Search PubMed⌕ Search

Biomedical subjects

H Morishita

Publications and source records attributed to H Morishita.

At least 19 recordsLinked to original sources
PubMed2006

Serum amiodarone and desethylamiodarone concentrations following nasogastric versus oral administration.

OBJECTIVE: Hospitalized patients unable to ingest anything by mouth require nutritional support by enteral feeding and administration of drugs through a nasogastric tube inserted into the digestive tract. Nasogastric administration of amiodarone may not always be equivalent to oral administration of amiodarone. METHODS: We collected 162 observations of serum amiodarone and desethylamiodarone metabolite concentrations from 93 patients within 60 days of starting treatment with amiodarone. Eight patients were given the drug nasogastrically and 85 patients, orally. The two groups, were compared in terms of their serum concentration/(dose/weight) (C/D) value. A ratio of serum amiodarone concentration to serum desethylamiodarone concentration (AMD/DEA) was calculated for each sample. In addition, the percentage drug recovery after nasogastric administration of amiodarone was analysed. RESULTS: Significant differences were observed in C/D values of amiodarone and desethylamiodarone and in AMD/DEA values of patients given amiodarone orally when compared with those given the drug nasogastrically. The C/D values of patients who received their medication nasogastrically were approximately 30% of the C/D values of patients who received their medication orally. Approximately 70% of the drug was recovered after it had passed through the nasogastric tube. CONCLUSIONS: To achieve similar concentrations, an approximately 3-fold increase in dosage of amiodarone was required when patients were given the drug nasogastrically rather than orally. This suggests that the absorption of amiodarone following nasogastric administration is poor when compared with oral administration. Therapeutic drug monitoring is necessary to optimize dose particularly during the early stages of amiodarone therapy.

Administration, Oral↗
PubMed2006

Genetic variations and haplotype structures of the ABCB1 gene in a Japanese population: an expanded haplotype block covering the distal promoter region, and associated ethnic differences.

As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks -1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms -1,789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2004

Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice.

Antioxidant activity and biological properties of ferulic acid (FA) are well recognized. This study was designed to estimate the potential utility of FA administered orally at low dosage for improvement of hyperglycemia in diabetes. With this aim we have evaluated the hypoglycemic effect of FA in two type diabetic animal models: (1) streptozotocin (STZ)-induced diabetic mice, a model of insulin-dependent diabetes mellitus (IDDM); (2) KK-Ay mice, a model of non-insulin dependent diabetes mellitus (NIDDM). In addition, we measured the production of thiobarbituric acid-reactive substances (TBARS) in brown adipose tissues of diabetic mice at the end of FA feeding experiment. FA at 0.01% and 0.1% of basal diet showed to suppress significantly blood glucose levels in STZ-induced diabetic mice. In KK-Ay mice 0.05% FA suppressed effectively blood glucose levels. In addition, FA inhibited the lipid peroxidation in brown adipose tissue of diabetic mice. Taken together, these findings suggest that dietary FA may be useful in alleviating oxidative stress and attenuating the hyperglycemic response associated with diabetes.

Animals↗
PubMed2003

Circulating leptin response to feeding and exogenous infusion of insulin in sheep exposed to thermoneutral and cold environments.

Leptin has been shown to regulate feed intake and energy expenditure. Insulin stimulates leptin secretion in rodents, but its action on leptin secretion is still obscure in ruminants. If insulin stimulates leptin secretion in ruminants, circulating leptin concentrations may change during exposure to cold, because of fluctuating insulin secretion and action in the cold environment. The present experiment was designed to determine whether feeding or exogenous administration of insulin affects circulating leptin levels in sheep exposed to thermoneutral and cold environments. Suffolk rams that were shorn and fed a diet once daily were subjected to a thermoneutral (20 degrees C) or cold (0 degrees C) environment for at least 1 week. Overall mean concentrations of plasma leptin in the feeding experiment were lower (P<0.05) in the cold environment than in the thermoneutral environment. Plasma leptin levels remained relatively unchanged after feeding in both environments, though plasma insulin response to feeding in both environments increased (P<0.01). The euglycemic clamps (insulin infusion rate: 4 mUkgBW(-1)min(-1) for 2 h) increased (P<0.01) circulating leptin concentrations in the thermoneutral, but not in the cold environment. These results suggest that lower circulating leptin levels in ruminants exposed to the cold environment could be partly due to the depressed insulin action on leptin secretion.

