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Y Ishii

Publications and source records attributed to Y Ishii.

At least 37 records · Page 2Linked to original sources
PubMed2005

Age-related changes of intracellular Abeta in cynomolgus monkey brains.

To confirm the intracellular accumulation of amyloid beta-protein (Abeta), we carefully performed immunohistochemistry using brains of cynomolgus monkeys of various ages. Cortical neurones and their large neurites were immunostained with antibodies against Abeta in young monkey brains. In aged monkey brains, intracellular Abeta localized within cortical neurones; no clear association was found between the presence of intracellular Abeta and senile plaques (SPs). Interestingly, we did not observe Abeta-immunoreactive cortical neurones in brains fixed with neutral buffered formalin. Western blot analyses of microsomal and nerve ending fractions derived from the brains of young to aged monkeys revealed that intracellular Abeta generation changed with age. In the microsomal fraction, the amount of Abeta42 significantly increased in brains from older monkeys (>30 years of age), and the amount of Abeta43 significantly decreased with age in the microsomal fraction. The amount of Abeta40 remained the same regardless of age. Biochemical analyses also showed that intracellular levels of each of these Abeta molecules significantly increased with age in nerve ending fractions. As we previously observed that a similar accumulation of presenilin1, beta-amyloid precursor protein (APP) and APP C-terminal fragment cleaved by beta-secretase in the nerve ending fractions obtained from brains with SPs, the accumulation of intracellular Abeta in this fraction may be closely related to formation of spontaneous SPs with age. Taken together, these results suggest that intensive investigation of age-related changes in the nerve ending will contribute to a better understanding of the pathogenesis of age-related neurodegenerative disorders such as sporadic Alzheimer's disease.

Aging↗
PubMed2005

Long-term outcome of per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer.

OBJECTIVE: The authors have performed per anum intersphincteric rectal dissection. With direct coloanal anastomosis for cases of lower rectal cancer in which the distal surgical margin is difficult to secure by the double stapling technique. The aim of this study was to evaluate the long-term outcome and to clarify the surgical indications for this operation. PATIENTS AND METHODS: Between 1993 and 2002, 31 patients underwent per anum intersphincteric rectal dissection with direct coloanal anastomosis. Of these, two patients (one stage 0 and one stage IV) were excluded from the analysis of oncological outcome. The remaining 29 patients formed the basis of this study. The median follow-up was 57 months (range 6-106 months). RESULTS: Local recurrence and distant metastasis developed in 9 and 3 patients, respectively. Local recurrence rate for pT1 was significantly lower than that for pT2/T3 disease. The local recurrence rate cases with tumours less than 3 cm was significantly lower than that for tumours sized 3 cm or more. The distant metastasis rate for cases with lymph node metastasis was significantly higher than that for cases without lymph node metastasis. There was an association between distant metastasis and TNM or pT stage. The overall survival rates for stage I, II and III were 85%, 80% and 89%, respectively. No significant difference was seen in total Cleveland Clinic incontinence score between per anum intersphincteric rectal dissection with direct coloanal anastomosis and the double stapling technique. CONCLUSION: The surgical indications of this operation should be limited to patients with T1 rectal cancer or tumours less than 3 cm.

Adult↗
PubMed2005

PYY3-36 as an anti-obesity drug target.

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Animals↗
PubMed2005

Sequence analysis of the MHC class II DPB1 gene in chimpanzees (Pan troglodytes).

The diversity of the MHC class II region in non-human primates is a focus of biomedical research because this region plays a crucial role in the recognition of antigens in the immune system. In particular, the chimpanzee [Pan troglodytes (Patr)], which belongs to the superfamily Hominoidea, has been used as a human model for the study of diseases such as human hepatitis C virus (HCV), human hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, to which only humans and chimpanzees are susceptible. In the present study, polymorphisms of the MHC-DPB1 gene (Patr-DPB1) in a chimpanzee colony in Japan were examined using a stepwise polymerase chain reaction (PCR) technique. In order to design a suitable primer pair which would amplify exon 2 of the Patr-DPB1 gene, a fragment of approximately 8 kb from exon 1 to exon 3 was amplified from chimpanzee genomic DNA. After designing a 500-bp primer pair at the 3' region of intron 1 and the 5' region of intron 2, analysis of DPB1 exon 2 alleles of each chimpanzee was carried out. Twenty-two chimpanzees were used in our study, and we identified seven alleles by sequence analysis on the Patr-DPB1 gene, including one new allele. The obtained nucleotide sequence patterns suggest that Patr-DPB1 alleles emerge by genetic variations such as the exchange of sequence motifs and the accumulation of point mutations.

