Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 37 records · Page 2Linked to original sources

PubMed2004

Property of thimerosal-induced decrease in cellular content of glutathione in rat thymocytes: a flow cytometric study with 5-chloromethylfluorescein diacetate.

There is a concern on the part of public health community that adverse health consequences by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the effect of thimerosal on cellular content of glutathione was examined on thymocytes obtained from 4-week-old rats using a flow cytometer and 5-chloromethylfluorescein diacetate. Thimerosal at concentrations ranging from 1 to 10 microM reduced the cellular content of glutathione in a concentration-dependent manner, and the complete depletion of cellular glutathione was observed when the cells were treated with 30 microM thimerosal. L-Cysteine significantly attenuated the actions of thimerosal to reduce the glutathione content and to increase the intracellular Ca2+ concentration. Prolonged incubation (24 h) with 1-3 microM thimerosal induced the apoptosis. The cytotoxic action of thimerosal was greatly augmented when the cells suffered oxidative stress induced by H2O2. It may be unlikely that thimerosal exerts potent cytotoxic action under the in vivo condition because the blood concentration of thimerosal after receiving vaccines does not seem to reach micromolar range and nonprotein thiols at micromolar concentrations are present in the blood.

Animals↗

PubMed2004

Differential diagnosis of neonatal mild hypergalactosaemia detected by mass screening: clinical significance of portal vein imaging.

The aetiology of hypergalactosaemia in 100 neonates detected by screening using the Paigen method is discussed. Hypergalactosaemia was transient in 94 cases and persistent in 6. The aetiology among transient cases was unknown in 55, delayed closure of the ductus venosus in 19, heterozygous UDP-galactose 4-epimerase (GALE) deficiency in 16, and heterozygous galactose-1-phosphate uridyltransferase (GALT) deficiency in 6. The aetiology among persistent cases was hepatic haemangioendothelioma with portovenous shunting in 2, and patent ductus venosus with hypoplasia of the intrahepatic portal vein, citrin deficiency, homozygous GALE deficiency, and heterozygous GALE deficiency in one patient each. The abnormalities of the portal system were identified ultrasonographically at the initial consultation and measurements of the total bile acid and alpha-fetoprotein concentrations were helpful in resolving the differential diagnosis. The causes of hypergalactosaemia varied, but a major cause was portosystemic shunt. Evaluation of patients with hypergalactosaemia should not be limited to enzymatic analysis, but should also include hepatic imaging, especially ultrasonography. Additionally, determination of total bile acids and alpha-fetoprotein is helpful in identifying the aetiology of hypergalactosaemia in infants.

Acute Disease↗

PubMed2004

A simple and rapid enzymatic assay for the branched-chain alpha-ketoacid dehydrogenase complex using high-performance liquid chromatography.

Maple syrup urine disease (MSUD) is caused by a congenital defect of the branched-chain alpha-ketoacid dehydrogenase complex (BCKADC), and is one of the target disorders in newborn screening. However, it is not always easy to confirm the diagnosis; conventional methods of enzyme assay require cell culture, isolation of mitochondria, or radioisotope-labelled reagents, and disease-causing mutations can exist in any of the genes encoding the three enzyme subunits. To realize a practical test for diagnostic confirmation, we developed a simple and rapid enzymatic assay for BCKADC. In this procedure, the production of isovaleryl-CoA from 2-ketoisocaproic acid was measured using high-performance liquid chromatography. Detection of the BCKADC product was significantly reproducible depending on concentration of the substrates. We applied the assay to two patients with MSUD and demonstrated pathologically low levels of residual activity in both subjects. These results indicate that our method is a practical and sensitive assay for BCKADC, and that it can be a useful adjunct in newborn screening for MSUD.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed2004

Bilateral Bowen's disease.

Multiple Bowen's disease may be difficult to differentiate from bowenoid papulosis because of its clinicopathological resemblance to bowenoid papulosis. We experienced a case of bilaterally and symmetrically developed multiple bowenoid lesions in a 71-year-old man previously diagnosed as having chronic lymphocytic lymphoma (CLL). Based on histological findings and the results of human papillomavirus examinations, we finally diagnosed this case as bilateral Bowen's disease. We speculate that the underlying immunosuppressive state due to CLL may have been associated with onset of the disease. We report the unique clinical picture, the differential diagnosis and the aetiology.

