Biomedical subjects

T Ishihara

Publications and source records attributed to T Ishihara.

At least 163 records · Page 9Linked to original sources

PubMed1999

[Clinical and bacteriological evaluation of ceftriaxone (CTRX) dosed once daily in children with community-acquired pneumonia].

Clinical and bacteriological evaluation was performed as follows on ceftriaxone (CTRX) at a dose of 50 mg/kg once daily to pediatric patients with community-acquired pneumonia. Of 48 subject patients, CTRX was markedly effective in 36 (75.0%), effective in 9 (18.7%), slightly effective in 2 (4.2%), and failure in 1 (2.1%), indicating the overall effective rate of 93.7%. In 47 (97.9%) patients with the exception of 1, it was observed during the period of administration that fever was resolved and clinical symptoms as well as radiographically abnormal shadows were found relieved or improved. Patients infected by an isolated strain accounted for 34 (70.8%), while those by multiple strains 14 (29.2%), indicating that either Streptococcus pneumoniae or Haemophilus influenzae, or both were detected in almost all patients (45 cases). Of the 48 patients, bacteriological effect was eliminated in 44 (91.7%), and replacement of the bacteria in the remaining 4 (8.3%). MIC90 of CTRX against detected bacteria was 0.2 microgram/ml with H. influenzae, < or = 0.025 microgram/ml with PSSP, 0.1 microgram/ml with PISP, and 0.39 microgram/ml with PRSP. Blood concentration of CTRX at 50 mg/kg upon completion of 1-hour drip intravenous infusion was 89.7 +/- 25.2 micrograms/ml, and 6.6 +/- 0.9 micrograms/ml at 24 hours after the completion, indicating that the concentrations had been well above the levels of MIC90 throughout the 24 hours. Abnormal symptoms, which were most likely adverse drug reactions, were not observed in any patients, and no abnormal changes were noted in patients, whose clinical lab values were taken before or after the administration. Situations may differ by region in Japan, however, infants under 3 are generally exempted from medical payment regardless of inpatients or outpatients. When hospitalized, psychological burden upon pediatric patients without guardians attended must be enormous. If they are over 3, there is a difference in medical costs between inpatients and outpatients, with greater economic burden on inpatients. Thus, it was considered worth attempting the outpatient treatment as one of new therapies for community-acquired pneumonia, though the outpatient treatment should not be encouraged without due consideration. Based on these results, CTRX dosed once daily to pediatric patients with community-acquired pneumonia is clinically and bacteriologically superior in usefulness. Further review may be necessary, however, it is considered that outpatient treatment can also serve as one of the options, if safety of once-a-day administration of CTRX can be established.

Ceftriaxone↗

PubMed1999

Increased plasma levels of mature form of adrenomedullin in patients with chronic renal failure.

BACKGROUND: Adrenomedullin (AM), a novel vasodilator peptide, is produced by C-terminal amidation reaction of AM-glycine. AM-glycine, an intermediate form of AM (iAM), is processed from pro AM. AM circulating in the human blood stream was found to consist of an amidated mature form (mAM) and iAM. Biological activity is exerted only by mAM. METHODS: To investigate the pathophysiological role of mAM in renal disease, we measured plasma concentrations of mAM as well as total AM (tAM), representing both mAM and iAM, in patients with various renal diseases. In addition, plasma ANP level was measured in all patients. RESULTS: The concentrations of plasma mAM in renal failure with dialysis (2.1 +/- 0.2 fmol/ml, mean +/- SEM) and without dialysis (1.2 +/- 0.2) were significantly (p < 0.05) higher than those in control group (0.5 +/- 0.1). However, the plasma ANP level was increased only in renal failure patients with dialysis. Plasma mAM levels were significantly correlated positively with serum creatinine levels and negatively with hematocrit. No significant difference was noted in the ratio of mAM/tAM between renal failure patients and healthy subjects. CONCLUSION: These results suggest that plasma mAM is increased in renal failure in relation to deterioration of renal function, while the amidation process of AM seems to be unaffected in patients with renal failure.

Adrenomedullin↗

PubMed1999

Chromosome aberrations in bone marrow cells from Japanese patients with thorotrastosis.

