Gluthatione-S-transferase P1 polymorphism I105V in familial and sporadic prostate cancer

Several reports suggest that the glutathione-S-transferase (GST) family of enzymes is involved in a variety of cancers, due to their carcinogen-detoxification properties. A polymorphism in codon 105 of the pi variant (GSTP1 I105V), which affects the enzymatic activity of the enzyme, has been linked to the incidence of cancers from different organs. However, the published data in prostate cancer (PCa) is controversial. Some studies report an association with the GSTP1 I105V polymorphism and sporadic PCa, whereas other studies report no association. Recently, one study showed a positive correlation between the GSTP1 I105V polymorphism and familial PCa in a Japanese population. In the present study, we assessed the correlation of the GSTP1 I105V polymorphism with familial and sporadic PCa in an American population. We analyzed DNA samples from 438 patients with familial PCa, 499 patients with sporadic PCa, and 510 controls. We found no significant association between the GSTP1 I105V polymorphism and familial or sporadic PCa when compared to the control group [odds ratio (OR) =1.0 (0.74-1.37); P=0.58]. Moreover, no association was found after stratification for age of diagnosis, Gleason grade, or lymph node involvement [OR =0.84 (0.65-1.09), P=0.37]. These data indicate that there is no associated risk for sporadic or familial PCa in American families containing the GSTP1 I105V polymorphism.     

COMT and DRD3 polymorphisms, environmental exposures, and personality traits related to common mental disorders

In a community sample of 2,327 Caucasians, we tested the hypotheses that polymorphisms in the COMT and DRD3 genes are associated with personality traits conferring vulnerability to anxiety, depression, or alcohol misuse, or with current symptoms of these; and that the association is stronger in persons who also have been exposed to stressor experiences. To conserve resources and to allow replication, the genetic analysis was undertaken in two stages. For the COMT polymorphism, no statistically significant associations were found in the first sample of 862 persons. The remainder of the sample was therefore not analysed for that gene. For the DRD3 polymorphism, those in the first sample with at least one of the Ser(9) alleles had significantly higher scores in neuroticism (p=0.006) and behavioral inhibition (p=0.003). There was a trend, failing to meet the 1% significance criterion, for those with this genotype also to have higher depression and anxiety. The groups did not differ in alcohol use. In persons with the Ser(9) allele who were also exposed to stressors, there was a higher level of depression at the 5% level; and the depression level was higher in homozygotes. But when the remainder of the sample (1,465) was analysed, none of the associations reached statistical significance. We conclude that neither the COMT nor DRD3 polymorphisms are associated with anxiety, depression, or alcohol abuse. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:102-107, 2000 Copyright 2000 Wiley-Liss, Inc.     

The synthesis of coliphage T1 DNA: Requirement for host dna genes involved in elongation

Available Escherichia coli mutants with temperature-sensitive mutations in genes essential for DNA replication have been used to investigate the host protein involvement in the DNA synthesis of bacteriophage T1. This study has shown that T1 is independent of the E. coli initiation gene products dnaA, dnaC, dnaI, dnaP, and dnaT. The gene products of the polC, dnaG, and dnaZ loci, know to be involved in the elongation events of replication, are required for a productive T1 infection. T1 was found to be independent of the functioning of the dnaB gene product in the four dnaB mutants tested.     

Human skin fibroblast in vitro tetraploidy. Flow cytometric DNA assay used to confirm metaphase assay in patients with various colonic diseases

One hundred twenty-two patients with various colon pathologies (43 colorectal carcinoma patients exclusive of the known autosomal dominant colorectal cancer syndromes, 31 patients with solitary colorectal adenomas, 27 patients with ulcerative colitis, and 21 controls with no evidence of colorectal cancer) were investigated for in vitro tetraploidy in dermal fibroblasts cultures using a metaphase assay for determination of numerical chromosomal alterations. Later, stationary cultures of these skin fibroblasts were investigated with DNA flow cytometry. There was good correlation between the percentage of tetraploid metaphase cells and the percentage of nuclei with a flow cytometric DNA index of 2. Using a linear discrimination function to classify the flow cytometric data, the peak with DNA index of 2 was the most important parameter, supplemented by the region with DNA index greater than 2, whereas the region with DNA index between 1 and 2 probably represented a different subpopulation. We have thus demonstrated that only the region with a DNA index of 2 or greater is suitable in determining in vitro tetraploidy in stationary skin fibroblast cultures.     

Effects of digoxin in infants with congested circulatory state due to a ventricular septal defect

Digoxin alone was used to treat a congested circulatory state in 21 infants (mean age, 2.7 months; mean weight, 3.8 kg) with a ventricular septal defect. The dose was adjusted on the basis of pharmacokinetics to achieve a mean steady-state concentration of 1.6 +/- 0.3 ng of digoxin per milliliter of serum. The mean red-cell level of sodium-potassium ATPase fell from 23.1 +/- 7.0 to 12.6 +/- 5.2 nmol per milligram per minute with treatment. Only 6 of the 21 patients had an inotropic response, as reflected by echocardiographic measurements, but the drug was of clinical benefit to 12 infants (including these 6). These results show that not all infants with a congested circulatory state due to a ventricular septal defect benefit from digoxin therapy. Furthermore, in some subjects clinical improvement occurs in the absence of a measurable inotropic response.     

Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury

The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE66(4Glu), an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE66(4Glu). However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis.     

Belief in the harmfulness of antidepressants: results from a national survey of the Australian public

BACKGROUND: Surveys of the public in several countries have found that negative attitudes towards antidepressants are common. However, there has been little research into the factors associated with these attitudes. METHODS: A national survey of 999 Australian adults assessed beliefs about the helpfulness or harmfulness of antidepressants for a person with depression and suicidal thoughts. Associated factors investigated were as follows: sociodemographic characteristics, exposure to depression, ability to recognize depression, beliefs about other depression interventions, beliefs about long-term outcomes with and without treatment, beliefs about causes, and stigmatizing attitudes. RESULTS: Around a quarter of Australian adults believe that antidepressants would be harmful for a person who is depressed and suicidal. This group was less educated, had less exposure to depression, showed poorer recognition of depression, was less favorable about other standard interventions including psychological ones, was less pessimistic about the long-term outcome if the person did not have treatment, and was more likely to see depression as due to weakness and to be under the individual's control. LIMITATIONS: The survey did not directly ask about reasons for believing that antidepressants would be harmful. CONCLUSIONS: Belief in the harmfulness of antidepressants is associated with a general lack of exposure to depression, leading to an underestimation of its seriousness and of the necessity for intervention.     

Identification, isolation, and characterization of a species-specific 30-kDa antigen of Oesophagostomum dentatum

In the search for a serology tool for the diagnosis of nonpatent as well as patent infections with Oesophagostomum dentatum in pigs a water-soluble, unglycosilated antigen of about 30 kDa specific for the third-stage larvae of the parasite was purified by ion-exchange chromatography. In Western blots, the antigen was first detected by antibodies at day 7 postinfection. Cross-reactivity with O. quadrispinulatum, Ascaris suum, or Trichuris suis was not detected. It is suggested that this protein is a suitable tool for the species-specific serodiagnosis of O. dentatum infection in pigs. Received: 15 June 1998 / Accepted: 28 September 1998     

Uptake of dehydroascorbic acid and ascorbic acid to isolated nerve terminals and secretory granules from ox neurohypophyses

When uptake of L-[14C]ascorbic acid ([14C]AA) to various organs in guinea-pigs was studied after intracardiac injection, the adenohypophysis, pars intermedia, and the neurohypophysis had an uptake per milligramme protein which was about half of the uptake to the adrenals. Adrenal uptake was 20 +/- 2.8 pmol mg-1 protein microCi-1 injected. The uptake to the different parts of the hypophysis was considerably higher than the uptake to pancreas, liver, kidney, spleen and other organs. When isolated nerve endings (neurosecretosomes) from ox neurohypophyses were incubated with a medium containing labelled dehydroascorbic acid ([14C]DHA), the uptake was much slower than when the medium contained labelled ascorbic acid. The uptake of [14C]DHA showed a linear dependence on concentration, and was not influenced by addition of Mg2+ and ATP. Addition of Mg2+ + ATP, omission of Ca2+ and Mg2+ or exchange of Na+ in the medium with K+ had no effect on the uptake of ascorbic acid. When isolated secretory granules from ox neurohypophyses were incubated with a medium containing [14C]DHA, uptake was considerably faster than the uptake when they were incubated in a medium containing [14C]AA. The uptake of dehydroascorbic acid was linear with the concentration in the medium and was not changed by addition of Mg2+ ATP. Addition of 10 mM NH4Cl or exchange of 120 mM K+ in the incubation medium with Na+ did not change the uptake of dehydroascorbic acid. The contents of copper, zinc, iron and cobalt were determined in isolated nerve endings (A) and membranes (B) as well as in lysate (C) from isolated neurosecretory granules. The results (in nmol mg-1 protein) were for Cu: (A): 0.25 +/- 0.01 (SEM), (B): 0.67 +/- 0.16, (C): 0.22 +/- 0.06; for Zn: (A): 0.53 +/- 0.13, (B): 6.97 +/- 0.75, (C): 1.8 +/- 0.53; and for Fe: (A): 15.6 +/- 1.9, (B): 6.92 +/- 0.32, (C): 3.15 +/- 0.43. In all preparations the cobalt content was below the detection limit (less than 5 pmol mg-1 protein).     

Storage telemetry of radionuclide tracers by implantable thermoluminescent dosimeters

A storage telemetrical method using thermoluminescent (TL) dosimeters for long-term measurements of incorporated radioactive substances in unrestrained rats has been developed. The system has been used in combination with radiotelemetrical registration of the circadian temperature rhythm. By sequential replacement of double TL dosimeters (60 mg, CaSO4:Dy) through an implanted silicon tube, the concentration of different radionuclides can be determined over long periods. The persistence of the circadian temperature rhythm indicates that the animals were unaffected by the experimental conditions. The relative uncertainty of the dosimeter system and the temperature transmitter is approximately +/- 2% (SD) at 5 mR exposures and +/- 0.05 degrees C, respectively. The weight of the system in total is 5.7 g. Disappearance studies (36-48 h) have been performed with the beta-emitters, 32P nad 42K, in subcutaneous tissues and tumor tissue. This TL method permits the repetition of an experiment on the same rat several times, and thereby avoids errors due to biological variations between animals.