Aged↗

PubMed2004

Establishment and characterization of two cell lines (HEC-155, HEC-180) derived from uterine papillary serous adenocarcinoma.

Uterine papillary serous adenocarcinoma (UPSC) is an uncommon histologic subtype of endometrial cancer that characteristically behaves aggressively with a poor prognosis. We established two novel cell lines derived from UPSC designated HEC-155 and HEC-180. Both cell lines have been growing steadily in monolayer cultures for over ten years. Overexpression of p53, Ki67 and p27 was detected in both cell lines by immunohistochemistry. Using a DNA sequencing technique, a point mutation of p53 was detected in exon 8, codon 286 in HEC-155 and in exon 6, codon 195 in HEC-180. These newly established cell lines should be useful for investigating the characteristics of UPSC.

Biopsy, Needle↗

PubMed2003

PTEN immunohistochemical expression is suppressed in G1 endometrioid adenocarcinoma of the uterine corpus.

PURPOSE: PTEN is a tumor suppressor gene that inhibits cell proliferation by regulating intracellular signaling pathways, and this activity can be abolished by mutations of the PTEN gene. This study was designed to examine the correlation of PTEN expression with the expression of cell cycle regulators and with clinicopathological parameters in endometrioid adenocarcinoma of the uterine corpus. METHODS: Tissue samples of 117 endometrioid adenocarcinomas in addition to those of 19 normal endometria and 20 endometrial hyperplasias were used for the study. Immunohistochemical staining for PTEN protein was performed with the labeled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. PTEN expression was represented as the staining score. RESULTS: Immunohistochemistry showed that the nuclei of cells were positive for PTEN. The PTEN staining score of normal endometrium was significantly higher in the proliferative phase than in the secretory phase. The scores of various endometrial hyperplasias were not significantly different from each other, regardless of the type of hyperplasia. The PTEN staining scores of endometrioid adenocarcinomas were 7.6+/-5.2 in G1, 9.6+/-5.2 in G2, and 11.9+/-3.7 in G3, and increased significantly as the histological grade increased. PTEN staining score was not significantly correlated with clinicopathological parameters such as FIGO stage, myometrial invasion, lymph-vascular space invasion (LVSI), lymph node metastasis or group, but was significantly correlated with labeling indices (LIs) of cell cycle regulators such as Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p27, and p53. The PTEN staining score of p53-wild cases was significantly lower than that of p53-mutant ones, but there was no significant difference of the score in cases with different PTEN gene status. PTEN expression was significantly lower in cases with both high levels of estrogen receptor and progesterone receptor. CONCLUSION: PTEN protein expression was decreased in well-differentiated and less growth-aggressive endometrial carcinoma with wild-type p53 gene and high levels of ER and PR. This suggests that disturbed PTEN expression occurs in an early phase of the tumorigenesis of well-differentiated endometrial carcinoma.

Adenocarcinoma↗

PubMed2003

Quantitative analysis of Fas and Fas ligand mRNAs in a feline T-lymphoid cell line after infection with feline immunodeficiency virus and primary peripheral blood mononuclear cells obtained from cats infected with the virus.

Apoptosis is frequently observed in feline lymphocytes in association with feline immunodeficiency virus (FIV) infection. In this study, to investigate the mechanism of FIV-induced apoptosis, levels of Fas and Fas ligand mRNAs were measured by real-time reverse transcription-PCR. In a feline T-lymphoid cell line the amounts of Fas ligand mRNA increased along with the induction of apoptosis after in vitro infection with FIV. In PBMC collected from 10 cats naturally infected with FIV, Fas ligand mRNA levels were significantly higher than those in PBMC from five uninfected cats. These results indicate that the increased expression of Fas ligand may be involved in the induction of apoptosis of lymphocytes in FIV infection.

Animals↗

PubMed2003

Immunohistochemical expression of cyclin E in endometrial adenocarcinoma (endometrioid type) and its clinicopathological significance.

