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Biomedical subjects

T Iwata

Publications and source records attributed to T Iwata.

At least 109 records · Page 6Linked to original sources

Failure of pre-diarrheal antibiotics to prevent hemolytic uremic syndrome in serologically proven Escherichia coli O157:H7 gastrointestinal infection.

A girl had hemolytic uremic syndrome after Escherichia coli O157:H7 infection, despite pre-diarrheal administration of an antibiotic that prevented detectable intestinal colonization. This report casts doubt on the advisability of antibiotic therapy for E coli O157:H7 infections and has implications for our understanding of the mechanism of this disorder.

Adult↗

Human parathyroid hormone (1-34) increases urinary excretion of lysosomal enzymes in rats.

The kidney is the major target of parathyroid hormone (PTH), and PTH influences the urinary excretion of calcium, phosphate and hydrogen ions. It was previously reported that the urinary, excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, transiently increases after human PTH (hPTH) (1-34) infusion in normal subjects and idiopathic hypoparathyroidism patients, but not in pseudohypoparathyroidism type I patients. Here we report that intravenous infusion of hPTH(1-34) to rats transiently increased the urinary excretion of various lysosomal enzymes, such as beta-glucuronidase and acid phosphatase as well as NAG. However, it did not affect the urinary excretion of tubular brush border membrane enzymes, i.e. alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transpeptidase. Human PTH(1-34) dose-dependently increased the urinary excretion of NAG in rats with a peak at 30 min, which returned to a baseline within 60 min. The increase in the urinary NAG excretion caused by hPTH(1-34) positively correlated with the increase in the urinary cAMP excretion (r = 0.844, p < 0.01), and infusion of dibutyryl cAMP at a dose of 20 mg/kg similarly increased the urinary excretion of NAG. These results suggested that the increase in the urinary excretion of lysosomal enzymes caused by hPTH(1-34) may be a functional response to hPTH(1-34) occurring in the renal tubules via PTH signaling pathway.

Acetylglucosaminidase↗

Dorsum sellae meningioma mimicking pituitary macroadenoma: case report.

BACKGROUND: A dorsum sellae meningioma is a rare occurrence. It is difficult to evaluate dorsum sellae meningiomas preoperatively from the viewpoint of neuroimaging. We report a rare case of dorsum sellae meningioma mimicking pituitary macroadenoma in a 73-year-old woman. CASE PRESENTATION: The patient presented with bitemporal hemianopsia and panhypopituitarism. Magnetic resonance imaging demonstrated a bright, homogeneously enhancing intra- and suprasellar mass and a hypointense region in this mass, which was interpreted as a dorsum sellae. Transsphenoidal extirpation was used because of a suspicion of nonsecreting pituitary macroadenoma. Histopathologically, the tumor was diagnosed as a meningioma. Superselective external carotid angiography before the second surgery revealed that the mass was supplied by the left accessory middle meningeal artery and appeared to originate from dorsum sellae. After preoperative embolization, the patient developed hyponatremia. The tumor was subtotally removed via a transcranial route, and the attachment to the dorsum sellae was coagulated extensively. She did well after a second surgical procedure. CONCLUSION: These radiologic findings may be useful in differentiating dorsum sellae meningioma from pituitary macroadenoma.

Adenoma↗

Rest-redistribution thallium-201 myocardial scintigraphic study in cardiac amyloidosis.

