Failure of B-cold lymphocytotoxins to enhance cadaveric renal allograft survival

In a three-year period between January 1980 and December 1982, 242 consecutive cadaver transplant recipients in one center were tested before transplantation by cytotoxicity against a random panel of T and B lymphocytes at 5 degrees C and 37 degrees C incubation. They were also tested for HLA-A, B, and DR antigens. Kidney transplants were carried out with the primary objective of achieving a two-DR match. Kidney transplants were carried out only in the absence of T-warm positive cross-matches. All patients were followed for a minimum period of one year after transplant. There have been no exclusions, and all causes of failure, including death, have been counted as graft losses. Patients were stratified according to HLA-A, B, and DR matches and were also divided into high-antibody and low-antibody groups. The recipients with no antibodies had the best one-year graft survival (66%). Recipients with B-cold antibodies did not have enhanced one-year graft survival (51%). Recipients with B-warm antibodies did indifferently (56%). The worst results were seen in recipients who had pretransplant T-warm antibodies (42%) though the number of patients in this group was small.     

Serum glycoproteins and prognosis in cancer of the head and neck

Alpha 1 acid glycoprotein, alpha 1 antitrypsin, haptoglobin, alpha 2 HS glycoprotein and prealbumin were studied in 44 patients with cancer of the head and neck and in a control group. The three primary glycoproteins were considerably elevated in the patients, particularly in stage IV. In the group of patients who died before 30 months after treatment the haptoglobin was significantly elevated compared to those who survived beyond this point. Only values for the alpha 1 acid glycoprotein greater than 150 mg/dl were a prognostic factor of similar precision to that of stage IV. This correlation could not be shown for the other glycoproteins.     

Dementia as a window to the neurology of art

Art is an expression of neurological function and how it organizes and interprets perception. Recent reports of changes in art performance among patients with frontotemporal dementia have provided an unexpected window to the neurology of art. They confirm that visual art is predominantly in the right hemisphere and suggest a neuroanatomical schema for artistic creativity. The right parietal region is critical for the visuospatial prerequisites of art, and the right temporal lobe integrates and interprets these percepts. The right temporal lobe appears necessary for extracting and exaggerating the essential features of an artistic composition. In contrast, the left parietal region and the left temporal lobe have inhibitory effects on artistic expression through attention to visuospatial detail and semantic labeling, respectively. Frontal-executive functions are also required for artistic expression, particularly right dorsolateral frontal initiation of a network for novelty-seeking behavior. Further study of art in dementia can profitably evaluate this proposed schema for the mechanisms of art in the brain.     

Plasma membrane stress failure in ventilator-injured lungs. A hypothesis about osmoregulation and the pharmacologic protection of the lungs against deformation injury

Cell injury and repair are invariable consequences of mechanical ventilation with large tidal volumes. Rate and amplitude of deforming stress affect numerous cell metabolic functions including host defense and wound repair. Recently, we have focused on the role of plasma membrane stress failure as a trigger for a pro-inflammatory response in mechanically ventilated lungs. We have developed both cell- and organ-based models to study this problem. Alveolar epithelial cells that are exposed to deforming stresses seek to maintain sublytic plasma membrane tension and may activate mechanisms of cell surface area regulation to control membrane tension. Interventions which either increase the amount of excess plasma membrane or enhance lipid trafficking should be cytoprotective against deformation induced injury. Osmotic manipulation may be one such intervention. Preconditioning the lungs with anisosmotic solutions may allow the cells to recruit excess plasma membrane and thus be more resistant to ventilator-induced lung injury.     

Validation of HPLC and UV spectrophotometric methods for the determination of meropenem in pharmaceutical dosage form

A high-performance liquid chromatographic method and a UV spectrophotometric method for the quantitative determination of meropenem, a highly active carbapenem antibiotic, in powder for injection were developed in present work. The parameters linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. Chromatography was carried out by reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm. The samples were prepared in water and the stability of meropenem in aqueous solution at 4 and 25 °C was studied. The results were satisfactory with good stability after 24 h at 4 °C. Statistical analysis by Student's t-test showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and can be used for the reliable quantitation of meropenem in pharmaceutical dosage form.     