PURPOSE: Cyclin E is known as a G1-S phase regulatory protein and its abnormal expression has been implicated in cellular proliferation. This study aimed to investigate the correlation of cyclin E expression with tumorigenesis of the endometrium, proliferative activity, and clinicopathological features of endometrial adenocarcinoma. METHODS: Immunohistochemical staining for cyclin E in addition to cyclin-dependent kinase 2 (cdk2), Ki67, p27, and p53 was performed by the labeled streptavidin-biotin method on formalin-fixed, paraffin-embedded tissues of normal endometria (20 cases), endometrial hyperplasias (20 cases), and endometrial adenocarcinomas (endometrioid type) (127 cases). Positive staining was expressed as a labeling index (LI) based on percentages of positive nuclei in tumor cells. RESULTS: Immunohistochemistry showed that the nuclei of the cells were positive for cyclin E. Both proliferative and secretory endometria, and endometrial hyperplasia regardless of type were negligible for cyclin E expression. The expression in normal endometrium and hyperplasia was significantly less than that in endometrial adenocarcinomas (P<0.0001). LIs of cyclin E in well-differentiated, moderately differentiated, and poorly differentiated endometrial adenocarcinomas were 31.5+/-33.3%, 37.8+/-31.9%, and 51.1+/-30.8%, respectively. Cyclin E expression increased significantly more in histological grades. The LI of cyclin E in carcinoma was positively correlated with that of cdk2, Ki67, and p53 but not with p27. The cyclin E expression was correlated with myometrial invasion and lymph-vascular space involvement, but not with FIGO stage, lymph node metastasis, coexisting endometrial hyperplasia, estrogen receptor, progesterone receptor, and menopause. CONCLUSION: Cyclin E as a complex with cdk2 is associated with carcinogenesis and disease progression in endometrial adenocarcinoma, and might be a prognostic indicator of endometrial adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Acute renal failure due to adenovirus-associated obstructive uropathy and necrotizing tubulointerstitial nephritis in a bone marrow transplant recipient.

Management of post-transplant complications caused by severe adenoviral infection remains a major therapeutic challenge. A 17-year-old male who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia developed complete anuria following hemorrhagic cystitis 34 days after the transplant procedure. The computed tomogram scan revealed bilateral hydronephrosis, indicating acute renal failure because of obstructive uropathy. The emergency procedure of percutaneous nephrostomy caused massive bleeding in the left kidney, which eventually required a nephrectomy. Adenovirus-positive severe necrotizing tubulointerstitial nephritis was the histopathological diagnosis. Post-transplant acute renal failure because of hydronephrosis, which could be complicated by adenovirus-induced renal parenchymal disease, is of great concern and may cause significant problems with interventional treatment.

Acute Kidney Injury↗

PubMed2003

Validation and verification of the ICRP biokinetic model of 32P: the criticality accident at Tokai-Mura, Japan.

Regrettably, a criticality accident occurred at a uranium conversion facility in Tokai-mura, Ibaraki, Japan, on 30 September 1999. Radioactivities of 32P in urine, blood and bone samples of the victims, who were severely exposed to neutrons, were measured. 32P was induced in their whole bodies at the moment of the first nuclear release by the reaction 31P (n, gamma) 32P and 32S (n, p) 32P. A realistic biokinetic model was assumed, as the exchange of 32P between the extracellular fluid compartment and the soft tissue compartment occurs only through the intracellular compartment, and the model was used for preliminary calculations. Some acute excretion of 32P, caused by decomposition or elution of tissues which occurred at the time of the accident, may have happened in the victims' bodies in the first few days. The working hypotheses in the present work should initiate renewed discussion of 32P biokinetics.

Bone and Bones↗

PubMed2003

Biokinetics of radiotellurium in rats.