BACKGROUND: Histopathological study in amyloid heart demonstrates that myocyte destructed by the extracellular deposition of amyloid protein together with viable myocyte is present. We hypothesized that rapid thallium washout may be found in amyloid heart as in regions which have a mixture of viable myocyte and scar tissue in patients with myocardial infarction. Thus, the purpose of this study was to evaluate the extent and severity of myocardial damage due to amyloid deposits using the washout rate of the tracer on rest-redistribution thallium-201 (201Tl) myocardial scans in cardiac amyloidosis patients. METHODS: Rest-redistribution 201Tl myocardial scintigraphy was performed in 5 patients with biopsy-proved systemic amyloidosis with cardiac involvement (amyloidosis group). The initial and delayed images were obtained 15 min and 4 h, respectively, after intravenous injection of the tracer of 111 MBq. Washout rate of the tracer was calculated. Twelve patients with no apparent heart disease served as controls (control group). RESULTS: Mean washout rate of the whole heart was higher in the amyloidosis group than in the control group (56 +/- 9% vs 36 +/- 6%, p < 0.001). Particularly, 4 of the 5 patients in the amyloidosis group presented a very high rate of thallium clearance which ranged from 57 to 61%, and died in less than a year. In the remaining 1 patient who had a normal washout rate of the tracer in the first study, it changed from 40 to 53% during the 5-year follow-up period. CONCLUSIONS: Washout rate in the setting of rest and delayed 201Tl images may represent the severity of amyloid depositions in the myocardium and may provide prognostic information.

Aged↗

A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors.

Missense mutations of human fibroblast growth factor receptor 3 (FGFR3) result in several skeletal dysplasias, including hypochondroplasia, achondroplasia and thanatophoric dysplasia. To study the function of FGFR3 in bone growth and to create animal models for the FGFR3-related inherited skeletal disorders, we introduced a point mutation (Lys644Glu) into the murine FGFR3 genome using a knock-in approach. We found that the Lys644Glu mutation resulted in retarded endochondral bone growth with severity directly linked to the expression level of the mutated Fgfr3. Mice heterozygous for the mutation ( Fgfr3(TD/+) ) expressed the mutant allele at approximately 20% of the wild-type level and exhibited a mild bone dysplasia. However, when the copy number of the mutant allele increased from one (Fgfr3(TD/+) to two (Fgfr3(TD/TD), the retardation of bone growth became more severe and showed phenotypes resembling those of achondroplasia patients, characterized by a dramatically reduced proliferation of growth plate cartilage, macrocephaly and shortening of the long bones, which was most pronounced in the femur. Molecular analysis revealed that expression of the mutant receptor caused the activation of Stat1, Stat5a and Stat5b, and the up-regulation of p16, p18 and p19 cell cycle inhibitors, leading to dramatic expansion of the resting zone of chondrocytes at the expense of the proliferating chondrocytes. The mutant growth plates consequently were in a less active state and generated fewer maturing and hypertrophic chondrocytes. These data provide direct genetic evidence that the point mutations in FGFR3 cause human skeletal dysplasias and uncover a mechanism through which the FGFR3 signals regulate bone growth by modulating expression of Stats and ink4 cell cycle inhibitors.

Amino Acid Substitution↗

Human parathyroid hormone (1-34) transiently increases the excretion of lysosomal enzymes into urine and the size of renal lysosomes.

It has been reported that the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, transiently increases in human after treatment with human parathyroid hormone (hPTH)(1-34). We report here that hPTH(1-34) caused transient changes in the size and density of rat renal lysosomes following urinary excretion of NAG and other lysosomal enzymes tested. Percoll density gradient centrifugation revealed that hPTH(1-34) slightly but significantly increased the fraction of high density lysosomes (around 1.12 g/ml) 5-10 min after the treatment with hPTH(1-34), with a concomitant decrease in the fraction of intermediate density lysosomes (1.07-1.08 g/ml). On electron micrographs, some lysosomes in proximal tubules but not in distal tubules showed a change in morphology from circular to oval, and became enlarged and electron-dense 5-10 min after the treatment with hPTH(1-34). These responses to hPTH(1-34) were also reversible and transient. NAG excreted in urine after treatment with hPTH(1-34) had the molecular mass of a mature form in lysosomes and/or endosomes and was not a prepro-and/or pro-form of the enzyme. Thus, the changes in the density and size of renal lysosomes appear to be associated with the exocytosis of lysosomal enzymes by hPTH(1-34).

Acetylglucosaminidase↗

Increased levels of epsilon and gamma isoforms of 14-3-3 proteins in cerebrospinal fluid in patients with Creutzfeldt-Jakob disease.

