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Biomedical subjects

Y Ohira

Publications and source records attributed to Y Ohira.

At least 19 recordsLinked to original sources

Metastatic hypopharyngeal carcinoma to the temporal bone.

Two cases of temporal bone metastasis by hypopharyngeal carcinomas are reported. One patient was a 43-year-old Japanese male who developed palsy of left oculomotor, trochlear, trigeminal, abducens and facial nerves. Carcinoma infiltrated the petrous portion of the left temporal bone. Tumor had destroyed a part of the facial canal and invading tumor cells were in contact with the perineurium. The other patient was a 59-year-old male who had no obvious facial nerve or otologic symptoms during the clinical course of his disease. Postmortem findings showed that carcinoma had invaded the right temporal bone and had produced extensive destruction of the facial canal. Degenerative findings were evident in the nerve. In the cases presented here, tumor resulted either from metastatic lymph nodes or had invaded through the suture of the temporal and sphenoid bones around the foramen lacerum to the middle cranial fossa and then infiltrated the temporal bone.

Adult

Temporal bone and brain stem histopathological findings in Cornelia de Lange syndrome.

The temporal bone and the brain stem of an infant with Cornelia de Lange syndrome, aged 9 months, were studied histopathologically. Abnormalities in the inner ear included short cochlea, dilated vestibule, and mesenchyme-filled perilymphatic spaces of the vestibule and semicircular canals. The inner and outer hair cells were normal. Many spiral ganglion cells, which normally would be located in the canal of Rosenthal, were seen in the internal auditory meatus. Some of the vestibular ganglion cells intruded into the facial nerve. The facial nerve formed a loose curve and the geniculum was difficult to recognize. The middle ear was filled with mesenchyme, and there was marked dehiscence of the facial canal. The brain stem, particularly the pons, was smaller than normal, while the fourth ventricle was dilated. The microscopic observation of the pons revealed weak staining with Luxol Fast Blue and decreased number of oligodendroglia. These findings suggested the malformation of the myelin of transverse fibers.

Brain Stem

Myonuclear number and myosin heavy chain expression in rat soleus single muscle fibers after spaceflight.

The effects of 14 days of spaceflight on myonuclear number, fiber size, and myosin heavy chain (MHC) expression in isolated rat soleus muscle fiber segments were studied. Single soleus muscle fibers from rats flown on the Spacelab Life Sciences-2 14-day mission were compared with those from age-matched ground-based control rats by using confocal microscopy and gel electrophoresis. Spaceflight resulted in a significant reduction in the number of fibers expressing type I MHC and an increase in the number of fibers expressing type IIx or IIa MHC. Space-flight also resulted in an increase in the percentage of fibers coexpressing more than one MHC and in the reexpression of the neonatal isoform of MHC in some fibers. Fiber cross-sectional area was significantly reduced in pure type I MHC-expressing fibers and in fibers coexpressing type I+II MHC but not in fibers expressing one or more type II MHC in the flight rats. The number of myonuclei per millimeter was significantly reduced in type I MHC-expressing fibers from the flight rats but was not significantly different in type I+II and type II MHC-coexpressing fibers. Fibers expressing neonatal MHC were similar in size to control fibers but had significantly fewer myonuclei per millimeter than flight fibers not expressing neonatal MHC. In type I MHC-expressing fibers, the reduction in fiber cross-sectional area was greater than the reduction in myonuclear number; thus the average cytoplasmic volume per myonucleus was significantly lower in flight than in control fibers. The reduction in both myonuclear number and fiber size of fibers expressing type I MHC after 14 days of spaceflight supports the hypothesis that changes in the number of myonuclei may be a contributing factor to the reduction in fiber size associated with chronic unloading of the musculature.

Animals

Spaceflight effects on beta-adrenoceptor and metabolic properties in rat plantaris.

