Biomedical subjects

H Iwata

Publications and source records attributed to H Iwata.

At least 343 records · Page 19Linked to original sources

PubMed1997

[Health conditions and life styles of residential elderly. Part 1. Characteristics and factors related to being healthy elderly persons from a survey of health life style].

A survey was conducted in a highland community of Gifu prefecture on 815 residential elderly persons, over 65 years old, utilizing self-administered questionnaires to study the degree of association between life style factors and health conditions. A total of 718 valid participants (90.6% of the total) were analyzed and cross-examined by applying Breslow's seven health factors, daily behavior factors, physical health consciousness, social mobility factors (13 behavior factors which were determined by the Institute of the Elderly) to determine associations with respondents health conditions. Of the participants, 310 were male and 408 were female with mean ages of 73.8 +/- 6.9 years old and 74.0 +/- 6.9 respectively. The survey results indicated that there were no prominent gender differences over the mobility rate and physical health consciousness among participants. However, it was also found that in the male participants the per person prevalence of past history of illness was higher than in females. In the daily activity analysis, female participants indicated a higher prevalence of difficulty in walking and balance maintenance while ascending and descending stairs. In the general daily activity analysis, male participants had a higher requirement for an aide. In social mobility, male participants recorded a high degree of self-reliance by being physically, socially, and intellectually active and the female participants by fulfilling their social responsibilities. Breslow's seven health indicators were applied and their evaluation points were calculated as 3.9 +/- 1.7 for male participants and 3.5 +/- 1.8 for female participants which showed a significantly higher score for the male participants. The survey also indicated that factors which increase the Breslow score for males, were having a spouse, hobbies, a satisfactory life, a habit of exercising, and non-smoking which in females an appropriate sleeping habit (not less than 7 hours), and working, were the positively related factors.

Activities of Daily Living↗

PubMed1997

Characterization and transplantation of agarose microencapsulated canine islets of Langerhans.

The bioartificial pancreas was designed to incorporate islet tissues and a selectively permiable membrane that isolates islets from the immune system of the recipient. The efficacy of agarose, a nontoxic polysaccharide, has been evaluated as a material of microcapsules to prevent allo- and xenograft rejection in rodents. The aim of this study is to demonstrate the possibility of the agarose microcapsule containing allo-islets as a bioartificial pancreas in canine model. In vitro viability of islets was determined by glucose challenge during perifusion experiments (n = 4). Insulin secretion from both encapsulated (enc.) and non-encapsulated (non-enc.) canine islets rose from initial basal levels of 0.09 (encap.), 0.07 (non-encap.) to the peak of 0.2 (encap.), 0.1 (non-encap.) in microU/islet/min after 5 minutes, then decreased to the basal level when the glucose challenge was discontinued. Auto-transplantation was performed in two dogs to evaluated in vivo viability and biocompatibility of encapsulated islets implanted into the splenic sinus by venouse reflux. Two weeks after auto-transplantation, the plasma insulin levels in the splenic vein and artery of two dogs were assayed. In the first dog, serum insulin level was 1 microU/ml both in the vein and the artery and increased, after glucagon (1.0 mg) injection, to levels of 9 microU/ml in the vein, but still kept 1 microU/ml in artery, as well as in the second one. Histological and electron-microscopical examination of the spleen revealed that encapsulated islets remained morphologically intact and the surface of agarose capsules showed no significant adherence of fibroblasts and inflammatory cells. Functional efficacy of the microencapsulated islets was determined using five totally-pancreatectomized diabetic dogs as recipients without immunosuppression. Defined quantity of microencapsulated islets from outbred mongrel donors were grafted through the catheter into omental tissue of the pancreatectomized recipients. All dogs had various degrees of reduced insulin requirements. In three of five recipients, the average fasting glucose values were controlled under 120 mg/dl for 28, 42, 49 days without exogenous insulin, which received totally 4.3 x 10(3), 7.3 x 10(3) and 1.0 x 10(4) (IE/kg) of microencapsulated islets, respectively. In conclusion, the present study indicates that the agarose-based microencapsulated islets can function in large diabetic animals, resulting in the independence of exogenous insulin therapy for prolonged periods without the need for immunosuppression.

