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Biomedical subjects

T Yanagihara

Publications and source records attributed to T Yanagihara.

At least 73 records · Page 4Linked to original sources
PubMed1999

Calcium increase in mouse skeletal muscles by triparanol: a drug to induce myotonic dystrophy-like clinical manifestations.

Triparanol (Trp) is known to cause clinical features similar to those seen in myotonic dystrophy, including myotonia, cataract and baldness. To explore the pathophysiological mechanism of myotonic dystrophy, we examined the effect of Trp on intracellular calcium in cultured skeletal myoblasts and myotubes as well as cardiac myocytes by using a fluorescent indicator. Trp preferentially induced increase of intracellular calcium in myotubes of skeletal muscles. Since the increase of calcium was inhibited by thapsigargin pretreatment but not by extracellular calcium elimination, it appears that triparanol might act mostly on intracellular calcium stores. Trp also inhibited the increase of calcium in myotubes induced by acetylcholine. Trp might cause myotonia possibly through the increase of intracellular calcium from intracellular stores.

Acetylcholine↗
PubMed1999

Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice.

We previously reported that the common toxic gain-of-function in various mutant copper-zinc superoxide dismutases (SOD1) seen in patients with familial amyotrophic lateral sclerosis (ALS) was an abnormal copper release from the enzyme protein. In this study, trientine and ascorbate, known to have a beneficial effect in an animal model of Wilson disease, were administered to transgenic mice overexpressing a mutated human SOD1 (G93A). The onset of neurological signs in the treated group was significantly delayed compared with that in the control group, and the time to reach total paralysis in the treated group was delayed as well. Since the agents used in this study cause low toxicity in animals and humans, this treatment may be a good candidate for clinical application.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Species differences in fodrin proteolysis in the ischemic brain.

There has been growing evidence that the breakdown of cytoskeletal proteins is an important biochemical change leading to ischemic neuronal death. In the present study, we investigated species differences in the susceptibility of fodrin to calpain activation induced by cerebral ischemia in gerbils, rats, and mice. In vivo fodrin proteolysis and degradation of microtubule-associated protein 2 after complete ischemia occurred more rapidly in the hippocampus and cerebral cortex of the gerbil brain than in the corresponding area of the rat and mouse brain. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 injected intraperitoneally before ischemia did not diminish fodrin degradation in the gerbil hippocampus. In vivo fodrin proteolysis was inhibited at 33 degrees C and enhanced at 41 degrees C compared with proteolysis at 37 degrees C during ischemia. However, in vitro fodrin proteolysis after addition of Ca2+ into the crude membrane fraction did not show any differences among three species. Although it is highly unlikely that the difference in the sensitivity of NMDA receptor or the sensitivity of calpain activation to calcium was the crucial determinant of susceptibility of fodrin degradation in the gerbil brain, the present study clearly demonstrated that fodrin in the gerbil brain was more susceptible to calpain activation induced by ischemia than that in the rat and mouse brains. Enhanced proteolysis may be one of the reasons neurons in the gerbil brain are highly vulnerable to ischemia.

Animals↗
PubMed1999

Ibudilast, a phosphodiesterase inhibitor, ameliorates experimental autoimmune encephalomyelitis in Dark August rats.

A phosphodiesterase inhibitor (PDEI), Ibudilast, which has been in wide use for the management of bronchial asthma and cerebrovascular disease in Japan, was tested for its clinical efficacy on experimental autoimmune encephalomyelitis (EAE) in Dark August rats. The severity of acute EAE was significantly ameliorated by prophylactic oral treatment with Ibudilast (10 mg/kg per day) starting on the day of immunization, although it did not modify the course of the disease when it was given after the onset of the first clinical sign of EAE. Histologically, inflammatory cell infiltration in the lumbar spinal cord was significantly reduced in Ibudilast-treated animals as compared to control animals. Ibudilast mildly suppressed MBP-induced proliferation of T cells in regional lymph nodes, the secretion of interferon-gamma from T cells activated by MBP in CFA, and the secretion of tumor necrosis factor-alpha from macrophages. While the in vitro studies did not suggest difference between Ibudilast and other PDEIs such as rolipram, the clinical dose of Ibudilast is approximately 200-fold higher than that of rolipram and the effective dose of Ibudilast was relatively close to what has been therapeutically used in patients. Thus, Ibudilast may be a candidate for clinical use for patients with multiple sclerosis. 1999 Elsevier Science B.V. All rights reserved.

