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.     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Synthesis of CCK-8 Tetrapeptide Fragment by Enzymatic Method

Cholecystokinin (CCK )isa polypeptidehor monecontaining 33aminoacidsresiduewithgastroin testinal,biliarandbrainactivities Itiswidelydis tributedinthevertebratecentralnervoussystem ,anditcanstimulateextensivelytheliberationofinsulinandglucagonfromtheLangerhansislets GreateffortshavebeendevotedtothesynthesisofCCK 8,itsderivativesandanalogues Amongthedifferentmethods ,theenzymaticmethodisthemosteffectiveonewithmanyadvantagesoverconventionalchemicalmethodologies :enzymespecificitysuppress essid…     

Sensory and motor aspects of saccade control

Summary The oculomotor reactions have recently attracted increasing attention for diagnostic purposes. This is in line with the view that the oculomotor system is one of the simpler, machine-like sensorimotor systems. This paper presents two examples to demonstrate that the complexity of sensorimotor processing may be higher than expected from the outcome of experiments under rather restricted stimulus conditions. In the first part it is shown that complex preprocessing including the evaluation of spatial gradients of visual structure is an integral part of the programming of reflex-like saccades. The second part concerns adaptivity of saccadic eye movements. The data demonstrate that saccadic gain control is highly specific to the direction of the saccade. It is suggested that many central deficits may be hidden as a consequence of the effect of specific adaptive mechanisms.This article was presented in part at the Symposium on Eye Movements and Psychopathology, Berlin, 23–24 June 1988     

Determination of bone mineral density by dual x-ray absorptiometry in patients with uncemented total hip arthroplasty.

Bone remodeling is an expected sequela with total hip arthroplasty (THA). Although there are several methods of estimating bone response in THA patients from radiographs, there are no accurate and generally accepted methods for quantitative determinations in vivo. In this study, we describe an application of dual x-ray absorptiometry (DXA) for measuring bone mineral content and bone mineral density in the proximal femur following THA. DXA is a noninvasive technique with minimal radiation exposure (< 5 mrem). Various aspects of measurement error (accuracy and reliability) of this application of DXA were determined in a series of studies reported here. Accuracy error (how similar are the measured and actual values) was < 1% determined in bone phantoms of four densities. Precision error (how reproducible are the measurements) was also < 1% at all four densities in the phantoms and was only slightly elevated (0.9-1.5%) in repeated measurements of implanted cadaver femora. Precision error in vivo, determined both from multiple replicates on five patients and from duplicate scans on 30 patients, was further elevated but remained < 5%. Contributions to precision error, rotation of the leg, and interoperator variability were assessed; none was found to elevate precision error appreciably. We suggest that DXA is a feasible method for quantifying bone response following THA, and will allow discrimination of small changes (> 5%) not previously measurable.     

SPECT follow-up of cerebral blood circulation after stroke]

rCBF SPECT investigations with 99mTc-HMPAO were performed in 22 completed ischemic stroke patients on average 2.5, 16.8 and 38.0 days after stroke onset. As control group, 12 neurologically healthy volunteers were examined with the same method. The overall sensitivity of the rCBF SPECT method in the detection of cerebral blood flow abnormalities was 91%, with a specificity of 83% and an accuracy of 88%. The rCBF study was highly effective, particularly in the acute phase of the disease. Regional increased tracer uptake or a false normal 99mTc-HMPAO distribution due to the developing hyperemia mostly complicated the rCBF image interpretations in the subacute period. In the chronic phase, the spatial resolution of the SPECT system limited the detection of the continuously retracted stroke lesions.     

Learning and sexual deficiencies in transgenic mice carrying a chimeric vasoactive intestinal peptide gene

The molecular mechanisms responsible for behavior are largely unknown. A state of the art model, paving the path from genes to behavior, is offered by transgenic animals. Candidate molecules are classic neuropeptides, such as vasoactive intestinal peptide (VIP). Transgenic mice harboring a chimeric VIP gene driven by the polyoma promoter were produced. Behavioral studies revealed learning impairment and prolonged retardation in memory acquisition in the genetically altered animals. Furthermore, reduced performance was observed when the male transgenic mice were tested for sexual activity in the presence of receptive females. Surprisingly, radioimmunoassays showed an approx 20% decrease in the VIP content of the transgenic mice brains. To directly assess genetically reduced VIP content as a cause for learning impairment, transgenic mice carrying diphtheria toxia-encoding sequences driven by the rat VIP promoter were created. These animals had reduced brain VIP and exhibited deficiencies in learning abilities, strongly supporting an important neurobiological function for VIP in vivo.     

Immunoglobulin G from subacute sclerosing panencephalitis brain as an immunological reagent.

"Natural" hemagglutinin titers against a panel of fixed erythrocyte antigens were determined for groups of Minnesota miniature swine reared conventionally, in a specific pathogen-free facility, and in germfree isolators. Sera were assayed for hemagglutination (HA) titers by the microtiter method against 12 species of erythrocytes stabilized by treatment with pyruvic aldehyde and formaldehyde. These erythrocytes were stable for up to 2 years and gave slightly enhanced HA titers as compared to fresh, unfixed erythrocytes. Of the sera from conventional swine tested, the highest "natural" HA titers were directed towards rabbit, cat, swine dog, and burro erythrocytes (greater than 1:1,000), intermediate titers were detected against human A, B, and O, and sheep, pig, and chicken erythrocytes (1:64 to 1:1,000), whereas the lowest titers were found against ox and goat erythrocytes (less than 1:8). Titers obtained with sera from specific pathogen-free swine were 2- to 16-fold lower than those of conventional swine, but were of a similar distribution with regard to the species of erythrocyte tested. Germfree swine sera uniformly exhibited HA titers less than 1:4 against all species of erythrocytes. The majority of these hemagglutinins were immunoglobulin M class but there were some agglutinins of immunoglobulin A class and a slight amount of immunoglobulin G class. Specificity of these agglutinins was examined by absorption tests. The results are consistent with the hypothesis that natural hemagglutinins develop due to dietary or microbial antigenic stimulation, or both.