Comparative spectral, electrophoretic and isoelectric properties of trematode haemoglobins

We have studied the role of DNA polymerase III, encoded in S. cerevisiae by the CDC2 gene, in the repair of yeast nuclear DNA. It was found that the repair of MMS-induced single-strand breaks is defective in the DNA polymerase III temperature-sensitive mutant cdc2-1 at the restrictive temperature (37 degrees C), but is not affected at the permissive temperature (23 degrees C). Under conditions where only a small number of lesions was introduced into DNA (80% survival), the repair of MMS-induced damage could also be observed in the mutant at the restrictive temperature, although with low efficiency. When the quantity of lesions increased (50% survival or less), the repair of single-strand breaks was blocked. At the same time we observed a high rate of reversion in the meth, his and trp loci of the cdc2-1 mutant under restrictive conditions. The results presented suggest that DNA polymerase III is involved in the repair of MMS-induced lesions in yeast DNA and that the cdc2-1 mutation affects the proofreading activity of this polymerase.     

Quantitative brain SPECT in Alzheimer's disease and normal aging

To improve the diagnostic utility of brain single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD), we have developed and evaluated an objective method of differentiating patients and healthy elderly controls using a quantitative image analysis protocol. HMPAO-SPECT image datasets from 29 patients with probable AD and 78 age-matched controls were registered to a common anatomic frame of reference. Activity levels within 120 standardized cortical volumes were determined by an automated procedure. Subjects were classified into normal and AD groups by quadratic discriminant analysis using two features: global average activity level and average normalized activity levels within the two clusters of standardized volumes identified as most significantly different in AD by analysis of covariance. The classification used split-half replication to ensure valid results. Classification performance quantified by the area under a binormal ROC curve fitted to the data was 0.923 +/- 0.036; at a threshold likelihood ratio of 1, the sample sensitivity was 91% and specificity was 86%. We conclude that quantitative SPECT accurately distinguishes AD patients from elderly controls.     

Pressure ulcers in community-resident persons with spinal cord injury: prevalence and risk factors

The prevalence and correlates of pressure ulcers in terms of their number, severity, and anatomical location were studied in a community-based sample of 100 men and 40 women with spinal cord injury. Thirty-three percent (n = 46) presented with one or more ulcers of at least one stage I severity when visually examined. Twenty-one individuals had more than one ulcer, the maximum number of ulcers being seven. Of 87 ulcers for which severity ratings were available, 30 (34.5%) were stage I, 33 (37.9%) were stage II, and 24 (27.6%) were either stage III or IV. Individuals with an ulcer exhibited more paralysis and were more dependent on others in activities of daily living. A greater proportion of blacks had more severe ulcers (stages III and IV) than their white counterparts. Persons with more severe ulcers incurred their injury later in life, and had significantly lower mean scores on the Occupation and Mobility dimensions of the Craig Handicap Assessment and Reporting Technique. The findings suggest that factors governing initial development of a pressure ulcer differ in part from those responsible for an ulcer progressing in severity.     

8-(3-Chlorostyryl)caffeine (CSC) is a selective A2-adenosine antagonist in vitro and in vivo

An adenosine antagonist, 8-(3-chlorostyryl)caffeine (CSC), was shown previously to be 520-fold selective for A2a-adenosine receptors in radioligand binding assays in the rat brain. In reversing agonist effects on adenylate cyclase, CSC was 22-fold selective for A2a receptors in rat phenochromocytoma cells (Kb 60 nM) vs. A1 receptors in rat adipocytes (Kb 1.3 microM). Administered i.p. in NIH mice at a dose of 1 mg/kg, CSC shifted the curve for locomotor depression elicited by the A2a-selective agonist APEC to the right (ED50 value for APEC shifted from 20 micrograms/kg i.p. to 190 micrograms/kg). CSC had no effect on locomotor depression elicited by an ED50 dose of the A1-selective agonist CHA. CSC alone at a dose of 5 mg/kg stimulated locomotor activity by 22% over control values. Coadministration of CSC and the A1-selective antagonist CPX, both at non-stimulatory doses, increased activity by 37% (P < 0.001) over CSC alone, suggesting a behavioral synergism of A1- and A2-antagonist effects in the CNS.     

Factors associated with male workers' engagement in physical activity: white collar vs. blue collar workers

The purpose of this study was to identify factors associated with male workers' participation in different kinds of physical activity, noting differences between white collar and blue collar workers. This study examined the variables, perceived health status, self efficacy, perceived barriers, age, education, income, and job category (Pender, 1987) for their association with physical activity. Self efficacy and perceived health status were the cognitive-perceptual factors that predicted physical activity. Job category (e.g., blue collar vs. white collar) was found to be a highly significant predictor of physical activity. Comparing physical job requirements with the individual worker capacity can suggest to the occupational health nurse physical fitness programs that are most appropriate for individual workers.     

