Selective activation by bryostatin-1 demonstrates unique roles for PKC epsilon in neurite extension and tau phosphorylation

The purpose of this study was to contrast the discharge patterns of the same motor units during movements and during isometric contractions that were produced with comparable torque-time characteristics. Subjects performed elbow flexion and extension movements with predetermined acceleration characteristics. The average acceleration and deceleration profiles for the movements were reproduced in the isometric setting by presenting the kinematic profiles as templates for torque production. Trained subjects were able to match the first agonist (AG1) and antagonist (ANT) electromyographic (EMG) bursts, but tended to produce a smaller second agonist burst (AG2) in the isometric contraction. Twenty-five motor units from triceps brachii were studied. The same motor units (with one exception) were recruited and subsequently discharged in a similar fashion in both the isometric and movement tasks in the AG1 and ANT EMG bursts, with fewer motor unit discharges in the AG2 burst in the isometric contraction. The central control mechanisms appear to be the same for the acceleration phase of movement and isometric contraction, but differ during the deceleration phase.     

Red-green colour blindness in the Tormes-Alberche Valley (Avila-Central Spain)

A population from a Central Spanish region (Tormes-Alberche Valley) has been investigated for the presence of red-green colour vision defects. A sample of 998 subjects (469 male and 529 female) was analyzed. To identify colour vision defects, Ishihara test plates were used. The red-green colour blindness percentage obtained was 4.69 +/- 0.976% for males (2.13% protan and 2.56% deutan types) and none of the females tested were found to be colour blind. These results are within the variation range of Mediterranean populations and lower than the usual frequencies among non-Mediterranean European samples.     

Health status of the over 60 years of age population and its relationship with sociodemographic factors (ANCO Project)

OBJECTIVE: To describe the health status of a population over 60 years and to study their relationship with several socio-demographic variables. DESIGN: A cross-sectional study, population based. SETTINGS: A community. PARTICIPANTS: A randomized sample of 1,103 non institutionalized people over 60 years living in the city of Cordoba (Spain). MEASUREMENTS AND MAIN RESULTS: By mean of a personal interview at home we used the OARS-MFAQ-VE questionnaire. Low self-rated health was associated with the age, to be female sex, a low cultural background, and a low income. Only 5.2% of the study people do not suffered any illness and 56% state that their health problems are major problems for doing their current activities. 4.9% declared to have some degree of physical incapacity. 3.7% of elderly population has an important cognitive deficit. CONCLUSIONS: The majority of elderly people has good health. Age is related with a poor health. Women have more health problems than men.     

BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer

BACKGROUND: To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families. METHODS: Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations. RESULTS: BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian cancer in a family. CONCLUSIONS: Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative.     

A CONSTITUTIVE MODEL FOR ELASTIC-PLASTIC DEFORMATION UNDER CYCLIC MULTIAXIAL STRAINING

Abstract— The yield criterion is interpreted as defining the metric of the stress space. Hydrostatic stresses correspond to null geodesies. The plastic strain increment represents a normal projection of the increment undergone by a certain scalar function (hardening function) which depends only on the distance between stress points. This establishes a flow rule formally equivalent to the Prandtl-Reuss equations. Consideration of un-loading processes leads to the analysis of equivalent paths and to the definition of a generalized length or separation which provides a new representation of kinematic hardening.     

Chronic hypertrophic gastropathy in a child resembling adult Menetrier''s disease

N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an initial period of 8 weeks. No objective responses were noted. PALA and 5-FU is inactive against gastric adenocarcinoma at the doses and schedule used in this trial.     

Determination of organochlorine pesticide and polychlorinated biphenyl residues in fatty fish by tandem solid-phase extraction cleanup

A rapid, multiresidue solid-phase extraction (SPE) technique for determination of organochlorine pesticide and polychlorinated biphenyl (PCB) residues in nonfatty fish was modified for use with fatty fish. In the modified procedures, samples are extracted with acetonitrile, and the extract is cleaned up with both C18 and Florisil SPE columns. Residues are determined by gas chromatography with electron capture detection. The original method was modified for use with fatty fish by reducing the amount of tissue extracted and by using an improved Florisil SPE cleanup. Recovery data are presented for 24 fortified organochlorine pesticide residues (0.12 ppm) and 3 fortified PCB residues (0.80 ppm) from flounder, bluefish, and shad samples, which contained 0.8, 5.4, and 22.6% fat, respectively. For the 3 types of fish, recoveries of 23 of 24 fortified organochlorine pesticide residues ranged from 55 to 129%, and recoveries of 3 fortified PCB residues ranged from 55 to 104%. There were no significant differences in recovery based on fish species and/or fat content for the majority of residues studied. This SPE method and the official AOAC method yielded comparable results for fish containing incurred organochlorine residues.     

Biology of chronic radiation effect on tissues and wound healing

Radiation therapy exerts both acute and chronic effects on normal tissue included within treatment fields. The physics of radiation therapy and treatment techniques to minimize deleterious effects of radiation are presented. Management of radiation-damaged skin is discussed. Radiation effect on tissue, wound healing, and tumorigenesis also are reviewed.     

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.     

Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade

Developmental neurotoxicity caused by chlorpyrifos exposure is generally thought to target cholinesterase but chlorpyrifos may also act on cellular intermediates, such as adenylyl cyclase, that serve global functions in the coordination of cell development. In the current study, neonatal rats were exposed to apparently subtoxic doses of chlorpyrifos (no weight loss, no mortality) either on Postnatal Days 1-4 or on Postnatal Days 11-14, and the effects on components of the adenylyl cyclase cascade were evaluated in brain regions that are enriched (forebrain) or sparse (cerebellum) in cholinergic innervation, as well as in a nonneural tissue (heart). In all three, chlorpyrifos evoked deficits in multiple components of the adenylyl cyclase cascade: expression and activity of adenylyl cyclase itself, functioning of G-proteins that link neurotransmitter and hormone receptors to cyclase activity, and expression of neurotransmitter receptors that act through this cascade. Disruption of signaling function was not restricted to transduction of cholinergic signals but rather extended to adrenergic signals as well. In most cases, the adverse effects were not evident during the immediate period of chlorpyrifos administration, but appeared after a delay of several days. These results suggest that chlorpyrifos can affect cell development by altering the activity and reactivity of the adenylyl cyclase signaling cascade, a major control point for trophic regulation of cell differentiation. The effects are not restricted to cholinergic targets, nor even to the central nervous system. Hence, disruption of cell development by chlorpyrifos is likely to be more widespread than previously thought.