PubMed Health⌕ Search

Biomedical subjects

T Singer

Publications and source records attributed to T Singer.

At least 19 recordsLinked to original sources
PubMed2001

Robertson's Mutator transposons in A. thaliana are regulated by the chromatin-remodeling gene Decrease in DNA Methylation (DDM1).

Robertson's Mutator transposable elements in maize undergo cycles of activity and then inactivity that correlate with changes in cytosine methylation. Mutator-like elements are present in the Arabidopsis genome but are heavily methylated and inactive. These elements become demethylated and active in the chromatin-remodeling mutant ddm1 (Decrease in DNA Methylation), which leads to loss of heterochromatic DNA methylation. Thus, DNA transposons in plants appear to be regulated by chromatin remodeling. In inbred ddm1 strains, transposed elements may account, in part, for mutant phenotypes unlinked to ddm1. Gene silencing and paramutation are also regulated by DDM1, providing support for the proposition that epigenetic silencing is related to transposon regulation.

Amino Acid Sequence↗
PubMed2001

[Innovative cell culture methods in drug development].

The animal studies necessary for drug registration are time-consuming, costly, and often stressful for the animals. Toxicological screening of drug candidates early in development with in vitro cell culture systems is therefore of relevance. In contrast to animal studies, in vitro cell culture methods are characterized by a low compound requirement and a short duration. Additionally it is possible to include mechanistic studies or to test for toxicity specific to humans. Therefore, early toxicological screening can provide a useful support for selecting the most promising drug candidate. Primary hepatocytes can be used to measure the cytotoxicity of a test compound. These results can be used to estimate general toxicity. Measuring endpoints like apoptosis, redox status, or gene expression profiles can help to answer mechanistic questions. The use of primary human hepatocytes provides early predictivity for hepatotoxicity specific to humans. Since teratogenic findings in animal studies often lead to abandonment of development, it is reasonable to use an in vitro embryotoxicity assay for early determination of the teratogenic potential of a compound, e.g. the embryonic stem cell test (EST) which was recently developed by ZEBET. In the EST embryonic stem cells are investigated for their preserved capability to differentiate into cardiomyocytes following drug exposure. In comparison cytotoxicity of the test substance is analyzed in embryonic stem cells and in differentiated fibroblast cells. In a validation study initiated by ECVAM the EST shows a high correlation with in vivo data.

Animal Testing Alternatives↗
PubMed2000

Comparison of clinical pathology parameters with two different blood sampling techniques in rats: retrobulbar plexus versus sublingual vein.

Blood samples were taken from the retrobulbar venous plexus or the sublingual vein of male HamIbm:Wist rats to compare clinical pathology parameters between the two sampling techniques. By analogy with a pharmacokinetic study, blood was sampled six times during one day from unfasted animals. After 3 weeks of recovery, blood was taken from fasted animals on a single occasion. In addition, prolactin and corticosterone levels were determined to compare stress-related effects between the two sampling methods. Body weight development and food consumption were similar after single as well as after repeated blood sampling for the two blood sampling techniques. Haemotological evaluation showed a gradual decrease in erythrocyte count, haemoglobin concentration and haematocrit after repeated blood sampling. Repeated withdrawal of blood samples over 24 h corresponding to approximately 22% of the total blood volume resulted in a decrease in red blood cell parameters by up to 30%. The withdrawal of approximately 10% of the total blood volume was associated with a decrease in these parameters by up to 10% and should not be exceeded for animal welfare reasons and to allow a reliable evaluation of data in a study. Repeated blood sampling was associated with an initial decrease in the number of white blood cells, mainly due to a reduction in lymphocytes; white blood cell counts were slightly increased one day after. The decrease in lymphocytes and the increase in neutrophils after repeated sampling were generally slightly more pronounced in the blood from the retrobulbar plexus than from the sublingual vein. Comparison of serum clinical chemistry data showed significantly higher activities of creatine kinase and aspartate aminotransferase in samples from the retrobulbar plexus. These findings suggest a higher degree of tissue damage with blood sampling from the retrobulbar plexus than from the sublingual vein. Despite a large inter-individual variability, higher mean values of prolactin on each occasion and corticosterone after a single sample in fasted animals indicate a higher stress associated with blood sampling from the retrobulbar plexus.

Amylases↗
PubMed1998

Effect of soluble complement receptor type 1 on reperfusion edema and neutrophil migration after lung allotransplantation in swine.