Alleles↗
PubMed2005

Varus-valgus balance and range of movement after total knee arthroplasty.

We performed a randomised, prospective study of 80 mobile-bearing total knee arthroplasties (80 knees) in order to measure the effects of varus-valgus laxity and balance on the range of movement (ROM) one year after operation. Forty knees had a posterior-cruciate-ligament (PCL)-retaining prosthesis and the other 40 a PCL-sacrificing prosthesis. In the balanced group (69 knees) in which the difference between varus and valgus was less than 2 degrees, the mean ROM improved significantly from 107.6 degrees to 117.7 degrees (p < 0.0001). By contrast, in the 11 knees which were unbalanced and in which the difference between varus and valgus laxity exceeded 2 degrees, the ROM decreased from a mean of 121.0 degrees to 112.7 degrees (p = 0.0061). We conclude that coronal laxity, especially balanced laxity, is important for achieving an improved ROM in mobile-bearing total knee arthroplasty.

Aged↗
PubMed2004

Satiety enhancement by selective orexin-1 receptor antagonist SB-334867: influence of test context and profile comparison with CCK-8S.

Acute systemic treatment with the selective orexin-1 (OX1R) antagonist SB-334867 reduces food intake in rats, an effect associated with an acceleration in behavioural satiety and unrelated to gross behavioural disruption, alterations in palatability, or toxicity. However, as enhanced satiety is behaviourally indexed by an earlier-than-normal transition from eating to resting, and since orexin-A has been implicated in mechanisms of arousal, it remains possible that sedation contributes to the anorectic effect of acute OX1R blockade. Previous work has shown that, when treated with SB-334867 (30 mg/kg, i.p.) 30 min before a 1h test with palatable food, rats begin to show appreciable levels of resting 10-15 min earlier than under control conditions (i.e. around 20 min versus 30-35 min into the session). The present results demonstrate that a 20 min increase in the injection-test interval (i.e. 50 min) had no significant impact on the anorectic, behavioural or weight gain effects of SB-334867 in non-deprived male rats. Most importantly, this altered treatment regimen led to a temporal profile of resting virtually identical to that previously observed with the more conventional 30 min injection-test interval. Although parallel studies indicated that the OX1R antagonist accelerated the onset of resting (and suppressed most active behaviours) even in the absence of food, an equianorectic dose of the natural satiety-related signal cholescystokinin octapeptide (CCK-8S; 5 microg/kg, i.p.) also produced very similar behavioural effects regardless of the presence of food. Together with evidence that SB-334867 preserves the structural integrity of natural feeding behaviour, does not induce nausea/illness or alter taste/palatability and fails to influence EEG measures of arousal/sleep, the present findings are consistent with the view that acute OX1R antagonism selectively enhances satiety. However, unlike the immediate short-circuiting of the satiety sequence induced by CCK-8S, the slower response to SB-334867 implies a more indirect mechanism of action.

Analysis of Variance↗
PubMed2004

Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis.

BACKGROUND: Probiotics are efficacious for treating and maintaining remission of ulcerative colitis. AIM: To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis. METHODS: Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment. RESULTS: Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group. CONCLUSION: Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results.

Adult↗
PubMed2004

Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

Animals↗
PubMed2004

Effect of total knee arthroplasty on patients' bone quality-ultrasound measurement of the calcaneus.

We used ultrasonographic heel measurements to compare the bone quality of patients who underwent total knee arthroplasty (TKA), age-matched controls and patients who suffered from hip fracture. The broadband ultrasound attenuation (BUA; dB/MHz) of the TKA (70), control (70) and hip fracture (107) groups was 42.2+/-15.5, 40.2+/-14.9 and 22.9+/-13.3, respectively. The hip fracture group was significantly different from both the TKA and control groups (P<0.0001). The TKA group had better BUA than the control group, although the difference was not significant (P=0.712). The increase in activity after artificial replacement of an arthritic joint might result in bone quality equivalent to that of controls. Considering that none of TKA patients suffered from hip fracture in the follow-up period, which ranged from 62 to 113 months, TKA might contribute to a decrease in the risk of later hip fracture, by allowing increased mobility and maintaining or improving bone quality.

Aged↗
PubMed2004

Differential effects of the selective orexin-1 receptor antagonist SB-334867 and lithium chloride on the behavioural satiety sequence in rats.

