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An increased oxidative stress may contribute to the development of diabetic nephropathy. We have recently reported that high glucose level stimulated superoxide production through protein kinase C (PKC)-dependent activation of NAD(P)H oxidase in cultured vascular cells. Here we show that 3-hydroxy-3-methylglutaryl CoA reductase inhibitor (statin) attenuates both high glucose level-induced and angiotensin II (Ang II)-induced activation of p42/44 mitogen-activated kinase (MAP kinase) in cultured human mesangial cells through inhibition of NAD(P)H oxidase activity. The intracellular oxidative stress in cultured mesangial cells was evaluated by electron spin resonance (ESR) measurement. MAP kinase activity was evaluated by western blot analysis using anti phospho-specific MAP kinase antibody and anti-ERK-1 antibody. Exposure of the cells to high glucose level (450 mg/dl) for 72 hrs significantly increased MAP kinase activity as compared to normal glucose level (100 mg/dl). This increase was completely blocked by the treatment of pitavastatin (5x10(-7) M) as well as a NAD(P)H oxidase inhibitor (diphenylene iodonium, 10(-5) M) in parallel with the attenuation of oxidative stress. Ang II-induced activation of MAP kinase was also completely blocked by pitavastatin as well as a diphenylene iodonium in parallel with the attenuation of oxidative stress. In conclusion, pitavastatin attenuated high glucose-induced and Ang II- induced MAP kinase activity in mesangial cells through inhibition of NAD(P)H oxidase. Thus, statins may have a potential as a therapeutic tool for early diabetic nephropathy.

We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-alpha induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoropyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue microarray consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy.

Pulmonary artery banding remains a useful procedure for special conditions. A 3-month-old girl diagnosed as Down syndrome with atrioventricular septal defect underwent pulmonary artery banding. We used polyester tape smeared with Bone Wax for this pulmonary artery banding. After 7 months period, the tape was easily dissected from surrounding tissue and removed at radical operation. Microscopic appearance showed that the tape was intact and no evidence of inflammation or mineralization. We believe Bone Wax smeared polyester tape accomplishes well as silicone impregnated one.

Spin relaxation from a triplet excited state to a singlet ground state in a semiconductor quantum dot is studied by employing an electrical pump-and-probe method. Spin relaxation occurs via co-tunneling when the tunneling rate is relatively large, confirmed by a characteristic square dependence of the relaxation rate on the tunneling rate. When co-tunneling is suppressed by reducing the tunneling rate, the intrinsic spin relaxation is dominated by spin-orbit interaction. We discuss a selection rule of the spin-orbit interaction based on the observed double-exponential decay of the triplet state.

The authors performed PINK1 mutation analysis of 51 families with autosomal recessive Parkinson disease (ARPD). They found two novel PINK1 mutations: one was a homozygous deletion (13516-18118del) and the other a homozygous missense mutation (C388R). Clinically, the patients with the deletion had dementia. Thus, early-onset PD with dementia may be considered PINK1-linked parkinsonism. Furthermore, patients with PINK1 mutations form 8.9% of parkin- and DJ-1-negative ARPD families.

Latanoprost and isopropyl unoprostone, which are analogues of prostaglandin F2alpha (PGF2alpha), are promising drugs for the reduction of intra-ocular pressure. However, they have been reported to have side effects, including hypertrichosis and hyperpigmentation of the eyelashes and periocular skin, and occasionally poliosis. In order to investigate these effects further, PGF2alpha, latanoprost and isopropyl unoprostone were applied to the dorsal skin of 7-week-old C57BL/6 mice, and hair length was measured during the treatment. The three molecules all showed stimulatory effects on the murine hair follicles and the follicular melanocytes in both the telogen and anagen stages, and stimulated conversion from the telogen to the anagen phase. PGE2 is known to act synergistically with PGF2alpha, and hence the influence of PGE2 was also examined. PGE2 did not induce distinct telogen-to-anagen conversion, but showed moderate growth stimulatory effects on early anagen hair follicles. In addition, we observed a case of hypertrichosis and trichomegaly with an excess of melanogenesis, leading to the emergence of white hair, suggesting that poliosis can occur as a side effect of eye treatment with solutions of PGF2alpha analogues. The stimulatory effects of PGF2alpha and PGE2 on hair growth have been discussed with regard to the role of protein kinase C and mast cells.

Objective: To investigate whether the myocardial performance index (MPI) can predict left ventricular functional outcome in patients with early recanalisation after anterior acute myocardial infarction (MI) and to determine when the index should be measured., Design: MPI was measured serially by two dimensional Doppler echocardiography after successful percutaneous coronary intervention (PCI). Left ventricular function was evaluated by echocardiography and left ventriculography. To assess coronary microvascular damage, the coronary flow velocity pattern was measured immediately after PCI with a Doppler guidewire., Setting: Hiroshima City Asa Hospital., Patients: 32 consecutive patients with their first anterior acute MI who had complete occlusion of left anterior descending coronary artery., Interventions: Successful PCI within six hours of symptom onset., Main Outcome Measures: Left ventricular anterior wall motion score index (A-WMSI), left ventricular end diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), and left ventricular end diastolic volume (LVEDV)., Results: There was a significant negative correlation between MPI on day 2 and the coronary diastolic deceleration time (r = -0.66, p < 0.002), as well as a significant positive correlation with the coronary diastolic deceleration rate (r = 0.74, p < 0.0001). MPI on day 2 was significantly correlated with the short and long term changes of A-WMSI and with the short term changes of LVEDP. Furthermore, MPI on day 2 was significantly correlated with the short and long term changes of LVEF (r = -0.52, p < 0.003, and r = -0.64, p < 0.0008, respectively) and of LVEDV (r = 0.51, p < 0.003, and r = 0.41, p < 0.05, respectively)., Conclusions: Doppler derived MPI on day 2, representative of the early coronary microvascular state, can predict the left ventricular functional outcome after early successful recanalisation of a patient's first anterior acute MI.

There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour-vessel tumour-nodal tumour (PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumour recurrence and death in 393 IDC patients based on the following histological classifications: (1) the pTNM classification, (2) the Nottingham Prognostic Index, (3) the modified Nottingham Prognostic Index, and (4) the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates (HRs) of tumour recurrence and death (P<0.05), independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumour recurrence and death (P<0.05), independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast.