Effects of 14 days of spaceflight on beta-adrenoceptor (beta-AR), mitochondrial enzyme activities, and fiber type composition were studied in plantaris muscles of male adult Sprague-Dawley rats. The beta-AR was analyzed in cross sections by quantitative autoradiography. The maximum binding capacity (Bmax) of beta-AR was significantly lowered (approximately 29%) after flight, but the recovery was not completed within 9 days in 1-G environment. Because the dissociation constant remained unchanged, it is suggested that the changes in the Bmax were caused by the alteration of receptor number. The activities of succinate dehydrogenase (SDH) measured in whole homogenates were subnormal (approximately -24%) in muscles sampled approximately 5 h after flight but they were normalized during 9 days of recovery. The percent composition of fiber types and beta-hydroxyacyl CoA dehydrogenase (HAD) activity did not change significantly due to spaceflight. It is suggested that the spaceflight-induced decrease of the Bmax of beta-AR in plantaris was accompanied by a lowered activity of a mitochondrial inner-membrane enzyme SDH but not a matrix enzyme HAD.

3-Hydroxyacyl CoA Dehydrogenases

Vertebral growth disturbance in rapidly growing rats during 14 days of spaceflight.

The effect of 14 days of spaceflight on the vertebrae of rapidly growing rats was studied. The hardness of the vertebrae was measured with a Knoop microhardness tester, and bone mineral density was measured from X-ray photographs. Histomorphometric examination was performed with a microcomputer-aided system. No significant difference (P > 0.05) was observed between flight rats and ground controls with regard to mechanical hardness or bone mineral density. However, histological examination revealed irregular thickening of the endosteal surface of cortical bone in the flight rats, whereas it was uniform in the ground controls. The relative area of lamellar bone showed a significant reduction (P < 0.001) in the flight rats. These findings suggest that the structural disturbances were due to retardation of endosteal modeling and remodeling. We conclude that delay of vertebral maturation can occur in rapidly growing rats after even short-term exposure to microgravity.

Animals

Cellular content of p53 protein in rat skin after exposure to the space environment.

The effects of stress in space, microgravity and space radiation, on living organisms are still unknown. We have examined the cellular content of p53 protein, a tumor-suppressor gene product, in skin from rats by the Western blot method using a blotting-amplification system. Three groups of rats were used. The first group was kept on Earth normally and showed hardly any detectable p53 protein. The second group made a 14-day flight into space on the second Spacelab Life Sciences-2 mission (F). The last group was subjected to the same kinds of stress as the rats in the second group except for spaceflight (SC). The F and the SC rats were killed on day zero (F-0 and SC-0 groups) and day nine (F-9 and SC-9 groups) after return. F-0 rats showed marked accumulation of p53 protein, whereas SC-0 rats showed a slight decrease. F-9 and SC-9 rats showed almost the same amount of p53 protein, but F-9 rats showed a slightly higher expression. From these results, it is suggested that the accumulation of cellular p53 protein is induced in rat skin cells by exposure to the space environment.

Animals

Thermogenic responses to high-energy phosphate contents and/or hindlimb suspension in rats.

Effects of chronic depletion of high-energy phosphate compounds by feeding beta-guanidinopropionic acid (beta-GPA) with or without hindlimb suspension (HS) on body temperature were studied in rats. Lower rectal and skin temperatures were observed in rats after 10 d of HS. Suspension-related enlargement of the interscapular brown adipose tissue (BAT), associated with adrenal hypertrophy, was seen. Feeding beta-GPA also caused a hypothermia and BAT enlargement. It is suggested that the hypothermic response to HS may be due to decreased contractile activity and metabolic rate in skeletal muscles, associated with stress. It is also speculated that the changes in the thermogenesis in rats fed beta-GPA might be related to a stimulated ATP synthesis with sacrificed heat production, but not associated with stress.

Animals

Increased growth of brown adipose tissue but its reduced thermogenic activity in creatine-depleted rats fed beta-guanidinopropionic acid.

To study the responses of thermogenic activity in brown adipose tissue (BAT) to creatine depletion, male Wistar rats were fed creatine analogue beta-guanidinopropionic acid (beta-GPA) for about 10 weeks. Compared to control rats, a marked decrease in the levels of high-energy phosphates, such as phosphocreatine and ATP, was noted in BAT of beta-GPA rats. Conversely, upward trends in other chemical components (DNA, glycogen, and total protein) in BAT as well as an increase in BAT mass were observed in beta-GPA rats, suggesting a tendency to hyperplasia of the BAT. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) in the mitochondria recovered from BAT of beta-GPA rats, however, was not increased in response to such changes but rather decreased. Moreover, uncoupling protein (UCP) content in the mitochondrial fraction of beta-GPA rats was significantly lower than that in control rats (the relative amounts were 77 +/- 6 and 100 +/- 4%, respectively). Nevertheless, surprisingly, the level of UCP mRNA was remarkably greater in beta-GPA rats than in control rats. These observations indicate that there is a discordance between BAT growth and activity in beta-GPA rats, thereby suggesting that a failure on and after UCP translation may be involved in the impairment of BAT thermogenic activity with creatine depletion. The impairment of BAT thermogenic activity, that is, UCP activity may indicate that uncoupling or heat production was inhibited in order to increase the ATP synthesis in BAT of beta-GPA rats in compensation for a reduction in the levels of high-energy phosphates (including ATP), with resultant hypothermia.