Administration, Oral↗
PubMed1999

Effect of coenzyme Q10 in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): evaluation by noninvasive tissue oximetry.

We evaluated the effect of coenzyme Q10 supplementation to two patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by using noninvasive tissue oximetry with near-infrared spectra of hemoglobin from the quadriceps muscle during bicycle ergometer exercise. Patients showed distinct oxygen consumption patterns reflecting the defect in oxidative phosphorylation and the impairment in oxygen utilization during exercise. Based on the oxygen consumption pattern, we considered one patient as having severe mitochondrial disorder and another patient as having mild one. After coenzyme Q10 supplementation, the oxygen consumption pattern of the patient with the severe form shifted to the mild one, while that of the patient with mild form remained unchanged. The shift of the pattern to the mild form correlated well with reduction of the sum of the serum lactate and pyruvate content during exercise. Noninvasive tissue oximetry may be useful to evaluate the effect of coenzyme Q10 supplementation to patients with mitochondrial encephalomyopathy including MELAS.

Adolescent↗
PubMed1999

Enzymatic assay for conjugated bilirubin (Bc) in serum using bilirubin oxidase (BOD).

We described an automated enzymatic assay for conjugated bilirubin (Bc) in serum using the Iatro D-Bil kit, with bilirubin oxidase (EC 1.3.3.5 BOD) from Myrothecium species. The specificity of the enzyme in the Iatro D-Bil kit was examined by analyzing unconjugated bilirubin (Bu), delta bilirubin (Bdelta), and Bc with high-performance liquid chromatography (HPLC), before and after the enzymatic reaction using BOD. The within-assay coefficients of variation (CV) of this method were 0.58 to 5.00% (n = 20) at 1.4 to 155.8 micromol/L. Day-to-day Cvs ranged from 1.61 to 7.14% at 1.2 to 182.1 micromol/L. The analytical recovery was 96 to 101%. The presence of ascorbic acid, reduced glutathione, L-cysteine, uric acid, urea, creatinine, glucose, lipemic material, anticoagulants, hemoglobin, or human serum albumin did not affect this assay system. The correlation coefficient between values obtained with the Iatro D-Bil kit (y) and HPLC method as reference for conjugated fractions (x) was; r = 0.983, y = 0.952x + 8.851 micromol/L, Sy/x = 11.97 (n = 56). We studied serum Bc levels, not including Bu and Bdelta, in patients with hepatic diseases or autoimmune hemolytic anemia. Levels of Bc obtained by the proposed method changed more rapidly than did those of direct bilirubin (D-Bil) obtained by diazo-dye method during the course of the diseases.

Anemia, Hemolytic↗
PubMed1999

Immunoelectron microscopic study of c-Fos, c-Jun and heat shock protein after transient cerebral ischemia in gerbils.

The neuroprotective role of the expression of heat shock protein (HSP) and immediate early gene remains unclear. Using immunoelectron microscopy, we examined the ultrastructural integrity of the neurons with expression of c-Fos, c-Jun and HSP70 in gerbils after transient cerebral ischemia and reperfusion. Induction of c-Fos and c-Jun was observed in the CA3 region resistant to ischemia, while HSP70 was expressed not only in the CA3 but also in the vulnerable CAI region. With immunoelectron microscopy, the expression of c-Fos/c-Jun and HSP70 was observed in the neurons which retained neuronal integrity except for mitochondrial swelling and polyribosomal disaggregation. In contrast, the CAI neurons without immunoreaction for HSP70 showed cytoplasmic vacuoles and parallel stacking of rough endoplasmic reticulum, the features associated with the process of delayed neuronal death. These findings suggested that c-Fos and c-Jun were induced selectively in reversibly damaged neurons, whereas HSP70 was up-regulated even in neurons with irreversible damage, but was more preferentially and intensely expressed in neurons with reversible damage.

