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Biomedical subjects

T Ito

Publications and source records attributed to T Ito.

At least 55 records · Page 3Linked to original sources

Anxiety accelerates T-helper 2-tilted immune responses in patients with atopic dermatitis.

BACKGROUND: Stress, which mediates anxiety, worsens skin symptoms in patients with atopic dermatitis (AD). The contribution of anxiety to immune dysfunction, which plays a critical role in the pathogenesis of AD, requires clarification. OBJECTIVES: To examine the relationship between anxiety and atopy-relevant immune function in AD. METHODS: Eighty-five patients with AD and 58 normal individuals without a history of allergic disorders were enrolled in this study. To assess anxiety, the state-trait anxiety inventory was completed for both groups. In the AD group, measurements were made of SCORAD scores, serum IgE levels, itching (visual analogue scale), blood eosinophil count and T-helper (Th) 1/Th2 ratio in the peripheral blood. RESULTS: Anxiety was significantly higher among the subjects with AD than the normal subjects, and trait anxiety (TA) was higher than state anxiety (SA) in the AD group. Serum total IgE levels were correlated positively with TA and the TA/SA ratio and inversely with SA, and the Th1/Th2 ratio was correlated inversely with TA and the TA/SA ratio. CONCLUSIONS: The patients with AD had higher anxiety levels than normal individuals, and those with a stronger perception of TA than SA showed enhanced serum IgE synthesis and Th2 shifting.

Adolescent↗

Interferon-gamma is a potent inducer of catagen-like changes in cultured human anagen hair follicles.

BACKGROUND: Interferon (IFN)-gamma appears to be an important hair cycle modulator in mice. It is unclear whether it has similar hair growth modulatory functions in human hair follicles. OBJECTIVES: To study whether IFN-gamma can be exploited to modulate the growth, pigmentation and/or cycling of organ-cultured human anagen scalp hair follicles, as an in vitro indicator system for how IFN-gamma affects human hair growth in vivo. This was correlated with the hair follicle expression patterns of IFN-gamma receptors alpha and beta. In addition, we wanted to establish a new, simple tool for the rapid experimental induction of catagen in vitro. METHODS: Normal human scalp hair follicles in the anagen VI stage of the hair cycle were cultured according to the method of Philpott et al., with or without IFN-gamma (50-1000 IU mL(-1)). Hair shaft elongation and pigmentation changes were measured, complemented by quantitative histomorphometry to assess changes in hair follicle cycling (hair cycle score), proliferation (Ki-67), melanogenesis (Masson-Fontana) and apoptosis (TUNEL). IFN-gamma receptors were also localized by immunofluorescence and EnVision technique. As transforming growth factor (TGF)-beta2 is a recognized key inducer of catagen in human hair follicles, TGF-beta2 expression was investigated by tyramide signal amplification and reverse transcription-polymerase chain reaction in anagen hair follicles treated with vehicle (phosphate-buffered saline) or IFN-gamma. RESULTS: IFN-gamma rapidly inhibited hair elongation in cultured human anagen hair follicles and induced morphological signs of catagen transformation after only 4 days of culture, i.e. faster than with other reported catagen-inducers (e.g. TGF-beta2). Proliferation was inhibited, apoptosis was increased and follicular melanogenesis was switched off in hair bulb keratinocytes treated in situ with IFN-gamma. Anagen hair follicles displayed strong IFN-gamma receptor alpha-like immunoreactivity, while the immunoreactivity for IFN-gamma receptor beta in the hair matrix was only weak. TGF-beta2 immunoreactivity and mRNA transcript levels were enhanced in hair follicles treated with IFN-gamma. CONCLUSIONS: These data suggest that IFN-gamma is a potent catagen inducer in normal human scalp hair follicles, which express cognate receptors, and show that IFN-gamma administration offers an excellent tool for experimental catagen induction in organ-cultured human hair follicles. This catagen induction probably occurs at least in part via upregulation of the recognized catagen-stimulatory growth factor TGF-beta2.

Apoptosis↗

Comparison between partial agonist (ME3412) and antagonist (alosetron) of 5-hydroxytryptamine 3 receptor on gastrointestinal function.