Aims: Few prospective studies have examined the relationship between lifestyle characteristics and the incidence of diabetes mellitus in an Asian general population. This study was undertaken to evaluate the risk factors for Type 2 diabetes in a population-based prospective study of middle-aged Japanese., Methods: We investigated 12,913 men and 15,980 women, aged 40-59 years at baseline (year 0), who participated in the Japan Public Health Center-based prospective study on cancer and cardiovascular diseases (JPHC Study) Cohort I. The participants were followed for up to 10 years. Incident cases of diabetes were identified by self-reporting of a physician's diagnosis on two questionnaires sent to each participant, one at year 5 and the second at year 10., Results: During the 10-year follow-up, 703 men and 482 women reported newly diagnosed diabetes. Age, body mass index (BMI), family history of diabetes and cigarette smoking were independent risk factors in both genders by multivariate analysis. Among men with a BMI < or = 22 kg/m2, a significant positive association was observed between the diabetes incidence and moderate (23.0 < 46.0 g/day) to high (> 46.0 g/day) alcohol consumption, odds ratio 1.91 (95% CI, 1.05-3.46) and 2.89 (1.63-5.11), respectively. Among men with a BMI > 22 kg/m2, a small non-significant increase in odds ratio was observed with alcohol consumption., Conclusions: Established risk factors for diabetes in western populations were also identified as predictors of the disease among Japanese. Moderate to high alcohol consumption was positively associated with the incidence of diabetes in Japanese lean (BMI < or = 22 kg/m2) men.

Aim: We elucidated the mitochondrial functions of brown adipocytes in intracellular signalling, paying attention to mitochondrial activity and noradrenaline- and forskolin-induced Ca(2+) mobilizations in cold-acclimated rats., Methods: A confocal laser-scanning microscope of brown adipocytes from warm- or cold-acclimated rats was employed using probes rhodamine 123 which is a mitochondria-specific cationic dye, and the cytoplasmic and mitochondrial Ca(2+) probes fluo-3 and rhod-2. X-ray microanalysis was also studied., Results: The signal of rhodamine 123 in the cells was decreased by antimycin A which effect was less in cold-acclimated cells than warm-acclimated cells. Cytoplasmic and mitochondrial Ca(2+) in cold-acclimated brown adipocytes double-loaded with fluo-3 and rhod-2 were measured. Noradrenaline induced the rise in cytoplasmic Ca(2+) ([Ca(2+)](cyto)) followed by mitochondrial Ca(2+) ([Ca(2+)](mito)), the effect being transformed into an increase in [Ca(2+)](cyto) whereas a decrease in [Ca(2+)](mito) by antimycin A or carbonyl cyanide m-chlorophenylhydrazone (CCCP). Antimycin A induced small Ca(2+) release from mitochondria. CCCP induced Ca(2+) release from mitochondria only after the cells were stimulated with noradrenaline. Further, forskolin also elicited an elevation in [Ca(2+)](cyto) followed by [Ca(2+)](mito) in the cells. The Ca measured by X-ray microanalysis was higher both in the cytoplasm and mitochondria whereas K was higher in the mitochondria of cold-acclimated cells in comparison to warm-acclimated cells., Conclusions: These results suggest that noradrenaline and forskolin evoked an elevation in [Ca(2+)](cyto) followed by [Ca(2+)](mito), in which H(+) gradient across the inner membrane is responsible for the accumulation of calcium on mitochondria. Moreover, cAMP also plays a role in intracellular and mitochondrial Ca(2+) signalling in cold-acclimated brown adipocytes.

The High-Intensity Proton Accelerator Project, named J-PARC, is in progress, with the aim of enabling studies on the latest basic science and the advancement of nuclear technology. In the project, a high-energy proton accelerator complex with the world's highest instantaneous intensity is under construction. In order to establish a reasonable shielding design, both simplified and detailed design methods were used in the shielding design of J-PARC. This paper reviews the present status of the radiation safety design study for J-PARC.

An irradiation field of high-energy neutrons produced in the forward direction from a thick tungsten target bombarded by 500 MeV protons was arranged at the KENS spallation neutron source facility. In this facility, shielding experiment was performed with an ordinary concrete shield of 4 m thickness assembled in the irradiation room, 2.5 m downstream from the target centre. Activation detectors of bismuth, aluminium, indium and gold were inserted into eight slots inside the shield and attenuations of neutron reaction rates were obtained by measurements of gamma-rays from the activation detectors. A MARS14 Monte Carlo simulation was also performed down to thermal energy, and comparisons between the calculations and measurements show agreements within a factor of 3. This neutron field is useful for studies of shielding, activation and radiation damage of materials for high-energy neutrons, and experimental data are useful to check the accuracies of the transmission and activation calculation codes.

The shrinking mechanism of comb-type grafted poly(N-isopropylacrylamide) gel was investigated by fluorescence spectroscopy and small-angle X-ray Scattering (SAXS). The SAXS reveals that the microdomain structure with characteristic dimension of 460A is developed in the comb-type grafted poly(N-isopropylacrylamide) gel during the shrinking process. Fluorescence spectroscopy together with SAXS observation suggests that the freely mobile characteristics of the grafted chains are expected to show the rapid dehydration to make tightly packed globules with temperature, followed by the subsequent hydrophobic intermolecular aggregation of the dehydrated graft chains. The dehydrated grafted chains created the hydrophobic cores, which enhance the hydrophobic aggregation of the networks. These aggregations of the NIPA chains contribute to an increase in void volume, which allow the gel having a pathway of water molecules by the phase separation.

Background: Many studies have shown that cigarette smoking is associated with elevated concentrations of total serum IgE. Few studies, however, have examined total IgE in relation to passive smoking exposure, especially in adults. This cross-sectional study investigated the association of active and passive smoking exposure with levels of total serum IgE in Japan., Methods: Study subjects were 981 pregnant women in Osaka. Total IgE levels were measured using UniCAP 1000 and were defined as elevated if they exceeded 170 ml/UI. Age, gestation, parity, family history of asthma, atopic eczema and allergic rhinitis, indoor domestic pets, family income, education and the mite allergen level in house dust were selected as potential confounding factors., Results: Current smoking of at least 15 cigarettes a day and 8.0 or more pack-years of smoking were independently related to an increased prevalence of elevated total serum IgE (adjusted odds ratios 3.40 and 2.51, 95% confidence intervals 2.12-5.47 and 1.55-4.06, respectively), and both cigarette smoking status and pack-years of smoking were significantly positively associated with total serum IgE levels, especially in subjects with a positive familial allergic history. There was no measurable association of exposure to environmental tobacco smoke (ETS) at home or at work with total serum IgE concentrations among those who had never smoked., Conclusions: Our results corroborate a positive relationship between active smoking and total serum IgE levels; however, this study failed to substantiate a positive association of ETS exposure with total IgE. Investigations with more precise and detailed exposure measurements are warranted.