Animals↗
PubMed1999

Comparison of late-second-trimester nonstress test characteristics between small for gestational age and appropriate for gestational age infants.

OBJECTIVE: To compare electronic fetal heart rate (FHR) monitoring characteristics between appropriate for gestational age (AGA) fetuses and small for gestational age (SGA) fetuses and to determine whether SGA fetuses have specific abnormalities at second-trimester electronic fetal monitoring (EFM), using nonstress test. METHODS: Among 953 children born from 1993-1996, we identified 500 singleton infants born after 36 weeks' gestation of uncomplicated pregnancies in whom second-trimester (24-27 weeks' gestation) EFM records were obtained. Individual components of FHR patterns (baseline rate, baseline FHR variability, presence of acceleration [at least 10 beats per minute for at least 10 seconds], and periodic or episodic deceleration [at least 25 beats per minute for at least 15 seconds]) and birth characteristics were compared between AGA and SGA infants, or between pregnancies with or without second-trimester decelerations. RESULTS: Among 500 infants, 443 were AGA and 57 SGA; 105 had and 395 did not have second-trimester decelerations. Baseline FHR variability (12.9+/-3.2 beats per minute) in SGA fetuses was significantly higher than variability (10.3+/-3.4 beats per minute) in AGA fetuses (P<.001). Small for gestational age fetuses were significantly more likely to have second-trimester decelerations than AGA fetuses (33.3% vs. 19.4%, P<.05). There were no significant differences in baseline rate and accelerations between AGA and SGA infants. Small for gestational age infants were more frequent in pregnancies with second-trimester decelerations, compared with those without second-trimester decelerations (18.1% vs. 9.6%, P<.05). Baseline FHR variability in pregnancies with second-trimester decelerations was significantly higher than in pregnancies without second-trimester decelerations (12.2+/-3.7 vs. 10.0+/-3.1 beats per minute, P<.001). CONCLUSION: Periodic or episodic decelerations and increased FHR variability during late second-trimester EFM were associated with an increased risk of SGA birth weight.

Cardiotocography↗
PubMed1999

DNA cleavage and proteolysis of microtubule-associated protein 2 after cerebral ischemia of different severity.

We report temporal profiles of cytoplasmic proteolysis and genomic DNA cleavage after cerebral ischemia of different severity in gerbils. Global forebrain ischemia by bilateral common carotid artery occlusion for 5 min with reperfusion, severe unilateral hemispheric ischemia by unilateral common carotid artery occlusion for 30 min with reperfusion, and complete ischemia by decapitation were used. The hippocampus was examined for proteolysis by using immunohistochemistry for microtubule-associated protein 2, DNA cleavage by using in situ nick-end labelling, and nuclear morphology by Hematoxylin staining. During evolution of delayed neuronal death after transient forebrain ischemia, loss of the immunoreaction for microtubule-associated protein 2 occurred almost in parallel with DNA cleavage in the CA1 region. In contrast, disappearance of the immunoreaction for microtubule-associated protein 2 was much faster than genomic DNA cleavage after unilateral hemispheric ischemia and reperfusion. The microtubule-associated protein 2 immunoreactivity was completely lost before development of changes in nuclear morphology or DNA cleavage after complete ischemia. The present study demonstrated the differences between necrosis and delayed neuronal death, but the nuclear morphology in the latter was not exactly the same as seen in apoptosis. Some elements of both necrotic and apoptotic machineries may work following transient ischemia, and the degree of ischemic insult may determine the character of cell death process.

