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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 145 records · Page 8Linked to original sources
PubMed2000

Immobilization depresses insulin signaling in skeletal muscle.

Prolonged immobilization depresses insulin-induced glucose transport in skeletal muscle and leads to a catabolic state in the affected areas, with resultant muscle wasting. To elucidate the altered intracellular mechanisms involved in the insulin resistance, we examined insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit (IR-beta) and insulin receptor substrate (IRS)-1 and activation of its further downstream molecule, phosphatidylinositol 3-kinase (PI 3-K), after unilateral hindlimb immobilization in the rat. The contralateral hindlimb served as control. After 7 days of immobilization of the rat, insulin was injected into the portal vein, and tibialis anterior muscles on both sides were extracted. Immobilization reduced insulin-stimulated tyrosine phosphorylation of IR-beta and IRS-1. Insulin-stimulated binding of IRS-1 to p85, the regulatory subunit of PI 3-K, and IRS-1-associated PI 3-K activity were also decreased in the immobilized hindlimb. Although IR-beta and p85 protein levels were unchanged, IRS-1 protein expression was downregulated by immobilization. Thus prolonged immobilization may cause depression of insulin-stimulated glucose transport in skeletal muscle by altering insulin action at multiple points, including the tyrosine phosphorylation, protein expression, and activation of essential components of insulin signaling pathways.

Animals↗
PubMed2000

Effect of acute hypoxia on vasopressin release and intravascular fluid during dynamic exercise in humans.

To test the hypothesis that acute hypoxia does not modify the relationship between plasma vasopressin concentration ([AVP](p)) and plasma osmolality (P(osmol)) during exercise and that the increase in [AVP](p) during exercise is due mainly to the exercise intensity-dependent increase in P(osmol), we examined [AVP](p) during a graded exercise in a hypoxic condition (13% O(2), N(2) balance) in seven healthy male subjects. A graded exercise in a normoxic condition on a separate day served as the control. Hypoxia reduced peak aerobic power (VO(2 peak)) by 32.4 +/- 2.7%. Blood samples obtained during rest and at around 25, 45, 65, 80, and 100% of VO(2 peak) of each of the respective conditions were used for analyses of intravascular water and electrolyte balance. The pattern of the changes in fluid and electrolyte balance in response to percent VO(2 peak) was similar between the two conditions. Plasma volume decreased linearly as percent VO(2 peak) increased while P(osmol) increased in a curvilinear fashion with a steep increase occurring at above approximately 66% VO(2 peak). Above this relative exercise intensity, plasma sodium, potassium, and lactate concentrations also increased, whereas plasma bicarbonate concentration decreased. Thus transvascular fluid movement at above approximately 66% VO(2 peak) was due to the net efflux of hypotonic fluid out of the vascular space in both conditions. The relationship between [AVP](p) and P(osmol) during exercise in response to relative exercise intensity was similar between the two conditions. The results indicate that acute mild hypoxia itself has no direct effect on vasopressin release, and it does not modify the relationship between [AVP](p) and P(osmol) during exercise. The results also support the hypothesis that exercise-induced vasopressin release is primarily stimulated by increased P(osmol) produced by hypotonic fluid movement out of the vascular space in a relative exercise intensity-dependent manner.

Acute Disease↗
PubMed2000

Modifying effects of propolis on MeIQx promotion of rat hepatocarcinogenesis and in a female rat two-stage carcinogenesis model after multiple carcinogen initiation.

The modifying effects of the dietary administration of water- and ethanol-extracted propolis produced in Brazil (WB and EB, respectively) on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) promotion of rat hepatocarcinogenesis were investigated in a medium-term liver bioassay system with use of male Fischer 344 rats. The number and area of glutathione S-transferase placental form (GST-P)-positive foci in rats given 0.5% WB were significantly increased compared with the group given MeIQx alone. Furthermore, the numbers of GST-P-positive foci were higher in rats given 0.1% WB or EB than in those given the basal diet alone. The modifying effects of propolis on other organs were also examined in female Fischer 344 rats given multiple carcinogens for initiation. Rats received water- and ethanol-extracted propolis produced in Brazil and Uruguay (WB, EB, WU, and EU, respectively) in the diet after exposure to three different carcinogens. The incidence of total mammary tumors was significantly lower in rats given EU than in the control group. These results indicate that a water extract of propolis exerts a cocarcinogenic effect on MeIQx hepatocarcinogenesis while promoting the effect at low dose in a two-stage hepatocarcinogenesis model. Moreover, they suggest that ethanol-extracted propolis may be an inhibitor of mammary gland carcinogenesis.