OBJECTIVE: Soluble complement receptor type 1 inhibits complement activation by blocking C3 and C5 convertases of the classical and alternative pathways. We evaluated the effect of soluble complement receptor type 1 on lung allograft reperfusion injury. METHODS: Left lung transplantation was performed in 13 weight-matched pigs (25 to 31 kg) after prolonged preservation (20 hours at 1 degree C). One hour after reperfusion the recipient contralateral right lung was excluded to assess graft function only. Complement activity and C3a levels were measured after reperfusion and at the end of the assessment. Extravascular lung water index, intrathoracic blood volume, and cardiac output were assessed during a 5-hour observation period. Gas exchange and hemodynamics were monitored. At the end of the 5-hour assessment period, myeloperoxidase assay and bronchoalveolar lavage were performed to assess neutrophil migration, and C5b-9 (membrane attack complex) deposits in the allograft were detected by immunohistochemistry. Two groups were studied. In group II (n = 6) recipient animals were treated with soluble complement receptor type 1 (15 mg/kg) 15 minutes before reperfusion. Group I (n = 7) served as the control group. RESULTS: Serum complement activity was completely inhibited in group II. In contrast to group I, C5b-9 complexes were not detected in group II allograft tissue samples. C3a was reduced to normal levels in group II (p = 0.00005). Extravascular lung water index was higher in group I animals throughout the assessment period (p = 0.035). No significant difference in allograft myeloperoxidase activity (p = 0.10) and polymorphonuclear leukocyte count of the bronchoalveolar lavage fluid (p = 0.057) was detected. CONCLUSION: Inhibition of the complement system by soluble complement receptor type 1 blocks local complement activation in the allograft and reduces posttransplantation reperfusion edema but does not improve hemodynamic parameters.

Animals↗
PubMed1998

Effect of a short period of warm ischemia after cold preservation on reperfusion injury in lung allotransplantation.

OBJECTIVE: A short period of warm ischemia during lung allograft implantation is inevitable. We studied the effect of 2 h of warm ischemia before implantation after 18 h of cold preservation on reperfusion edema and pulmonary hemodynamics in a large animal model. METHODS: Left lung transplantation was performed in ten weight-matched pigs (25-31 kg). Donor lungs were flushed with 1.5 l cold (1 degree C) LPD solution and preserved for 20 h. In Group I (n = 5) the grafts were preserved for 20 h at 1 degree C and topically cooled with ice slush during implantation until reperfusion. In Group II (n = 5) lungs were stored at 1 degree C for 18 h followed by 2 h preservation at room temperature (20 degrees C). Topical cooling was not used during implantation. At 1 h after reperfusion the recipient contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), intrathoracic blood volume (ITBV), mean pulmonary artery pressure (PAP) and cardiac output (CO) were assessed during a 4 h observation period. Quantitative myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substance (TBARS) levels as an indicator for lipid peroxidation were determined in allograft tissue samples taken 5 h after reperfusion. RESULTS: In Group II a tendency to improved pulmonary vascular resistance and cardiac output was noted. Surprisingly, lung edema, assessed by EVLWI, did not increase in animals with warm ischemia. Even a tendency to a reduced EVLWI was noted. However, differences between groups did not reach statistical significance. Gas exchange did not differ statistically significant between groups. CONCLUSION: Our results indicate that a short period of warm ischemia before reperfusion does not lead to increased pulmonary edema. In animals with a short period of warm ischemia before reperfusion, even a tendency to reduced posttransplant lung reperfusion injury was noted. In this model, topical graft cooling during lung implantation did not improve posttransplant graft function.

Animals↗
PubMed1998

Three new dominant C1 suppressor alleles in Zea mays.

Three new dominant suppressor mutations of the C1 transcription regulator gene in maize--C1-I delta 1, C1-I delta 2 and C1-I delta 3--are described that suppress anthocyanin colouration in kernels similar to the function of the C1-I standard inhibitor. The C1-I delta mutations were induced by imprecise excision of an En/Spm transposon in the third exon of the C1 gene. These transposon footprints cause a frameshift in the C1 open reading frame that leads to truncated proteins due to an early stop codon 30 amino acids upstream of the wild-type C1 protein. Therefore, the C1-I delta gene products lack the carboxy-terminal transcriptional activation domain of C1. The C1-I standard allele also lacks this domain and in addition differs in 17 amino acids from the wild-type C1 allele. The new C1-I delta alleles provide evidence that deletion of the carboxy-terminal activation domain alone is sufficient to generate a dominant suppressive effect on the function of wild-type C1.