Both mammals and birds can concentrate urine hyperosmotic to plasma via a countercurrent multiplier mechanism, although evolutionary lines leading to mammals and birds diverged at an early stage of tetrapod evolution. We reported earlier (Nishimura H, Koseki C, and Patel TB. Am J Physiol Regul Integr Comp Physiol 271: R1535-R1543, 1996) that arginine vasotocin (AVT; avian antidiuretic hormone) increases diffusional water permeability in the isolated, perfused medullary collecting duct (CD) of the quail kidney. In the present study, we have identified an aquaporin (AQP) 2 homolog water channel in the medullary cones of Japanese quail, Coturnix coturnix (qAQP2), by RT-PCR-based cloning techniques. A full-length cDNA contains an 822-bp open reading frame that encodes a 274-amino acid sequence with 75.5% identity to rat AQP2. The qAQP2 has six transmembrane domains, two asparagine-proline-alanine (NPA) sequences, and putative N-glycosylation (asparagine-124) and phosphorylation sites (serine-257) for cAMP-dependent protein kinase. qAQP2 is expressed in the membrane of Xenopus laevis oocytes and significantly increased its osmotic water permeability (P(f)), inhibitable (P < 0.01) by mercury chloride. qAQP2 mRNA (RT-PCR) was detected in the kidney; medullary mRNA levels were higher than cortical levels. qAQP2 protein that binds to rabbit anti-rat AQP2 antibody is present in the apical/subapical regions of both cortical and medullary CDs from normally hydrated quail, and the intensity of staining increased only in the medullary CDs after water deprivation or AVT treatment. The relative density of the approximately 29-kDa protein band detected by immunoblot from the medullary cones was modestly higher in water-deprived/AVT-treated quail. The results suggest that 1) medullary CDs of quail kidneys express a mercury-sensitive functioning qAQP2 water channel, and 2) qAQP2 is at least partly regulated by an AVT-dependent mechanism. This is the first clear identification of AQP2 homolog in nonmammalian vertebrates.

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.

For colorectal carcinomas as well as colonic polyps we investigated the expression of a newly discovered gene, hRFI, which is isolated by the yeast two-hybrid screening using hTid as a bait and expressed highly in esophageal carcinomas. Immunohistochemical staining was performed on 48 colorectal carcinomas and 77 colorectal polyps consisting of 70 adenomas and 7 hyperplastic polyps using the antibody of hRFI. We analyzed the expression of hRFI and the correlation between the percentage of staining of each and their clinico-pathological characteristics. Protein coding by hRFI was specifically and diffusely expressed in most of the cancerous regions of the colorectum. Also, in the early stage of colorectal adenomas, staining of hRFI was focal, and the percentage area of diffuse staining increased as the degree of dysplasia progressed. Although all normal colorectal glands and most hyperplastic polyps (71.4%) showed no staining of hRFI, most colorectal adenomas and carcinomas (93.2%) showed a focal or diffuse staining (P<0.001). Furthermore, the percentage of diffuse staining in carcinomas (81.3%) was significantly higher than in adenomas (5.7%) (P<0.001). hRFI is highly expressed in colorectal carcinomas. In the adenoma-carcinoma sequence, hRFI is involved at the initial tumor formation and its diffuse expression is associated with colorectal carcinogenesis. This evidence suggests that hRFI may act as an oncogenic molecule affecting the apoptotic pathway.

We performed peripheral nerve allografting in rats with spinal cord injury, and measured motor function and axonal membrane potential as well as Ca(2+) concentration of the nerve grafting spinal cord area by using a behavior observation system and a confocal laser-scanning microscope, respectively. In our experiments, we produced a model of peripheral nerve grafting after spinal cord injury by peripheral nerve allografting (sciatic nerve) in rats with spinal cord injury (thoracic cord hemisection). The group with spinal cord injury that underwent peripheral nerve grafting showed improvement in motor function, a significant increase in the axonal action potential, and a slight increase in the Ca(2+) concentration compared with the group that did not undergo nerve grafting.

Stable water-soluble diammonium tris(2-hydroxypropionato)titanate(IV) [ammonium trilactatotitanate(IV)], (NH4)2[Ti(C3H4O3)3], was prepared in the crystalline form. According to the X-ray single-crystal diffraction data, this compound crystallizes in the cubic cell with a = 11.649(4) angstroms, space group P2(1)3 (no. 198), and has Z = 4 molecules per unit cell. The 13C NMR data and Raman and IR spectra support the determined structure. The absence of nonbonded functional groups restricts the formation of oligomers in contrast to the reported speciation of citratoperoxotitanate(IV) complexes., (Copyright 2004 American Chemical Society)

The patient was a 27-year-old man who had been diagnosed as having hyperthyroidism and with an anterior mediastinal mass which was reduced in size after anti-thyroid therapy. This mass was thought to be thymic hyperplasia associated with hyperthyroidism. An anterior mediastinal mass accompanying hyperthyroidism should be surgically treated when it dose not regress after an appropriate antithyroid therapy or there is a clinical suspicion of malignancy.

The potentiometric response characteristics of electrodes based on organic trialkyl/aryl-tin compounds combined with various amounts of anionic additive (NaTFPB) were investigated in 0.1M bis-Tris-H(2)SO(4) buffer solution at pH 7.0. The best result for phosphate sensing was obtained for the electrode membrane containing tributyltin chloride and 25mol% NaTFPB, where the electrode exhibits high selectivity towards phosphate anions with a slope of -60mV per decade. It was demonstrated that the interference from more lipophilic anions is drastically suppressed (log K (ij)(pot ), i=H(2)PO(4)(-): salicylate, 0.5; SCN(-), -0.8; ClO(4)(-), -2.3) under this optimized measurement conditions.