Therapeutic use of 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonists for diarrhoea-predominant irritable bowel syndrome may be accompanied by constipation. We hypothesized that ME3412, 5-chloro-2-(1,4-diazacycloheptan-1-yl)-7-methylbenzoxazole, a novel partial agonist of the 5-HT(3) receptor, would minimize constipation without reducing antidiarrhoeal activity. Receptor binding studies showed that ME3412 is highly selective for the human 5-HT(3) receptor (K(i) = 1.51 nmol L(-1)). A 5-HT(3) receptor agonist, 2-methyl-5-HT, caused contractile response in the isolated guinea-pig ileum and accelerated secretion in the guinea-pig colonic mucosal preparation. ME3412 and 5-HT(3) receptor antagonist, alosetron, antagonized the 2-methyl-5-HT-induced responses with similar potency in insurmountable and surmountable manner, respectively. ME3412 caused weak agonism in isolated ileum strips and also in the colonic mucosa with intrinsic activity of 0.09 and 0.59, respectively. In conscious dogs, alosetron (3 microg kg(-1) i.v.) suppressed the migrating motor complex (MMC), whereas a relatively high dose (300 microg kg(-1)) of ME3412 was required for inhibition of MMC. ME3412 and alosetron suppressed 5-HT induced-diarrhoea in mice. In contrast, ME3412 did not significantly affect colonic propulsion compared with alosetron. These results imply that the partial agonist may relieve diarrhoea with low risk of inducing constipation.

Animals↗

Heavy alcohol intake, homocysteine and Type 2 diabetes.

Although moderate alcohol intake is associated with reduced risk of atherosclerotic disease in both the general population and in diabetic patients, a recent report suggests that heavy alcohol intake facilitates the development of atherosclerosis exclusively in diabetic individuals. We studied cross-sectionally the effects of the interaction between ethanol consumption category and the prevalence of diabetes on plasma total homocysteine (tHcy), a risk factor for atherosclerotic disease, in middle-aged men. Heavy drinking was associated with elevated tHcy levels only in diabetic subjects but not in non-diabetic subjects. Plasma tHcy of heavy drinkers (average ethanol consumption > 30 ml/day) was higher than that of abstainers in the diabetic subgroup (10.25 +/- 3.39 vs. 8.88 +/- 1.94 micromol/l, P < 0.05), whereas tHcy levels in heavy drinkers were comparable with that of abstainers in the non-diabetic subgroup (9.36 +/- 2.52 vs. 9.12 +/- 2.10 micromol/l, NS). In a two-factor anova, significant interaction was observed on the effects of ethanol consumption category and diabetes prevalence on tHcy levels (P < 0.01). Confounding factors including folate, vitamin B(12), creatinine, age or cigarette smoking did not contribute to the interaction. These findings may partly explain the reported association between heavy drinking and atherosclerosis in diabetic subjects.

Alcohol Drinking↗

Structural comparison of ten serotypes of staphylocoagulases in Staphylococcus aureus.

Staphylocoagulase detection is the hallmark of a Staphylococcus aureus infection. Ten different serotypes of staphylocoagulases have been reported to date. We determined the nucleotide sequences of seven staphylocoagulase genes (coa) and their surrounding regions to compare structures of all 10 staphylocoagulase serotypes, and we inferred their derivations. We found that all staphylocoagulases are comprised of six regions: signal sequence, D1 region, D2 region, central region, repeat region, and C-terminal sequence. Amino acids at both ends, 33 amino acids in the N terminal (the signal sequences and the seven N-terminal amino acids in the D1 region) and 5 amino acids in the C terminal, were exactly identical among the 10 serotypes. The central regions were conserved with identities between 80.6 and 94.1% and similarities between 82.8 and 94.6%. Repeat regions comprising tandem repeats of 27 amino acids with a 92% identity on average were polymorphic in the number of repeats. On the other hand, D1 regions other than the seven N-terminal amino acids and D2 regions were less homologous, with diverged identities from 41.5 to 84.5% and 47.0 to 88.9%, respectively, and similarities from 53.5 to 88.7% and 56.8 to 91.9%, respectively, although the predicted prothrombin-binding sites were conserved among them. In contrast, flanking regions of coa were highly homologous, with nucleotide identities of more than 97.1%. Phylogenetic relations among coa did not correlate with those among the flanking regions or housekeeping genes used for multilocus sequence typing. These data indicate that coa could be transmitted to S. aureus, while the less homologous regions in coa presumed to be responsible for different antigenicities might have evolved independently.

3' Flanking Region↗

Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease.

