Seroepidemiological study of infection with West Nile virus in Karachi, Pakistan, in 1983 and 1985

The prevalence of West Nile (WN) virus infection in Karachi, Pakistan, was unknown until 1982. It had been noticed that there were more than a few patients with encephalitides in Karachi, and it was supposed that Japanese encephalitis (JE) cases would be found among them. Therefore, a seroepidemiological study was conducted to define the prevalence of WN virus infection and the possible occurrence of JE virus infection in the Karachi area. Prevalences of haemagglutination inhibition (HI) and neutralization (NT) antibodies against WN virus were studied among 81 serum samples (in July, 33 samples; in September, 48) during 1983, and among 156 paired serum samples that were collected twice, in July and October of 1985. Nearly the same antibody-positive rates were obtained in July of both years (1983: HI 55%; 1985: HI 53%; NT 50%); the rates increased slightly during September/October (1983: HI 65%; 1985: HI 59%, NT 54%). Among 156 paired samples in 1985, 20 (13%) and 12 (8%) showed positive- or negative-antibody conversion between July and October. Two serum samples from each of 156 residents obtained in July had a significantly higher NT antibody titre against JE virus than against WN virus (in case 1, JE 1:80, WN less than 1:10; in case 2, JE 1:40, WN less than 1:10). This is the first report to show the prevalence of WN virus infection in Karachi, Pakistan.     

Intracellular nucleic acid sensors and autoimmunity

A collection of molecular sensors has been defined by studies in the last decade that can recognize a diverse array of pathogens and initiate protective immune and inflammatory responses. However, if the molecular signatures recognized are shared by both foreign and self-molecules, as is the case of nucleic acids, then the responses initiated by these sensors may have deleterious consequences. Notably, this adverse occurrence may be of primary importance in autoimmune disease pathogenesis. In this case, microbe-induced damage or mishandled physiologic processes could lead to the generation of microparticles containing self-nucleic acids. These particles may inappropriately gain access to the cytosol or endolysosomes and, hence, engage resident RNA and DNA sensors. Evidence, as reviewed here, strongly indicates that these sensors are primary contributors to autoimmune disease pathogenesis, spearheading efforts toward development of novel therapeutics for these disorders.     

An enzyme immunoassay for a metabolite of a new sleep inducer (450191-S), a ring-opened derivative of 1,4-benzodiazepine, in human serum

A competitive enzyme immunoassay was developed for metabolites of 450191-S, a ring-opened derivative of triazolobenzodiazepines, in human serum. Three kinds of labelled antigens, beta-D-galactosidase conjugates, and antisera from three kinds of immunogens, bovine serum albumin conjugates, were tested and the hapten heterologous assay was selected. B/F separation was performed using immobilized second antibody and the enzyme activity was measured using fluorescent substrate. One of the serum metabolites, the carboxyl form, was extracted from acidified serum and measured by the assay. The minimum detectable concentration was 1.5 ng/ml in serum, 15 pg/tube. The intra-assay and inter-assay variances were 5.5% and 7.7% at 6 ng/ml of serum, respectively. Standard curves of other related metabolites were assessed with various combinations of labelled antigens and antibodies.     

Modulation of tetrodotoxin-resistant sodium channels by dihydropyrazole insecticide RH-3421 in rat dorsal root ganglion neurons

The effects of the dihydropyrazole insecticide RH-3421 on the retrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal root ganglion (DRG) neurons were studied using the whole-cell patch clamp technique. RH-3421 at 10 nM to 1 microM completely blocked action potentials. The sodium currents were irreversibly suppressed by 1 microM RH-3421 in a time- and a dose-dependent manner and the IC50 value of RH-3421 was estimated to be 0.7 microM after 10 min of application. RH-3421 blocked the sodium currents to the same extent over the entire range of test potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by 1 microM RH-3421 application In contrast, both fast and slow steady-state sodium channel inactivation curves were shifted in the hyperpolarizing direction in the presence of 1 microM RH-3421. It was concluded that RH-3421 bound to the resting and inactivated sodium channels to cause block with a higher affinity for the latter state.     

Gender difference in QTc prolongation of people with mental disorders

Background

We examined gender difference in QTc interval distribution and its related factors in people with mental disorders.

Methods

We retrospectively reviewed medical charts of patients discharged from a university psychiatric unit between November 1997 and December 2000. Subjects were 328 patients (145 males and 183 females) taking psychotropics at their admission. We examined patient characteristics, medical history, diagnosis, and medication before admission.

Results

Mean QTc interval was 0.408 (SD = 0.036). QTc intervals in females were significantly longer than those in males. QTc of females without comorbidity was significantly longer than that of males.

Conclusion

The influence of gender difference on QTc prolongation in people with mental disorders merits further research.

     

Effects of intra- and extrahepatic portal systemic shunts on insulin metabolism

To study the effects of intra- and extrahepatic portal-systemic shunts on insulin degradation, 11 patients with liver cirrhosis and 7 noncirrhotic patients with liver disease were studied with percutaneous transhepatic catheterization. Insulin levels in portal and peripheral blood were measured simultaneously for 1-2 hr after intravenous administration of glucose. The degrees of intra- and extrahepatic portal-systemic shunting were measured with this technique using 131I-macroaggregated albumin and 99mTc-macroaggregated albumin. The amount of insulin secreted and insulin degraded were assessed from the areas under blood concentration curves for portal and peripheral blood. Insulin degradation was significantly reduced in cirrhotics compared to noncirrhotics with liver disease, although there was no difference in the amount of insulin secreted between these two groups. It was also correlated significantly with the degree of intrahepatic shunting but not with the degree of extrahepatic shunting. These results suggest that intrahepatic shunting plays an important role in the reduction of insulin degradation in cirrhosis.     