Animals↗

PubMed1996

Low Frequency Loss of Heterozygosity in the BRCA1 Region in Japanese Sporadic Breast Cancer.

To investigate the possible involvement of the BRCA1 gene in Japanese sporadic breast cancer we have analyzed loss of heterozygosity (LOH) at the BRCA1 region (17q12-q22) in 101 sporadic breast cancers using 5 microsatellite markers, such as D17S250, D17S846, D17S855, D17S579, and NME1. The frequency of LOH in each markers was 14.9%(11/74), 11.9 %(8/67),14.3%(12/84),5.3%(4/75), and13.3%(9/68),respectively. The incidence of LOH in at least one of 5 markers was 23.8%(24/101). The LOH at the BRCA1 region did not significantly correlate with clinicopathologic factors. Despite using a microdissection method, the LOH frequency in our series was relatively lower than other reports, especially in Western countries. We suggest that the BRCA1 gene might play only a limited role as a tumor suppressor gene in the majority of Japanese sporadic breast cancers.

Journal Article↗

PubMed1996

Evidence of a novel redox-linked activation mechanism for the Src kinase which is independent of tyrosine 527-mediated regulation.

The kinase activity of p60c-src has been shown to be basically regulated through phosphorylation and dephosphorylation of Y527. We found that catalytic activity of the immunoprecipitated c-Src kinase from NIH3T3 cells was elevated several folds by exposure to 0.5-50 microM of sulfhydryl-reactive Hg2+. Vmax of the kinase was increased whereas Km was decreased. N-acetylcysteine neutralized this Hg2+ effect, suggesting a critical role of the Hg2+-mediated sulfhydryl modification of the kinase in the mechanism. Addition of protein tyrosine phosphatase inhibitor Na3VO4 into the reaction mixture did not inhibit the Hg2+-mediated activation. Further study revealed that Hg2+ was capable of activating the v-Src kinase lacking Y527 and the c-Src kinase from mutant cells defective of the Y527-phosphorylating Csk kinase. Cyanogen bromide cleavage maps of radiolabeled Src proteins showed that Hg2+ selectively promoted the autophosphorylation at Y416 and that the previously in vivo radiolabeled phosphorous on Y527 was not deleted during the promotion of Y416 autophosphorylation by Hg2+. Phosphoamino acid analysis demonstrated selective promotion of phosphorylation at tyrosine but not at serine/threonine. Not like bivalent Hg2+, monovalent p-chloromercuribenzenesulfonic acid was incapable of activating c-Src kinase. These results suggest a novel Y416 phosphorylation-linked activation pathway for Src kinases which is initially triggered independent of Y527-mediated or serine/threonine phosphorylation-linked regulation, possibly through sulfhydryl-based protein structural modification for functional alteration.

3T3 Cells↗

PubMed1996

Microsatellite instability in in situ and invasive sporadic breast cancers of Japanese women.

We studied the timing of microsatellite instability (referred to as replication error; RER) presentation during human breast carcinogenesis using tissue microdissected from both in situ and invasive breast cancers of Japanese women. We analyzed 100 breast cancer specimens for RER at nine genomic loci on seven chromosomes. Eight of the 100 cases (8%) were RER-positive at one or more chromosomal loci. Additionally; we obtained genomic DNA from two of four RER-positive patients with an intraductal component, both of which showed microsatellite instability in in situ foci. This finding indicates that microsatellite instability may be an early event during human breast carcinogenesis.

Breast Neoplasms↗

PubMed1996

Microsatellite instability in sporadic human breast cancers.

Human breast-cancer specimens from 100 patients were analyzed for microsatellite instability (referred to as replication error; RER) at 12 genomic loci on 7 chromosomes, and results were correlated with clinicopathologic characteristics. In 42 of 100 breast-cancer patients, we investigated whether RER was associated with the amplification of oncogenes and/or suppression of tumor-suppressor genes. Of the 100 patients, 8 (8%) were RER-positive at one or more chromosomal loci. The majority of RER-positive patients had early-stage disease with ER-positive tumors, suggesting that RER occurs early in breast tumorigenesis. However, no significant correlation was observed between RER and oncogenes or tumor-suppressor genes. Thus, the mechanism of RER in sporadic human breast cancer may be independent of the multi-step carcinogenesis caused by the alterations of oncogenes and tumor-suppressor genes.

