Differences in circadian variation of cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage by situation at onset

Background

The precise time of stroke onset during sleep is difficult to specify, but this has a considerable influence on circadian variations of stroke onset.

Aim

To investigate circadian variations in situations at stroke onset—that is, in the waking state or during sleep—and their differences among subtypes.

Methods

12 957 cases of first‐ever stroke onset diagnosed from the Iwate Stroke Registry between 1991 and 1996 by computed tomography or magnetic resonance imaging were analysed. Circadian variations were compared using onset number in 2‐h periods with relative risk for the expected number of the average of 12 2‐h intervals in the waking state or during sleep in cerebral infarction (CIF), intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH).

Results

ICH and SAH showed bimodal circadian variations and CIF had a single peak in all situations at onset, whereas all three subtypes showed bimodal circadian variations of stroke onset in the waking state only. These variations were different in that CIF showed a bimodal pattern with a higher peak in the morning and a lower peak in the afternoon, whereas ICH and SAH had the same bimodal pattern with lower and higher peaks in the morning and afternoon, respectively.

Conclusions

Sleep or status in sleep tends to promote ischaemic stroke and suppress haemorrhagic stroke. Some triggers or factors that promote ischaemic stroke and prevent haemorrhagic stroke in the morning cause different variations in the waking state between ischaemic and haemorrhagic stroke.Stroke occurrence shows chronobiological variations,¹ such as circannual variations, circaseptan variations and circadian variations. Various patterns have been reported but no conclusions have yet been reached on circadian variations. The circadian variations of stroke onset may differ according to subtype or reporter, and are classified as cerebral infarction (CIF) with a single peak^2,3,4,5,6 or double peaks,^7,8 subarachnoid haemorrhage (SAH) with a single peak⁹ or double peaks,^{6,10,11,12,13,14} and intracerebral haemorrhage (ICH) with double peaks.^6,10,12 Most previous studies have not treated the three major subtypes simultaneously. Only three reports^6,7,8 discussed all the three subtypes, but the number of cases of ICH, especially of SAH, was too small for investigation of circadian variation. This may have led to differences in the conceived patterns of circadian variation. Large numbers of cases in population‐based samples are required to investigate and compare the circadian variations of stroke onset among subtypes. For investigation of the triggers and risk factors of stroke onset, it is necessary to determine the circadian variations of stroke onset with precise times. The precise time of stroke onset during sleep is difficult to specify, but this has a considerable influence on circadian variations of stroke onset.We investigated circadian variation in stroke onset by situations at onset in CIF, ICH and SAH in a Japanese population, by using stroke registry data. We also investigated the differences in circadian variations, triggers and risk factors among subtypes.     

VAMP4 and its cognate SNAREs are required for maintaining the ribbon structure of the Golgi apparatus

Background

The Golgi apparatus is at a crossroads between anterograde and retrograde trafficking. It exhibits a twisted ribbon-like network in the juxtanuclear region of vertebrate cells. Vesicle-associated membrane protein 4 (VAMP4) is a unique v-SNARE expressed exclusively in trans-Golgi networks (TGN), where it regulates retrograde trafficking from the early endosome to the TGN with its cognate SNARE partners Syntaxin 6, Syntaxin 16, and Vti1a.

Immune responses of graft mesenteric lymph node in small bowel transplantation

BACKGROUND: The high proportions of lymphoid tissues are thought to be one of the underlying factors inducing severe allograft rejection following small bowel transplantation. Mesenteric lymph nodes (MLN) contained in the intestinal graft are not only a source of donor-derived professional antigen-presenting cells, but also offer a field for immune interaction between donor and host cells. We investigated immune responses in graft MLNs with or without FK506 to develop a novel strategy to control small bowel allograft rejection. MATERIALS AND METHODS: Heterotopic small bowel transplantations were performed from Brown Norway donors to Lewis recipients. Changes in population of lymphocytes, expressions of costimulatory molecules, apoptosis, and cytokine profiles in graft MLNs were evaluated. RESULTS: The increase in apoptotic cells and cytokine responses relating to rejection in the graft MLNs developed prior to those in graft jejunum. While donor lymphocytes in graft MLNs were rapidly replaced to host-derived lymphocytes independent of FK treatment, increase in CD8(+) T cells in host population was seen only in recipients without FK506 treatment. The expressions of B7 molecules on donor cells in graft MLNs were significantly lower in the recipients with FK treatment. CONCLUSIONS: Immune responses in graft MLNs have significant impact on the outcome of the small bowel allograft. Apoptosis of graft MLN cells was well correlated with and ahead of progression of acute rejection. Modulation of costimulatory molecules on donor-derived MLN cells in the allograft and specific suppression of host CD8(+) T cells are possible ways to control severe rejection after allogeneic small bowel transplantation.     

Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer

Background

Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction.

Methods

RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity.

Results

In the retrospective phase, repeated random validation yielded ~68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis of peritoneal-relapse-free survival showed a significant difference between the “good signature group” and “poor signature group” (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse.