Adipose Tissue, Brown

Effects of creatine and beta-guanidinopropionic acid on the growth of Ehrlich ascites tumor cells: i.p. injection and culture study.

Growth of Ehrlich ascites tumor (EAT) cells in the abdominal space of mice or in cell culture was studied in response to i.p. injection or addition, respectively, of creatine or creatine analogue beta-guanidinopropionic acid (beta-GPA). The increase in body weight of the mice due to cancer growth was less in the beta-GPA-injected than in the creatine- or sham-injected group. The volume of abdominal ascites and total cell counts at 11th day after implantation of EAT cells was significantly less in the beta-GPA than in the other groups. The proliferation rate of EAT cells in the beta-GPA group was 27% and 35% of the creatine- and sham-injected groups, respectively. Supplementation of creatine tended to enhance the growth of EAT cells. The creatine concentration in ascites fluid was approximately 4-times greater than in blood plasma of sham-injected control mice. But the creatine content in EAT cells was significantly reduced to approximately 50% in response to beta-GPA injection. Cell culture without creatine caused a significant decrease in viability. The viability was improved, however, by addition of either creatine or serum into the medium. By contrast, it was not significantly increased by addition of serum alone which caused only a minor elevation of the creatine level (23 microM). It is suggested that EAT cell growth is inhibited by lowering the availability of creatine in association with some unknown factors in serum or ascites fluid.

Abdomen

Effects of beta-guanidinopropionic acid-feeding on the patterns of myosin isoforms in rat fast-twitch muscle.

Administration of beta-guanidinopropionic acid (beta-GPA) to rats as 1% of their diet for 6 weeks led to an accumulation of beta-GPA and beta-GPA-phosphate and to a depletion of creatine and phosphocreatine in the fast-twitch plantaris muscle. Adenosine triphosphate concentration was also decreased. Electrophoretic analyses were performed to investigate the effects of beta-GPA on the patterns of fast (FM) and slow (SM) isomyosins, myosin heavy chain (HC) isoforms and myosin light chain (LC) isoforms. The relative concentrations of fast isomyosins FM1 and FM2 decreased, whereas slow isomyosin SM increased. The increase in slow isomyosin corresponded to an increase in the relative concentration of the slow myosin HCI. The changes of the myosin light chain pattern consisted of increases in the relative concentrations of the two slow isoforms, LC1sb and LC2s, and decreases in the fast isoforms LC2f and LC3f. These results demonstrate that beta-GPA administration, leading to a depletion in energy-rich phosphates and a reduced phosphorylation potential, has an impact on myosin isoform expression in rat fast-twitch skeletal muscle.

Adenosine Triphosphate

Responses of brown adipose tissue activity to unloading in rats.

To study the responses of thermogenic activity in brown adipose tissue (BAT) to unloading, male Wistar rats were hindlimb suspended for 10 days. Compared with control rats, a significant increase in the BAT-to-body mass ratio and considerable differences in chemical components in BAT were observed in the hindlimb-suspended rats. These findings indicate a marked increase in the thermogenic capacity in BAT of the experimental group. Likewise, the thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) was markedly greater in the mitochondria recovered from BAT of the hindlimb-suspended rats than in those from the control rats (1,610 +/- 450 vs. 202 +/- 132 pmol recovered). Moreover, the uncoupling protein content in the BAT mitochondrial fraction of the hindlimb-suspended rats was significantly higher (1.6-fold) than that in the control rats. As was expected, the uncoupling protein mRNA expression was greater in hindlimb-suspended rats than in control animals. These results suggest that chronic hindlimb suspension leads to an increase in both the thermogenic capacity and the activity in BAT of rats.

Adipose Tissue, Brown

Human fiber size and enzymatic properties after 5 and 11 days of spaceflight.