Neurotoxicodynamics of the Interaction between Ciprofloxacin and Foscarnet in Mice

The potential for convulsions induced by the coadministration of ciprofloxacin (CPFX) and foscarnet (PFA) may be due not to a change in the distribution of CPFX to the brain but to a potential CPFX-induced inhibition of γ-aminobutyric acid (GABA)-GABA_A receptor binding in the presence of PFA.     

Frequency of going outdoors predicts long-range functional change among ambulatory frail elders living at home

The purpose of the study was to investigate the relationships between frequency of going outdoors and subsequent functional and psychosocial changes over a 20-month period. Data were collected from community-dwelling 107 frail elders who could walk independently but who still needed some assistance to live on their own. Functional and psychosocial status at baseline and follow-up were compared among three groups defined by the frequency of going outdoors: (1) four or more times a week, (2) one to three times a week and (3) less than once a week. At baseline, elders going outdoors more often were less functionally impaired, more socially active, and less depressed than elders going outdoors less often. There was a significant difference in change over time of activities of daily living (ADLs) (p=0.002) among the three groups, even when controlling for baseline differences, and the scores of those who went outdoors almost daily were least likely to decline. More of those going outdoors four or more times a week at baseline were still living at home at follow-up than those in the other two groups (p=0.048). These results suggest that the frequency of going outdoors can predict changes in ADLs over at least a 20-month period.     

Neonatal correlates of adverse outcomes in very low‐birthweight infants in the NICU Network

Background: The aim of the present study was to explore the relationships among neonatal morbidity, interventions and death or adverse neurodevelopmental outcomes in very low‐birthweight (VLBW) infants. Methods: Subjects were infants with birthweight ≤1500 g who were cared for in the tertiary neonatal intensive care units in Japan. Multiple logistic regression analysis was performed to examine the odds ratios (OR) and 95% confidence intervals (CI) of neonatal factors for death or cerebral palsy (CP) and death or developmental delay (developmental quotient <70 or delay judged by physicians) at 3 years of age after adjusting for biological and prenatal variables. Results: Of the 3104 subjects, 257 died and 1826 were evaluated at 3 years of age. Cystic periventricular leukomalacia (PVL; OR, 23.9; 95%CI: 11.0–51.7), gastrointestinal perforation (OR, 8.5; 95%CI: 2.8–25.4), intraventricular hemorrhage (IVH) grade 3 or 4 (OR, 3.1; 95%CI: 1.3–7.2) and sepsis (OR, 2.6; 95%CI: 1.4–4.8) were neonatal factors significantly associated with an increased risk of death or CP. Significant correlates with death or developmental delay were cystic PVL (OR, 7.9; 95%CI: 3.7–16.8), gastrointestinal perforation (OR, 6.3; 95%CI: 1.9–20.8), sepsis (OR, 2.8; 95%CI: 1.6–4.8), IVH grade 3 or 4 (OR, 2.6; 95%CI: 1.2–5.7), chronic lung disease at 36 weeks of corrected gestational age (OR, 1.6; 95%CI: 1.1–2.4) and treatment for retinopathy of prematurity (ROP; OR, 1.5; 95%CI: 1.0–2.3). Conclusion: Cystic PVL, gastrointestinal perforation, IVH and sepsis correlated with both death or CP and death or developmental delay in VLBW infants. Chronic lung disease at 36 weeks and treatment for ROP were associated with death or developmental delay, but not with death or CP.     

Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study

Matsukuma S, Takeo H, Kono T, Nagata Y & Sato K
(2012) Histopathology  61, 857–862 Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study Aims: This study has attempted to elucidate the clinicopathological features of aberrant cytokeratin 7 (CK7) expression by centrilobular hepatocytes. Methods and results: A total of 113 liver biopsy specimens from patients with common non‐neoplastic liver diseases, including hepatitis B or C, non‐alcoholic steatohepatitis, alcoholic liver disease and other diseases were examined. In 56 specimens (49.6%), CK7‐positive centrilobular hepatocytes (CK7 + CHs) were identified and sometimes showed binuclear features. CK7 + CHs were associated with patients’ older age (P = 0.004), higher serum levels of aspartate aminotransferase (P = 0.016) and γ‐glutamyltransferase (P = 0.006), centrilobular fibrosis (P < 0.001), prominent thickening of hepatocytic plates (P < 0.001) and higher scores of total and periportal CK7‐positive hepatocytes (both P < 0.001), but were not correlated with gender, steatosis, serum levels of total bilirubin or alanine aminotransferase. In 55 cases of hepatitis B and hepatitis C only, CK7 + CHs were related to a higher stage of fibrosis (P = 0.006). Conclusion: CK7 + CHs occur relatively frequently in non‐neoplastic liver disease, associated with centrilobular scarring and the presence of CK7‐positive periportal hepatocytes, and appear to be a non‐specific phenomenon with respect aetiology of underlying disease. CK7 + CHs may represent age‐dependent activation of hepatic progenitor cells or a regenerative phenomenon of hepatocytes themselves, both of which might contribute to liver regeneration.