Alkylating Agents↗
PubMed2000

A Na+/Ca2+ exchanger inhibitor, KB-R7943, caused negative inotropic responses and negative followed by positive chronotropic responses in isolated, blood-perfused dog heart preparations.

Effects of a Na+/Ca2+ exchanger inhibitor, KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), on the sinoatrial nodal pacemaker activity, atrial contractility and ventricular contractility were investigated in the isolated and blood-perfused right atrium and left ventricle of the dog. KB-R7943 (0.03- 3 micromol) induced negative inotropic effects and negative followed by positive chronotropic effects in the right atrium and negative inotropic effects in the left ventricle. Neither atropine nor hexamethonium affected the cardiac responses to KB-R7943. Propranolol attenuated the positive chronotropic response to KB-R7943 but imipramine did not. Tetrodotoxin potentiated the positive chronotropic response to KB-R7943 in 6 of 11 isolated atria. When NaCl infusion increased atrial contractile force and atrial rate, KB-R7943-induced negative inotropic and chronotropic responses were attenuated in a dose-dependent manner. CaCl2 infusion potentiated the negative chronotropic response to KB-R7943 but did not affect the inotropic response significantly. On the other hand, ouabain (17 nmol) attenuated the negative inotropic response, but not chronotropic response, to KB-R7943. These results suggest that KB-R7943-induced cardiac effects relate to the Na+ activity, probably mediated through the Na+/Ca2+ exchanger, and the Na+/Ca2+ exchanger modifies the pacemaker activity and myocardial contractility in the dog heart.

Animals↗
PubMed2000

The structural mechanism for iron uptake and release by transferrins.

Transferrins are a group of iron-binding proteins that control the levels of iron in the body fluids of vertebrates by their ability to bind two Fe3+ and two CO3(2-). The transferrin molecule, with a molecular mass of about 80 kDa, is folded into two similarly sized homologous N- and C-lobes that are stabilized by many intrachain disulfides. As observed by X-ray crystallography, each lobe is further divided into two similarly sized domains, domain 1 and domain 2, and an Fe3+-binding site is within the interdomain cleft. Four of the six Fe3+ coordination sites are occupied by protein ligands (2 Tyr residues, 1 Asp, and 1 His) and the other two by a bidentate CO3(2-). Upon uptake and release of Fe3+, transferrins undergo a large-scale conformational change depending on a common structural mechanism: domains 1 and 2 rotate as rigid bodies around a rotation axis that passes through the two antiparallel beta-strands linking the domains. The extent of the rotation is, however, variable for different transferrin species and lobes. As a Fe3+ release mechanisms at low pH from the N-lobes of serum transferrin and ovotransferrin, the structural evidence for 'dilysine trigger mechanism' is shown. A structural mechanism for the Fe3+ release in presence of a non-synergistic anion is proposed on the basis of the sulfate-bound apo crystal structure of the ovotransferrin N-lobe. Domain-opened structures with the coordinated Fe3+ by the two tyrosine residues are demonstrated in fragment and intact forms, and their functional implications as a possible intermediate for iron uptake and release are discussed.

Animals↗
PubMed2000

Sequential observation of 2,6-dimethylaniline-induced nasal lesions in a rat two-stage nasal carcinogenesis model after initiation with N-bis(2-hydroxypropyl) nitrosamine.