Income,education, and blood pressure in adults in Jamaica,a middle-income developing country

BACKGROUND: At present, little is known about how socioeconomic status (SES) is related to blood pressure (BP) and hypertension in developing countries. This cross-sectional study examined associations between SES and BP in 2082 adults from a peri-urban area of Jamaica, a middle-income developing country. METHODS: Hypertension (systolic BP >/=140 mmHg, diastolic BP >/=90 mmHg or current hypertensive medication use) was estimated based on self-reported medication use and the mean of the second and third of three manual BP measurements. Income and education were self-reported. Linear or logistic regressions were used to estimate multivariate associations between BP or hypertension and SES. RESULTS: Hypertension prevalence was 20% in men and 28% in women. In both men and women, the income distributions of BP and hypertension were non-linear, indicating elevated levels in low as well as in high-income groups. In contrast to the negative relationships typical for industrialized countries, multivariate-adjusted BP and hypertension were highest in the wealthiest women. In men with some high school education, income was positively associated with BP, while there were negative associations in men with lesser education. Unlike women, mean BP were highest in poor men with limited education. Low SES men were also least likely to receive diagnosis and treatment. CONCLUSIONS: Socioeconomic status is related to BP and hypertension in Jamaica, although relationships are non-linear. Behavioural and environmental factors that explain elevated BP among both low and high SES adults in developing countries must be identified to develop effective prevention strategies.     

Factors that affect the quality of cytologic cervical cancer screening along the Mexico-United States border

OBJECTIVE: The purpose of this study was to identify the factors that affect the quality of cytologic cervical cancer screening conducted in public sector clinics in Sonora, Mexico. STUDY DESIGN: We assessed the quality of cervical cytology before and after a 2-hour training session and the implementation of cervical spatulas and endocervical brushes. Additionally, we conducted a cross-sectional study of reproductive aged women who attended public clinics in paired border communities in Sonora and Arizona. Cervical cytologic specimens (n=2436) were collected and compared for adequacy and cytologic diagnosis and for the prevalence of human papillomavirus infection. RESULTS: The training intervention achieved significantly improved the rates of satisfactory but limited smears and unsatisfactory smears. The cross-sectional study revealed comparable quality indicators for cytologic specimens that were collected in Sonora and Arizona clinics. CONCLUSION: A high-quality cytology-based cervical cancer screening program is possible in public sector clinics in Sonora, with indicators similar to those achieved in comparable Arizona clinics.     

Alternative splicing disrupts a nuclear localization signal in spleen tyrosine kinase that is required for invasion suppression in breast cancer

Spleen tyrosine kinase (Syk) is a candidate tumor (metastasis) suppressor that is highly expressed in mammary epithelial cells. Loss of Syk expression through promoter hypermethylation is associated with increased invasiveness in a subset of breast cancer. Here, we show that in addition to full-length Syk [Syk(L)], an alternatively spliced variant, Syk(S), is frequently expressed in breast cancer cells. Syk(S) is identical to Syk(L), except that it lacks 23 amino acid residues (deletion) within the interdomain B (IDB) of Syk. We also show that the aberrant expression of Syk(S) occurs frequently in primary breast tumors but never in matched normal mammary tissues, suggesting a contribution of Syk(S) to mammary tumor progression. Expression of Syk(L) suppressed breast cancer cell invasiveness. In contrast, Syk(S) expression did not affect the cell invasion potential. This differential phenotypic response is accompanied by their different subcellular localization. Immunocytochemical studies and nuclear and cytoplasmic fractionation experiments indicated that Syk(L) could enter the nucleus, whereas Syk(S) was located exclusively in the cytoplasm. Five basic residues in deletion were found to be critical in determining Syk(L) nuclear transport and invasion suppression activity; mutations completely excluded Syk(L) from the nucleus and blocked Syk(L)-inducible invasion suppression. Moreover, IDB acted as an autonomous nuclear localization signal to facilitate nuclear transport of a heterologous protein. Thus, the IDB of Syk(L) contains a nuclear localization signal that is responsible for Syk(L) nuclear translocation. The correlation of the nuclear localization and invasion suppression function of Syk(L) indicated that nuclear Syk possesses biological activities associated with tumor suppression in mammary epithelial cells.