The aim of the present study was to examine the association between daily omega-3 fatty acid intake and depression in Japanese cancer patients. Omega-3 fatty acid intake in 771 patients with newly diagnosed primary lung cancer was evaluated using a food-frequency questionnaire, and the prevalence of depression was examined using the cutoff values for the depression subscale included in the Hospital Anxiety and Depression Scale. After adjustment for potential confounding factors, the odds ratio (OR) for depression among patients in the highest quartile of the total eicosapentaenoic acid- (C20:5n-3) and docosapentaenoic acid (C22:6n-3)-intake group compared with patients in the lowest quartile was not significantly different. On the other hand, the OR among the highest quartile of alpha-linolenic acid (C18:3n-3) intake (adjusted OR=0.50, 95% CI: 0.31-0.71, P for trend=0.004) and the highest quartile of total omega-3 fatty acid intake (adjusted OR=0.55, 95% CI: 0.35-0.88, P for trend=0.022) were significantly different. These results suggest that total eicosapentaenoic acid and docosapentaenoic acid intake might not be associated with depression in Japanese patients with newly diagnosed lung cancer, but that alpha-linolenic acid intake and total omega-3 fatty acid intake might be.

This study investigates anaemia related to the sufficiency of dietary iron intake of school-aged children in the Kzyl-Orda region of Kazakhstan. We conducted a cross-sectional study of 97 school-aged children living in Kzyl-Orda. Blood samples were collected for measuring haemoglobin. Dietary intake data were obtained from 24-h dietary recalls. Iron bioavailability was estimated with algorithms adjusting for absorption enhancers (meat, fish and poultry, and vitamin C) and inhibitors (tea and phytates) consumed in the same meal. The median total iron intakes were adequate compared with the median basal iron requirement; however, the median bioavailable iron intakes were well below the median absorbed iron requirement. Available iron was 6.9-7.2% of the total iron intake after adjusting for the absorption enhancers, and was reduced by 3.1-4.4% after adjusting for both enhancers and inhibitors. After adjustment for energy intake, higher iron intake was significantly associated with a decreased prevalence of anaemia (odds ratio, 0.39; 95% confidence interval, 0.16-0.93; P=0.034). Some evidence suggested an association between bioavailable iron intake after adjustment of absorption enhancers and inhibitors (odds ratio, 0.43; 95% confidence interval, 0.18-1.01; P=0.053). In conclusion, low bioavailability of dietary iron seems related to anaemia in the region. Although iron fortification or supplementation programmes can be useful for promoting the anaemia prevention control programme, further efforts for nutritional education suited for family level dietary practice are necessary.

A 48-year-old woman was admitted for surgery on a lung tumor found incidentally. Her medical history showed a synovial sarcoma of left inguinal region which was resected 12 years ago. We performed segmentectomy of left S4 + 5 to removed the metastatic tumor. Histological examination revealed that the tumor was metastatic synovial sarcoma. Synovial sarcoma can metastasize to lung frequently but such a long disease free interval as 12 years is quite uncommon.

Evidence on the association between salt intake and gastric cancer is sparse, especially in prospective studies. We conducted a population-based prospective study in Japan, where the majority of men has been infected with Helicobacter pylori. A total of 18 684 men and 20 381 women aged 40-59 years who reported their dietary habits and did not report any serious disease at baseline were followed from 1990 to 2001. A total of 486 cases, 358 men and 128 women, with histologically confirmed gastric cancer were documented among them. The quintile category of salt intake was dose-dependently associated with gastric cancer risk in men after adjusting for potential confounding factors (P for trend <0.001), while a trend was not clear in women (P for trend=0.48). Although stratification by study area, with varied salt intake and gastric cancer incidence, attenuated the observed clear associations with salt and salted foods, the frequency categories of highly salted foods such as salted fish roe and salted fish preserves were strongly associated with the risk in both sexes. Restriction of salt and salted food intake is a practical strategy to prevent gastric cancer in areas with high risk.

Aims: To develop immunoglobulin heavy chain variable (VH) gene probes that are shorter and more flexible in position for monitoring minimal residual disease (MRD) in childhood leukaemia (ALL), using minor groove binder (MGB) technology., Methods: All VH germline sequences registered in the database were aligned and the consensus regions were determined. The reliability of the MGB probes was compared with non-MGB probes in all 24 cases of ALL., Results: Ten MGB probes (16 to 18 mers) were designed that enabled all the germline sequences on the database to be analysed, whereas the conventional non-MGB probes (21 to 27 mers) did not allow the analysis of four of the VH1 and five of the VH3 germline sequences. The sequencing results in five of the 24 cases of ALL were not matched to the non-MGB probes., Conclusions: MGB technology allows shorter probes to be designed, enabling MRD to be detected in childhood ALL. This would provide a considerable reduction in cost for a large MRD study.

Purpose: To evaluate the long-term outcome following use of osteochondral autografts for the treatment of osteonecrosis of the femoral condyle., Methods: Clinical, radiographic and arthroscopic findings were evaluated at follow-up. Patients were 14 women and 2 men, with a mean age of 64.9 years (range, 58-74 years). The osteochondral lesion was equivalent to Lotke 1-B in 12 knees, and was equivalent to 1-C in 4 knees. Preoperative femoral tibia angle ranged from 178 degrees to 190 degrees., Results: The follow-up period ranged from 28 months to 111 months (mean, 67 months). Functional scores improved from 60 to 75 preoperatively to 80 to 100 postoperatively, and the grafts were satisfactorily accepted. Patients with a femoral tibia angle of less than 180 degrees in particular were found to respond favourably., Conclusion: Transplant surgery using osteochondral autografting appeared effective for the treatment of osteonecrosis of femoral condyle.

The large conus artery transversing the right ventricular outflow tract may cause more confusion and concern in the surgery of tetralogy of Fallot with a small pulmonary annulus than other well-known coronary anomalies. We experienced an infantile case that precipitated into a critical left ventricular failure caused by transection of a large conus artery for the transannular right ventricular outflow tract reconstruction and rescued the patient with an extracorporeal lung-heart-assist system. Preoperative precise diagnosis of coronary anatomy should serve to protect against fatal mistakes, and various techniques for repair must be chosen individually for this subset of anomalies.