Male F344 rats received diet containing 3,000 ppm 2,6-dimethylaniline (DMA) after initiation with a single subcutaneous injection of 2,400 mg/kg of N-bis(2-hydroxypropyl)nitrosamine (DHPN), and histological and electron microscopic examinations of the nasal cavity were performed at 4, 13, 26 and 52 weeks to examine sequential changes induced by DMA. Severe atrophy of Bowman's glands and epithelial disarrangement were apparent from week 4, followed by dilatation and/or proliferation of Bowman's glands, degeneration of epithelial cells, and proliferation of undifferentiated epithelial cells from week 13. Focal glandular hyperplasias, dysplastic foci, and adenomas were observed from week 26, and carcinomas at 52 week. These nasal lesions were mostly evident in the olfactory mucosa in the nasal cavity, and their severity and/or incidences, other than atrophy of Bowman's glands, increased with the treatment period. Electron microscopically, carcinoma cells demonstrated desmosomes, dense secretory granules identical to those in normal Bowman's glands, a basement membrane, and microvilli. These results suggest that Bowman's glands are the target of DMA, giving rise to nasal carcinomas after DHPN-initiation.

Adenoma↗
PubMed2000

Toxicity and blood concentrations of xylazine and its metabolite, 2,6-dimethylaniline, in rats after single or continuous oral administrations.

To cast light on whether the carcinogenic risk of 2,6-dimethylaniline (DMA), a metabolite of xylazine, may increase by ingestion of edible tissues from domestic animals treated with xylazine, the following studies of xylazine and DMA were performed. In Experiment I, male F344 rats received a single oral administration of 150 mg/kg of xylazine hydrochloride. Rats showed symptoms suggesting loss of sensation and pain immediately after the treatment. These signs had disappeared after 3 hr, but the animals died of hydrothorax and pulmonary edema by 9 hr. The plasma concentration of xylazine was 2.88 +/- 0.95 micrograms/ml at 15 min, and then decreased to 0.10 +/- 0.01 microgram/ml at 6 hr. The plasma level of DMA remained at 0.03 to 0.04 microgram/ml during the measurement period. In Experiment II, male F344 rats were fed a diet containing 1000 ppm of xylazine hydrochloride, regarded as the maximum tolerated dose, for 4 weeks. No clear clinical signs were evident and the plasma levels of xylazine and DMA were at the detection limit (0.02 microgram/ml) or less, although follicular cell hypertrophy of the thyroid was observed in all the treated animals. In Experiment III, male F344 rats were fed a diet containing 3000 ppm or 300 ppm of DMA for 4 weeks. Histological changes, such as atrophy of Bowman's gland and irregular arrangement of olfactory epithelial cells, were only observed in the olfactory epithelium of the 3000 ppm group. The plasma levels of DMA were 0.20 to 0.36 microgram/ml in the 3000 ppm group, but under the detection limit in the 300 ppm group. These results suggest that the probability of nasal carcinogenic effects of DNA on consumers via ingestion of edible tissues from food-producing animals treated with xylazine is extremely low, since DMA levels in the blood of rats subjected to continuous administration of high doses of xylazine remained under the detection limit.

Administration, Oral↗
PubMed2000

Early development of zooxanthella-containing eggs of the corals Pocillopora verrucosa and P. eydouxi with special reference to the distribution of zooxanthellae.

Some hermatypic corals spawn eggs that contain zooxanthellae. We followed development of zooxanthella-containing eggs of two such species, Pocillopora verrucosa and P. eydouxi. We also documented changes in the distribution pattern of zooxanthellae during development. Oocytes of both species took up zooxanthellae 3 to 4 days before spawning. At first, zooxanthellae were evenly distributed in oocytes, but they later moved to the hemisphere that contained the germinal vesicle. After fertilization, early cleavage events were holoblastic, progressing by furrow formation. The first cleavage furrow started at the hemisphere that contained zooxanthellae, dividing the zooxanthellate complement of the zygote about equally into the two blastomeres. The second division divided each blastomere into one zooxanthellae-rich cell and one with few zooxanthellae. With continued cell division, blastomeres containing zooxanthellae moved into the blastocoel. The blastocoel disappeared at about 5 h after the first cleavage, and the central region of the embryo was filled with cells containing either zooxanthellae or lipid droplets, forming a stereogastrula. Our results suggest that only blastomeres that had been determined to develop into gastrodermal cells receive zooxanthellae during cleavage. This determination appears to take place, at the latest, by the second cell division at the four-cell stage.