Breast Neoplasms↗

PubMed1996

Tyrosine phosphorylation is crucial for growth signaling by tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2).

[3H]Thymidine (TdR) incorporation by human osteosarcoma cell line MG-63 was significantly stimulated at as early as 3 h after the addition of either TIMP-1 or TIMP-2 alone. Maximum stimulation was attained at a concentration of either 20 ng/ml (0.71 nM) TIMP-1 or 1.0 ng/ml (46 pM) TIMP-2. Tyrosine kinase inhibitors such as genistein, erbstatin, and herbimycin A almost completely inhibited the [3H]TdR incorporation stimulated by either of the TIMPs. However, essentially no effect was observed with H-89, H-7, bisindolylmaleimide and K-252a. These inhibition studies suggest a crucial role for tyrosine kinase in the signal transduction of TIMPs. Phosphotyrosine-containing proteins were significantly elevated by the treatment with both TIMPs. We also found that either TIMP stimulated an increase in mitogen-activated protein (MAP) kinase activity, suggesting that MAP kinase plays a role in TIMP-dependent growth signaling.

Benzoquinones↗

PubMed1996

Occurrence of PG-Lb, a leucine-rich small chondroitin/dermatan sulphate proteoglycan in mammalian epiphyseal cartilage: molecular cloning and sequence analysis of the mouse cDNA.

PG-Lb is a chondroitin/dermatan sulphate proteoglycan first isolated from chick embryo limb cartilage. It had been assumed that osteoglycin represents its mammalian homologue. However, partial amino acid sequences of a novel proteoglycan from bovine epiphyseal cartilage showed high identity with those of chick PG-Lb (P. Neame, L. Rosenberg and M. Höök, personal communication). Reverse transcriptase PCR using degenerate oligonucleotide primers gave a cDNA fragment that might correspond to mouse PG-Lb. We isolated a clone from a cDNA library of newborn mouse epiphyseal cartilage using the cDNA fragment as a probe. The cloned cDNA was 1430 bp long and contained a 966 bp open reading frame which encoded the core protein consisting of 322 amino acid residues. The deduced amino acid sequence showed a high overall identity with chick PG-Lb (about 62%, reaching about 80% over the carboxyl two-thirds). In addition, the amino acid sequence contained a signal peptide, six cysteine residues at the invariant relative position to chick PG-Lb, six leucine-rich repeats at the carboxyl two-thirds, three possible glycosaminoglycan-attachment sites (two sites at the N-terminal side and one site at the C-terminus) and two possible Asn-glycosylation sites near the C-terminus. Northernblot analysis demonstrated the specific expression of a 1.5 kb message in cartilage and testis. These structural features and the characteristic expression suggest that the cloned molecule is mouse PG-Lb.

Amino Acid Sequence↗

PubMed1996

A perfluorochemical prevents ischemia-reperfusion injury of muscle.

This investigation evaluated the effect of oxygenated perfluorochemical (PFC) perfusion on the viability of ischemic skeletal muscle compared to hypothermic preservation. Twenty-five hindlimbs of 13 white rabbits were divided into five groups: a PFC group (7 hr of ischemia with 6 hr of PFC perfusion), a PFC/ reperfusion group (8 hr of ischemia with 6 hr of PFC perfusion and 1 hr reperfusion), a hypothermia group (7 hr of ischemia with 6 hr of 4 degrees C cold preservation), a hypothermia/reperfusion group (8 hr of ischemia with 6 hr of 4 degrees C cold preservation and 1 hr of reperfusion), and a control group. The levels of adenine nucleotides, creatine phosphate, hypoxanthine, xanthine, and lipid peroxide were determined in each group. In the PFC and PFC/reperfusion groups, the ATP level remained at 90% of that in the control group. The hypoxanthine level in the hypothermia/reperfusion group was decreased to 70% of that in the hypothermia group and the xanthine level was increased to 130%. In the PFC and PFC/reperfusion groups, hypoxanthine and xanthine levels were much lower and were similar to those in the control group. Lipid peroxide levels were also lower in the PFC and PFC/reperfusion groups than in the hypothermia/reperfusion group. Electron microscopy showed that endothelial cells from the PFC/reperfusion groups were not swollen. These results suggest that PFC perfusion is superior to hypothermia in inhibiting the generation of free radicals and in preventing ischemia-reperfusion injury of skeletal muscle.