BACKGROUND AND AIMS: A characteristic feature of Crohn's disease (CD) is mesenteric adipose tissue hypertrophy. Mesenteric adipocytes or specific proteins secreted by them may play a role in the pathogenesis of CD. We recently identified adiponectin as an adipocyte specific protein with anti-inflammatory properties. Here we report on expression of adiponectin in mesenteric adipose tissue of CD patients. METHODS AND RESULTS: Mesenteric adipose tissue specimens were obtained from patients with CD (n = 22), ulcerative colitis (UC) (n = 8) and, for controls, colon carcinoma patients (n = 28) who underwent intestinal resection. Adiponectin concentrations were determined by enzyme linked immunosorbent assay, and adiponectin mRNA levels were determined by real time quantitative reverse transcription-polymerase chain reaction. Tissue concentrations and release of adiponectin were significantly increased in hypertrophied mesenteric adipose tissue of CD patients compared with normal mesenteric adipose tissue of CD patients (p = 0.002, p = 0.040, respectively), UC patients (p = 0.002, p = 0.003), and controls (p<0.0001, p<0.0001). Adiponectin mRNA levels were significantly higher in hypertrophied mesenteric adipose tissue of CD patients than in paired normal mesenteric adipose tissue from the same subjects (p = 0.024). Adiponectin concentrations in hypertrophied mesenteric adipose tissue of CD patients with an internal fistula were significantly lower than those of CD patients without an internal fistula (p = 0.003). CONCLUSIONS: Our results suggest that adipocytes in hypertrophied mesenteric adipose tissue produce and secrete significant amounts of adiponectin, which could be involved in the regulation of intestinal inflammation associated with CD.

Adipocytes↗

Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats.

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibutyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. AIM: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. METHODS: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 microg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. RESULTS: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, alpha-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. CONCLUSIONS: : Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.

Actins↗

Lower urinary tract function in patients with pituitary adenoma compressing hypothalamus.

BACKGROUND: The micturition reflex is under the tonic influence of suprapontine structures including the anteromedial frontal cortex, basal ganglia, and hypothalamus. However, there have been few reports about the role of the hypothalamus on the lower urinary tract (LUT) function in humans. OBJECTIVE: To investigate LUT function in patients with pituitary adenomas. METHODS: Urodynamic studies were carried out in three patients with LUT symptoms who had pituitary adenomas extending upwards to the hypothalamus. RESULTS: All three male patients (age 28 to 62 years) developed LUT symptoms (urinary urgency and frequency (3); urinary incontinence (3); voiding difficulty and retention (2)) along with weight loss, psychiatric symptoms, unsteady gait, and/or visual disturbances. One had the syndrome of inappropriate secretion of antidiuretic hormone, but none had diabetes insipidus. Two had resection of the tumour and subsequent radiation therapy, but LUT dysfunction persisted. The third patient had partial resection of the tumour to ameliorate hydrocephalus. Urodynamic studies showed detrusor overactivity during the storage phase in all patients; during the voiding phase there was underactive detrusor in two and non-relaxing sphincter in one. CONCLUSIONS: Hypothalamic lesions can cause severe LUT dysfunction in both the storage and voiding phases of micturition. This may reflect the crucial role of the hypothalamus in regulating micturition in humans.

Adenoma↗

Lower urinary tract function in dementia of Lewy body type.

OBJECTIVE: Dementia of Lewy body (DLB) type is the second commonest degenerative cause of dementia and autonomic dysfunction has been recognised in DLB. Lower urinary tract (LUT) function in DLB has not been fully delineated. We investigated LUT function in DLB by evaluating clinical and urodynamic data. METHODS: We examined 11 patients (eight men, three women; age range 65-81; disease duration 2-14 years) with probable DLB. Urodynamic studies consisted of: measurement of postvoid residual in all patients, uroflowmetry in five, and electromyography (EMG) cystometry in seven. RESULTS: All patients had symptoms of LUT: urinary incontinence (urgency type/functional type due to dementia and immobility/both urgency and stress type in 7/2/1 patients, respectively); night-time frequency; urgency; and daytime frequency and voiding difficulty. Seven had postvoid residuals, and three had residual urine volume >100 ml. Decreased urinary flow was seen in all five and detrusor overactivity in 5/7 patients who underwent flowmetry and EMG cystometry, respectively. Low compliance detrusor (storage phase, n = 2; with bethanechol supersensitivity), an underactive detrusor (n = 4), an acontractile detrusor (n = 1), and detrusor-sphincter dyssynergia (voiding phase) (n = 1) were also seen; 2/3 patients who underwent motor unit potential analysis had neurogenic changes. CONCLUSION: LUT dysfunction is a common feature in DLB, not only due to dementia and immobility, but also to central and peripheral types of somato-autonomic dysfunction.