Animals↗
PubMed2000

Temperature-Responsive surface for novel co-culture systems of hepatocytes with endothelial cells: 2-D patterned and double layered co-cultures.

We have developed two novel cell co-culture system, without any on cell type combination limitation, utilizing a polymer surface which is temperature-sensitive with respect to its cell adhesion characteristics. One system involves a patterned co-culture of primary hepatocytes with endothelial cells utilizing patterned masked of the electron-beam cured, temperature-responsive polymer, poly (N-isopropylacrylamide) (PIPAAm) by masked electron beam irradiation. Hepatocytes were cultured to confluency at 37 degrees C on these surfaces. When the culture temperature was reduced below 32 degrees C, cells detached from the PIPAAm-grafted areas without any need for trypsin. Endothelial cells were then seeded onto the same surfaces at 37 degrees C. These subsequently seeded endothelial cells adhered only to the now-exposed PIPAAm-grafted domains and could be co-cultured with the hepatocytes initially seeded at 37 degrees C in well-ordered patterns. The other system involves a double layered co-culture obtained by overlaying endothelial cell sheets of the designed shape onto hepatocyte monolayers. The endothelial cells adhered and proliferated on the PIPAAm-grafted surface, as on polystyrene tissue culture dishes at 37 degrees C. By reducing the temperature, confluent monolayers of cells detached from the PIPAAm surfaces without trypsin. Because the recovered cells maintained intact cell-cell junctions together with deposited extracellular matrix, the harvested endothelial cell sheets, with designed shapes, were transferable and readily adhered to hepatocyte monolayers. Stable double layered cell sheets could be co-cultivated. These two co-culture methods enabled long-term co-culture of primary hepatocytes with endothelial cells. Hepatocytes so co-cultured with endothelial cells maintained their differentiated functions, such as albumin synthesis for unexpectedly long periods. These novel two co-culture systems offer promising techniques for basic biologic researches upon intercellular communications, and for the clinical applications of tissue engineered constructs.

Acrylic Resins↗
PubMed2000

[Local recurrence in complete resection for non-small cell lung cancer].

307 patients with complete resection for non-small cell lung cancer between 1989 and 1996 were examined to evaluate the clinical features of local recurrence. Postoperative recurrence was observed in 104 of the 307 patients. At the first recurrence, local recurrences occurred in 21 (20%) of the 104 patients, distant metastases in 72 (69%), and combined recurrences in 11 (11%). 32 patients had local recurrences in 47 localizations, bronchial stump recurrences occurred in 11 (34%) of 47 localizations, hilarmediastinal lymph node metastases in 18 (56%), supraclavicular lymph node metastases in 10 (31%), contralateral mediastinal lymph node metastases in 1 (0%), and malignant effusion in 7 (22%). Lymph node metastases in the hilusmediastinum were the most common mode of the local recurrences (22%), and each mode of solely subclavian lymph node metastases and malignant effusion was 16%. The incidence of local recurrences increased as invasion into the lymphatic and/or blood vessels was demonstrated (p < 0.05). The results of our study implies that despite of lymph node dissection, latent disease persisted in the small lymphatic and/or blood vessels from hilus to subclavian sites. Postoperative adjuvant therapy including radiation will be beneficial to improvement of local control for patients invaded to lymph and/or blood vessels.

Adult↗
PubMed2000

Acute and chronic effect of alcohol on Ca2+ channels in hepatic stellate cells.