Alleles↗
PubMed1997

Haemodynamic effects of pneumoperitoneum in elderly patients with an increased cardiac risk.

We studied the haemodynamic changes induced by pneumoperitoneum (PP) in elderly patients with increased cardiac risk (ASA class III; n = 10; age 72.3 +/- 8.8 years, mean +/- SD, P < 0.05; group 2) and compared the results with patients at normal risk (ASA class I, II; n = 12; age 55.6 +/- 11.8 years; group 1). Thermodilution measurements were performed after induction of general anaesthesia (T1), after onset of PP (T2, intraabdominal pressure 14 mmHg) and after additional 15 degrees head-up tilt (T3). In both groups PP, as compared with T1, induced a significant increase in mean arterial pressure (MAP, mmHg, group 1: 77 +/- 14 to 96 +/- 18, P < 0.05/group 2: 75 +/- 10 to 102 +/- 18, P < 0.01), mean pulmonary artery pressure (MPAP, mmHg: 15 +/- 5 to 22 +/- 4, P < 0.01/18 +/- 3 to 25 +/- 5, P < 0.01), central venous pressure (CVP, mmHg: 7 +/- 2 to 15 +/- 3, P < 0.01/7 +/- 2 to 12 +/- 2, P < 0.01), pulmonary capillary wedge pressure (PCWP, mmHg: 9 +/- 4 to 16.3, P < 0.01/8 +/- 2 to 15 +/- 6, P < 0.01) and in systemic vascular resistance (SVR, dynes s cm-5: 1415 +/- 375 to 1873 +/- 412, P < 0.01/ 1502 +/- 360 to 2067 +/- 647, P < 0.01). Cardiac index (CI, L min-1 m-2: 2.3 +/- 0.3 to 1.9 +/- 0.3, P < 0.05/2.2 +/- 0.4 to 2.2 +/- 0.5 P = 0.76) and oxygen delivery index (DO2I, mL min-1 m-2: 388 +/- 54 to 324 +/- 61, P < 0.05/358 +/- 69 to 353 +/- 82, P = 0.77) decreased in group 1 but not in group 2. Heart rate, stroke Index, pulmonary vascular resistance, arteriovenous oxygen content difference and oxygen consumption index were unchanged. After head-up tilt MAP (mmHg, 92 +/- 15, P < 0.05/ 101 +/- 17, P < 0.01), MPAP (mmHg, 20 +/- 3, P < 0.01/22 +/- 4, P < 0.05), CVP (mmHg, 12 +/- 2, P < 0.01/10 +/- 2, P < 0.01) and PCWP (mmHg, 12 +/- 3, P < 0.05/12 +/- 5, P < 0.05) remained elevated compared with T1 in both groups, SVR (dynes s cm-5, 1575 +/- 372, P = 0.13/1793 +/- 528, P < 0.01) in group 2 only. No complications occurred. The results indicate that PP is associated with significant but relatively benign haemodynamic changes. Anaesthesia for laparoscopic cholecystectomy may be performed safely also in elderly ASA class III patients with increased cardiac risk. An adequate haemodynamic monitoring is recommended.

Aged↗
PubMed1997

Accuracy and clinical performance of a continuous intra-arterial blood-gas monitoring system during thoracoscopic surgery.

Accuracy and performance of the only currently available intra-arterial blood-gas monitoring system (Paratrend 7, PT7) were assessed in 23 patients during thoracoscopic surgery using one-lung ventilation. Over a wide range of values for arterial PO2 (6.1-61.1 kPa), PCO2 (4.1-9.5 kPa) and pH (7.19-7.50), 138 arterial blood-gas values obtained by PT7 were compared with corresponding in vitro laboratory blood-gas measurements. We found good clinical performance with the PT7 and good agreement between PT7 values and in vitro measurements for arterial PO2 (bias (1.96 SD) = 0.38 (9.52) kPa), PCO2 (0.31 (0.76) kPa) and pH (-0.017 (0.065)). Also, the bias for sequential changes between two, consecutive times was not significantly different from the ideal value of 0. We conclude that the PT7 is helpful in monitoring patients during thoracoscopy.

Adult↗
PubMed1996

A descriptive study of emergency admissions to Farview State Hospital.