Biopsies from the vastus lateralis muscle were obtained from three astronauts before and after two 5-day flights and from five astronauts before and after one 11-day flight (space shuttle flights: STS-32, -33, and -34). Muscle fibers from two separate samples from each biopsy were classified as type I and II or as type I, IIA, and IIB by using qualitative myofibrillar adenosinetriphosphatase (ATPase) staining. Cross-sectional area (CSA), number of capillaries per fiber, and the activities of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar ATPase were determined from one sample of fibers of each myofibrillar ATPase type. Postflight biopsies had 6-8% fewer type I fibers than preflight. Mean fiber CSAs were 16-36% smaller after the 11-day flight with the relative effect being type IIB > IIA > I. Mean fiber CSAs were 11 and 24% smaller in type I and II fibers after 5 days of flight. Myofibrillar ATPase activities increased in type II but not in type I fibers after flight, whereas SDH activity was unaffected in either fast or slow fibers. GPD activity in type I fibers was approximately 80% higher (P > 0.05) postflight compared with preflight. Myofibrillar ATPase/SDH ratios in type II fibers were higher after than before flight, suggesting that some fast fibers were more susceptible to fatigue after flight. The GPD/SDH ratios were elevated in some type I fibers after spaceflight. The number of capillaries per fiber was 24% lower after than before flight, whereas the number of capillaries per unit CSA of muscle tissue was unchanged. These data suggest that adaptations in the size, metabolic properties, and vascularity of muscle fibers can occur rapidly in the space environment. These adaptations were qualitatively similar to those observed in animals after actual or simulated spaceflight conditions for short periods.

Adenosine Triphosphatases

Radiofrequency catheter ablation for ventricular tachycardia with a right bundle branch block pattern and left axis deviation.

Ventricular tachycardia (VT) with right bundle branch block QRS morphology and left axis deviation originating in the inferolateral apical segment of the left ventricle was found in a 24-year-old man without overt structural heart disease. Intracardiac recordings during VT showed atrioventricular dissociation with the earliest activation at an apical inferolateral site in the left ventricle, where Purkinje fiber potentials were recorded fusing in the ventricular electrogram. Ventricular pacing was performed at this site, and yielded a QRS morphology identical to the VT. Radiofrequency current was applied and resulted in the complete elimination of VT.

Adult

Effects of chronic iron deficiency anemia on brain metabolism.

The effects of chronic iron deficiency anemia on brain (cortex) metabolism were estimated by 31P-nuclear magnetic resonance spectroscopy and biochemical analyses in male Wistar rats. Iron deficiency anemia was induced by supplying diet containing either approximately 2 or approximately 6 ppm Fe. Control diet was supplemented with 100 ppm Fe as ferric citrate. After 8-9 weeks, blood hemoglobin levels were approximately 13, 5, and 3 g/100 ml in the 100 ppm, 6 ppm, and 2 ppm Fe group, respectively. The blood lactate levels at rest in these groups were approximately 3, 5, and 6 mM. The blood glucose concentration also tended to be elevated in iron-deficient rats. The high-energy phosphate contents in brain were not affected by iron deficiency. The activities of succinate dehydrogenase and cytochrome oxidase per unit protein in the 2 ppm Fe group were significantly less than in the 100 ppm Fe group, but those activities were not significantly affected by feeding diet with 6 ppm Fe. The activities of lactate dehydrogenase in iron-deficient group tended to be elevated but not significantly. The activities of non-iron containing mitochondrial enzymes, citrate synthase and beta-hydroxyacyl CoA dehydrogenase, were unchanged. It is suggested that the brain has a higher tolerance to iron deficiency than skeletal muscle in terms of the metabolic characteristics, although this may be associated with a lower level of neural activity.

3-Hydroxyacyl CoA Dehydrogenases

Changes of contractile properties of extensor digitorum longus in response to creatine-analogue administration and/or hindlimb suspension in rats.

Changes of contractile properties of extensor digitorum longus in response to hindlimb suspension and/or altered high-energy phosphate contents were studied in rats. A reduction of high-energy phosphates, especially phosphocreatine, was seen in rats fed creatine analogue beta-guanidinopropionic acid (beta-GPA), but they were elevated after 10-d supplementation of creatine. The one-half relaxation time was increased by feeding beta-GPA, but was normalized by creatine supply. The fatigue resistance of creatine-depleted muscle was significantly improved, but tended to decrease by suspension and creatine supply, although it was still better than that in the control diet group. It is indicated that the contractile properties of muscle are influenced by the high-energy phosphate content. It is also suggested that the endurance capacity may be influenced by the mitochondrial respiratory capacity, but not necessarily by the levels of high-energy phosphates.

