12 patients.

Peripheral T-cell lymphomas of the angioimmunoblastic lymphadenopathy (AILD) type roughly correspond to lymphogranulomatosis X (LgX). They are currently treated with prednisone, either as a single treatment or with combination chemotherapy. However, both approaches are associated with high risks in this usually elderly patient population (median age 64 years). While looking for therapeutic alternatives to avoid these problems, the efficacy of low dose recombinant interferon-alpha 2a was examined. Patients received 3 x 10(6) IU daily as a subcutaneous (s.c.) injection. Those who achieved a complete remission continued with a maintenance treatment of 3 x 10(6) IU s.c. three times per week. A total of 14 patients received interferon. Twelve were evaluable for response. Six received interferon as primary and six as secondary treatment after the failure of previous treatment with prednisone or chemotherapy. Complete remissions were achieved in four, partial remissions in another four of 12 patients, whereas in the remaining four patients no change or progressive disease was observed. The median remission duration was 3.5 months; the longest durations of complete remissions were 6+ and 7 months. It is concluded that low dose interferon-alpha is an effective and well tolerated drug in T-cell lymphomas of the AILD (LgX) type. It is useful for salvage treatment in patients with contraindications or refractory to combination chemotherapy. It may be useful in adjuvant or maintenance treatment.

Aged↗

PubMed1990

Childhood obsessive-compulsive disorder: a prospective follow-up study.

Twenty-five of 27 patients (93%) who had participated in a study of severe primary obsessive-compulsive disorder with onset in childhood or adolescence, were seen 2-7 yrs after initial examination (mean, 4.4 yrs). They were compared to a group of normal controls matched for age, sex and IQ and followed up for the same period. Continued psychopathology was striking for the patients, with only seven (28%), three males and four females, receiving no psychiatric diagnosis at follow-up. Seventeen subjects (68%) still had obsessive-compulsive disorder, 12 patients (48%) had another psychiatric disorder, most commonly anxiety and/or depression; neither initial response to clomipramine or any other baseline variable predicted outcome.

Adolescent↗

PubMed1989

Clinical, psychophysiological, and neurological characteristics of volunteers with impaired smooth pursuit eye movements.

Two hundred eighty-five volunteers from a community college were screened on campus for accuracy of their smooth pursuit eye movements (SPEM) by electrooculograph (EOG). Those volunteers with the least and the most accurate SPEM were recalled to the laboratory for a comprehensive evaluation of clinical and demographic characteristics, family history, neurological status, and psychophysiological and biological measures, including SPEM [repeat EOG test and infrared (IR) test], an electroencephalogram, auditory and visual evoked potentials, reaction time (RT), the continuous performance task (CPT), platelet monoamine oxidase (MAO), plasma amine oxidase, and dopamine-beta-hydroxylase (DBH). Low-accuracy SPEM was associated with social isolation, inadequate rapport, eccentricity, and a variety of related schizotypal or schizophrenia-like characteristics, but not with generalized psychopathology or other demographic/medical/clinical history variables. Low-accuracy SPEM also was associated with neurological and psychophysiological abnormalities frequently observed in schizophrenic patients. These results suggest that impaired SPEM may reflect an underlying central nervous system dysfunction that is specifically associated with clinical and biological characteristics related to schizophrenia, even in the absence of overt schizophrenia.

Adult↗

PubMed1984

Computerized tomography and neuropsychological test measures in adolescents with obsessive-compulsive disorder.

The authors administered CAT scans and neuropsychological tests to 16 adolescents with obsessive-compulsive disorder (mean age +/- SD = 13.7 +/- 1.6 years) and 16 matched controls. The patients had a mean ventricular-brain ratio (VBR) significantly higher than the controls' and showed spatial-perceptual deficits similar to those found in patients with frontal lobe lesions. Memory, reaction time, and decision time did not differ significantly from controls'. Neurodevelopmental examination of seven patients yielded a high frequency of age-inappropriate synkinesias and left hemibody signs. These results suggest CNS dysfunctioning in children with obsessive-compulsive disorder, with possible right cerebral involvement. However, the patients' neuropsychological test deficits and VBRs were not correlated.

Adolescent↗

PubMed1981

Behavioral and autonomic effects of caffeine in normal boys.

Following a 1-week baseline, 19 normal boys (mean age 9.8 +1.8 years) ingested either caffeine (5 mg/kg) or placebo twice a day for a 2-week period per condition in a double-blind crossover study (total study duration of 5 weeks) to study the behavioral, autonomic and side effects of caffeine. Mothers of the whole sample and children who were low caffeine users could distinguish between drug conditions by side effects. Caffeine increased autonomic reactivity of low users only. Behavioral and autonomic results were ambiguous for high users indicating possible caffeine withdrawal symptoms. While 'caffeinism' may occur in children, either self-selection and/or tolerance may prevent its occurrence in naturally selected diets.

Arousal↗