BACKGROUND: Hepatic stellate cells have been reported to play important roles in the regulation of hepatic microcirculation via cell contraction. Increase in intracellular calcium concentration is required to induce cell contraction. We have already reported the existence of L-type voltage-operated Ca2+ channels (VOCC), such as smooth muscle cells. On the other hand, alcohol has been known to disturb hepatic microcirculation. In this study, we evaluated the effect of acute and chronic treatment of alcohol on VOCC in rat hepatic stellate cells. METHODS: Stellate cells isolated from rats were cultured with or without 100 mM ethanol for up to 14 days. VOCC were detected by the patch clamp technique. Cells cultured for 14 days without ethanol were exposed to ethanol to investigate calcium current during membrane depolarization. alpha-Smooth muscle actin (alpha-SMA) was stained by indirect immunofluorescence. RESULTS: In the control model, VOCC were recognized in cells cultured for more than 7 days. Detection of VOCC increased from 9% on day 7 to 55% on day 14. On the other hand, VOCC in cells treated chronically with 100 mM ethanol appeared earlier than in the control and the incidences were significantly higher than those of the control accompanied with an early activation of cells. In contrast, simultaneous exposure to ethanol during the membrane depolarization inhibited Ca2+ current. CONCLUSIONS: The expression of Ca2+ channels in stellate cells were up-regulated by the chronic treatment of alcohol accompanied with the transformation to myofibroblast-like phenotype. However, alcohol itself inhibited Ca2+ current.

Actins↗
PubMed2000

Epithelial-mesenchymal interaction in gastric mucosal restoration.

In this review article we discuss the role of growth factors in gastric ulcer healing using an in vitro wound repair model with gastric epithelial and mesenchymal cells. Several growth factors accelerate gastric epithelial and mesenchymal wound healing in vitro with acceleration of cell migration and proliferation. Epidermal growth factor, transforming growth factor-alpha (TGFalpha), hepatocyte growth factor, and insulin accelerate predominantly gastric epithelial wound healing; and TGFbeta and basic fibroblast growth factor predominantly accelerate gastric mesenchymal wound healing. Platelet-derived growth factor-betabeta and insulin-like growth factor-1 (IGF-1) accelerate both significantly. Among these growth factors, IGF-1 produced from fibroblasts plays a key role in the gastric epithelial-mesenchymal interaction during the process of gastric wound healing.

Animals↗
PubMed2000

[The relationship between the tumor uptake of gallium-67 and the effect of cisplatin-based preoperative chemotherapy or chemoradiotherapy for lung cancer].

Cisplatin has been usually used as the chemotherapy for lung cancer presurgically, though it is still difficult to predict downstaging of tumor from this drug. Four patients who underwent surgery achieved pathologic complete remissions in response to preoperative cisplatin-based chemotherapy with or without radiation. All of the Ga-67 citrate images in the four patients showed markedly increased uptake in tumors. According to the literatures, both Ga-67 and cisplatin binds to transferrin in the blood and transfers into the cells through transferrin-receptors expressed on the cell surface. The mechanism for Ga-67 and cisplatin uptake into tumor cells were alike. Marked tumor uptake on Ga-67 scintigraphy suggested that cisplatin-based chemotherapy or chemoradiotherapy was efficacious.

Aged↗
PubMed2000

Clinical studies on bronchial asthma caused by contact with hamsters.

Bronchial asthma induced by contact with hamsters and other small rodents is receiving higher attention from the medical profession not only because of the problem of laboratory animal allergies (LAA), but also because of increasing household allergens for asthma, since keeping these pets has become more common in Japanese homes. The present report describes our studies on the backgrounds of nine patients with asthma who kept Dzungarian Dwarf hamsters as household pets. The following features were recognized among patients with bronchial asthma induced by contact with hamsters: 1) earlier onset of symptoms than for keeping other household pets, at an average of 14.7 months or within 12 months in 78% of the cases following the start of pet keeping; 2) adults ranging from their late 30s to 40s who have children of primary school age; 3) dwelling in apartments; 4) relatively high level of serum IgE and ECP; 5) positive for both immediate and late type asthmatic responses on an inhaling induction test; and 6) rapid remission after the cessation of pet keeping.

Adult↗
PubMed2000

[A 90-day repeated dose toxicity study of madder color in F344 rats: a preliminary study for chronic toxicity and carcinogenicity studies].