Procainamide: a perspective on its value and danger

Procainamide remains one of the most widely used antiarrhythmic agents in clinical practice. Currently, it is widely used alone or in combination with class I agents (eg, mexiletine or tocainide) to prevent recurrent ventricular tachycardia or symptomatic nonsustained ventricular tachycardia. Procainamide is also used for short-term treatment of ventricular tachycardia and a variety of supraventricular tachycardias, primarily atrial flutter and atrial fibrillation. Long-term procainamide therapy is limited by a number of systemic side effects, primarily lupus-like syndrome, gastrointestinal disturbances, and autoimmune blood dyscrasias. Procainamide levels can be useful in initial dose titrations; however, QRS and QT interval measurements help prevent drug toxicity. It is recommended that patients being started on antiarrhythmic therapy with procainamide be admitted to the hospital for monitoring to ensure that their QT interval is not excessively prolonged.     

Depressive symptomatology in persons with spinal cord injury who reside in the community

Depressive symptomatology was studied in a community-based sample of 100 men and 40 women with spinal cord injury. The mean for the Center for Epidemiologic Studies Depression Scale was higher than that reported previously for the general population, and the mean for women was higher than that for men. Findings from the Mobility dimension of the Craig Handicap Assessment and Reporting Technique (CHART) suggested that differences between men and women in degree of mobility within home and community partly mediate the gender difference in depressive symptomatology. Other CHART dimensions, Social Integration and Occupation, were inversely related with depression scores, although these dimensions did not differentiate men and women. A statistically significant relationship was not obtained between depression and disability, assessed by a self-report version of the Functional Independence Measure, or between depression and impairment, reflected by the ASIA Total Motor Index Score. Depression was not related with the presence of either pressure ulcers or presumptive evidence of urinary tract infection.     

Growth arrest-specific gene 6 (Gas6)/adhesion related kinase (Ark) signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt

We identified Ark, the mouse homolog of the receptor tyrosine kinase Axl (Ufo, Tyro7), in a screen for novel factors involved in GnRH neuronal migration by using differential-display PCR on cell lines derived at two windows during GnRH neuronal development. Ark is expressed in Gn10 GnRH cells, developed from a tumor in the olfactory area when GnRH neurons are migrating, but not in GT1-7 cells, derived from a tumor in the forebrain when GnRH neurons are postmigratory. Since Ark (Ax1) signaling protects from programmed cell death in fibroblasts, we hypothesized that it may play an antiapoptotic role in GnRH neurons. Gn10 (Ark positive) GnRH cells were more resistant to serum withdrawal-induced apoptosis than GT1-7 (Ark negative) cells, and this effect was augmented with the addition of Gas6, the Ark (Ax1) ligand. Gas6/Ark stimulated the extracellular signal-regulated kinase, ERK, and the serine-threonine kinase, Akt, a downstream component of the phosphoinositide 3-kinase (PI3-K) pathway. To determine whether ERK or Akt activation is required for the antiapoptotic effects of Gas6/Ark in GnRH neurons, cells were serum starved in the absence or presence of Gas6, with or without inhibitors of ERK and PI3-K signaling cascades. Gas6 rescued Gn10 cells from apoptosis, and this effect was blocked by coincubation of the cells with the mitogen-activated protein/ERK kinase (MEK) inhibitor, PD98059, or wortmannin (but not rapamycin). These data support an important role for Gas6/Ark signaling via the ERK and PI3-K (via Akt) pathways in the protection of GnRH neurons from programmed cell death across neuronal migration.     

Apoptotic process in the monkey small intestinal epithelium: 2. Possible role of oxidative stress

Recent findings suggest that intracellular oxidants are involved in the induction of apoptosis and this type of cell death can be inhibited by various antioxidants. In our accompanying paper, we have shown apoptosis in the villus tip cells of the monkey small intestinal epithelium. The aim of the present study was to evaluate the possible relationship between oxidative stress, antioxidant levels and the apoptotic process in the monkey small intestinal epithelium. Monkey small intestinal epithelial cells were isolated into different fractions consisting of villus, middle and crypt cells. Mitochondrial function was assessed by the reduction of the tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), with and without succinate. The extent of lipid peroxidation was assessed by measuring the formation of conjugated diene, depletion of polyunsaturated fatty acids and alpha-tocopherol. Level of antioxidant enzymes like, superoxide dismutase (SOD), catalase, glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase were also quantitated in various cell fractions. MTT reduction was significantly decreased in villus cells as compared to the cells from other fractions and this was evident even in presence of the respiratory substrate, succinate. Increased formation of conjugated diene and depletion of polyunsaturated fatty acids were seen in villus and crypt cells as compared to middle fraction cells. The alpha-tocopherol level was decreased in both villus and crypt cells as compared to cells from middle region. Significant decrease of SOD activity was seen in the villus tip cells and a slight decrease was seen in the crypt fractions. Glutathione dependent enzymes like GST, GPx and GSH reductase showed higher activity in the villus fractions. A similar observation was also seen in the catalase activity. This study has shown that although oxidative stress is seen in both villus and crypt cells, decreased mitochondrial function was seen in villus tip cells which may be responsible for apoptotic process in the intestinal epithelium.