Background: The Aral Sea region is a natural area seriously polluted by human activities. Recent surveillance revealed the increased prevalence of diverse chronic diseases in children., Aims: To investigate the function of renal tubules, which are most at risk of damage as a result of heavy metal intoxication, in children of the Aral Sea region., Methods: A group of 205 children living in Kazalinsk, close to the Aral Sea, and a group of 187 children living in Zhanakorgan, far from the Aral Sea, were examined by means of random urine samples. Both urinary N-acetyl-beta-D-glucosaminidase (NAG; U/mmol Cr) and beta2 microglobulin (BMG; microg/mmol Cr) were calculated for each subject., Results: Mean urinary NAG and BMG were both significantly higher in Kazalinsk than in Zhanakorgan (NAG: 0.77 (0.58) and 0.62 (0.37) U/mmol Cr; BMG: 41.8 (54.8) and 22.5 (20.4) microg/mmol Cr, respectively; mean (SD), p < 0.01). The number of children with abnormal values of NAG (>1.5 U/mmol Cr) was significantly more prevalent in Kazalinsk than in Zhanakorgan (7.9% and 2.6%, respectively, p < 0.05)., Conclusion: Renal tubular function of children around the Aral Sea region is profoundly impaired. This should be taken into account when considering the health problems of this area.

Objective: To examine associations between rate of eating and macronutrient and dietary fiber intake, and body mass index (BMI)., Design: Cross-sectional study., Subjects: A total of 1695 18-y-old female Japanese dietetic students., Measurements: Macronutrient intake (protein, carbohydrate, and fat) and dietary fiber intake were assessed over a 1-month period with a validated, self-administered, diet history questionnaire. Body height and weight and rate of eating (according to five categories) were self-reported., Results: Among the nutrients examined, only dietary fiber intake weakly, but significantly, and negatively correlated with BMI in a multiple regression analysis. The rate of eating showed a significant and positive correlation with BMI. The mean BMI was higher by 2.2, 1.5, 1.0, and 0.5 kg/m(2) in the 'very fast', 'relatively fast', 'medium', and 'relatively slow' groups, respectively, compared with the 'very slow' rate of eating group. This correlation remained evident after adjustment for nutrient intake., Conclusions: Rate of eating showed a significant and positive correlation with BMI, whereas only dietary fiber intake showed a weak correlation with BMI.

We have measured temperature dependences of sound velocity for both longitudinal and transverse sound in nuclear-ordered U2D2 solid 3He with several crystal orientations along the melting curve. The sound velocity change was proportional to T4 for all sound modes and crystal orientations and was attributed to the nuclear-spin part of the internal energy. We extracted six-independent elastic stiffness of the nuclear-spin part and obtained Grüneisen constants of the spin wave velocity for four-independent strains. Grüneisen constants for compressional strain were larger than those for shear strain. Using the multiple-spin-exchange model, we explain the anisotropy of Grüneisen constants in tetragonal symmetry.

The finite element method was used to calculate temperature and thermal stress distribution as a result of hot/cold liquid in the mouth. This numerical study was carried out using axisymmetric finite element models and the tooth model was endodontically treated restored with cast post and cores. The two tooth models evaluated were Ti-Ti alloy and NiCr-AuPd alloy as post material and crown material with porcelain. First, temperature changes on the restored tooth as a result of hot/cold liquid in the mouth were calculated and then the thermal stress as a result of temperature changes were carried out. A fortran computer program was developed for this study. The tooth was assumed isotropic, homogenous, elastic and symmetrical. The distribution of temperature and thermal stress versus time were plotted for four critical points.

The objectives of this study were to estimate the prevalence of anemia and iron deficiency among schoolchildren in the Aral Sea region of Kazakhstan and to determine the various factors associated with anemia in this population. We conducted a cross-sectional study of randomly selected schoolchildren. Blood samples were collected for measuring hemoglobin (Hb), serum ferritin (SF), total iron binding capacity (TIBC), and other hematological indices, and subjects were screened for anemia and iron deficiency. Associations between Hb concentration and SF, TIBC, anthropometric, and socioeconomic data were evaluated using regression analysis. The prevalence of anemia was 49.8 per cent although levels were mostly mild. Twenty-two per cent of the children were iron depleted (SF < 12 microg/l). Of the anemic children, 32.4 per cent were found to have iron deficiency anemia (anemia with SF < 12 microg/l). There were significant positive correlations between the levels of Hb and SF, but a negative correlation with serum TIBC. Age, mean corpuscular volume (MCV) and SF were found to be significantly related to Hb by stepwise multiple regression analysis. Multiple logistic regression analysis revealed that anemia was independently related to living district, education of father, and child's age. The results suggest that iron deficiency is an important determinant of anemia in this population; however, whole anemia cannot be solely explained by iron deficiency. Further studies are needed for consideration of micronutrients status, parasite infestation, hereditary disorders, and exposure to environmental pollutants.

The patient was 67-year-old woman with mitral valve restenosis and regurgitation, tricuspid insufficiency, and left atrial dilatation who underwent mitral valve replacement, tricuspid valvuloplasty, and left atrial plication. The patient developed right ventricular (RV) failure due to RV infarction when she was weaned from cardiopulmonary bypass (CPB). Therefore, CPB was resumed to be followed by intra-aorta balloon pumping (IABP). However, complete response was not obtained. Thus, right ventricular support was performed using a centrifugal pump, and the patient could be weaned from CPB. Three days after surgery, the right ventricular support was discontinued, and IABP was removed 7 days after surgery without marked changes in hemodynamics. Although RV failure due to RV infarction is a serious intraoperative complication, favorable results were obtained by combination therapy with IABP and right ventricular support using a centrifugal pump in our patient.

Magnesium diboride, MgB2, has the highest transition temperature (T(c) = 39 K) of the known metallic superconductors. Whether the anomalously high T(c) can be described within the conventional BCS (Bardeen-Cooper-Schrieffer) framework has been debated. The key to understanding superconductivity lies with the 'superconducting energy gap' associated with the formation of the superconducting pairs. Recently, the existence of two kinds of superconducting gaps in MgB2 has been suggested by several experiments; this is in contrast to both conventional and high-T(c) superconductors. A clear demonstration of two gaps has not yet been made because the previous experiments lacked the ability to resolve the momentum of the superconducting electrons. Here we report direct experimental evidence for the two-band superconductivity in MgB2, by separately observing the superconducting gaps of the sigma and pi bands (as well as a surface band). The gaps have distinctly different sizes, which unambiguously establishes MgB2 as a two-gap superconductor.