The prison population in the United States has grown steadily in the past 15 years. Farview State Hospital in Waymart, Pennsylvania annually provides service to approximately 350 to 400 inmates. This is less than 10 percent of the potential need for psychiatric treatment for the state. Emergency psychiatric admissions are a burden on the mental health system, as these inmates are given priority. This descriptive study identified profiles of emergency admissions for the period of July 1, 1990 to June 30, 1993. During this time, 86 emergency admissions occurred. Differences between state correctional and local county prison inmate admissions are described. The short stays of emergency admissions indicate that Farview is achieving its goal of stabilization of the mentally disordered inmate for return to the correctional facility. More research needs to be done to compare emergency and regular admissions for both diagnosis and length of stay.

Adult↗
PubMed1996

Finding our way.

Explore the source record for details and available documents.

Dentistry↗
PubMed1995

Chronic alcohol feeding inhibits atherogenesis in C57BL/6 hyperlipidemic mice.

Although there is abundant clinical evidence that the consumption of alcohol (ethanol) in moderate amounts has a protective effect on coronary artery disease, the mechanism of this effect is not understood. The prevailing theory supported by a limited number of clinical and experimental animal studies indicates that the ability of alcohol to elevate serum high-density lipoprotein cholesterol levels is an important mechanism. Although there have been a large number of studies on the effects of alcohol on serum lipoprotein and apolipoproteins on coronary artery disease, there have been very few that have, at the same time, looked directly and systematically at its effects on the histopathological development of atherosclerotic lesions. In the following studies we employed the hyperlipidemic C57BL/6 female mouse model and formulated an all liquid high fat atherogenic diet to provide the mice with the 3% or 6% alcohol. After 22 weeks on this diet, alcohol markedly inhibited the development of fatty streak atherosclerotic lesions in a dose-dependent fashion. Surprisingly, there was a dose-dependent decrease in plasma high-density lipoprotein cholesterol values, which suggests that high-density lipoprotein alterations play little or no role in the amelioration of atherosclerosis in this model.

Animals↗
PubMed1994

An insertion element of the extremely thermophilic archaeon Sulfolobus solfataricus transposes into the endogenous beta-galactosidase gene.

Three phenotypically stable mutants of the extremely thermophilic archaeon Sulfolobus solfataricus have been isolated by screening for beta-galactosidase negative colonies on plates with X-Gal (5-bromo-4-chloro-3-indolyl-beta-D- galactopyranoside). From one of these mutants an insertion element, designated ISC1217, was isolated and characterized. Sequence analysis of ISC1217 and of the regions adjacent to the insertion site in the beta-galactosidase gene revealed features typical of a transposable element: ISC1217 contained terminal inverted repeats and was flanked by a direct repeat of 6 bp. The 1147 bp sequence contained an open reading frame encoding a putative protein of 354 amino acid residues and, overlapping this, two smaller open reading frames on the opposite strand. There were approximately 8 copies of the insertion element in the S. solfataricus genome. ISC1217 did not cross-hybridize with DNA of other Sulfolobus species. All three independently isolated beta-galactosidase mutants of S. solfataricus arose by transposition of ISC1217 or a related element.

Amino Acid Sequence↗
PubMed1994

Is dysthymia a different disorder in the elderly?

OBJECTIVE: This study evaluated elderly dysthymic patients in a late life depression clinic and compared their clinical features to previous findings in young adult dysthymic patients. METHOD: Of 224 consecutive elderly outpatients, 40 (17.9%) met criteria for dysthymic disorder. A semistructured interview was used to obtain history, the Structured Clinical Interview for DSM-III-R--Patient Version and the Structured Clinical Interview for DSM-III-R Personality Disorders were used to make DSM-III-R diagnoses, and standard rating instruments for depression were administered. RESULTS: The gender distribution was equal and major stressors were common. The mean age at onset of dysthymia was 55.2 years (SD = 15.4), with an average illness duration of 12.5 years (SD = 14.2). Early onset (before 21 years of age) and secondary dysthymia were rare. A history of major depression earlier during the course of dysthymic illness, comorbid anxiety disorders, and personality disorders were relatively uncommon. Cross-sectionally, cognitive and functional symptoms were more prominent than vegetative symptoms. CONCLUSIONS: Dysthymia is not uncommon among depressed elderly outpatients who present for treatment. Elderly dysthymic patients differ from young adult dysthymic patients, who are mostly female with an early onset and who frequently have comorbid axis I and axis II disorders. Most elderly dysthymic patients do not appear to be young dysthymic patients who simply grew older, and the DSM-III-R subtyping of dysthymia into early/late onset and primary/secondary may not apply to the elderly. Further clinical studies of "pure" dysthymic disorder appear feasible in the elderly, and these are clearly needed.

Adult↗