Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 145 records · Page 8Linked to original sources

PubMed1999

Permeation of PEO-PBLA-FITC polymeric micelles in aortic endothelial cells.

PURPOSE: To determine aortic endothelial cells permeation ability and mechanisms of the aqueous block copolymeric micelles, poly(ethylene oxide)-poly (beta-benzyl L-aspartate) (PEO-PBLA) chemically conjugated with fluroescein isothiocyanate (FITC) by transport study and confocal laser scanning microscopy. METHODS: The block copolymers' PEO-PBLA-FITC was first synthesized and characterized by gel permeation chromatography (GPC) reflect index, UV, fluorescence detectors, and critical micelles concentrations (CMC), and atomic force microscopy (AFM). Permeation ability and mechanisms of polymeric micelles in aortic endothelial cells were evaluated by incubating with NaF, NaN3, wortmannin, cytochalasin B inhibitors, at 20 degrees C, and under reverse conditions. FITC and latex particles (40 nm) were also used for comparison of transport ability. The extent of localization of uptake polymeric micelles was established by confocal laser scanning microscopy. RESULTS: The size of the aqueous PEO-PBLA-FITC polymeric micelles was detected at around 56 nm with unimodal distribution by AFM. The CMC test revealed the fluorescence intensity increased to around 0.01-0.05 mg/ml. NaF, NaN3, wortmannin, cytochalasin B, 20 degrees C, and reverse experiments inhibited the absorption of polymeric micelles through aortic endothelial cells with apparent permeability coefficients (P) of 18.07 +/- 1.03 to 12.98 +/- 0.93, 11.31 +/- 0.77, 12.44 +/- 1.23, 6.40 +/- 0.23, 11.11 +/- 0.46, and 10.22 +/- 1.09 x 10(-7) cm/sec, respectively. Also, the permeation of FITC and latex on aortic endothelial cells was 70.02 +/- 4.71, and 2.05 +/- 0.41 x 10(-7) cm/sec, respectively. Confocal laser microscopy showed that fluorescent compounds were distributed in the intracellular cytoplasm and nucleus. CONCLUSIONS: PEO-PBLA-FITC copolymeric micelles in an aqueous system were transported by energy-dependent endocytosis with 18.07 x 10(-7) cm/sec penetrated range and were localized on intracellular and nucleus endothelial cells.

Animals↗

PubMed1999

Gallstone disease risk in relation to body mass index and waist-to-hip ratio in Japanese men.

OBJECTIVE: To examine the relation of body mass index (BMI) and waist-to-hip ratio (WHR) to gallstones and postcholecystectomy risk in middle-aged Japanese men. DESIGN: Cross-sectional study. SUBJECTS: We used 174 men with prevalent gallstones, 104 with postcholecystectomy and 6909 with normal gallbladder in the consecutive series of 7637 men aged 48-59y receiving a preretirement health examination at four hospitals of the Japan Self-Defense Forces between 1986 and 1994. MEASUREMENTS: Gallbladder status was assessed by abdominal ultrasonography after an overnight fast. BMI was calculated as weight in kilogram divided by height in square meters, and WHR was used as a measure of central obesity. Analysis of the WHR was limited to a subset of data for the period 1991-1994 (gallstones 113, postcholecystectomy 66 and normal gallbladder 4410). RESULTS: After adjustment for hospital, rank in the Self-Defense Forces, cigarette smoking, alcohol use and glucose tolerance, BMI was significantly associated with an increased risk of both prevalent gallstones and postcholecystectomy. WHR also showed a significant positive association with each of the two conditions. When BMI and WHR were mutually adjusted for, both of the obesity indices tended to be associated positively with prevalent gallstones and postcholecystectomy. CONCLUSION: These findings indicate that obesity is associated with increased gallstone risk in men.

Asian People↗

PubMed1999

Total inhibition of high shear stress induced platelet aggregation by homodimeric von Willebrand factor A1-loop fragments.

