Biomedical subjects

K Nagano

Publications and source records attributed to K Nagano.

At least 19 recordsLinked to original sources

PubMed2001

Mechanism of urinary tract crystal formation following biphenyl treatment.

Coadministration of biphenyl and KHCO3 in the diet of male rats for 13 weeks produced urine crystals, which, by means of LC-MS/MS analyses, were determined to be composed of the potassium salt of 4-hydroxy-biphenyl-O-sulfate (4-HBPOSK). Biphenyl alone or biphenyl with KCl or NaHCO3 in the diet did not produce urine crystals. It was found that the higher concentration of potassium in the urine and the alkaline pH induced by feeding KHCO3 to rats resulted in the formation of urine crystals of 4-HBPOSK due to 4-HBPOSK solubility being lower in urine than in plasma. Urine crystals of 4-HBPOSK produced hyperplasia of the transitional epithelium of the ureter, ureteral obstruction, and hydronephrosis in the urinary tract.

Animals↗

PubMed2001

Functional imaging of the brain in sedated newborn infants using near infrared topography during passive knee movement.

Near infrared topography was used for functional imaging of the sensorimotor cortex of newborn infants during passive knee movement under sedated sleep. Contralateral knee movement caused a marked increase in oxyhemoglobin and total hemoglobin from the baseline values at almost all locations in the primary sensorimotor area of all neonates and a decrease in local deoxyhemoglobin in six of seven neonates. During ipsilateral knee movement, oxyhemoglobin and total hemoglobin showed slighter changes at a few locations, equal to 30% (mean) and 29% (mean) of the changes that occurred with contralateral stimulation, respectively. The mean times corresponding to maximal changes were 11.9 s for oxyhemoglobin and 19.1 s for deoxyhemoglobin, demonstrating that oxyhemoglobin has a much faster response than does deoxyhemoglobin.

Brain Mapping↗

PubMed2001

Estimation of regional cerebral blood flow distribution in infants by near-infrared topography using indocyanine green.

Near-infrared topography with indocyanine green was used to measure regional cerebral blood flow (rCBF) in the temporal lobes of infants. The mean rCBF in infants without neural abnormality was 14.5 +/- 3.1 ml/100 g/min, and the rCBFs in the fronto-temporal, temporal, and occipito-temporal regions were 15.1 +/- 3.9, 15.4 +/- 3.3, and 14.6 +/- 3.3 ml/100 g/min, respectively. Moreover, in one asphyxiated infant with infarction and one infant with subdural and intracerebellar hemorrhage, it was demonstrated that the area of defective blood flow could be detected as well as it can by SPECT. This technique makes it possible to estimate rCBF distribution in infants at the bedside. Thus, in the future, evaluation of various neonatal illnesses should be feasible.

Asphyxia Neonatorum↗

PubMed2001

A 10-year-old boy with Marfan syndrome exhibiting cerebrovascular abnormalities.

A young male with Marfan syndrome, diagnosed at the age of 10 years, presented with conspicuous elongation and tortuosity of the internal carotid, middle cerebral, vertebral and basilar arteries on cranial magnetic resonance and computed tomography angiography. There is a little mention of cerebral blood vessel examinations in the guidelines of the American Academy of Pediatrics for Marfan syndrome. Guidelines may be provided for the evaluation of cerebrovascular system for the patients with Marfan syndrome who have family history of Marfan syndrome as well as a family history of death from subarachnoid hemorrhage.

Cerebrovascular Disorders↗

PubMed2001

Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts.

OBJECTIVES: This study was designed to test the hypothesis that cardiac myocytes have greater vulnerability to oxidative stress compared with cardiac fibroblasts. BACKGROUND: The function of cardiac myocytes differs from that of fibroblasts in the heart, but differences in their response to oxidative stress have not been extensively studied. METHODS: Cardiomyocytes and fibroblasts from F344 neonatal rat hearts were cultured and exposed to different concentrations of hydrogen peroxide (H(2)O(2)) and menadione (superoxide generator). The mitogen-activated protein kinase (MAPK) proteins were assayed after oxidative stress; cell death was determined by trypan blue staining and deoxyribonucleic acid (DNA) ladder electrophoresis. RESULTS: The cardiac myocytes were significantly more vulnerable than the fibroblasts to oxidative damage, showing substantial DNA fragmentation and consistently poor cell survival after exposure to H(2)O(2) (100 to 800 microM), while the cardiac fibroblasts demonstrated little or no DNA fragmentation, and superior cell survival rates both over time (from 1 to 72 h after 100 microM) and across increasing doses of H(2)O(2) (100 to 800 microM). The p42/44 extracellular signal-regulated kinases were phosphorylated in both cell types after exposure to H(2)O(2), but significantly more in cardiac fibroblasts. However, p38 MAPK and c-jun NH(2)-terminal kinase were phosphorylated more in the cardiac myocytes compared to cardiac fibroblasts. This was also the case after exposure to menadione. CONCLUSION: Taken together, these results suggest that oxidative stress causes greater injury and cell death in cardiac myocytes compared with cardiac fibroblasts. It is possible that the signaling differences via the MAPK family may partly mediate the observed differences in vulnerability and functional outcomes of the respective cell types.