Animals↗
PubMed2001

Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice.

Mice that lack caspase-3, which functions in apoptosis, were generated by gene targeting and shown to undergo hearing loss. The ABR threshold of the caspase-3(-/-) mice was significantly elevated compared to that of caspase-3(+/+) mice at 15 days of age and was progressively elevated further by 30 days. Distortion product otoacoustic emissions were not detectable in caspase-3(-/-) mice at 15 days of age. Caspase-3(-/-) mice exhibited marked degeneration of spiral ganglion neurons and a loss of inner and outer hair cells in the cochlea at 30 days of age, although no such changes were apparent at 15 days. The degenerating neurons manifested features, including cytoplasmic vacuolization, distinct from those characteristic of apoptosis. Spiral ganglion neurons and cochlear hair cells thus appear to require caspase-3 for survival but not for initial development. The mapping of both the human caspase-3 gene and the locus responsible for an autosomal dominant, nonsyndromic form of hearing loss (DFNA24) to chromosome 4q35 suggests that the caspase-3(-/-) mice may represent a model of this human condition.

Aging↗
PubMed2001

Impaired fertility in female mice lacking urinary trypsin inhibitor.

Urinary trypsin inhibitor (UTI) is a serine proteinase inhibitor that is found in blood and urine. To investigate the physiological functions of UTI in vivo, we generated UTI-deficient mice by gene targeting. The mice showed no obvious abnormalities and appeared healthy. However, the females displayed a severe reduction in fertility. Wild-type embryos developed normally when transplanted into UTI-deficient female mice, suggesting that UTI-deficient females have a normal ability to maintain pregnancy. The number of naturally ovulated oocytes from UTI-deficient mice was greatly reduced compared with that from wild-type mice. Histologically, oocytes with disorganized corona radiata were frequently seen in the ovaries of UTI-deficient mice after hormonal stimulation. When ovaries from UTI-deficient mice were transplanted into wild-type mice, pups derived from the transplanted ovaries were obtained, suggesting that the ovary of UTI-deficient mice functions normally if UTI is supplied from the systemic circulation. These results demonstrate that UTI plays an important role in the formation of the stable cumulus-oocyte complex that is essential for oocyte maturation and ovulation.

Animals↗
PubMed2001

Twin pregnancy consisting of 46, XY heterozygous complete mole coexisting with a live fetus.

Complete hydatidiform mole and coexistent fetus (CMCF) is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic diseases. The aim of this study was to reveal a potential risk factor and to determine optimum management of CMCF cases. Molar tissues are cytogenetically divided into two types, homozygous and heterozygous. The molar tissue of our case showed a 46, XY heterozygous complete mole. Genomic DNA was analyzed by the polymerase chain reaction using sets of unlabelled forward and Cy-5-labelled reverse primers for DNA marker loci. The patient developed persistent trophoblastic disease (PTD) with lung metastasis. Since 1980 there have been 13 reports (including our case) that cytogenetically revealed CMCF and clarified the clinical outcome. Nine of the 16 CMCF cases before 21 weeks of gestation and seven of the 12 CMCF cases after 22 weeks of gestation developed PTD. The incidence of PTD from CMCF was not related to the gestational age at termination or delivery. There were 10 case reports that analyzed the zygosity of a mole, heterozygous or homozygous. Two of six homozygous and three of four heterozygous moles in CMCF cases developed PTD. A heterozygous mole is thought to be a high risk factor for the incidence of PTD. Cytogenetic study is clinically useful for the optimum management of CMCF cases.