Adenine Nucleotides↗

PubMed1996

Flow Cytometric Assay of c-erbB-2 Protein in Fine Needle Aspirates of Fresh and Frozen Human Breast Cancer Tissues.

Using FCM (flow cytometry), we analyzed the ErbB-2 (c-erbB-2 protein) status of 61 breast cancer tissue samples obtained by FNAB (fine-needle aspiration biopsy). The number of cancer cells collected by FNAB from fresh samples was 1.7+/-0.7 x10&sup5;, 2.5 +/-0.6 x10&sup5;, and 4.0+/- 0.8x10 &sup5;, by single, double and triple aspirations, respectively. A mean of 3.0+/-0.6 x10&sup5;cells was collected on three aspirations from frozen samples. The number of cells collected on three aspirations was sufficient for the measurement of ErbB-2. Cells with higher ErbB-2 levels than those of normal human lymphocytes were designated ErbB-2 positive cells. The mean overall for ErbB-2 positive cell rates was 20.5 +/- 27.9 % (mean+/-SD). The rates were 27.9 +/- 31.6 % in patients with recurrence and 15.9 +/- 24.4% in patients without recurrence. When the cut-off value was set at 20% of the positive cell rate (P =0.008, generalized Wilcoxon test), patients with ErbB-2 negative tumors showed highly significantly longer survival without recurrence (P=0.008, generalized Wilcoxontest) and better overall survival rates (P=0.013) than patients with ErbB-2 positive tumors. Among 61 specimens, 16 (26.2%) scored positive for ErbB-2 by FCM. These finding indicated that the analysis of ErbB-2 status using FCM of samples obtained by FNAB should be useful for preoperatively evaluating the prognosis of patients with breast cancer.

Journal Article↗

PubMed1996

IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones.

We investigated the role of IL-12 in proliferation of various Th cell clones (class II-alloreactive (4-86 and 4-55) and keyhole limpet hemocyanin + self I-Ek-reactive (9-16)) following stimulation with Ag on APCs. These clones proliferated in response to stimulation with rIL-2, rIL-12, or Ag/APC. The proliferation induced by Ag/APC stimulation was not affected by anti-IL-2 Ab but was markedly inhibited by anti-IL-12 Abs. Consistent with this finding was the absence of detectable IL-2 activity in culture supernatants 12 to 48 h after Ag/APC stimulation, and the detection of significant levels of IL-12 in an Ab-capture bioassay. IL-12 was produced within 12 h after Ag/APC stimulation, reaching a peak after 18 to 24 h. The production of IL-12 in cultures of Th clones and APC contrasted with the production of IL-2 but not IL-12 upon allostimulation of primary T cells and the inhibition of their proliferation exclusively by anti-IL-2 Abs. Analysis of the expression of IL-12-binding sites on Th cells revealed low levels of IL-12 receptors in resting Th clones but high IL-12R levels 2 to 3 days after Ag/APC stimulation, declining gradually thereafter. The changes in IL-12R expression levels correlated closely with the IL-12 responsiveness of Th populations at various times after Ag/APC stimulation; Th populations obtained 3 and 10 days after Ag/APC stimulation exhibited very high and weak or marginal responsiveness to rIL-12, respectively, whereas the responses to rIL-2 were comparable in both Th populations. These results indicate that the Ag/APC-stimulated proliferation of terminally differentiated Th clones, in contrast to naive T cells, depends on the production of IL-12 by APC and on the simultaneous up-regulation of IL-12R on Th cells rather than on an IL-2 autocrine mechanism.

Animals↗

PubMed1996

Experimental chemonucleolysis with chondroitinase ABC in monkeys.