Animals↗
PubMed1999

Myelin-associated oligodendrocytic basic protein is essential for normal arrangement of the radial component in central nervous system myelin.

We previously reported that myelin-associated oligodendrocytic basic protein (MOBP) was abundantly expressed in the central nervous system (CNS) myelin, and shared several characteristics with myelin basic protein (MBP). In particular, a cluster of positively charged amino acids was considered to facilitate compaction of the cytoplasmic face of the myelin sheath, as in the case of MBP. However, the contribution of MOBP in forming and maintaining the myelin sheath still remains unclear. Recent investigations showed that one isoform of MOBP was expressed in the embryo prior to myelination, and MOBP isoforms were colocalized with the microtubular network and nucleus in vitro. To explore the role of MOBP in vivo, we generated MOBP-deficient mice and analysed the CNS myelin. Surprisingly, the compact myelin was formed, however, the myelin from MOBP-deficient mice exposed to hexachlorophene, a known dysmyelinating agent, showed widening of the major dense lines. These results suggest that MOBP is not essential for myelin formation, but reinforces the apposition of the cytoplasmic faces of the myelin sheath. A striking phenotype of MOBP-deficient mice was the presence of the straight 'condensed' radial component. This component has been described as a tight junction-like complex running radially and zig-zag through the CNS myelin sheath between inner and outer mesaxons. These results suggest that MOBP is essential for normal arrangement of the radial component.

Animals↗
PubMed1999

A combined analysis of regional energy metabolism and immunohistochemical ischemic damage in the gerbil brain.

By combining immunohistochemical technique with microassay methods, we analyzed regional energy metabolism in vulnerable and tolerant areas of gerbil brains during evolution of neuronal damage after bilateral common carotid artery occlusion for 10 min with subsequent reperfusion. Four animals were used for each reperfusion period. Based on the information from the immunohistochemical examination, we dissected out vulnerable and tolerant subregions of the hippocampus, cerebral cortex, and thalamus from freeze-dried 20-microm-thick sections, and measured the levels of creatine phosphate (P-Cr), adenine nucleotides, guanine nucleotides, and purine bodies by HPLC, and the levels of glucose, glycogen, and lactate by an enzyme-immobilized column method. There were no significant differences in the levels of metabolites between vulnerable and tolerant subregions of control brains. After reperfusion, both vulnerable and tolerant subregions recovered preischemic metabolic profiles by 2 days. Although the regional differences between vulnerable and tolerant subregions were minimal at each reperfusion period, there were delays in the recovery of P-Cr, ATP, and/or total adenine nucleotides in all vulnerable subregions. A decline of P-Cr, ATP, and GTP levels without change in %ATP, AMP, or purine bodies occurred after reperfusion for 3 days, coinciding with the development of immunohistochemical damage by the immunoreaction for microtubule-associated protein 1A. The results supported the notion that subtle but sustained impairment of energy metabolism caused by mitochondrial dysfunction in the early reperfusion period might trigger delayed neuronal death in vulnerable subregions.

Adenine Nucleotides↗
PubMed1999

Molecular cloning of a novel member of the HSP110 family of genes, ischemia-responsive protein 94 kDa (irp94), expressed in rat brain after transient forebrain ischemia.