Adult↗
PubMed2001

Microsatellite instability in transforming growth factor-beta 1 type II receptor gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis.

It has been reported that transforming growth factor (TGF)-beta, which plays an integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), suppresses proliferation of alveolar epithelial cells in vitro. Although hyperplastic lesions of alveolar lining epithelial cells (ALECs) are characteristic pathologic features of IPF, the mechanism of their involvement in the pathogenesis has not yet been extensively studied. On the assumption that the hyperplastic ALECs have escaped from the growth-inhibitory effects of TGF-beta, we searched for mutations in the microsatellite of the TGF-beta receptor type II (T beta RII) gene. To detect a deletion in the polyadenine tract in exon 3 of the T beta RII gene, cells were isolated by microdissection from lung sections of IPF patients, and DNA was extracted from these cells and amplified by high-fidelity polymerase chain reaction. A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in nine sites from five patients. The mutation was also detected in smooth muscle-like cells of the thickened pulmonary artery. In some tissue areas where the deletion was detected, low T beta RII expression was confirmed by immunohistochemical staining. These data suggest that microsatellite instability in the T beta RII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and that this genetic disorder might play a partial role in the pathologic changes of IPF.

Adult↗
PubMed2001

Improvement of anti-Hu-associated paraneoplastic sensory neuropathy after chemoradiotherapy in a small cell lung cancer patient.

A 66-year-old man developed progressive painful dysesthesia in his hands and feet over 3 months. His vibration sense was impaired and sensory nerve action potentials of the limbs were not evoked. Biopsy of the peroneal nerve revealed sensory neuropathy. Positive anti-Hu antibody facilitated delineation of a right hilar mass and a metastatic lymph node in thoracic CT scan. He was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. A complete response was achieved through chemotherapy (carboplatin and etoposide) and subsequent radiation therapy. Notably, his neurological conditions, although not changed during the hospitalization, gradually improved afterwards.

Aged↗
PubMed1999

Existence and pharmacological properties of dopamine D4 receptors in guinea pig vas deferens.

This study was carried out to identify subtypes of dopamine D2-like receptors in guinea pig isolated vas deferens. Dopamine had no effect on the muscle tone in the presence of prazosin, an alpha1-adrenoceptor antagonist. However, contractile responses to adenosine triphosphate (ATP), noradrenaline and acetylcholine were potentiated in a concentration dependent manner by dopamine in the presence of prazosin. This potentiation was not inhibited by raclopride, an antagonist for dopamine D2 and D3 receptors. However, the potentiation of ATP- and noradrenaline-induced contraction was inhibited by clozapine and 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3b][1,4]benzodiazepine (JL-18), dopamine D4 receptor antagonists. Further, the potentiation of noradrenaline- and acetylcholine-induced contraction was also inhibited by spiperone, an antagonist for dopamine D2, D3 and D4 receptors. These results suggest that the dopamine D4 receptor is located on the postsynaptic site of guinea pig vas deferens and that activation of the dopamine D4 receptor enhances contractile responses to agonists without affecting muscle tone.

Animals↗
PubMed1998

Existence of postsynaptic dopamine D2 receptor as an enhancer of contractile response in vas deferens.

Effects of dopamine and (+/-)-2-(N-phenylethyl-N-propyl)amino-5-hydroxy-tetralin hydrochloride (N-0434), a dopamine D2 receptor agonist, in the presence of prazosin on the ATP- and acetylcholine-induced contraction were investigated in the guinea-pig vas deferens in order to test for the existence of postsynaptic dopamine receptors. The contraction induced by ATP was potentiated by dopamine and N-0434. This potentiation was antagonized by spiperone, a dopamine D2 receptor antagonist, but not by a dopamine D1 receptor antagonist and an alpha2-adrenoceptor antagonist. Similar results were also observed by acetylcholine as well as ATP. The contraction induced by transmural nerve stimulation in the presence of alpha-adrenoceptor antagonists was also potentiated by N-0434, and this potentiation was antagonized by spiperone. The results suggest that dopamine D2 receptors are located on the postsynaptic site of guinea-pig vas deferens and that the contractile responses to ATP and acetylcholine are potentiated via activation of dopamine D2 receptor.