Exposure of bone marrow cells to alpha-particle radiation causes various types of chromosome abnormalities and hematological malignancies. We performed chromosome analysis of hematopoietic stem cells from the bone marrow of 52 Japanese patients with thorotrastosis and 21 age-matched controls. The frequency of cells with stable chromosome abnormalities was significantly higher in the patients with thorotrastosis. Further studies found 14 clonal chromosome aberrations in cells from 11 patients (21.2%); clones observed in the cells from 2 of these patients had high frequencies of chromosome abnormalities. In one case, 68 to 100% of the cells analyzed had a large partial loss in the short arm of chromosome 1 and a translocation between the short arms of chromosomes 2 and 3 [46,XY,1p-,t(2p+;3p-)]. The cells from the other patient contained a clone with partial loss of both the short and long arms of chromosome 5 (46,XX,5p-,5q-). The frequency of this clone has been constant for the last 15 years (6-24%). We also analyzed bone marrow mononuclear cells from 17 of the patients for mutations of the TP53 tumor suppressor gene (formerly known as p53). However, no mutation was found in any of the cells, including those from the 2 patients with abnormal clones. Moreover, repeated medical examinations showed no evidence of leukemia or myelodysplasia in these patients. Our study suggests that exposure of bone marrow cells to alpha-particle radiation may induce clonal chromosomal aberrations at a high frequency.

Aged↗

PubMed1998

Characterization of a Caenorhabditis elegans recA-like gene Ce-rdh-1 involved in meiotic recombination.

A recA-like gene was identified in the Caenorhabditis elegans genome project database. The putative product of the gene, termed Ce-rdh-1 (C. elegans RAD51 and DMC1/LIM15 homolog 1), consists of 357 amino acid residues. The predicted amino acid sequence of Ce-rdh-1 showed 46-60% identity to both RAD51 type and DMC1/LIM15 type genes in several eukaryote species. The results of RNAi (RNA-mediated interference) indicated that repression of Ce-rdh-1 blocked chromosome condensation of six bivalents and dissociation of chiasmata in oocytes of F1 progeny. Oogenesis did not proceed to the diakinesis stage. Accordingly, all the eggs produced (F2) died in early stages. These results suggest that Ce-rdh-1 participates in meiotic recombination.

Animals↗

PubMed1998

Enhanced AP-1 binding in brain induced by D1 and D2 agonists in methamphetamine-sensitized rats.

The activator protein-1 (AP-1) binding activities induced by a separate challenge with SKF38393 and quinpirole after 1 weeks' abstinence from chronic methamphetamine (4 mg/kg/day, 14 days) were increased significantly in the striatum, nucleus accumbens and cingulate cortex compared with the saline-treated controls. Quinpirole-, but not SKF38393-induced AP-1 binding activities were still significantly higher after a 4-week abstinence period in the chronic methamphetamine group than in the chronic saline control group. Downward sniffing, which occurred following a quinpirole-challenge, was significantly intensified after both a 1 and 4 weeks' abstinence from chronic methamphetamine. These results indicate that chronic administration of methamphetamine induces alterations of the interactions of dopamine D1 and D2 receptors which are reflected as enhanced AP-1 binding activities.

Animals↗

PubMed1998

A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity.

A novel C to A mutation in the sterol 27-hydroxylase gene (CYP27) was identified by sequencing amplified CYP27 gene products from a patient with cerebrotendinous xanthomatosis (CTX). The mutation changed the adrenodoxin cofactor binding residue 362Arg to 362Ser (CGT 362Arg to AGT 362Ser), and was responsible for deficiency in the sterol 27-hydroxylase activity, as confirmed by expression of mutant cDNA into COS-1 cells. Quantitative analysis showed that the expression of CYP27 gene mRNA in the patient represented 52.5% of the normal level. As the mutation occurred at the penultimate nucleotide of exon 6 (-2 position of exon 6-intron 6 splice site) of the gene, we hypothesized that the mutation may partially affect the normal splicing efficiency in exon 6 and cause alternative splicing elsewhere, which resulted in decreased transcript in the patient. Transfection of constructed minigenes, with or without the mutation, into COS-1 cells confirmed that the mutant minigene was responsible for a mRNA species alternatively spliced at an activated cryptic 5' splice site 88 bp upstream from the 3' end of exon 6. Our data suggest that the C to A mutation at the penultimate nucleotide of exon 6 of the CYP27 gene not only causes the deficiency in the sterol 27-hydroxylase activity, but also partially leads to alternative pre-mRNA splicing of the gene. To our knowledge, this is the first report regarding effects on pre-mRNA splicing of a mutation at the -2 position of a 5' splice site.