Radiotellurium is present in the environment primarily due to its release during nuclear reactor accidents. Little is known of tellurium metabolism in juveniles, although the element is relatively abundant and has a number of industrial uses. A biokinetic study of radiotellurium in rats was performed using gamma-ray counting. Wistar strain rats were used to determine the uptake of H2(123m)TeO3 by the whole-body retention of juvenile rats and the conceptus in relation to its gestational stages, by measurements in the placenta, fetal membranes, fetal fluid and fetus. The whole-body retention of 123mTe in juvenile rats was higher than that of adult rats. The relative concentration in the placenta and fetal membranes was higher than in the fetus. No activity was observed in the fetal fluid. These results indicate that the placenta and fetal membranes play significant roles as barriers to the transfer of 123mTe into the fetus. The ratio, relative concentration in fetus/relative concentration in mother (C(F)/C(M)), was calculated. The C(F)/C(M) ratio was dependent on the stage of gestation and ranged from 0.2 to 0.5. A little 123mTe was transferred to the suckling rats through the mother's milk when the isotope was administered intravenously to the mother.

Administration, Oral↗

PubMed2003

[The surgical technique of heart displacement during off-pump coronary artery bypass grafting in the exposure of the anastomotic site of posterior descending artery].

Heart displacement during off-pump coronary artery bypass grafting (OPCAB) is necessary to expose the anastomotic site. However, such displacement causes hemodynamic deterioration especially in the exposure of the circumflex branches and posterior descending artery (PDA). In this study we present two different cardiac positioning for the exposure of the anastomotic site of PDA. To expose the mid-portion of PDA the heart is vertically displaced by fixing the suction cup of the heart positioner on apex. To expose the proximal portion of PDA the suction cup is attached on the acute margin of the right ventricle (off apex). By using these 2 different techniques properly, hemodynamic deterioration can be avoided during OPCAB for PDA.

Anastomosis, Surgical↗

PubMed2002

Effect of muscle length on the recruitment property of single motor units in humans.

In order to examine the effect of muscle length on the recruitment property of a single motor unit (MU), the action potentials of the MU in the human gastrocnemius muscle were recorded during voluntary isometric contraction at different knee joint angles. We found that the recruitment property of MU, which is determined by relationship of recruitment threshold torque (T-th) and ramp contraction speeds, changed as the knee joint angle was changed from 0 degrees to 90 degrees. The decrease of T-th with contraction speed occurred only when the muscle was held long. This result indicates that the MU recruitment property, which decrease of T-th with higher contraction speed, needs both central command and Ia inputs to the alpha-motoneuron.

Action Potentials↗

PubMed2002

Peripheral nerve regeneration through alginate gel: analysis of early outgrowth and late increase in diameter of regenerating axons.

Our previous study revealed that alginate gel cross-linked with covalent bonds promoted peripheral nerve regeneration in the cat and rat. The present study analyzed nerve regeneration through alginate gel in the early stages within 2 weeks and the late stages up to 21 months after implantation. Four days after surgery, regenerating axons grew without Schwann cell investment through the partially degraded alginate gel, being in direct contact with the alginate without a basal lamina covering. Numerous mast cells infiltrated into the alginate. One to 2 weeks after surgery, regenerating axons were surrounded by common Schwann cells to form small bundles, with some axons at the periphery being partly in direct contact with alginate. At the distal stump, numerous Schwann cells had migrated into the alginate 8-14 days after surgery. They had no basal laminae. The diameter of regenerated myelinated fibers was small (approximately 1 micro m) at 8 weeks, but increased in diameter, having a distribution pattern similar to that of normal nerve 21 months after surgery. Much better nerve regeneration was found in alginate gel-, than collagen sponge-, and fibrin glue-implanted distal stump 12 months after surgery. These results indicate that alginate gel has good biocompatibility for regenerating axon outgrowth and Schwann cell migration, and that regenerated fibers can have a diameter as thick as that of normal fibers in the long term. Alginate gel is a promising material for use as an implant for peripheral nerve regeneration.

Alginates↗

PubMed2002

Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer.