Adenosine Triphosphate↗
PubMed1998

Internalization of urinary trypsin inhibitor in human uterine fibroblasts.

We have characterized the molecular species and internalization of urinary trypsin inhibitor (UTI) in human uterine fibroblasts. Link protein (LP) has previously been identified as one of the cell-associated UTI binding proteins. The truncated forms of UTI were readily detectable in the cells after incubating the cells with purified UTI. Immunoblotting analysis with a panel of domain-specific antibodies revealed that the UTI species lacked the amino-terminal domain of UTI, but contained the carboxyl-terminal domain. We have examined whether LP is involved in the UTI internalization in the cells. Internalization of 125I-labelled UTI was blocked by the intact UTI, but not by the carboxyl-terminal domain of UTI. Treatment with a polyclonal antibody to the UTI binding domain of LP partially inhibited UTI binding to the cells, but did not significantly prevent UTI internalization. In addition, preincubation of the cells with hyaluronidase reduced the UTI binding to the cells, but had no effect on the rate with which UTI was internalized. These data allow us to conclude that there are at least two different mechanisms for internalization of UTI. The major one is via unknown UTI receptors in a Ca2+, Mg2+-sensitive manner and another is via LP.

Calcium↗
PubMed1998

Use of the harmonic scalpel for nephron sparing surgery in renal cell carcinoma.

PURPOSE: The harmonic scalpel is a new tool for excising and coagulating tissue with ultrasound using higher frequencies than an ultrasonic aspirator. We evaluated the usefulness of the harmonic scalpel in nephron sparing surgery. MATERIALS AND METHODS: We used the harmonic scalpel to incise the renal parenchyma during nephron sparing surgery in 10 patients with renal cell carcinoma. RESULTS: Bleeding from the renal parenchyma was minimal but hemostasis of the larger vessels was not obtained even when the harmonic scalpel was used at maximal coagulation power. The cut surface of the kidneys, especially the vessels, were more clearly recognized than if an ultrasonic aspirator had been used, enabling hemostasis by figure-of-8 suture. CONCLUSIONS: The harmonic scalpel is useful for obtaining a clear parenchymal stump and hemostasis during nephron sparing surgery, although complete hemostasis of the arcuate or larger vessels cannot be achieved.

Carcinoma, Renal Cell↗
PubMed1998

Inhibition in vitro linoleic acid peroxidation and haemolysis by caffeoyltryptophan.

Antioxidant activities of caffeoyltryptophan were investigated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging system, the superoxide anion generation system and the superoxide anion-mediated linoleic acid peroxidation system. At 10 microM, caffeoyltryptophan showed greater scavenging activity on DPPH than dl-alpha-tocopherol or ascorbic acid. DPPH radical scavenging activity of caffeoyltryptophan increased dose-dependently at concentrations ranging from 1 to 50 microM; 1 mol of caffeoyltryptophan reacted with ca 4 mol of radical. Caffeoyltryptophan caused 80% inhibition of superoxide anion generation at 50 microM. The inhibitory activity of caffeoyltryptophan was as strong as that of 5-caffeoylquinic acid. Caffeoyltryptophan inhibited the formation of conjugated diene from linoleic acid. The inhibitory activity increased in the order caffeic acid < 5-caffeoylquinic acid < caffeoyltryptophan < dl-alpha-tocopherol. Effects on the in vitro haemolysis and peroxidation of mouse erythrocytes induced by H2O2 were also examined. Caffeoyltryptophan exhibited strong inhibitory activities; Tryptophan was ineffective in these systems. These data suggest that caffeoyltryptophan may be a natural antioxidant in the human diet and, as such, may intervene in toxicological processes that are mediated by radical mechanisms.

Animals↗