Alternative Splicing↗

PubMed1998

An ion channel of the degenerin/epithelial sodium channel superfamily controls the defecation rhythm in Caenorhabditis elegans.

Ultradian rhythms are widespread phenomena found in various biological organisms. A typical example is the defecation behavior of the nematode Caenorhabditis elegans, which repeats at about 45-sec intervals. To elucidate the mechanism, we studied flr-1 mutants, which show very short defecation cycle periods. The mutations also affect some food-related functions, including growth rate, the expulsion step of defecation behavior, and the regulation of the dauer larva (a nonfeeding, special third-stage larva) formation in the unc-3 (Olf-1/EBF homolog) background. The flr-1 gene encodes a novel ion channel belonging to the DEG/ENaC (C. elegans degenerin and mammalian epithelial sodium channel) superfamily. A flr-1::GFP (green fluorescent protein) fusion gene that can rescue the flr-1 mutant phenotypes is expressed only in the intestine from embryos to adults. These results suggest that FLR-1 may be a component of an intestinal regulatory system that controls the defecation rhythm as well as other functions.

Activity Cycles↗

PubMed1998

Material analysis end-station of the Hyogo-ken beamline at SPring-8.

Plans to construct surface-analysis equipment which will be placed on beamline BL24XU of SPring-8 are presented. There are three experimental hutches in BL24XU, which are available simultaneously by using diamond monochromators as beam splitters. The purpose of the surface-analysis equipment is the simultaneous measurement of fluorescent and diffracted X-rays in grazing-incidence geometry. The instrument is equipped with a solid-state detector (SSD) and a flat position-sensitive proportional counter (PSPC) combined with analysing crystals for X-ray fluorescence (XRF) analysis. A curved PSPC and the goniometer that mounts the SSD used for XRF are also installed for X-ray diffraction. X-ray fluorescence holography and polarized X-ray emission spectroscopy modes are available, so three-dimensional images of atomic configurations and also the anisotropic structure of materials will be studied.

Journal Article↗

PubMed1998

Susceptibility of Opioid Peptides and Myofibrillar Proteins to Carp Cathepsin L.

The ability of carp cathepsin L to degrade opioid peptides and separate myofibrillar proteins was examined. The enzyme differentially released fragments from leucine-enkephalin, alpha-neoendorphin, and dynorphin, in which the common cleavage site of the enzyme was determined to be a Gly2-Gly3 bond. A Leu5-Arg6 bond in alpha-neoendorphin and dynorphin was also commonly cleaved by the enzyme. At a protein ratio of the enzyme to myofibrillar protein of 1:500, the preferences of the enzyme appeared to be myosin > tropomyosin > troponins T, I, and C > actin > alpha-actinin. Myosin heavy chain was completely degraded into some fragments by the enzyme within 30 min, and all of them underwent further degradation during subsequent incubation. Although troponins and tropomyosin were also completely degraded by the enzyme within 24 h, a small amount of actin and a large amount of alpha-actinin remained undegraded.

Journal Article↗

PubMed1998

Thiazolidinedione induces the adipose differentiation of fibroblast-like cells resident within bovine skeletal muscle.

To investigate the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in adipocyte formation within the skeletal muscle of beef cattle, fibroblast-like cells were isolated from the longissimus muscle of cattle and cultured with activators of murine PPARgammaA thiazolidinedione T-174, which is a specific ligand for PPARgamma, stimulated adipose differentiation (evaluated by counting differentiated adipocytes under microscopic observation) in a dose-dependent fashion. A peroxisome proliferator Wy14,643 which strongly activates the alpha isoform of murine PPAR also stimulated differentiation but its potency was weaker than that of T-174. Unexpectedly, 15-deoxy-Delta12,14-prostaglandin J2, which is believed to be an endogenous ligand for PPARgamma, could not induce adipose differentiation in doses which have been found to be effective on rodent cells. Immunoblotting analysis confirmed the significant expression of PPARgamma protein in fibroblast-like cell cultures prepared from bovine skeletal muscle. In conclusion, bovine skeletal muscle contains adipose precursor cells expressing functionally active PPARgamma.

Adipocytes↗

PubMed1998

Lymphocytic adenohypophysitis: skull radiographs and MRI.