We established four hybridoma cell lines producing monoclonal antibodies (MAbs) against 14-3-3 proteins. Immunoblot analysis revealed that epsilon and gamma isoforms were specifically increased in premortem cerebrospinal fluid samples from patients with sporadic Creutzfeldt-Jakob disease. Furthermore, dot immunoblot analysis showed that MAbs were more specific for native antigen than polyclonal antibodies were.

14-3-3 Proteins↗

Generation of free radicals and the damage done to the sarcoplasmic reticulum during reperfusion injury following brief ischemia in the canine heart.

Free radical generation was studied by the electron spin resonance (ESR) technique using alpha-phenyl N tert butyl nitrone (PBN) in a brief ischemia-reperfusion model of the canine heart, and correlated with biochemical changes of the sarcoplasmic reticulum (SR). ESR spectra (aH=0.3-0.4mT, aN=1.43-1.58mT) were observed as PBN spin adducts, which peaked at levels 5-fold above the control levels at 5 min after reperfusion. The simulated coupling constants of PBN spin adducts suggested that the sample should contain at least 2 carbon-centered radicals at 5 min after reperfusion (radical A: aH=0.350mT, aN=1.485mT; radical B: aH=0.370mT, aN=1.615 mT). At this time point, a significant reduction in Ca-ATPase activity of the SR was found without degradation of the major ATPase protein. Superoxide dismutase (SOD) significantly reduced the intensity of the PBN spin adduct signals and preserved the Ca-ATPase activity of the SR to 80% of the control level. Reperfusion injury after brief ischemia may be the result of inactivation of intracellular Ca-ATPase by free radicals generated during reperfusion, and SOD contributes to the protective effect by scavenging the radicals.

Animals↗

Promoter polymorphism of the beta2 bradykinin receptor gene is associated with essential hypertension.

The present study examined the genetic contribution of the human beta2 bradykinin receptor gene in Japanese subjects with essential hypertension, and identified a -58T/C polymorphism of the core promoter that might be responsible for essential hypertension in Japanese. The study consisted of 100 hypertensive subjects and 100 age- and sex-matched controls. The allelic frequencies were 0.575 for the C allele and 0.425 for the T allele in hypertensive subjects, and 0.465 for the C allele and 0.535 for the T allele in normotensive subjects. The allelic frequencies were in Hardy-Weinberg equilibrium. Significant differences between hypertensive and normotensive subjects were seen in the genotypes distribution (p=0.049) and allelic frequencies (p=0.028), and the beta2 bradykinin receptor gene variant was associated with human essential hypertension in this Japanese population. This new marker may provide a valuable tool for assessing the risk for putative bradykinin-associated common diseases, such as hypertension, and cardiovascular diseases with genetic determinism. These results suggest that the -58 polymorphism of the human beta2 bradykinin receptor gene is an independent risk factor for essential hypertension in the Japanese population.

Adult↗

[Resected case of synchronous double cancer of lung and ovarium].

A 45-year-old woman was admitted to our department for a tumor shadow in the right lung on chest rentogenogram and chest CT. Detailed examination led to the diagnosis of simultaneous lung cancer and ovarian cancer. No abnormality was found in the liver. Serum AFP level was 113.8 ng/ml preoperatively, but deceased upper lobectomy of the right lung to 11.4 ng/ml on the 15th day postoperatively. Immunohistochemical study revealed positive staining of carcinoma cells with anti AFP serum.

Adenocarcinoma↗

[Effectiveness of hypoallergenic rice-by cast analysis].

Rice is the main food taken every day in Japan. We introduced hypoallergenic rice (95% of albumin and globulin were taken off by hyperpressure method) for 4 weeks to 7 atopic dermatitis patients (m 3, f 4), 11 mo-4 y 8 m (mean 3 y 2 m) who showed the RAST score of rice 1 or more. Stimulation Index by CAST (cellular antigen stimulation test) were compared before and after taking the rice (50-100 g). By albumin (0.1-100 micrograms/ml), maximum decreases of S.I. were 22.4-96.5% (mean 70.9) and by globulin maximum decreases of S.I. were (0.1-100 micrograms/ml) 33.3-97.0% (mean 72.9). In all the patients the skin conditions were improved.