In Japan we have a standardized protocol for the management of gestational trophoblastic diseases issued by the Japan Society of Obstetrics & Gynecology in 1988. Hydatidiform moles should be treated by evacuating the uterus. Patients must then be followed up until serial weekly serum hCG titres fall to undetectable levels. Our hCG regression curve post-evacuation is quite useful for the detection of persistent trophoblastic diseases. Persistent trophoblastic diseases develop in about 10-15 per cent of patients after molar evacuation in Japan. We classify persistent trophoblastic diseases into three groups: (1) post-molar persistent hCG; (2) invasive mole or metastatic moles; and (3) choriocarcinoma. Investigations into any possible metastases are carried out as soon as possible in affected patients. Post-molar persistent hCG presents no focus or histological findings except persistent elevated hCG, although single agent chemotherapy is required. In the other two groups with focus, it is very difficult to get histological specimens to make accurate diagnoses unless surgery is done. For the selection of the most appropriate chemotherapy, what we call a 'Diagnostic Score' is applied to differentiate choriocarcinoma from invasive moles or metastatic moles clinically in patients falling into these two groups. This unique 'Diagnostic Score' for the detection of choriocarcinoma plays an important role in initial management in our protocol.

Background: Bone marrow (BM) cells have been shown to augment local angiogenesis by differentiating vessels themselves and/or secreting paracrinally angiogenic growth factors. Herein, the angiogenic effects of intra-arterial BM mononuclear cell (BM-MNC) transplantation were evaluated in a rat ischemic hindlimb model., Methods: Unilateral hindlimb ischemia was created by excising the femoral artery and its branch in Lewis rats. BM-MNCs were isolated by centrifugation through a Histopaque density gradient. One week after excision of the unilateral femoral artery, BM-MNCs (5 x 10(6) cells, Group A, n = 6) or PBS (Group B, n = 7) were injected into the ischemic thigh skeletal muscles at the six points with a gauge needle. Another injection of BM-MNCs (3 x 10(7) cells, Group C, n = 6) or PBS (Group D, n = 7) was administered via the indwelling catheter in the right common iliac artery., Results: Four weeks after the BM-MNC transplantation, angiographic examination revealed the development of collateral vessels in both BM-MNC-transplanted groups. The difference in skin temperature between right and left hindlimbs was significantly reduced in both BM-MNC-transplanted groups (0.93 +/- 0.15 vs. 2.84 +/- 0.35 vs. 1.20 +/- 0.26 vs. 2.61 +/- 0.37 degrees C, Group A vs. Group B vs. Group C vs. Group D, p < 0.05). Moreover, immunohistochemical analysis demonstrated that capillary endothelial cells were increased in both BM-MNC-transplanted groups., Conclusion: BM-MNC implantation was able to induce functional neovascularization in rat ischemic hindlimb. The intra-arterial administration offered similar levels of angiogenic activity as intramuscular injection., (Copyright 2003 S. Karger AG, Basel)

The chronological changes in intracellular Ca(2+)concentrations ([Ca(2+)](i)) were analysed during heat-induced apoptosis in human lung cancer cell lines LK-2 (squamous cell carcinoma) and LU65A (large cell carcinoma). In LK-2 cells, increased [Ca(2+)](i) levels were maintained at levels between 250-350 nm 9 h after heat-shock. Treatment with BAPTA, an intracellular Ca(2+) chelator, prior to heat-shock, decreased the frequency of heat-induced apoptosis in LK-2, while thapsigargin, a selective endoplasmic reticulum Ca(2+)-ATPase inhibitor, did not change the number of apoptotic cells, regardless of the presence or absence of Ca(2+)-supplemented medium. In LU65A cells, treatment with BAPTA or thapsigargin did not alter the apoptotic rates. Western blotting demonstrated that, although expression of Bax and Bcl-2 were not changed by heat-shock, p53 expression was elevated in LK-2, but not LU65A cells. Immunohistochemistry showed that p53 was localized predominantly in the cytoplasms of LK-2 cells, suggesting that p53 protein is not functional in LK-2. Heat-shock also elevated activities of caspase-3, -8 and -9 in both cell lines. It is concluded that a temporal increase in [Ca(2+)](i) is the important initiating factor in hyperthermia-induced apoptosis in LK-2 cells and that, in these two lung cancer cell lines, apoptosis may occur through 'cross-talk' between p53-independent mitochondrial and death receptor pathways.

Objectives: Left ventricular (LV) mechanical unloading is known to reduce the hemodynamic demands of failing LV, resulting in improved myocyte contractility. This study was designed to examine effects of LV unloading on beta-adrenergic receptor (BAR) expression and ischemic susceptibility to ischemia reperfusion., Methods: Five groups were studied: group 1 [unloading myocardial infarction (MI), n = 6], MI hearts 2 weeks after coronary ligation subjected to LV unloading by heterotopic heart transplantation for 2 weeks; group 2 (2-week MI, n = 6), MI hearts left for 2 weeks without unloading; group 3 (4-week MI, n = 6), MI hearts left for 4 weeks without unloading; group 4 (control, n = 6), normal (non-MI) hearts as a control with no interventions, and group 5 (unloading control, n = 5), normal (non-MI) hearts subjected to LV unloading for 2 weeks. Then, all hearts were isolated and subjected to 20 min of global ischemia and 60 min of reperfusion on Langendorff apparatus. LV pressures and coronary flow were measured throughout the experiment. Either total BAR density or beta(2)-adrenergic receptor (B2AR) mRNA expression in the noninfarcted myocardium was determined by radioligand binding assays or real-time quantitative RT-PCR, respectively., Results: LV unloading improved postischemic functional recovery (unloading MI vs. 2-week MI vs. 4-week MI: 74 +/- 6 vs. 54 +/- 5 vs. 51 +/- 4%; p < 0.05 vs. unloading MI). LV unloading restored B2AR mRNA expression (unloading MI vs. 2-week MI vs. 4-week MI: 4.78 +/- 0.21 vs. 2.80 +/- 0.19 vs. 2.24 +/- 0.17 x 10(7) copy/microg total RNA; p < 0.05 vs. unloading MI)., Conclusion: LV mechanical unloading restored B2AR mRNA expression and improved postischemic functional recovery., (Copyright 2003 S. Karger AG, Basel)