Under high shear stress, the binding of von Willebrand factor (VWF) A1-loop domain to platelet glycoprotein (GP) Ib alpha occurs as the earliest event in thrombus formation. Therefore recombinant VWF A1-loop fragments could be of therapeutic use in blocking this interaction as competing ligands. We have prepared three homodimeric VWF A1-loop fragments [315 kD Fr III (a homodimer of amino acid [aa] residues 1-1365 of the subunit), 220 kD Fr (a homodimer of aa residues 1-708 of the subunit), and 116 kD Fr (a homodimer of aa residues 449-728 of the subunit) and two monomeric fragments [39/34 kD Fr (a monomer of aa residues 480/481-718 of the subunit] and His-rVWF465-728 (a monomer of aa residues 465-728 of the subunit)], and assessed their potency as inhibitors of botrocetin-induced VWF binding to GPIb alpha and high shear stress induced platelet aggregation mediated by intact VWE All these fragments completely inhibited botrocetin-induced VWF binding to GPIb alpha at a final concentration of 40-200 microM. The homodimeric A1-loop fragments also totally inhibited high shear stress induced platelet aggregation at a final concentration of 0.45-2.0 microM in the following order: 315 kD Fr > or = 220 kD Fr >> 116 kD Fr. In contrast, the monomeric A1-loop fragments were only partial inhibitors of high shear stress induced platelet aggregation even at a final concentration of 20 microM, and their IC50s were 13-39 times higher than those of the homodimers. These results indicate that the homodimeric structure of the A1-loop fragment is important for optimal molecular interaction with GPIb alpha under high shear stress.

Humans↗

PubMed1999

Case report: mucinous cholangiocarcinoma featuring a multicystic appearance and periportal collar in imaging.

A case of mucinous cholangiocarcinoma (CC), a rare histological type of CC, featuring unusual images is reported. The patient was hospitalized because of acute development of jaundice and fever. Computed tomography demonstrated multiple cystic lesions in the liver and a band-like low density area parallel to the intrahepatic portal vein, a so-called 'periportal collar'. Endoscopic cholangiography revealed a stricture of the hepatic duct with slight upstream dilatation. Cytology of the bile juice and fine-needle aspiration of the cystic lesion in the liver disclosed mucinous carcinoma. The patient died of multiorgan failure 3 weeks after admission. The autopsied liver showed that multiple mucus lakes were lined with adenocarcinoma cells and signet ring cells were floating in the mucus lakes. The cancer cells had spread along the portal tract and invaded into the hepatic parenchyma.

Adenocarcinoma, Mucinous↗

PubMed1999

Non-traumatic renal arteriopelvic fistula.

PURPOSE: In the present paper, we report on a 34-year-old female with macroscopic hematuria due to a nontraumatic renal arteriopelvic fistula (APF). The patient initially presented at another hospital with asymptomatic macroscopic hematuria. Following abdominal ultrasonography, computed tomography (CT) and laboratory data, no abnormal findings were seen. Therefore, the patient was referred to Teine Keijinkai Hospital for a more precise evaluation of the urinary tract and vascular abnormality. METHODS/RESULTS: Endoscopically, there was bleeding from the right ureteral orifice, so the patient was admitted for further examination. No abnormal findings were seen on urinary cytology and following an intravenous pyelogram. A selective right lower polar renal arteriogram revealed arterial extravasation directly into the pelvis before the venous phase, so APF of the kidney was diagnosed. The patient had no history of urinary tract trauma, so the APF was thought to be idiopathic. After transcatheter arterial embolization (TAE) with a gelatine sponge, macroscopic and microscopic hematuria disappeared and a low-density area was seen in the middle pole of the right kidney in an abdominal CT scan 4 days after TAE. This was thought to be renal infarction due to TAE. CONCLUSIONS: After discharge, the patient had no further hematuria.

Adult↗

PubMed1999

Growth factor and matrix molecules preserve cell function on thermally responsive culture surfaces.

Thermally-responsive culture surfaces were designed using copolymers of N-isopropylacrylamide, 4-(aminomethyl)styrene, and acrylic acid. These surfaces contained functional amine and carboxyl groups, which allowed biomolecules to be grafted by amide formation. Epidermal growth factor (EGF), and extracellular matrix (ECM) molecules (collagen type IV, and chondroitin sulfate) were investigated, as surface-grafted biomolecules, for their ability to stimulate cell attachment, proliferation, and function by signaling only from the basal side of cultured cells. Surface analysis of biomolecule-grafted porous inserts showed covalent binding of biomolecules to either amine or carboxyl groups. Multiple attachment to amine and/or carboxyl groups served as cross-linking points that made the polymer hydrogel permanently adherent to the culture surface. Immunofluorescence microscopy techniques gave positive identification of grafted biomolecules. Grafting of EGF improved cell proliferation versus that on nongrafted controls, or controls grafted only with ECM molecules. ECM grafting induced cell attachment on attachment-resistant surfaces. Analysis of trans-epithelial resistance, fluid transport, and polarized g-glutamyl transpeptidase activity indicated that simultaneous grafting of both EGF and ECM produced better polarized cell function than nongrafted controls, or controls grafted with only one type of biomolecule. Covalent grafting of biomolecules did not interfere with cells ability to detach from thermally responsive surfaces upon temperature decrease.