Recent studies have shown that acute systemic administration of the selective orexin-1 receptor antagonist SB-334867 significantly reduces food intake in rats. Although this anorectic action of orexin-1 receptor blockade is associated with an acceleration in the transition from eating to resting, it is widely recognised that the behavioural indices of satiety are not dissimilar to those of illness. In this context, Experiment 1 confirmed a significant anorectic effect of 90 (but not 60) mg/kg lithium chloride (LiCl) in male rats presented with palatable mash in the home-cage environment. Experiment 2 employed a continuous monitoring technique to contrast the effects of LiCl (90 mg/kg) and SB-334867 (10 and 30 mg/kg) on food intake and behaviour during a 1-h test with palatable mash. SB-334867 dose-dependently inhibited food intake, with the higher dose producing a comparable degree of appetite suppression (approximately 40%) to that seen with LiCl. Despite equivalent anorectic action, the two compounds produced very different effects on behaviour. LiCl reduced active behaviours (locomotion, rearing, grooming and sniffing), slowed the rate of eating and disrupted the behavioural satiety sequence (BSS). In contrast, SB-334867 (30 mg/kg) decreased the duration of feeding and grooming, and modestly accelerated the transition between eating and resting. Furthermore, whereas LiCl failed to alter posttreatment bodyweight gain, SB-334867 (30 mg/kg) produced a significant weight loss in the 24-h period immediately following injection. Overall, the divergent profiles obtained with equianorectic doses of LiCl and SB-334867 provide convincing evidence for the behavioural selectivity of SB-334867-induced anorexia.

Animals↗
PubMed2004

Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones.

Some regulators of plant growth and differentiation have been shown to induce the differentiation of several human myeloid leukemia cells, and might be effective as differentiation inducers to control acute myelogenous leukemia cells. In this study, the growth-inhibiting and differentiation-inducing effects of jasmonates on human myeloid leukemia cells were examined. Several myeloid leukemia cells were cultured with methyl jasmonate (MJ) and its derivatives. Cell differentiation was determined by nitroblue tetrazolium-reducing activity, morphological changes, alpha-naphthyl acetate esterase activity and expression of differentiation-associated surface antigens. MJ induced both monocytic and granulocytic differentiation of HL-60 cells. MJ activated mitogen-activated protein kinase (MAPK) in the cells before causing myelomonocytic differentiation. MAPK activation was necessary for MJ-induced differentiation, since PD98059, an inhibitor of MAPK kinase, suppressed the differentiation induced by MJ. MJ also induced the differentiation of other human leukemia cell lines. Introduction of a double bond at the 4,5-position greatly enhanced the differentiation-inducing activity of MJ. MJ and its derivatives potently induce the differentiation of some myelomonocytic leukemia cells. One novel derivative is a particularly promising therapeutic agent for the treatment of leukemia.

Cell Differentiation↗
PubMed2004

Early pathophysiologic feature of arthropathy in juvenile dogs induced by ofloxacin, a quinolone antimicrobial agent.

Arthropathy in dogs induced by ofloxacin, a quinolone antimicrobial agent, was pathophysiologically investigated. In the in vivo studies, ofloxacin was administered orally once or twice at 20 mg/kg/day to male juvenile (3-month-old, n=3) or adult (36-month-old, n=2) dogs, and the humeral and femoral heads were examined pathologically. Unlike adult dogs, fluid-filled vesicles were macroscopically observed on the articular surfaces of one juvenile dog 24 hours after a single treatment with ofloxacin. These lesions were seen in all juvenile dogs by twice dosing. Microscopically, fissures or cavity formations in the middle zone of the articular cartilage were noted only in juvenile dogs. Furthermore, the cartilage matrix from the abnormal area to the articular surface showed a decreased safranin-O staining intensity, suggesting proteoglycan depletion. Ultrastructurally, chondrocytes in the middle zone of juvenile dogs displayed dilatation of the cisternae in the rough endoplasmic reticulum as an initial hallmark. In the in vitro studies, chondrocytes isolated from the articular cartilage of naive juvenile dogs were exposed to ofloxacin at 6.3-100 microg/ml for 24 hours. Although no changes were noted in the deoxyribonucleic acid synthesis, protein synthesis, or proteoglycan release at concentrations of up to 100 microg/ml, the proteoglycan synthesis was evidently decreased in a dose-dependent manner from 12.5 microg/ml. The results obtained suggest that the inhibitory action of ofloxacin on proteoglycan syntheses in the chondrocytes may largely contribute to the early morphologic features in the articular cartilage of the juvenile dog.

Age Factors↗
PubMed2003

Effects of systematic variation in presatiation and fasting on the behavioural satiety sequence in male rats.