Adult↗

[The influence of ketamine on the bispectral index, the spectral edge frequency 90 and the frequency bands power during propofol anesthesia].

To investigate the influence of ketamine on the bispectral index (BIS), the spectral edge frequency 90 (SEF 90) and relative power in four frequency bands (beta, alpha, theta, sigma), we studied 13 patients (ASA I-II) undergoing elective surgery. In the first study (n = 7), we administered ketamine (1.0 mg.kg-1, bolus, i.v.) during propofol anesthesia. Thirty minutes after the administration, BIS, SEF 90 and relative beta power increased significantly. In the second study (n = 6), bolus administration of ketamine (0.5 mg.kg-1 i.v.) followed by continuous infusion was started during propofol anesthesia. The infusion rate of ketamine was 0.5 mg.kg-1.h-1 for 30 minutes and then increased to 1.0 mg.kg-1.h-1. BIS, SEF 90 and relative beta power increased significantly after ketamine administration, but the parameters did not change in dose-related manner. We conclude that further investigation is necessary to use electroencephalographic parameters as an indicator of the anesthesia depth during propofol/ketamine anesthesia.

Analgesics↗

[The effect of intraoperative mild hypothermia on the development of perioperative cardiac ischemia].

We evaluated the risk of perioperative cardiac ischemia associated with mild hypothermia as adjunct management for neurosurgical procedures. Forty-seven elective neurosurgical patients were randomly assigned to either hypothermic group (H, n = 24) or normothermic one (N, n = 23). Patients in group H were cooled to and maintained at 34.5 degrees C (tympanic membrane temperature) and rewarmed after main neurosurgical manipulation, while those in group N were kept in normothermic state. Cardiac ischemia was diagnosed with Holter electrocardiogram monitored for 24 hours after admission to the operating room. No differences were observed in demographic data including age, gender, weight, height, rate of having cardiac disease, anesthesia methods, and contents of surgery. Temperature was significantly lower in group H than N both at the lowest point (34.6 +/- 0.5 vs 35.9 +/- 0.6, mean +/- SD) and at the conclusion of anesthesia (35.9 +/- 0.9 vs 36.5 +/- 0.5). Electrocardiographic ST segmental depression was observed in 3 (group H) and 5 cases (group N), and postoperative shivering occurred in 3 (group H) and 2 cases (group N), respectively. Those incidences were not statistically significant (chi-square test, P was set at 0.05). We concluded that intraoperative mild hypothermia might not increase the risk of perioperative cardiac ischemia in patients for neurosurgical procedures.

Adult↗

[A case of bladder tumor producing granulocyte colony-stimulating factor].

A case of bladder tumor producing granulocyte colony-stimulating factor (G-CSF) is reported. A 78-year-old male presented with macroscopic hematuria. Cystoscopy demonstrated a large bladder tumor. Drip infusion pyelography and computerized tomography of the chest, abdomen and pelvis revealed right hydronephrosis, but did not reveal any metastasis. Total cystectomy and construction of bilateral cutaneous ureterostomy was performed. Histologically, the tumor consisted of sarcomatoid carcinoma with foci of transitional cell carcinoma (G3 > G2), showing marked infiltration of polymorphonuclear leukocytes. Immunohistochemical examination revealed a high concentration of G-CSF in the tumor specimen. Preoperatively, the white blood cell, count in the peripheral blood and serum G-CSF concentration were elevated, 45,400/mm3 and 73.4 pg/ml, respectively. After surgery these values became normal. This is the 19th reported case of G-CSF producing bladder tumor in Japan. The prognosis of the reported cases of G-CSF producing bladder tumor has been very poor. Fourteen of the reported 19 cases died within one year. This patient should be carefully followed up.