Amides↗

PubMed1999

Status of health promotion programme implementation in small-scale enterprises in Japan.

This study was conducted to determine the status of the implementation of health promotion programmes (HPPs) in Japanese small-scale enterprises (SSEs). A survey was conducted in 1996 using a questionnaire mailed to all the member construction companies (n = 772) of a health insurance society, and a response rate of 84% was obtained. Health examination was most frequently conducted (90%), followed by exercise/fitness programmes (17%), smoking measures (12%), health guidance (11%) and nutrition education (6%). Mental health programmes and the government-advocated Total Health Promotion Plan (THP) were implemented at less than 2% of SSEs. The implementation rates for these programmes, except for smoking measures and the THP, were higher at large enterprises than at SSEs. The employment rate for occupational physicians (OPs) was 9% and 49% at SSEs and large enterprises, respectively. The activity most frequently conducted by OPs was health examination, followed by curative services and health education. Advising employees to undergo re-examination or more valid examination after the annual health examination was most frequently conducted by non-health professionals.

Health Care Surveys↗

PubMed1999

Purification and further characterization of enteropeptidase from porcine duodenum.

Enteropeptidase [EC 3.4.21.9] is a membrane-bound serine endopeptidase present in the duodenum that converts trypsinogen to trypsin. We previously cloned the cDNA of the porcine enzyme and deduced its entire amino acid sequence [M. Matsushima et al. (1994) J. Biol. Chem. 269, 19976-19982]. In the present study, we purified the porcine enzyme approximately 2,200-fold in a 12% yield from a duodenal mucosal extract to apparent homogeneity by an improved procedure comprising four steps of chromatography including benzamidine-Sepharose affinity chromatography. Lectin blotting analysis suggested that the enzyme is glycosylated mainly with N-linked carbohydrate chains of the tri- and/or tetraantennary complex type. The H and L chains of the enzyme were separated into two major bands upon SDS-PAGE under reducing conditions, suggesting that the enzyme mainly comprises two isoforms, a higher molecular weight form and a lower molecular weight form. The enzyme was also separated by lectin affinity chromatography into two major fractions, named isoforms I and II, which corresponded to the higher and lower molecular weight forms, respectively. These two isoforms appeared to be different only in the carbohydrate moiety, having essentially the same enzymatic properties. The enzyme was optimally active at pH 8.0 toward Gly-Asp-Asp-Asp-Asp-Lys-beta-naphthylamide, and was inhibited strongly by various serine proteinase inhibitors. Furthermore, it was also strongly inhibited by E-64 [L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane], a cysteine proteinase inhibitor. Substrate specificity studies involving various synthetic peptides indicated that acidic residues at the P2, P3, and/or P4 positions are especially favorable for maximal activity, but are not absolutely necessary, at least in the cases of peptide substrates.

Animals↗

PubMed1999

Contribution of peripheral chemoreception to the depression of the hypoxic ventilatory response during halothane anesthesia in cats.

BACKGROUND: The effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia. METHODS: Cats were anesthetized with pentobarbital sodium and alpha-chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs-Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%. RESULTS: The hypoxic ventilatory response was depressed in a dose-dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.80%. CONCLUSION: The hypoxic ventilatory response is depressed by a high dose of halothane through a peripheral effect at the carotid body.

Anesthetics, Inhalation↗

PubMed1999

Reduction of the side effects of an antitumor agent, KRN5500, by incorporation of the drug into polymeric micelles.

For intravenous (i.v.) injection of a water-insoluble antitumor drug, KRN5500, we have successfully incorporated KRN5500 into polymeric micelles. In the present study, in vitro and in vivo anti-tumor activity against several human tumor cell lines and toxicity in mice of polymeric micelles incorporating KRN5500 (KRN/m) were evaluated in comparison with those of the prototype KRN5500. KRN/m was found to express similar antitumor activity to KRN5500 in the in vitro and in vivo systems. However, the vascular damage and liver focal necrosis observed with KRN5500 i.v. injection were not seen when KRN/m was administered i.v. Therefore, we expect that KRN/m will be superior to KRN5500 for clinical use and that the methodology of polymeric micelle drug carrier systems can be applied to other water-insoluble drugs.

Animals↗

PubMed1999

Clinical course, surgical management, and long-term outcome of moyamoya patients with rebleeding after an episode of intracerebral hemorrhage: An extensive follow-Up study.