STUDY DESIGN: Experimental chemonucleolysis with chondroitinase ABC as compared with chymopapain was investigated in monkeys. The effects of these two enzymes were analyzed morphologically and biochemically. OBJECTIVES: The results of the present study facilitate the clinical application of chondroitinase ABC. SUMMARY OF BACKGROUND DATA: Many experimental studies on chemonucleolysis with chondroitinase ABC have been reported mostly in rabbits. Further examination in animals that are more similar to humans is necessary for its clinical application. METHODS: Ten mature rhesus monkeys were used. Lumbar intervertebral discs from six monkeys were injected with either chondroitinase ABC, chymopapain, or physiologic saline. The animals were killed not more than 6 weeks after injection, and their discs were examined morphologically and biochemically. The remaining four monkeys were used for a longer follow-up study to determine the changes in chondroitinase ABC-injected discs. RESULTS: Degenerative changes of discs were more severe with the injection of chymopapain, although the content of hyaluronic acid, chondroitin sulfate, and dermatan sulfate decreased more with the injection of chondroitinase ABC. In a longer follow-up study, chondroitinase ABC-injected discs recovered somewhat morphologically and biochemically. CONCLUSIONS: The results confirm that selective degradation is achieved with chondroitinase ABC in vivo in monkeys and that chondroitinase ABC is less toxic to discs than chymopapain is. From these considerations, chondroitinase ABC is believed to have a high potential for clinical application.

Animals↗

PubMed1996

Promotion and control of selective adhesion and proliferation of endothelial cells on polymer surface by carbon deposition.

The adhesion and proliferation of endothelial cells can be drastically improved when cultivated on a carbon-deposited polymer surface. When the surface of segmented polyurethane, in which endothelial cells are not capable of proliferating, is modified by carbon deposition, cell adhesion and proliferation occurred selectively on the carbon-deposited region. Carbon deposition to a tissue culture-treated polystyrene surface on which cells are capable of proliferating further promoted cell spreading and proliferation. Cell patterning on carbon-deposited segmented polyurethane was also attempted by controlling the direction or region of cell proliferation. Carbon deposition onto the polymer surface brought about a decrease in the water contact angle of the surface. Precoating fibronectin or laminin on the carbon-deposited polymer surface brought about cell adhesion and proliferation in the carbon-deposited region, but not in the non-carbon-deposited region. Our data suggest that promotion of cell proliferation on a carbon-deposited surface is probably due to selective adhesion of adhesive proteins to the surface.

Animals↗

PubMed1996

mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in interface tissue around implants in loosening total hip arthroplasty.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) play an important role in tissue destruction and remodeling. Nine samples of cement interface tissues from nine patients who had failed cemented total hip arthroplasty (THA) were obtained for revision of THA and analyzed on mRNA expression of MMPs and TIMPs. The preoperative serial radiographic examinations revealed an apparent clear zone around all implants. We excluded septic loosening as one of the factors affecting THA. Three samples were obtained from three different sites of the acetabular interface tissue in each patient. After extraction of total RNA from 27 samples, we used the reverse-transcriptional polymerase chain reaction (RT-PCR). mRNA of MMP-1, -2, -3, -9, and TIMP-1 and -2 was detected in the interface tissue. MMP-10 mRNA was not detected, yet MMP-1 and MMP-3 mRNA were commonly observed. TIMP-2 mRNA was also strongly expressed compared to TIMP-1. It was thus demonstrated that MMPs and TIMPs were produced locally in the cemented tissue of THA loosening. These findings may suggest that MMPs and TIMPs expressed around the implants play a critical role in the progression of aseptic loosening of THA.

Aged↗

PubMed1996

Histological analysis of microencapsulated dopamine-secreting cells in agarose/poly(styrene sulfonic acid) mixed gel xenotransplanted into the brain.