Aged↗

When is Onuf's nucleus involved in multiple system atrophy? A sphincter electromyography study.

BACKGROUND: External anal sphincter (EAS) electromyography (EMG) abnormalities can distinguish multiple system atrophy (MSA) from Parkinson's disease in the first five years after disease onset. However, the prevalence of the abnormalities in the early stages of MSA is unknown. OBJECTIVES: To present EAS-EMG data in the various stages of MSA. METHODS: 84 patients with "probable" MSA were recruited (42 men, 42 women; mean age 62 years (range 47 to 78); mean disease duration 3.2 years (0.5 to 8.0; <1 year in 25%); 50 cerebellar form (MSA-C), 34 parkinsonian form (MSA-P)). EAS motor unit potential (MUP) analysis and EMG cystometry were carried out in all patients. RESULTS: The overall prevalence of neurogenic change of the EAS MUP was 62%-52% in the first year after disease onset, increasing to 83% by the fifth year (p<0.05); it also increased with severity of gait disturbance (p<0.05), storage and voiding disorders, and detrusor sphincter dyssynergy (NS). The neurogenic change was not correlated with sex, age, MSA-P/C, postural hypotension, constipation, erectile dysfunction in men, underactive or acontractile detrusor, or detrusor overactivity. In 17 incontinent patients without detrusor overactivity or low compliance, urinary incontinence was more severe in those with neurogenic change than in those without (p<0.05). CONCLUSIONS: Involvement of Onuf's nucleus in MSA is time dependent. Before the fifth year of illness, the prevalence of neurogenic change does not seem to be high, so a negative result cannot exclude the diagnosis of MSA.

Aged↗

Collagenofibrotic glomerulonephropathy in a cynomolgus macaque (Macaca fascicularis).

Collagenofibrotic glomerulonephropathy (CFGN) is characterized by the deposition of type III collagen within the mesangial matrix and the absence of mesangial cell proliferation. A case of CFGN in a 2.7-year-old female cynomolgus macaque was investigated in the present study. Clinically, the animal was shown to have severe systemic edema along with hypoproteinemia. At necropsy, the kidneys were swollen and pale. The glomerular lesions were characterized by massive diffuse and global accumulation of fibrous materials in the mesangial areas. Neither mesangial cell proliferation nor changes in other organs were found. The fibrous materials were confirmed by the results of immunohistochemical and electron microscopic findings to consist mainly of randomly arranged, curve-shaped, twisted, and entwined type III collagen. This is the first case report of CFGN in nonhuman primates to date.

Animals↗

[The correlation between flow pattern during cardiopulmonary bypass and patency of the coronary artery bypass grafts].

Recently the availability of transit time flow measurement (TTFM) is reported especially in off-pump coronary artery bypass grafting (CABG). But little is known about TTFM findings in on-pump CABG. We examined the correlation between the TTFM flow pattern and the angiography findings in on-pump CABG. The subjects consisted of 52 patients who underwent on-pump CABG and angiography early after operation. In these patients, 55 internal thoracic artery (ITA), 17 gastroepiploic artery (GEA), 13 saphenous vein graft (SVG) and 41 radial artery (RA) were tested with TTFM during cardiopulmonary bypass (CPB). TTFM demonstrated a diastolic filling pattern in 53 ITA, 16 GEA, 13 SVG and 36 RA. The angiography revealed that all these grafts were perfectly patent with the exception of a GEA with a flow competition pattern. TTFM revealed an abnormal flow pattern in 2 ITA (these 2 grafts were revised during CPB and the angiography demonstrated their perfect patency), 1 GEA (to and fro pattern), 0 SVG and 5 RA (the abnormal pattern was due to graft spasm in 3 of 5, and the angiography revealed their perfect patency, however, the angiography detected stenosis in the remaining 2 grafts). The present study found that the TTFM flow pattern during CPB correlated well with the angiography findings. TTFM during CPB was useful to detect graft failure, and grafts were revised safely during CPB.

Aged↗

[Advantages of side-to-side anastomosis in the assessment and revision of coronary artery bypass grafting].