We report the skull radiograph, CT and MRI findings in three patients with lymphocytic adenohypophysitis mimicking pituitary adenoma. All cases were associated with pregnancy. CT demonstrated a pituitary mass but did not differentiate lymphocytic adenohypophysitis from pituitary adenoma. The skull radiographs showed either a normal sella turcica or minimal abnormalities; they did not show ballooning or destruction. The MRI appearances were distinctive: relatively low signal on T1-weighted images; preservation of the bright posterior pituitary lobe despite the presence of a relatively large pituitary mass, less common in macroadenomas; marked contrast enhancement compared with pituitary macroadenomas; and dural enhancement adjacent to a pituitary mass.

Adenoma↗

PubMed1998

Prolactin-secreting macroadenoma in a prepubertal girl.

Prolactin-secreting adenoma, which usually presents with amenorrhea and galactorrhea syndrome, is quite rarely diagnosed in the prepubertal age group. We reported a rare case of a prepubertal prolactin-secreting adenoma and discuss its clinical, radiological and histological features. An 8-year-old girl presented with headache, progressive visual deterioration and precocious puberty. The serum prolactin level was 57.8 ng/ml. Computerized tomography and magnetic resonance imaging revealed an invasive suprasellar tumor. The tumor was partially resected through an interhemispheric approach in a first operation, and residual tumor was resected through the right pterional approach in a second operation. The histological diagnosis was a prolactin-secreting adenoma with high cellular pleomorphism. The Ki-67 labeling index was 5.7%, indicating aggressive biological behavior. Postoperatively, the patient was prescribed bromocriptine as maintenance therapy, and the serum prolactin level became normalized. There is a tendency for diagnosis of a prepubertal prolactin-secreting adenoma to be delayed because there are no endocrinological manifestations. Therefore, the tumor tends to become larger and invasive. Although it is rarely experienced, a prolactin-secreting adenoma should be considered in the differential diagnosis of a large, invasive parasellar lesion in the prepubertal age group.

Bromocriptine↗

PubMed1998

Sequential changes in cardiac structure and function in patients with Duchenne type muscular dystrophy: a two-dimensional echocardiographic study.

BACKGROUND: Most patients with progressive muscular dystrophy of the Duchenne type (DMD) die of respiratory failure at approximately 20 years of age. However, some patients with DMD die of heart failure in relatively short periods of time. We investigated the long-term progression of cardiac impairment in patients with DMD by two-dimensional echocardiography. METHODS: We monitored 74 patients for 4 years with two-dimensional echocardiography. Patients were classified into four groups according to the 8-grade Swinyard-Dever system. We also evaluated the echocardiographic features of 22 other patients with DMD with studies performed within 1 year before their deaths. RESULTS: During the 4-year follow-up the left ventricle expanded, and regional left ventricular wall motion abnormalities developed in the posterior wall and apex. Almost all patients had myocardial dysfunction that progressed in parallel with their Swinyard-Dever stage. However, in a few patients who died of congestive heart failure, left ventricular dilation and circumferential left ventricular wall motion were severely impaired. CONCLUSIONS: Myocardial impairment is accelerated in patients with DMD who died of heart failure. Two-dimensional echocardiography is a useful tool for the early diagnosis of left ventricular dysfunction and provides useful information for the treatment of patients with DMD.

Adult↗

PubMed1998

Theta rhythms associated with sucking, crying, gazing and handling in infants.

In order to specify the locations and to clarify the electrophysiological significance of the transitory rhythmic theta activities detected on scalp electrodes in infants, we performed simultaneous EEG and video recording with power spectral map analysis in 29 normal infants of less than 1 year of age. The rhythmic theta activities appeared in posterior temporal regions with sucking or crying, in the parietal region with gazing, and in the frontal region with handling. Each specific location of the theta rhythm seemed to correspond to the functional localization in the infant's brain. We thus concluded that these rhythmic theta activities might originate from direct cortical activation, or from the cortical activation driven by the neuronal impulses from the limbic system through the connection between that system and the cortex.

Brain Mapping↗

PubMed1998

Counteraction of retinoic acid and 1,25-dihydroxyvitamin D3 on up-regulation of adipocyte differentiation with PPARgamma ligand, an antidiabetic thiazolidinedione, in 3T3-L1 cells.

Retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3) inhibited adipocyte differentiation of 3T3-L1 preadipocytes in the presence of thiazolidinedione, a specific ligand for peroxisome proliferator-activated receptory (PPARgamma). These fat-soluble vitamins repressed the up-regulated protein expression of PPARgamma2 during the first 40 hours of initiation of 3T3-L1 preadipocyte differentiation. Compared with RA, 1,25 (OH)2 D3 inhibited PPARgamma2 expression more effectively and caused concomitantly a greater inhibition of adipocyte differentiation. These results suggest that the inhibitory action of adipocyte differentiation by RA or 1,25 (OH)2 D3 is exhibited through direct repression of the expression of PPARgamma2 protein, even in the presence of its ligand. They also raise the intriguing possibility that attenuation or amplification of the pharmacological effects of thiazolidinedione that are dependent on PPARgamma in adipose cells is caused by alteration of the levels of these fat-soluble vitamins.

3T3 Cells↗

PubMed1998

Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and urinary prostaglandin levels in rats with obstructive jaundice.

BACKGROUNDS/AIMS: No study has so far been conducted to clarify whether the presence of hyperbilirubinemia is detrimental to liver and renal functions. In the present study, the effects of polyethylene glycol-modified bilirubin oxidase (PEG-BOX) therapy on liver and renal function tests, hepatic energy charge and urinary prostaglandin levels were evaluated in a rat model of obstructive jaundice. METHODS: Sprague-Dawley rats were used in the experimental model of obstructive jaundice. PEG-BOX or an equivalent amount of PEG alone was intravenously injected into the animals and sampling of blood and urine, and liver harvesting were done sequentially after bile duct ligation. RESULTS: Conventional liver function tests showed no difference between PEG-BOX and control groups. However, bilirubin concentrations in the peripheral blood and liver tissue specimens markedly decreased, and the hepatic energy charge significantly increased in the PEG-BOX group as compared to controls. The blood concentration of bile acid was lower, but its urinary excretion was higher in the PEG-BOX group than in the control group. In vitro incubation of PEG-BOX with serum from rats with obstructive jaundice decreased the concentration of bilirubin but not that of bile acid. The urinary levels of prostaglandin E2 and the thromboxane B2/6-keto-prostaglandin Fla ratio were significantly lower in the PEG-BOX group than in the control group. CONCLUSIONS: The systemic reduction of bilirubin concentration may contribute to normalization of the urinary levels of prostaglandins and thromboxane B2, to decrease in serum bile acid levels, and to improvement of the hepatic energy charge in obstructive jaundice. These findings suggest that preoperative improvement of jaundice may be beneficial to patients with obstructive jaundice.

Animals↗

PubMed1998

Hyperammonemia reduces water immersion--restraint stress gastric ulcers in rats.

1. The influence of hyperammonemia (produced by the continuous intraperitoneal infusion of ammonium acetate for 6 days) on stress-induced gastric ulcer formation was investigated in conscious rats. 2. Continuous ammonium acetate infusion significantly reduced stress-induced gastric ulceration concomitant with an increase in gastric blood flow, as determined using radioactive microspheres. The serum levels of L-arginine as well as nitrite and nitrate (oxidative byproducts of nitric oxide) were increased by ammonium acetate infusion. 3. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive nitric oxide synthase inhibitor, substantially attenuated the increase in gastric blood flow caused by ammonium acetate infusion and diminished the protective effect on gastric ulceration. 4. These findings suggest that the synthesis of endogenous nitric oxide from L-arginine is accelerated by continuous ammonium acetate infusion when the urea cycle remains intact and has a substantial cytoprotective effect on the stomach, probably through maintaining the gastric mucosal microcirculation.

Acetates↗

PubMed1998

QT dispersion in dipper- and nondipper-type hypertension.

The aim of this study was to identify the relationship of QT dispersion on 12-lead electrocardiograms and left ventricular mass index on echocardiograms associated with the circadian rhythm of blood pressure (BP). Heart rate and BP were monitored every 30 min for 48 h in 62 patients with essential hypertension using an ambulatory BP monitoring device. The patients were divided into four groups according to gender and circadian BP pattern (nocturnal BP dipper or nondipper). The patients were classified as dippers if their daytime BP decreased by at least 10% during the night and all the other subjects were classified as nondippers. Age, body mass index, and 48-h mean BP were similar among the four groups. During the night-rest period, the systolic and diastolic BP were significantly decreased in dipper-type hypertensives. The maximum QTc interval and QTc dispersion were longer in nondippers than in dippers. Left ventricular mass index (LVMI) had a tendency to increase in nondippers. The nocturnal reduction of BP significantly correlated with QTc dispersion and LVMI. The QTc dispersion significantly correlated with LVMI and interventricular septum thickness.

Adult↗