To identify genes induced by transient forebrain ischemia, we used the mRNA differential display technique in the four-vessel occlusion model in rats. Some genes were identified as candidates that encode ischemia-responsive protein, and one of them was cloned as ischemia-responsive protein 94 kDa (irp94) from the rat hippocampal cDNA library. Sequence analysis suggested that rat irp94 was a transcriptional variant or a homologue of mouse apg-2 and human heat shock protein (hsp) 70RY and a member of the HSP110 family, because IRP94 was >90% identical to APG-2 and HSP70RY and approximately 60% identical to the other members of the HSP110 family. Although irp94 mRNA was constitutively expressed in the normal hippocampus, it was clearly enhanced 4-24 h after ischemia for 10 (1.9-fold increase) and 15 min (3.4-fold increase). These changes mainly occurred in neuronal cells, as judged by the localization of irp94 mRNA using in situ hybridization histochemistry. On the other hand, hyperthermic stress did not enhance irp94 mRNA expression, suggesting that irp94 expression was enhanced under ischemic stress and not related to the heat shock signaling mechanism. Our study suggested that irp94, a novel member of the HSP110 family, might play an important role in the environment altering neuronal functions, especially after transient forebrain ischemia.

Animals↗
PubMed1999

Saline infusion contrast intrauterine sonographic assessment of the endometrium with high-frequency, real-time miniature transducer in normal menstrual cycle: a preliminary report.

Normal endometrial texture was visualized using saline infusion contrast intrauterine sonography with a specially developed 20 MHz flexible catheter-based high-resolution, real-time miniature (2.4 mm outer diameter) ultrasound transducer in primary infertile women (n = 15) with a normal menstrual cycle. All the women had <2 years infertility duration and were studied in proliferative, and early or mid-secretory phases. Before intrauterine sonography, transvaginal sonographic assessment of the endometrium was conducted. The overall image clarity was subjectively compared between intrauterine and transvaginal sonography. Most endometrial textures in both proliferative and secretory phases were viewed more easily with intrauterine rather than transvaginal sonography, and this was especially true with an intrauterine saline infusion technique. Moreover, it was possible to obtain finer image quality of very small endometrial interfacial and internal textures with intrauterine sonography. However, the depth of penetration of the ultrasound beam is only approximately 2 cm, therefore examination of larger pathological endometrial lesions is markedly limited because of the shallow scanning range of the high-frequency transducer. Intrauterine sonography may be a valuable tool in imaging endometrial texture in normal menstrual cycle, and possibly in infertility practice, complementing and not replacing transvaginal sonography.

Computer Systems↗
PubMed1999

Hepatocyte growth factor concentration in the early second-trimester amniotic fluid does not predict fetal growth at birth.

The purpose of this study was to evaluate whether hepatocyte growth factor (HGF) concentrations in the early second-trimester amniotic fluid predict fetal growth at birth. HGF and insulin-like growth factor-I (IGF-I) concentrations in the early second-trimester amniotic fluid were measured in 12 pregnancies with small for gestational age (SGA) infants, 84 pregnancies with appropriate for gestational age (AGA) infants, and eight pregnancies with large for gestational age (LGA) infants. HGF concentrations were measured from the early second-trimester amniotic fluid samples using an enzyme-linked immunosorbent assay. IGF-I concentrations were measured from the early second-trimester amniotic fluid samples using an immunoradiometric assay. Maternal age in AGA group (34.2 +/- 5.5 years) was significantly lower than in SGA (37.9 +/- 3.0 years) and LGA (37.6 +/- 3.3 years) groups (P < 0.05). There were no significant differences for parity or gestational age at amniocentesis among the groups. There were significant differences for birth age, birth weight, neonatal height, and placental weight among the groups (P < 0.05). HGF concentrations in SGA, AGA and LGA groups were 16.9 +/- 6.6, 16.7 +/- 9.0 and 20.2 +/- 14.8 ng/ml respectively (not significant). There was no correlation between amniotic fluid HGF concentrations and birth weight, height or placental weight. There were also no significant differences for amniotic fluid IGF-I concentrations among the three groups. These results suggest that differences in HGF concentrations in the early second-trimester amniotic fluid do not predict fetal growth at birth. Further study is needed to clarify the role of high HGF concentrations in early second-trimester amniotic fluid during pregnancy.

Adult↗
PubMed1999

Comparison of alterations in fetal regional arterial vascular resistance in appropriate-for-gestational-age singleton, twin and triplet pregnancies.