Purpose: Cellular mechanisms of excitatory neuromuscular transmission in circular smooth muscles of the seminal vesicle were investigated., Materials and Methods: Circular smooth muscles of the seminal vesicle of the guinea pig were isolated. Changes in membrane potential produced by transmural nerve stimulation were recorded using intracellular microelectrode techniques. Changes in the intracellular Ca ion concentration induced by transmural nerve stimulation were measured in preparations loaded with Ca indicator fura-PE3. Responses produced by bath applied norepinephrine and alpha,beta-methylene adenosine triphosphate (ATP) were also examined., Results: Transmural nerve stimulation evoked excitatory junction potentials that triggered action potentials and also caused transient increases in [Ca2+] (Ca transients). Nifedipine abolished action potentials, leaving underlying excitatory junction potentials unchanged, and reduced the amplitude of Ca transients. Excitatory junction potentials were blocked by alpha,beta-methylene ATP or guanethidine but not by phentolamine. A train of transmural nerve stimulation evoked oscillatory changes in membrane potential and [Ca2+], which were abolished by phentolamine or inhibited by nifedipine. Nifedipine insensitive components were abolished by cyclopiazonic acid. Norepinephrine depolarized the membrane and elicited oscillatory potentials with an associated elevation in [Ca2+]. These responses were inhibited by nifedipine and abolished by additional application of cyclopiazonic acid. Transient depolarization with an associated increase in [Ca2+] was elicited by alpha,beta-methylene ATP and [Ca2+] responses but no potential changes were inhibited by nifedipine., Conclusions: Circular smooth muscles of the guinea pig seminal vesicle receive a projection of sympathetic nerves that release norepinephrine to initiate slow depolarization through the activation of alpha-adrenoceptors. These nerves also release ATP to elicit excitatory junction potentials. Neurally released norepinephrine and ATP are increased [Ca2+] by the influx of Ca2+ through L-type Ca2+ channels and also by the release of Ca2+ from internal stores.

The purpose of this study was to calculate the temperature and thermal stress distribution as a result of hot/cold liquid in the mouth. This numerical study was carried out using three-dimensional finite element models and the tooth model was crowned with Au-Pd alloy, Ni-Cr alloy and porcelain. In the first part of the study, temperature changes as a result of hot/cold liquid in the mouth were calculated. In the second part, the thermal stresses caused by temperature changes were obtained. The tooth was assumed isotropic, homogenous, elastic and unsymmetrical. The authors using fortran 77 prepared all calculation programs. The distribution of temperature and thermal stress were plotted for some critical points.

Previously, we discovered a novel type of depolarization wave in the embryonic chick brain by using a multiple-site optical recording technique with a fast voltage-sensitive dye. This depolarization wave traveled widely over almost all the region of the CNS. This profile has raised the possibility that the depolarization wave plays some global roles in development of the CNS, rather than contributing to a specific neuronal circuit formation. To obtain more information concerning this issue, in the present study, we examined whether the depolarization wave was triggered by various types of peripheral nerve inputs. Stimulation applied to the vagus, glossopharyngeal, cochlear and trigeminal nerves evoked widely spreading depolarization waves with similar spatiotemporal distribution patterns. The developmental sequence of wave expression was parallel to the development of the excitatory postsynaptic potentials in each sensory nucleus. The depolarization wave was accompanied by a Ca(2+)-wave, suggesting that not only electrical synchrony, but also large-scale Ca(2+)-transients may affect developmental processes in the embryonic brain. Furthermore, we found that the depolarization wave also occurred spontaneously. The waveform and distribution patterns of the spontaneous optical signals were similar to those of the cranial nerve-evoked depolarization wave. These results demonstrated that the depolarization wave in the embryonic chick brain is triggered by multiple sources of external and endogenous activity. This profile supports the idea that this depolarization wave may not serve as a simple regulator of specific neuronal circuit formation, but might play more global roles in CNS development., (Copyright 2003 IBRO)

Examination of 38 human melanoma samples by Western blotting analysis with anti-gelsolin antibodies showed that a new 85 kDa truncated gelsolin (GSNp85), co-expressed with wild-type gelsolin, was frequently expressed in vertical growth phase melanomas (Clark level II-IV) and metastatic growth phase melanomas. The GSNp85 truncate was not expressed in radial growth phase melanomas (Clark level I), acquired naevi, other skin cancers or normal skin tissues. Peptide-sequencing analysis revealed that GSNp85 lacks the C-terminal domain of wild-type gelsolin at the region containing the caspase-8 recognition site IETD. Caspase-8 processing was detected in GSNp85-positive but not GSNp85-negative melanomas. These data suggest that GSNp85 is a cleavage product of caspase-8 and may be useful as a new marker for the vertical or metastatic growth phase of malignant melanoma.

Peritoneal dissemination is the most frequent type of recurrence in patients with gastric cancer with serosal exposure, irrespective of whether they have undergone curative gastrectomy. The purpose of this study was to establish a method to detect micrometastatic cells in the abdominal cavity and predict peritoneal recurrence in patients with such gastric carcinomas. A total of 86 patients with gastric carcinoma, undergoing gastrectomy, were examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect carcinoembryonic antigen (CEA) mRNA in abdominal lavage fluid. Twenty-four cases without serosal exposure were negative, while all 13 cases with macroscopic peritoneal dissemination were positive for CEA mRNA. Among the 49 cases with macroscopic serosal invasion and without peritoneal metastasis, cancer cells were detected in 27 cases with RT-PCR while in only 6 cases with conventional cytology. All cytologically-positive cases were also positive for CEA mRNA. Among the 27 CEA-positive cases, 15 patients (56%) relapsed with peritoneal metastasis within 12 months after gastrectomy. In contrast, none of the 22 CEA-negative cases had peritoneal recurrence within 16-60 months of observation, whereas in 43 cytologically-negative cases, 10 patients relapsed with peritoneal recurrence. As compared with conventional cytological examination, this method would be clinically more beneficial for detecting free cancer cells in the peritoneal cavity and for predicting peritoneal recurrence in gastric carcinoma with serosal invasion.

We quantitatively investigated the change in nitric oxide (NO) in the hypothalamic paraventricular nucleus (PVN) and its effect on cardiovascular regulation during shaker stress (SS) using brain microdialysis in awake rats. Male Wistar rats were fed either N(G)-nitro-L-arginine methyl ester (L-NAME, 0.7 g/L) or tap water for 2 weeks. Two days after implantation of an arterial catheter and guide shaft, a microdialysis probe was placed to perfuse the PVN with degassed Ringer solution at 2 microl/min in awake normotensive Wistar (CONTROL) and chronic L-NAME-treated hypertensive rats. After the rat was placed in a plastic cage set on a shaker, the blood pressure and heart rate was monitored and 10-min SS was loaded at a frequency of 200 cycles/min. Dialysate samples were analyzed by NO analyzer (based on the Griess reaction) every 10 min, and NOx (NO(2)(-) + NO(3)(-)) was measured. Plasma NOx was also measured before and after SS. Pressor responses elicited by SS were significantly greater in L-NAME-treated rats than in the CONTROL. Although NOx in the PVN dialysate were increased by SS in the CONTROL, these responses were attenuated in chronic L-NAME-treated rats. Resting plasma NOx were higher in the CONTROL than in L-NAME-treated rats. SS elicited no difference between two groups in plasma NOx. These results indicated that NO within the PVN, but not in systemic circulation, may play a role on the attenuation of the pressor responses elicited by SS. The dysfunction of NO release within the PVN may, in part, play a role in the exaggerated pressor responses in acute environmental stress.