PC12 cells were encapsulated within agarose/poly-(styrene sulfonic acid) (agarose/PSSa) mixed gel and xenotransplanted into the brains of guinea pigs. The immunoprotection capability and biocompatibility of the agarose/PSSa microcapsules were evaluated. Tyrosine hydroxylase-positive PC12 cells within the microcapsules were observed in all guinea pigs at least 5 weeks after transplantation. PC12 cells had a relatively uniform small size and occasionally formed cell clusters; however, cell necrosis was not apparent. The host reaction to agarose/PSSa microcapsules was minimal. The degree of glial fibrillary acidic protein-positive astrocyte density around the microcapsules was similar to that around the injection tracks. Necrosis around the brain/microcapsule interface was not apparent as assessed by Nissl staining. Normal-appearing neurons were observed in close vicinity to the capsule. High-performance liquid chromatography with electrochemical detection showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. We conclude that encapsulation using agarose/PSSa mixed gel can not only isolate the enclosed cells from the host immune system but can also allow diffusional exchange of nutrients and neurotransmitters. Encapsulation using agarose/PSSa mixed gel may expand the range of donor tissues for neural transplantation.

Animals↗

PubMed1996

Distribution, biomagnification, and elimination of butyltin compound residues in common cormorants (Phalacrocorax carbo) from Lake Biwa, Japan.

Concentrations of butyltin compounds (BTs) were determined in various body tissues of common cormorants (Phalacrocorax carbo) collected from the Lake Biwa, Japan. Elevated concentrations of butyltins were detected in the feathers of cormorants. Among other organs and tissues, butyltin levels were also higher in the kidney (290+/-150 ng/g) and liver (270+/-260 ng/g), ranging from 115 to 544 ng/g and 142 to 1007 ng/g (wet wt basis), respectively. The accumulation of BTs in cormorant bodies was in the order of MBT>DBT>TBT and their organ specific burdens were in the order of muscle>/=feathers>skin>liver>rest of the tissues and organs. The higher levels of BTs residues in feather suggested the excretion of about one fourth of their body burden during a complete molting cycle, which has been a natural detoxification mechanism in these birds. Based on the whole body concentrations of BTs in cormorants (42-160 ng/g wet wt) and fish (10-55 ng/g wet wt) biomagnification factors were assessed to be in the range of 1.1-4.1. To our knowledge, this is the first fundamental study to substantially indicate the contamination and kinetics of BTs in wild birds.

Animals↗

PubMed1996

Magnetic resonance imaging in osteoarthrosis of the dysplastic hip.

We performed magnetic resonance imaging (MRI) in osteoarthrosis (OA) of 35 dysplastic hips in 28 patients using a 1.5-Tesla superconductive magnet. MR images were compared with conventional radiographs and arthrograms. MRI demonstrated cartilage irregularity and joint space narrowing in 17 hips earlier than did radiographs. Acetabular labrum tears were observed in 24 hips by MRI and in 23 hips by arthrography, suggesting that the former may be as useful as the latter. Osteophytes, joint effusion and synovial proliferation can be identified better by MRI than by conventional radiography. An MR grading system was established according to the thickness of the cartilage and sclerosis of the acetabulum or femoral head. This system can be a powerful tool to recognize the early stage of OA. MRI can demonstrate directly the severity of OA, including early degeneration of articular cartilage and acetabular labrum tear.

Hip Dislocation, Congenital↗

PubMed1996

Histological changes in brain tissue and vasculature after intracarotid infusion of organic solvents in rats.

Organic solvents, such as ethanol or dimethyl sulphoxide (DMSO), have been used in liquid embolic agents. To investigate the effects of these solvents on the cerebral blood vessels and cerebral tissue, we subjected Wistar rats weighing 250-300 g to internal carotid artery infusion of 0.2 ml diluted ethanol (10%, 40% or 70%) or anhydrous DMSO (100%). Some rats were sacrificed 5 min after the infusion and the remainder at 10 days. Rats injected with ethanol at high concentration or DMSO showed extensive exudation of Evans blue at the site of injection 5 min after infusion, together with full-thickness necrosis of the wall of vessels and swelling of brain cells. In contrast, rats injected with 10% or 40% ethanol solution showed necrosis of only the intimal layer and partial necrosis of the medial layer and no brain swelling was observed. These findings suggest that ethanol at low concentration can be used as a relatively safe solvent for liquid embolic substances.

Animals↗