Aged↗

Induction of human gamma delta T cells in myasthenia gravis thymus transplanted SCID mice.

BACKGROUND: TCR-gamma delta cells develop by extrathymic differentiation and might play an important role in thymectomy-resistant myasthenia gravis (MG) patients. In this study, we show development of human TCR-gamma delta cells in periphery of SCID mice by transplantation of human MG thymus or thymoma. METHODS: Three pieces of thymoma tissue and four of non-thymoma thymic tissues were obtained from MG patients by thymectomy. Each tissue was transplanted into 5-6 weeks old female SCID mice by intraperitoneal injection or surgical implantation. Rate of human TCR-positive cell development and its subtypes (TCR-alpha beta, TCR-gamma delta) were measured in the mice blood at one, three, and six weeks after the transplantation. RESULTS: Human TCR-positive cells were detected three weeks after transplantation. Rate of TCR-gamma delta T cell development got higher in thymoma transplanted group than in non-thymoma transplanted group. CONCLUSIONS: We could successfully develop human mature T cells in SCID mice by transplantation of human MG thymus or thymoma.

Aged↗

Oxidative stress induces differential gene expression in a human lens epithelial cell line.

PURPOSE: To identify differentially expressed genes in a human lens epithelial cell line exposed to oxidative stress. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) differential display was used to evaluate differential gene expression in a human lens epithelial cell line (SRA 01-04) when cells were exposed for 3 hours to a single bolus of 200 microM hydrogen peroxide. Differentially expressed genes were identified through DNA sequencing and a nucleotide database search. Differential expression was confirmed by northern blot and RT-PCR analyses. RESULTS: Using 18 primer sets, 28 RT-PCR products were differentially expressed between control and hydrogen peroxide-treated cells. In stressed cells, mitochondrial transcripts nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 4 and cytochrome b were downregulated 4-fold. Of the cytoplasmic mRNAs, glutamine cyclotransferase decreased 10-fold, whereas cytokine-inducible nuclear protein, alternative splicing factor 2, and beta-hydroxyisobutyryl-coenzyme A hydrolase increased 2-, 4-, and 10-fold, respectively. Analysis of mitochondrial transcripts in a 24-hour time course showed that NADH dehydrogenase subunit 4 mRNA decreased by 2-fold as early as 1 hour after oxidative stress, whereas the rate of decrease was slower for cytochrome b, cytochrome oxidase III, and 16S rRNA. CONCLUSIONS: Oxidative stress induced specific expressed gene changes in hydrogen peroxide-treated lens cells, including genes involved in cellular respiration and mRNA and peptide processing. These early changes may reflect pathways involved in the defense, pathology, or both of the lens epithelium, which is exposed to oxidative stress throughout life.

Blotting, Northern↗

A novel molecular determinant for cAMP-dependent regulation of the frog heart Na+-Ca2+ exchanger.

Na+-Ca2+ exchanger is one of the major sarcolemmal Ca2+ transporters of cardiac myocytes. In frog ventricular myocytes the exchanger is regulated by isoproterenol via a beta-adrenoreceptor/adenylate-cyclase/cAMPdependent signaling pathway providing a molecular mechanism for the relaxant effect of the hormone. Here, we report on the presence of a novel exon of 27-base pair insertion, which generates a nucleotide binding motif (P-loop) in the frog cardiac Na+-Ca2+ exchanger. To examine the functional role of this motif, we constructed a full-length frog heart Na+-Ca2+ exchanger cDNA (fNCX1a) containing this exon. The functional expression of fNCX1a in oocytes showed characteristic voltage dependence, divalent (Ni2+, Cd2+) inhibition, and sensitivity to cAMP in a manner similar to that of native exchanger in frog myocytes. In oocytes expressing the dog heart NCX1 or the frog mutant (DeltafNCX1a) lacking the 9-amino acid exon, cAMP failed to regulate Na+-dependent Ca2+ uptake. We suggest that this motif is responsible for the observed cAMP-dependent functional differences between the frog and the mammalian hearts.

Adenylyl Cyclases↗