Preclinical research on the neurobiology of appetite regulation is increasingly employing detailed behavioural assessment in addition to measures of food intake. One of the most widely used approaches examines treatment effects on the behavioural satiety sequence (BSS), a concept describing the predictable pattern of behavioural change (feeding-->grooming-->resting) associated with the process of satiation in rats, mice and other mammals. Surprisingly, however, comparatively little published detail is available concerning the impact of more natural appetite modulators on the BSS. In two separate experiments, a continuous monitoring technique was used to calibrate the effects of prefeeding (3, 6 and 9 min) and prior fasting (3, 6 and 12 h) on the microstructure of rat behaviour during a 1 h test with palatable mash. Prefeeding significantly increased eating latencies and reduced both food intake and total duration (but not frequency) of feeding behaviour. The reduction in time spent eating was most evident during the first 15 min of the test when feeding is normally at peak levels. Although behavioural structure was fully preserved in all test conditions, the two larger preloads resulted in shifts to the left (i.e., an acceleration) in the BSS. In contrast, fasting for 6 and 12 h (but not 3 h) increased food intake and duration (but not frequency) of feeding behaviour in the early part of the test. All fasting conditions (including 3 h) produced considerable shifts to the right (i.e., a delay) in the BSS, confirming the greater sensitivity of this measure relative to food intake per se. The potential utility of these reference profiles is discussed in relation to drug-induced changes in food intake and the BSS.

Animals↗
PubMed2003

Palatability, food intake and the behavioural satiety sequence in male rats.

Food intake is influenced not only by nutritional status but also by diverse environmental factors. Indeed, a unique quality of food reward is its strong modulation by palatability cues, such as taste, with animals generally preferring diets that are sweet and avoiding those that are either bitter or sour. As appetite suppressants (including those currently in development) could alter food intake by modifying taste sensitivity and/or palatability, the aim of the present study was to characterise the influence of taste adulteration on the normal structure of feeding behaviour, i.e., the behavioural satiety sequence (BSS). Adult male rats were initially habituated both to the basic test diet (mash) and the test arena. Following stabilisation of basal intake, a continuous monitoring technique was used to profile behaviour in weekly 1-h sessions during which the animals were presented, in counterbalanced order, with the basic diet (control) or one of four taste-adulterated variants (0.015% quinine, 0.04% quinine, 0.2% saccharin, 0.3% saccharin). Food intake was strongly suppressed by the higher quinine concentration but was not significantly altered by any of the other additives. Behavioural analysis revealed that this anorectic-like response to 0.04% quinine-adulterated food was associated with a significant reduction in the peak feeding response, highly atypical intermittent food sampling/digging and the virtual absence of resting behaviour. Importantly, this pattern of behavioural change is readily distinguishable from those seen in response to other manipulations that reduce intake, including selective anorectics, sedatives and psychostimulants. Despite the lack of significant effect on food intake or the duration of feeding behaviour, dietary adulteration with 0.015% quinine (and, to a lesser degree, 0.3% saccharin) produced some effects on behavioural structure/time course consistent with a mild aversive response, i.e., bouts of midsession food sampling and a delay in the transition from eating to resting. Data are discussed in relation to the specific behavioural signature to quinine-induced anorexia and its potential utility in identifying appetite suppressants that may modify intake via changes in taste sensitivity and/or palatability.

Animals↗
PubMed2003

Blood flow per unit retinal nerve fibre tissue volume is lower in the human inferior retina.

AIM: To determine if perfusion per unit tissue volume of retinal nerve fibre layer and optic nerve head in the inferior sector is lower than in the superior sector. METHODS: Heidelberg retinal tomogram (HRT) for topographic measurement of optic nerve head and retinal nerve fibre layer and Heidelberg retinal flowmeter (HRF) for retinal blood flow were performed on 19 normal healthy subjects. Measurements from the superior and inferior sectors were compared. The perfusion/nerve fibre ratio (PNR); the blood flow per unit retinal nerve fibre tissue volume, was calculated in each sector with a formula; HRF flow measurements divided by HRT measurements. RESULTS: Retinal nerve fibre layer thickness in the inferior retina was significantly higher than in the superior retina (p<0.05). There were, however, no differences in retinal blood flow between the superior and inferior retinal sectors. The PNR in the inferior sector were significantly lower than in the superior sector (p=0.047 for HRF mean flow/rim volume and p = 0.0282 for HRF 75th percentile flow/rim volume). CONCLUSIONS: The inferior sector of retinal nerve fibre layer and optic nerve head may have lower blood flow per unit nerve tissue volume compared to the superior sector. This result suggests that the inferior sector is more vulnerable to elevated intraocular pressure (IOP) and ischaemic insults in glaucomatous optic neuropathy.

Adult↗