Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Anti-CD40 antibody stimulates the VLA-4-dependent adhesion of normal and LFA-1-deficient B cells to endothelium.

We have demonstrated that anti-CD40 antibody stimulates the heterotypic adhesion of B cells to endothelial cells. This has been shown by using normal B lymphocytes and B-cell lines in a quantitative adhesion assay. When B cells, B-cell lines and Epstein-Barr virus (EBV)-transformed B cells from a patient with leucocyte adhesion deficiency (LAD) were stimulated with anti-CD40 antibody, they were found to adhere to both untreated and interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC), and to the lung carcinoma line A549. To identify the adhesion receptors responsible for this anti-CD40-induced adhesion, cells were pretreated with blocking antibodies prior to assay. Our results indicate that anti-CD40-stimulated adhesion of tonsillar B cells, B-cell lines RPMI-8866, JY, and an EBV-transformed LAD-cell line were predominantly dependent on the very late antigen-4 (VLA-4)-vascular cell adhesion molecule (VCAM) interaction. Anti-CD40-induced adhesion appears to be dependent on the activation of protein tyrosine kinase and protein kinase C and on the presence of divalent cations.     

Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.     

An Unexplained Death: Hannah Greener and Chloroform

Background: Reports of major and minor sequelae following lidocaine spinal anesthesia have generated interest in an alternative short-acting intrathecal agent. Of the available anesthetics suitable for short-duration spinal anesthesia, prilocaine is perhaps the most promising agent. However, data comparing the neurotoxicity of these agents are lacking. Accordingly, the present experiments investigate whether prilocaine and lidocaine differ with respect to sensory impairment and histologic damage when administered intrathecally in the rat.

Methods: Ninety rats were divided into three groups to receive an intrathecal infusion of 2.5% prilocaine in saline, 2.5% lidocaine in saline, or normal saline. The animals were assessed for persistent sensory impairment 4 days after anesthetic administration using the tail-flick test. Three days later, the animals were killed, and specimens of the spinal cord and nerve roots were obtained for histopathologic examination.

Results: Prilocaine and lidocaine produced equivalent elevations in tail-flick latency that differed significantly from saline. Histologic injury scores with prilocaine were greater than with lidocaine, but this difference did not reach statistical significance.     

Cutaneous afferent activity in the median nerve during grasping in the primate

Neural activity was recorded from the median nerve of a monkey during grasping and lifting, using a chronically implanted cuff electrode. At the onset of lifting, there was an initial dynamic response during which the intensity of the neural signal increased rapidly. This neural response attained its peak value well before the displacement, the load force or the grip force. The time course and peak of the rectified, integrated neurogram were best correlated with the rate of change of grip force. The neural activity declined exponentially to a steady value following the initial peak. During steady holding the mean amplitude of the neurogram was best correlated with the mean grip force. At the end of the holding phase there was a short burst of neural activity as the monkey relaxed the grip force and released the object. During some blocks of trials pulse perturbations were applied to the object. When the monkey did not increase the grip force in advance of the perturbation, the perturbation produced a relatively large displacement of the object and a burst of neural activity whose onset coincided with the onset of displacement. When the monkey anticipated the perturbation by increasing the grip force during the holding period preceding the perturbation, the perturbation produced a relatively small displacement and relatively little increase in neural activity.