The objective of this longitudinal study was to evaluate alterations in fetal vascular resistance of fetal peripheral arteries with advancing gestation in singleton appropriate-for-gestational-age (S-AGA), twin appropriate-for-gestational-age (Tw-AGA) and triplet appropriate-for-gestational-age (Tri-AGA) infants. Colour Doppler flow imaging and pulsed Doppler ultrasonographic examinations were performed on 35 S-AGA, 52 Tw-AGA and 12 Tri-AGA fetuses. The pulsatility index for middle cerebral artery (MCAPI), umbilical artery (UAPI), descending aorta (DAPI), splenic artery (SAPI), renal artery (RAPI) and femoral artery (FAPI) was measured as vascular resistance every 2 weeks after 15 weeks of menstrual age until delivery. Optimal models and normal ranges for pulsatility index for each artery in each group were generated. The alterations in various fetal regional arterial pulsatility indices with advancing gestational age showed no significant differences in S-AGA, Tw-AGA and Tri-AGA infants, respectively. These results suggest that there is no significant difference for regional arterial vascular resistance in AGA fetuses among singleton, twin, and triplet pregnancies, whereas there was a slight difference in fetal growth pattern among singleton, twin, and triplet pregnancies described in our previous investigation.

Adult↗
PubMed1999

Laparoscopy-assisted intrapelvic sonography with a high-frequency, real-time miniature transducer for assessment of the Fallopian tube: a preliminary report.

Our purpose was to visualize normal and abnormal Fallopian tubes using laparoscopy-assisted intrapelvic sonography with a specially developed 20 MHz flexible catheter-based high-resolution, real-time miniature (2.4 mm outer diameter) ultrasound transducer in infertile women. A total of 21 women (20 infertile, one with unilateral hydrosalpinx, and one tubal pregnancy) were studied with pelvic saline effusion under laparoscopy. Fimbriae were clearly depicted with a cockscomb-like form in 95% of patients. All ampullae were visualized, and mucosal layers were clearly distinguished from muscle layers in 70% of patients. Scanty intratubal effusion was noted in 50% of patients, and tubal spastic findings were found in 10% of patients. In all, 60% of isthmuses were detected, and mucosal layers were distinguished from muscle layers in 30%. In the subject with hydrosalpinx, the tubal wall was thinner, and it was not possible to distinguish between muscle and mucosal layers. In the subject with a tubal pregnancy, the amniotic membrane and decidua were depicted more clearly than by transvaginal sonography. In conclusion, laparoscopy-assisted intrapelvic sonography with a high-frequency, real-time miniature transducer may be useful in the assessment of tubal texture and function in tubal disorders, possibly in infertility practice.

Fallopian Tube Diseases↗
PubMed1999

Three-dimensional ultrasonographic evaluation of ovarian tumours: a preliminary study.

Our objective was to determine the accuracy of three dimensional (3D) ultrasonography in the differentiation of ovarian tumours. Women (n = 20) with ovarian tumours (13 benign and seven malignant) were first examined using two-dimensional (2D) ultrasonography and were then evaluated with three-dimensional (3D) ultrasonography. All patients underwent surgery within 7 days of 2D and 3D ultrasonographic evaluations, and a histopathological diagnosis was made. A 2D ultrasonographic diagnosis of malignancy was done using an established scoring system. Diagnostic criteria for ovarian malignancy by 3D ultrasonography were: irregular thick septa, irregular papillary projection, mostly solid tumour, high echogenicity, and irregular inner wall. Compared with 2D ultrasound, 3D ultrasound had a significantly higher specificity (P < 0.005) and accuracy (P < 0.01), and a significantly lower false positive rate (P < 0.005). Our results suggest that 3D ultrasonography might be a better means of differentiating between malignant and benign ovarian tumours. However, in view of the small number of ovarian tumours, these observations must be considered preliminary.

Adult↗