Conclusions

Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.     

Low-risk profile for cardiovascular disease and mortality in Japanese.

BACKGROUND: Some studies focusing on low-risk profiles for cardiovascular disease have been reported in Western countries. Yet, few reports have examined, with substantial longevity, the low-risk profile for cardiovascular disease in the Japanese population. This study examines whether having a favorable risk factor profile yields lower all-cause mortality and whether the proportion of those with a low-risk profile is larger in the Japanese population. METHODS AND RESULTS: A total of 8,339 men and women aged 30-69 years without a history of cardiovascular diseases for 19 years, who had participated in the 1980 National Survey on Circulatory Disorders after being randomly selected from throughout Japan, were followed. Low risk was defined as having all of the following baseline characteristics: blood pressure (BP) <120/80 mmHg; no antihypertensive medication; serum cholesterol 160-240 mg/dl (4.14-6.22 mmol/L); no history of diabetes; and non-smoker. The long-term mortality of the low-risk group was compared with that of others using the Cox proportional hazard model. The prevalence of low risk was 9.4% of all participants. The multivariate-adjusted hazard ratios for low-risk individuals compared with others were as follows: 0.33 (95% confidence intervals (CI), 0.15-0.74) for cardiovascular disease and 0.63 (95% CI, 0.46-0.88) for all-cause mortality. The most attributable risk factor for all-cause mortality was high BP (>or=120/80 mmHg). CONCLUSION: Japanese individuals with favorable cardiovascular disease risk profiles had lower mortality from cardiovascular disease and all-causes than those without.     

Specific alcoholic beverage and blood pressure in a middle-aged Japanese population: the High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

The purpose of this study was to clarify the effects of popular Japanese alcoholic beverages on blood pressure. We performed a cross-sectional study on 4335 Japanese male workers using baseline data from an intervention study. We defined six groups according to the type of alcoholic beverage that provided two-thirds of the subject's total alcohol consumption: beer, sake (rice wine), shochu (traditional Japanese spirits), whiskey, wine and others. The partial regression coefficients of daily alcohol intake (1 drink=11.5 g of ethanol) to systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 0.87(P<0.001, standard error (s.e.)=0.09) and 0.77(P<0.001, s.e.=0.06), respectively. A comparison among the types of alcoholic beverages mainly consumed revealed significant differences in SBP and DBP. Both SBP and DBP were highest in the shochu group. However, an analysis of covariance adjusting for total alcohol consumption resulted in the disappearance of these differences. Although after adjustment for total alcohol consumption, the shochu group exhibited a significant positive association with 'high-normal blood pressure or greater' (odds ratio 1.43, 95% confidence interval 1.06-1.95) compared with the beer group, this significant relation disappeared after adjusting for the body mass index (BMI), urinary sodium and potassium excretion. The pressor effect, per se, of popular Japanese alcoholic beverages on blood pressure may not be different among the types of alcoholic beverages after adjusting for other lifestyle factors.     

Functional assessment of coronary artery flow using adenosine stress dual-energy CT: a preliminary study

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT as controls. We reconstructed an iodine map and composite images at 120 kV (120 kV images) using raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in the coronary artery proximal to the distal portion on both the iodine map and 120 kV images. Coronary enhancement ratio (CER) was calculated by dividing mean attenuation in the coronary artery by attenuation in the aortic root, and was used as an estimate of coronary enhancement. Coronary stenosis was identified as a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map showed that CER was significantly lower for ischemic territories (0.76 ± 0.06) or stenosed coronary arteries (0.77 ± 0.06) than for non-ischemic territories (0.95 ± 0.21, P = 0.02) or non-stenosed coronary arteries (1.07 ± 0.33, P < 0.001). The 120 kV images showed no difference in CER between these two groups. Use of CER on the iodine map separated ischemic territories from non-ischemic territories with a sensitivity of 86% and a specificity of 75%. Our quantification is the first non-invasive analytical technique for assessment of coronary artery flow using cardiac CT. CER on the iodine map is a candidate method for demonstration of alteration in coronary artery flow under adenosine stress, which is related to the physiological significance of coronary artery disease.     

Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice.

The transplantation of the human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 into severe combined immunodeficient (SCID) mice was found to produce a disseminated pattern of leukaemia similar to that seen in man. The intravenous injection of 10(7) HSB-2 cells was associated with a universally fatal leukaemia. Histopathological examination of animals revealed the spread of leukaemia initially from bone marrow to involve all major organs including the meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 MAb HB2 to the ribosome-inactivating protein saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT) to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. When SCID mice were injected with 10(6) HSB-2 cells and then treated 8 days later with a single intravenous dose of 10 micrograms of immunotoxin there was a significant therapeutic effect evidenced by the numbers of animals surviving in the therapy group compared with untreated controls (chi 2 = 5.348, P = 0.021). These results demonstrate the useful application of human leukaemia xenografts in SCID mice and the potential therapeutic effect of an anti-CD7 immunotoxin in human T-ALL.