With the advent of drug eluting stents in percutaneous coronary intervention, required quality level of coronary artery bypass grafting (CABG) has been elevating. To obtain nearly perfect patency of bypass grafts, intraoperative assessment and repair of abnormal grafts are helpful. We report systematic revision and safe repair technique of arterial grafts in CABG. Side-to-side instead of commonly used end-to-side anastomosis of arterial grafts is the first step in this technique. When any abnormalities are noted in intraoperative flowmetry of a graft, the distal surgical clip is removed. Free flow of the graft is measured. A coronary probe is gently inserted into the graft and the coronary artery. Vasodilators can be injected into the graft if necessary. When direct revision of the anastomosis is indicated, the graft is cut longitudinally from the distal end up to just proximal to the anastomotic site. The shape of the anastomosis can be observed directly without removing sutures. When re-anastomosis is not indicated, the distal remnant graft tissue is folded back and utilized as a patch. Thus the graft can be easily closed without narrowing.

Anastomosis, Surgical↗

Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation.

The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.

Animals↗

Control of an outbreak of highly pathogenic avian influenza, caused by the virus sub-type H5N1, in Japan in 2004.

An outbreak of highly pathogenic avian influenza (HPAI), caused by the virus sub-type H5N1, occurred at four premises in three prefectures in Japan during January and March 2004. As a result, 274,654 poultry died or were slaughtered. This was the first outbreak of HPAI in Japan since 1925. (The earlier outbreak was caused by H7N7.) The disease was successfully eradicated within three-and-a-half months, following an eradication campaign that included depopulating the affected premises, implementing movement controls and intensive surveillance. Control measures were conducted in accordance with the National Manual of HPAI Control. However, during the eradication campaign, some key issues arose, such as delays in notification by the affected farmers. As a result of these experiences, the relevant laws and HPAI Control Manual have been appropriately revised.

Animals↗

PI3K-AKT pathway mediates growth and survival signals during development of fetal mouse lung.

We examined the roles of the PI3K-AKT signalling pathway in fetal lung development. By Western blotting, phosphorylated AKT (pAKT) was highly expressed in fetal days 12 and 14 with decreased expression thereafter. By immunohistochemistry, pAKT was expressed mainly in the respiratory epithelium of early fetal days. We examined the effects of fibroblast growth factor 1 (FGF1), PI3K inhibitors (LY294002 and wortmannin), MAPK inhibitor (PD98059) and both of FGF1 and each inhibitor on lung morphogenesis, BrdU incorporation and apoptosis. In the FGF1-treated explants, the number of terminal buds and BrdU-labelled cells increased significantly, while the LY294002-, wortmannin-, PD98059-treated explants demonstrated obvious decreases. The effects by FGF1 were inhibited by LY294002, wortmannin and PD98059. Regardless of the presence of FGF1, the LY294002-, wortmannin- and PD98059-treated explants increased apoptosis revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay in the mesenchyme of the explants. At the same time, the effect of LY294002, wortmannin, PD98059 on expression of surfactant apoprotein C (SPC) were also studied. The LY294002 and wortmannin treatments showed decreased expression of SPC. These findings suggest that the PI3K-AKT signalling pathway plays a pivotal role in mouse lung development through various biological processes.

Androstadienes↗

Advantages of laparoscope-assisted surgery for recurrent Crohn's disease.

BACKGROUND: Laparoscopic surgery has been applied to patients with primary Crohn's disease, and its beneficial outcomes have been already investigated. However, there is no systematic study of laparoscopic surgery for patients with recurrent diseases. METHODS: We performed reoperation for 43 patients with recurrent Crohn's disease, including 23 patients who underwent laparoscope-assisted surgery. RESULTS: For all the patients, laparoscope-assisted surgery could be performed safely, even if the patients had been treated previously by open surgery or had undergone multiple abdominal procedures. Conversion to open or hand-assisted laparoscopic surgery was necessary for 16 patients (69.6%) because of dense adhesions (11 cases) or bulky tumor (5 cases). Importantly, even if the procedure was converted, the skin incision was significantly shorter than with open surgery, and postoperative recovery was faster, especially for the patients who underwent conversion to hand-assisted laparoscopic surgery. CONCLUSIONS: Laparoscope-assisted surgery is feasible and advantageous in reoperation for patients with recurrent Crohn's disease.

Adult↗