A 90-day toxicity study of madder color was performed in F344 rats by feeding the pellet diet containing 0, 0.6, 1.2, 2.5 and 5.0% of test substance to clarify its toxic potential and to determine the dose levels for the following chronic toxicity/carcinogenicity studies. Body weight gain and food consumption were dose-dependently decreased at 1.2% or more in males and at 2.5% or more in females throughout the experimental period. All animals were survived until the end of experiment and subjected to autopsy. Hematologically, the following parameters were fluctuated in relation to the treatment: decreases in the red blood cells, hemoglobin, and hematocrit in females at 2.5% or more; increase of platelets in males at 2.5% or more, and in females at 5%; increase in white blood cells in males at 5%. Serum protein parameters were also affected by the treatment in males at 1.2% or more and in females at all doses. Increase in the serum calcium level was observed in males at 2.5% or more and in females at 5%. Serum inorganic phosphorus level was also increased in males at 1.2% or more and in females at 2.5% or more. At autopsy, both absolute and relative kidney weights of females increased dose-dependently at 0.6% or more. Relative liver weight in females also increased at 1.2% or more. Histopathologically, microvesicular vacuolar degeneration of proximal tubules was observed in the kidney of both sexes (males at 1.2% or more; females at 0.6% or more). In addition, mononuclear cell infiltration (both sexes) and hyaline casts and tubular regeneration (male) appeared in the kidney at 5%. In the female liver, focal liver cell necrosis associated with mononuclear cell infiltration was evident at 5%. The results demonstrate the toxic effects of madder color on the liver (in females at 5%) and kidney (in males at 1.2% or more; in females at 0.6% or more) of F344 rats when treated orally for 90 days. In addition, toxicities in hematopoietic system and/or bone would probably be appeared when rats are treated with 1.2% or more of madder color for long-term over 90 days. NOAEL was determined to be 0.6% in males, but could not be determined in females under the condition of this study. Based on the results of this study, the dose levels for subsequent chronic toxicity and carcinogenicity studies were determined to be 0.2, 1.0 and 5.0%, and 2.5 and 5.0%, respectively.

Administration, Oral↗
PubMed2000

[A 90-day repeated dose oral toxicity study of magnesium chloride in F344 rats].

In order to examine the toxicity of magnesium chloride hexahydrate, four groups of 10 male and 10 female F344 rats received the compound by dietary supplementation at 2.5, 0.5, 0.1 or 0% for 90 days. No treatment-related death was observed during the study. Transient soft stool and sustained increase in water consumption were observed both in males and females of the 2.5% group and slight reduction in body weight gain was noted in the high-dose males. There were no toxic changes in food consumption, organ weights, hematology and biochemistry, and histopathological examinations in any treated-groups. Based on these results, the no-observed-adverse-effect-level was estimated to be 0.5%, and 2.5% is considered to be appropriate as highest dose for a 2-year carcinogenicity study.

Administration, Oral↗
PubMed1999

Post-initiation effects of a super critical extract of propolis in a rat two-stage carcinogenesis model in female F344 rats.

Post-initiation modifying effects of dietary administration of a super critical extract of propolis on major organs were examined using a two-stage carcinogenesis model. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, i.g.), 7,12-dimethylbenz[a]anthracene (DMBA, i.g.), 1,2-dimethylhydrazine (DMH, s.c.) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, in drinking water) during the first 3 weeks for initiation, and then administered diet containing 0.1 or 0.01% propolis for 33 weeks. Further groups were treated with the carcinogens alone, 0.1% propolis alone or basal diet alone. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. The incidence and multiplicity of mammary carcinomas were significantly decreased by the 0.1 and 0.01% propolis treatments. In the urinary bladder, the incidence of PN hyperplasia but not tumors was, in contrast, significantly increased by 0.1% propolis. Similarly, the number and area of glutathione S-transferase placental form (GST-P)-positive liver foci were significantly elevated with this high dose. The results indicate that a low dose of a super critical extract of propolis may find application as a potent chemopreventor of mammary carcinogenesis.

1,2-Dimethylhydrazine↗