BACKGROUND AND PURPOSE: Revascularization surgery for moyamoya patients is believed to prevent cerebral ischemic attacks by improving cerebral blood flow. However, measures preventing the occurrence of hemorrhagic moyamoya in patients have not yet been established in the literature due to the low rate of hemorrhage onset as well as the originally limited numbers of patients with moyamoya disease, poor understanding of the clinical course of rebleeding, correct surgical management, and long-term outcome. We present here the results of an overall survey of patients with hemorrhagic moyamoya disease in a district of Miyagi Prefecture in Japan and examine their clinical course, efficacy of revascularization surgery, and long-term outcome. METHODS: This study included 28 moyamoya patients with episodes of intracranial hemorrhage between 1976 and 1988. The mean follow-up period was 14.2 years. There were 4 males and 24 females, aged 7 to 69 years (mean 39.2 years). Cerebral angiography and CT scans were performed for all patients. Surgical treatment was performed in 19 patients (67. 9%), and 10 patients (35.7%) underwent revascularization surgery. We observed the clinical course of all 28 patients. We also studied the relationship between the efficacy of surgical treatment and long-term outcome. RESULTS: Five of the 28 patients (17.9%) died of the initial intracranial hemorrhage, and 2 patients died of other causes. Rebleeding occurred in 6 of the remaining 21 patients (28. 6%). The interval to rebleeding ranged from 2 to 20 years (mean 7.3 years). Of these 6 patients, 4 died of rebleeding. Rebleeding was observed in 1 of 8 patients who underwent bypass surgery and in 5 of 13 patients who did not, which suggested that rebleeding was less likely to occur in patients who had undergone bypass surgery. However, there was no significant difference in rebleeding ratio or mortality between patients with and those without revascularization surgery (P>0.05). CONCLUSIONS: In this study, we compiled the results of meticulous follow-up conducted over the past 10 years for patients with hemorrhagic moyamoya disease. Because hemorrhagic moyamoya disease is known for its high rate of mortality at the time of rebleeding and often causes rebleeding long after the initial episode (as much as 20 years later), implementation of long-term preventive measures for rebleeding is necessary. This suggests that a long-term prospective study of a large number of patients with hemorrhagic moyamoya disease is required to determine whether bypass surgery prevents rebleeding of hemorrhagic moyamoya disease.

Adolescent↗

PubMed1999

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers.

Two types of thermo-responsive hydrogels are synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTs) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacryl amide-co-N,N-dimethylacrylamide) (poly(IPAAm-co-DMAAm)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37 degrees C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31 degrees C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36 degrees C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.

Absorption↗

PubMed1999

Effect of media constituents on the formation by halophilic yeast of the 2 (or 5)-ethyl-5 (or 2)-methyl-4-hydroxy-3 (2H)-furanone aroma component specific to miso.

The formation of HEMF [2 (or 5)-ethyl-5 (or 2)-methyl-4-hydroxy-3 (2H)-furanone] by yeast was examined in an attempt to investigate its mechanism and involved factors. HEMF formation was promoted by yeast cultivation in a heat-sterilized medium which included glucose, ribose, and a nitrogenous compound such as an extract of shoyu koji, poly-peptone, casamino acid, or an amino acid (glutamic acid, threonine, serine, or alanine).

Culture Media↗

PubMed1999

Association between alcohol intake and subjective health: the Sotetsu Study.

Subjective health and alcohol intake are important predictors of mortality. There have been few epidemiological studies, however, of the relationship between alcohol consumption and subjective health among the Japanese. The purpose of this study is to investigate the association between alcohol consumption and subjective health. The study subjects were 2,020 Japanese male employees, who were free from serious disease conditions. The data on subjective health and alcohol consumption were obtained by means of self-reported questionnaire. The subjects who responded "poor health" in the answer to the question about the subjective health status were considered to be in ill-health. Ethanol intake per day was calculated by multiplying the frequency of drinking by the ethanol intake per drinking occasion and summing up for each alcoholic beverage. Age, smoking status, physical activity, and sleeping hours were treated as confounding factors. As a result, subjects who consumed 25-36 or 49 g ethanol or more per day had a significantly lower risk of self-rated ill-health compared with those who had never drunk, and a significantly inverse trend was found independent of age, smoking status, physical activity, and sleeping hours. In conclusion, moderate drinkers have a lower risk of self-rated ill-health among Japanese male employees investigated.

Adolescent↗

PubMed1999

Protein metabolism in critical illness: methodologies and their problems underlying in kinetic studies using isotope tracers in vivo.

