Epidemiology and cause of deaths among women in rural Bangladesh

A total of 542 women aged 15 to 44 years died during the 10-year period 1976 to 1985 in the control area of Matlab, an area with a population of 90,000, representative of many other rural areas of southern Bangladesh. The corresponding age-specific mortality rate was 290 per 100,000 women 15-44 years. These deaths have been analysed retrospectively, using information collected through the Demographic Surveillance System set up by the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) and verbal autopsies conducted in the homes. Of these deaths, 175 (32%) were due to infectious diseases, 163 (30%) to direct obstetric complications, 67 (12%) to injuries, and the remaining 26% to other causes. Cause-specific and proportionate mortality rates showed a positive association with age for deaths due to infectious diseases, non-infectious diseases and unspecified causes, and an inverse association with age for deaths due to injuries. These rates showed a peak in the intermediate age group 25 to 34 years for deaths due to direct obstetric causes. No consistent trends were visible when annual rates were studied over time. Prior to death, 42% of the women were attended by traditional practitioners, and 33% were not attended at all. Demographic impact is discussed, emphasizing the contribution of obstetric causes to overall mortality. Priorities for health policy implications are proposed, focusing upon a strong maternity care programme, and improved availability of female health personnel, in the context of the socio-cultural constraints imposed on women in poor rural areas.     

Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer

Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.     

IFN-gamma-enhanced allergen penetration across respiratory epithelium augments allergic inflammation

BACKGROUND: Respiratory allergen contact is the critical event in the elicitation and boosting of allergen-specific immune responses, as well as in the induction of immediate and late inflammatory reactions. OBJECTIVE: We sought to investigate the influence of various factors of allergic inflammation on the integrity and barrier function of respiratory epithelium for allergens. METHODS: We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of intact respiratory epithelium and used purified iodine 125-labeled recombinant major birch pollen allergen (rBet v 1) to study the extent, kinetics, and factors influencing transepithelial allergen penetration. RESULTS: Culture supernatants from activated allergen-specific T H 1 clones decreased transepithelial resistance. A screening of various factors (histamine, IFN-gamma, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-8, IL-12, and TNF-alpha) identified IFN-gamma as a potent factor capable of reducing epithelial barrier properties and enhancing transepithelial allergen penetration. Increased submucosal allergen concentrations caused by IFN-gamma-mediated reduction of epithelial barrier function provoked a more than 7-fold augmentation of histamine release from sensitized basophils. CONCLUSION: These results demonstrate that the T H 1 cell-derived cytokine IFN-gamma facilitates allergen penetration through the respiratory epithelium and thereby can aggravate allergic inflammation.     

Enhanced expression of Fas-associated proteins in decidual and trophoblastic tissues in pregnancy-induced hypertension

PROBLEM: To determine if feto-placental tissues from gestations complicated by pregnancy-induced hypertension (PIH) have altered expression of Fas-associated proteins. METHOD OF STUDY: The expression of several Fas-related proteins was determined in fetal membranes, decidua, and placentas obtained from PIH-affected (n = 12, age range 32-36 weeks) and normal (n = 6, age range 37-41 weeks) gestations. Paraffin-embedded tissue sections were stained with specific monoclonal antibodies to Fas, Fas ligand (FasL), caspase-3, and bax. RESULTS: We observed greater expression of Fas and FasL in amnion and decidua from PIH-affected gestations than in normal controls. Intense staining was observed only in the perivascular endothelium (caspase-3) and in decidual cells (bax) from PIH gestations. CONCLUSION: Differential expression of Fas-related proteins in fetal membranes, decidua, and placentas from PIH-affected gestations is consistent with increased apoptosis, and suggests activation of the Fas/FasL pathway in a tissue-specific manner.     

Neural basis for verb processing in Alzheimer's disease: an fMRI study

Patients with probable Alzheimer's disease (AD) have difficulty understanding verbs. To investigate the neural basis for this deficit, the authors used functional magnetic resonance imaging to examine patterns of neural activation during verb processing in 11 AD patients compared with 16 healthy seniors. Subjects judged the pleasantness of verbs, including MOTION verbs and COGNITION verbs. Healthy seniors and AD patients both activated posterolateral temporal and inferior frontal regions during judgments of verbs. These activations were relatively reduced and somewhat changed in their anatomic distribution in AD patients compared with healthy seniors, particularly for the subcategory of MOTION verbs, but AD patients showed minimal activation in association with COGNITION verbs. These findings imply that poor performance with verbs in AD is due in part to altered activation of the large-scale neural network that supports verb processing.     

Characterizing point spread functions of two-photon fluorescence microscopy in turbid medium

In recent years, fluorescence microscopy based on two-photon excitation has become a popular tool for biological and biomedical imaging. Among its advantages is the enhanced depth penetration permitted by fluorescence excitation with the near-infrared photons, which is particularly attractive for deep-tissue imaging. To fully utilize two-photon fluorescence microscopy as a three-dimensional research technique in biology and medicine, it is important to characterize the two-photon imaging parameters in a turbid medium. We investigated the two-photon point spread functions (PSFs) in a number of scattering samples. Gel samples containing 0.1-microm fluorescent microspheres and Liposyn III were used as phantoms mimicking the turbid environment often found in tissue. A full characterization of the two-photon PSFs of a water and oil immersion objective was completed in samples composed of 0, 0.25, 0.5, 1, and 2% Liposyn III. Our results show that up to depths of about 100 (oil) and 200 microm (water), the presence of scatterers (up to 2% Liposyn III) does not appreciably degrade the PSF widths of the objectives.     

Quantification of the morphological features of a full microvascular network

Investigations into the changes that occur in microvasculature following the surgical procedure called delay have brought about the need for a computer system capable of quantifying the morphological features of a full microvascular network in terms of average vessel length, diameter, and tortuosity. Both the formulaic conventions that have been developed to measure these quantities as well as their implementation in the form of a HP-9000/UNIX based computer software system that we developed specifically for this purpose are discussed. Reliability studies performed using the final system to measure the microcirculatory network of a mouse latissmus dorsi muscle (LDM) showed 95% confidence intervals within 5% of means and coefficients of variability within 7% of means for all quantities measured in large (150–300 μm), medium (50–150 μm), and small (<50 μm) diameter vessels. These variations were significantly smaller than the changes that were observed in a preliminary study comparing these microvascular network parameters before and after delay in the hairless mouse LDM, showing the proposed quantification methods to be well suited to the study of the microvascular changes following delay. It is hoped that the formulaic conventions, implementation process and reliability data will provide a useful comparison for other researchers interested in measuring similar features of microcirculatory networks.