Dose-escalation study was performed to evaluate the maximum tolerated dose, recommended dose and toxicity profile of weekly irinotecan with daily carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Thirty-one previously untreated patients with unresectable stage III non-small-cell lung cancer were enrolled in this study. Patients received weekly irinotecan plus carboplatin (20 mg x m(-2) daily for 5 days a week) for 4 weeks and thoracic radiotherapy (60 Gy in 30 fractions). The irinotecan dose was escalated from 30 mg x m(-2) in increments of 10 mg x m(-2). Four irinotecan dose levels were given and 30 patients were assessable. Their median age was 62 years (range: 52-72 years), 28 had a performance status of 0-1 and two had a performance status of 2, 12 had stage IIIA disease and 18 had IIIB disease. There were 19 squamous cell carcinomas, 10 adenocarcinomas, and one large cell carcinoma. The dose-limiting toxicities were pneumonitis, esophagitis, thrombocytopenia and neutropenia. The maximum tolerated dose of irinotecan was 60 mg x m(-2), with two patients developing grade 4 pulmonary toxicity and one patient died of pneumonitis (grade 5). The recommended dose of irinotecan was 50 mg x m(-2). Other grade 3 or 4 toxicities were nausea and vomiting. Three patients achieved complete remission and 15 had partial remission, for an objective response rate of 60.0%. The median survival time was 14.9 months, and the 1- and 2-year survival rates were 51.6% and 34.2%, respectively. The study concluded that the major toxicity of this regimen was pneumonitis. This therapy may be active against unresectable non-small-cell lung cancer and a phase II study is warranted.

Aged↗

PubMed2002

Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening.

Type II citrullinaemia (CTLN2) is an adult- or late childhood-onset liver disease characterized by a liver-specific defect in argininosuccinate synthetase protein. The enzyme abnormality is caused by deficiency of the protein citrin, which is encoded by the SLC25A 13 gene. Until now, however, few cases with SLC25A13 mutations have been reported in children with liver disease. We describe an infant who presented with neonatal hepatitis in association with hypergalactosaemia detected by neonatal mass screening. DNA analysis of SLC25A13 revealed that the patient was homozygous for a IVS11+1G>A mutation. This case suggests that SLC25A13 mutant should be suspected in neonatal patients with hypergalactosaemia of unknown cause.

Citrullinemia↗

PubMed2002

Secretion of natriuretic peptides caused by an epileptic attack.

OBJECTIVE: To describe clinical features of a patient with secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) during an epileptic attack. PATIENT: A 65-year-old woman experienced frequent bouts of polyuria, pyrexia and general fatigue after several years of a cerebral contusion involving the left fronto-temporal lobe caused by a traffic accident. Her urine output and urinary sodium excretion increased, and plasma ANP and BNP concentrations were markedly high during each attack. Electroencephalography (EEG) showed serial seizure discharge in the left anterior temporal region during the attacks, indicative of epileptic focus. CONCLUSION: ANP and BNP secretions probably were triggered by epileptic stimulation on the diencephalon beyond the focus.

Aged↗

PubMed2002

Rapidly progressive dementia syndrome associated with a novel four extra repeat mutation in the prion protein gene.

OBJECTIVE: To gain a better understanding of how mutations of the prion protein (PrP) gene are responsible for progressive dementia syndrome and to clarify the correlation between genotype and phenotype, which should help to explain how the prion promotes neurological symptoms. BACKGROUND: Genetic prion diseases are associated with point or insertional mutations in the PrP gene. The insertional mutations described so far consist of one to nine extra octapeptide repeats, except three repeats. Insertions of one to four extra octapeptide repeats cause Creutzfeldt-Jakob disease (CJD) in patients without a family history of neurological disorders. CJD generally presents as progressive dementia. METHODS: Routine clinical assessment and sequence analysis of the PrP gene of DNA from a 56 year old Japanese man with progressive dementia syndrome. RESULTS: Sequence analysis disclosed a novel four octapeptide repeat insertion within the PrP gene. The patient was initially affected by progressive cerebellar and brainstem signs; a few months later myoclonus and rapidly progressive dementia appeared. These symptoms were similar to those of sporadic CJD. CONCLUSION: Taken together with previous investigations of CJD patients with insertional mutations, the current observation strengthens the notion that small octapeptide insertions from one to four extra repeats within the PrP gene cause CJD, which is characterised by late onset after the sixth decade, rapid progression, death within a few months, and lack of a family history of neurological disorders, the latter suggesting incomplete penetrance. Different patients with four extra octapeptide repeats have different patterns of extra insertions, suggesting that progression of the disease depends on the number of extra repeats.

Creutzfeldt-Jakob Syndrome↗