Animals

[Secondary tumor of the temporal bone with internal auditory meatus involvement--histopathological study].

Nineteen cases of secondary tumor of the temporal bone with involvement of the internal auditory meatus (IAM) were studied. The cases were classified into 4 invasion modes; direct extension from head and neck tumors (12 cases), hematological dissemination (3 cases), diffuse leptomeningeal carcinomatosis (3 cases), and direct extension of tumors from the intracranium (1 case). There were some differences in the manner in which the tumor had spread among these 4 modes. In most cases involving "direct extension from head and neck tumors", the tumor had invaded the pyramis, and then the Eustachian tube and the middle ear. When the inner ear or the IAM was involved, it was directly invaded by massive tumor. In all cases of "hematological dissemination", metastatic tumor was found bilaterally, but there were some differences in the manner of invasion between the two sides. In "leptomeningeal carcinomatosis" and "intracranial tumor", the tumor had invaded the temporal bone bilaterally via the IAM. In the IAM, cochlear and inferior vestibular nerves were more vulnerable to tumor invasion than facial and superior vestibular nerves. It was suggested that there are some differences in vulnerability to tumor invasion between the superior and inferior vestibular nerves. The bottom of the IAM presented a barrier-like effect against the spread of tumor from the IAM to the labyrinth. In some cases, however, there was massive tumor invasion of the internal ear directly from the IAM. Whether denervation of the ganglionic neurons (spiral or vestibular) causes secondary degeneration of peripheral sensory endorgans remains controversial. In some cases in our series, degeneration of the auditory or vestibular peripheral organs might be attributed to denervation of neurons in the spiral or vestibular ganglia. In other cases, however, auditory and vestibular peripheral organs remained intact despite severe degeneration of ganglionic neurons.

Adolescent

Insulin stimulates the expression of basic fibroblast growth factor in rat brown adipocyte primary culture.

The effect of insulin on the hyperplasia of brown adipose tissue (BAT) was investigated using the primary culture of rat brown adipocyte precursor cells (RBAC). Results showed insulin to significantly increase the number of RBAC, but not bovine capillary endothelial cells, in the presence of fetal bovine serum. Insulin also increased the expression of basic fibroblast growth factor (bFGF) mRNA and the related protein in the primary culture of RBAC. In addition, insulin enhanced the capillary growth in an in vitro angiogenesis model in which microvascular fragments and RBAC isolated from rat BAT were grown in coculture. The level of bFGF-related protein in the coculture was higher in the presence of insulin than in the absence of insulin. These findings suggest that insulin may play an important role in the proliferation as well as in the differentiation of brown adipocytes, with resulting hyperplasia of BAT (including the formation of new capillaries) through increased production of bFGF in brown adipocytes.

Adipocytes

Norepinephrine stimulates the expression of fibroblast growth factor 2 in rat brown adipocyte primary culture.

To elucidate the role of norepinephrine (NE) in the hyperplasia of brown adipose tissue (BAT), we investigated the effects of NE on the expression of fibroblast growth factor-2 (FGF-2) in rat brown adipocyte primary culture and on capillary growth in an in vitro angiogenesis model in which microvascular fragments and brown adipocyte precursor cells isolated from rat BAT were grown in coculture. NE significantly increased the number of brown adipocyte precursor cells. The NE effect on cell proliferation was greatly inhibited by anti-FGF-2-specific antibody. Likewise,NE considerably increased the levels of FGF-2 mRNA and the antigen in brown adipocyte primary culture. The ability of NE to stimulate the expression of FGF-2 mRNA was blocked by actinomycin D or was inhibited partly by propranolol. Moreover, NE considerably increased the in vitro capillary growth and the level of FGF-2 antigen in the coculture. These results suggest that NE is a crucial factor to mediate FGF-2 production, in part via the beta-adrenergic receptor, in rat brown adipocytes and to stimulate the cell proliferation and capillary growth in BAT by an autocrine/paracrine mechanism.

Adipocytes