The response to critical illness involves alterations in all aspects of metabolic control, favoring catabolism of body protein. In particular, as the result of the alteration of protein metabolism, body protein loss occurs, which has been reported to be inversely correlated with the survival of critically ill patients. Despite the availability of various therapeutic modalities aiming to prevent loss of body protein pool such as total parenteral nutrition, and enteral nutrition that has made to provide excessive calories as a form of energy substrate and protein itself, the loss of body protein could not be prevented. Loss of body protein store occurs as a consequence of the alteration of intermediate metabolism that works for the production of energy substrate. This alteration of substrate metabolism may link to the alteration of protein metabolism. However, no specific factors regulating protein metabolism have been identified. Thus, further investigations evaluating amino acid and protein metabolism are required to obtain a better understanding of the metabolic regulation in the body, which may lead to the development of novel and more effective therapeutic modalities for nutrition in the future.

Critical Illness↗

PubMed1999

Selective delivery of adriamycin to a solid tumor using a polymeric micelle carrier system.

The anticancer drug, adriamycin (ADR), was incorporated by physical entrapment into polymeric micelles for selective delivery to a murine solid tumor colon adenocarcinoma 26 (C 26). In vivo antitumor activity of ADR was greatly enhanced by this incorporation into polymeric micelles. Using one polymeric micelle delivery system, the tumor completely disappeared at two doses, while free ADR exhibited a fair inhibition effect on tumor growth only at the maximum tolerated dose. Biodistribution analysis revealed that the physically entrapped micellar ADR accumulated at tumor sites in a highly selective manner. These results indicate that these polymeric micelles are a promising system for delivering hydrophobic anticancer drugs selectively to solid tumor sites using a passive targeting mechanism.

Adenocarcinoma↗

PubMed1999

Resumption of work after aneurysmal subarachnoid hemorrhage in middle-aged Japanese patients.

OBJECT: Previous reports on the results of treatment for aneurysmal subarachnoid hemorrhage (SAH) have been based only on activities of daily living after discharge, whereas resumption of work has received insufficient attention. Most Japanese work under a lifetime employment system, and it is best for those who have recovered from SAH to return to work for their previous employer. The present study was conducted to determine the extent to which discharged patients who have suffered an SAH resume their former occupations in Japan, focusing on those between 40 and 49 years of age, who usually have a strong desire to return to work. METHODS: The participants consisted of 193 patients with SAH. Based on the results of telephone interviews or written questionnaires, their work status at 1 year after onset was analyzed. The work resumption rates for patients with Hunt and Kosnik neurological Grades 1 or 2 on admission were higher than for those with Grades 3 or 4 (p = 0.015) and lower for patients with basilar artery aneurysms than for those with aneurysms at other sites (p = 0.028). With regard to premorbid occupation, the work resumption rates were high (80%) for professionals and engineers, many of whom were public servants, or teachers at junior or senior high schools. The resumption rates were also high for primary industry workers (80%), but lowest (20%) for professional drivers (p = 0.04-0.001). The work resumption rate was lower for women than for men (p = 0.01). CONCLUSIONS: These findings indicate that resumption of work is determined not only by medical factors, but also by social factors including gender, type of occupation, employment system, and socioeconomic background.

Activities of Daily Living↗

PubMed1999

[Pharmacokinetic analysis of cefozopran in neonatal infections--population pharmacokinetics using nonmem].

This report describes the results on pharmacokinetics, efficacy and safety of cefozopran (CZOP) in neonatal patients. Enrolled patients were 136 in total whose informed consents to enter this study had been given by their parents. Among them, blood samples were collected from 42 neonates to analyze concentrations of CZOP by population pharmacokinetics (PPK) methods. Based on this analysis, the average pharmacokinetic parameters of CZOP and the variabilities of them in different morbid pharmacological backgrounds and in different subjects were evaluated. This PPK analysis showed that clearance (CL) and distribution volume (Vd) of CZOP could be estimated by the following equations; CL = 0.0452 x WT1.75 (in the case of the postnatal age of over than 1 day) CL = 0.623 x 0.0452 WT1.75 (in the case of the postnatal age of 1 day or less) Vd = 0.455 x WT where WT indicates body weight in kg. The coefficients of variation among individual subjects on CL and Vd were found to be 20.7% and 20.0%, respectively. From this PPK analysis it was indicated that the elimination of CZOP is dependent on the postnatal age and is approximately 38% lower in the younger group than in the older group. Therefore, it could be concluded that, though the cases of evaluation were small in number, adjustment of dosing of CZOP is necessary, particularly in prolongation of intervals of administration, in cases of postnatal age of 1 day or less.

Cephalosporins↗