Expression of the EP4 receptor, a prostaglandin (PG)E2 receptor subtype, as well as disease suppression by the administration of a selective EP4 agonist (ONO-AE1-329) was investigated in the colorectal mucosa of rats with dextran sodium sulphate (DSS)-induced colitis. Rats were given drinking water containing 3% DSS for 2 weeks. Expression of EP4 receptor mRNA was barely detectable under normal conditions according to reverse transcription-polymerase chain reaction (RT-PCR). By 1 week after the initial administration of DSS, the receptor mRNA was strongly expressed. After ONO-AE1-329 was administered intracolonically to rats with DSS colitis for 7 consecutive days, erosion and ulceration decreased. Peripheral white blood cell (WBC) counts became less elevated. Interleukin (IL)-1beta and growth-regulated gene product/cytokine-induced neutrophil chemoattractant (GRO/CINC-1) concentrations in colorectal mucosa were lower than in colitis control group (IL-1beta: 12.8 +/- 4.6 and 30.8 +/- 6.2 microg/mg protein, P < 0.05; GRO/CINC-1: 15.5 +/- 3.0 and 39.2 +/- 5.4 microg/mg protein, P < 0.05), and the expression of the corresponding cytokine mRNA was strongly suppressed. IL-10 concentration was higher than in control group (14.5 +/- 1.7 and 7.9 +/- 1.2 microg/mg, P < 0.05), and the mRNA was more strongly expressed. These results suggest that the EP4 receptor is important in colonic inflammation, and that PGE2 suppresses DSS colitis at least partly via the EP4 receptor and the above cytokine changes. Intracolonic administration of selective EP4 agonist might have therapeutic applicability in inflammatory bowel disease such as ulcerative colitis.

Apoptosis-inducing caspases have been tested for immunomodulatory effect on a gene gun-delivered DNA vaccine which expresses influenza hemagglutinin. Attenuated murine caspase 2 and a chimera of murine caspase 2 prodomain and human caspase 3 strongly enhanced humoral and cell-mediated immune response to hemagglutinin when they were co-administered with an immunogen DNA. In contrast, wild-type caspases did not enhance the DNA-raised immune response. Caspase dose-dependent antibody response curve revealed that the antibody level was in inverse relation to the amount of administered caspase. These findings indicate that bland apoptosis of antigen-harboring cells can elicit enhanced immune responses. Extensive apoptosis interferes with the generation of immune response. Gene gun delivery involving caspases elicited type-2 immune responses that characterized with dominant IL-4 and IgG1 production. ELISPOT assays showed that CD4 T cells were preferentially activated, while CD8 T cell response remained at marginal level. Using attenuated caspases for gene gun DNA vaccination is a useful approach to amplify type-2 immune responses.

The precise role of microsatellite instability (MSI) in the development of multiple colorectal cancers has not been elucidated. In the present study, the authors examined MSI and the clinicopathological features of both cancers and concomitant adenomas in nonfamilial multiple synchronous colorectal cancer (multiple CC) patients. Fifty adenomas and 108 cancers were obtained from the surgically resected specimens of 51 multiple CC patients. Nine microsatellite markers were used to determine MSI by polymerase chain reaction (PCR). The frequency of MSI-H adenomas in multiple CC patients was higher than that in single CC patients, while MSI-H frequency of cancers was similar to that in single CC patients. There was a tendency that, in multiple CC patients, when a patient has an MSI-H adenoma, he/she also has MSI-H cancer. The clinicopathological features of multiple CC were similar to those of single CC except the ratio of mucinous cancer and concomitant adenomas. According to this study, in some multiple CC patients, genetic instability seems to play an important role in the development of cancers as well as adenomas. We regard MSI testing for multiple CC patients is useful to distinguish "MSI-related" multiple CC from "MSI-unrelated" multiple CC, and MSI-related multiple CC should be followed up carefully as hereditary nonpolyposis colorectal cancer (HNPCC) patients.

Background: Inhibition of Na(+)/H(+) exchange has been shown to provide functional protection during ischemia and reperfusion in mature heart. This study was undertaken to elucidate the effect of Na(+)/H(+) exchange inhibitor HOE642 in the aged rabbit heart., Methods: Isolated rabbit hearts were subjected to 1 h of left descending coronary artery (LAD) ischemia and 1 h of reperfusion. To determine the effects of HOE642 on ischemia/reperfusion injury, seven aged or mature hearts received the Na(+)/H(+) exchange inhibitor HOE642 (1 microM) for 15 min before the ischemia and for 30 min after reperfusion. Seven aged (more than 135 weeks) or mature (15-20 weeks) rabbit hearts served as a control (untreated) with no interventions. Left ventricular pressures, monophasic action potentials and coronary flows were measured throughout the experiment and infarct size was detected at the end of experiment., Results: (1) In the mature hearts, HOE642 improved postischemic functional recovery (63.1 +/- 5.0% vs. 84.4 +/- 5.4%, mature untreated vs. mature HOE, p < 0.05) and reduced infarct size as compared to untreated hearts (42.0 +/- 2.5% vs. 24.8 +/- 2.3%, mature untreated vs. mature HOE, p < 0.05). (2) Although infarct size in aged untreated hearts was significantly decreased as compared to mature untreated hearts (42.0 +/- 2.5% vs. 19.3 +/- 1.6%, mature untreated vs. aged untreated, p < 0.05), there are no significant differences regarding postischemic functional recovery between mature and aged untreated hearts (63.1 +/- 5.0% vs. 59.5 +/- 5.9%, mature untreated vs. aged untreated, p = n.s.). (3) In the aged hearts, HOE642 improved postischemic functional recovery as compared to untreated hearts (59.5 +/- 5.9% vs. 85.9 +/- 8.1%, aged untreated vs. aged HOE, p < 0.05)., Conclusion: Na(+)/H(+) exchange inhibitor HOE642 is effective against ischemia-reperfusion injury in senescent as well as mature hearts., (Copyright 2002 S. Karger AG, Basel)