Animals↗

PubMed2001

Cerebral metabolism and regional cerebral blood flow during moderate systemic cooling in newborn piglets.

BACKGROUND: Clinical trials of hypothermic therapy in asphyxiated infants have started recently. However, clinical studies have been delayed by the difficulty in selecting infants with a bad neurological prognosis and by the concern regarding adverse effects of hypothermia. The purpose of this study is to examine the effects of systemic cooling on cerebral metabolism (CMR) and the regional cerebral blood flow (rCBF) in newborn piglets. METHODS: The rCBF in the seven parts of the brain were measured with colored microspheres. The blood samples for the measurement of cerebral oxygen consumption (CMRO2) and cerebral glucose consumption (CMRglc) was collected from the umbilical artery and the superior sagittal sinus. RESULTS: Reductions of cerebral cortex temperature to 32 degrees C decreased blood flow in all brain regions. In particular, blood flow in the brainstem decreased more significantly than in any other region. The total cerebral blood flow (CBF), CMRO2 and CMRglc, respectively, decreased to 32.3+/-3.9 mL/100 g per min, 2.8+/-1.0 mLO2/100 g per min and 22+/-12 mmol/100 g per min at 32 degrees C (41, 53 and 46% of the initial value). The CBF decreased in parallel with CMRO2 and CMRglc down to 35 degrees C, but CBF decreased to a greater extent than CMRO2 and CMRglc at below 35 degrees C. CONCLUSIONS: The indication of hypothermic therapy and the degree of cooling have to be performed very carefully. Systemic cooling is especially dangerous for the total asphyxiated infants who might have damage to the brainstem because the blood flow in the brainstem has significantly decreased during hypothermia.

Animals↗

PubMed2001

Infection of hepatitis A virus in Japanese haemophiliacs.

OBJECTIVES: Outbreaks of hepatitis A virus (HAV) infection in haemophiliacs have been reported from many countries. The aim of this study was to determine the prevalence of hepatitis A virus antibody (HAVAb) in Japanese haemophiliacs. METHODS: Sixty-seven male haemophiliacs were recruited for this study of HAV infection. We also compared the rate of HAV infection with that of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis G virus (HGV). RESULTS: Fifteen of 67 haemophiliacs (22.4%) were positive for HAVAb. Prevalence of HAVAb was significantly higher in haemophiliacs than in Japanese normal subjects previously reported (P= 0.0001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and prevalence of HIV, HCV, and HGV were not statistically different between HAVAb positive and HAVAb negative haemophiliacs. We suggest that the use of clotting factor concentrates is closely associated with HAV infection, but HAV infection does not have an effect on clinical course. CONCLUSIONS: Administration of clotting factor concentrates may increase risk of HAV infection in haemophiliacs.

Adolescent↗

PubMed2001

Fatal bleeding from a residual vein at the esophageal ulcer base after successful endoscopic variceal ligation.

Endoscopic variceal band ligation (EVL) is now one of the accepted treatment options for esophageal varices, and the safety of this procedure has been proved. However, we experienced a patient who had a fatal massive bleeding after successful EVL for ruptured esophageal varix. Postmortem study revealed a residual vein at the base of the esophageal ulceration associated with the ligation, which was believed to be the site of the fatal bleeding. His platelet counts and prothrombin time were not very impaired. Our case indicates that fatal massive bleeding can occur in patients after successful EVL without specific risk factors and indicates the importance of the awareness of the possibility of these complications.

Esophageal and Gastric Varices↗

PubMed2001

Long working hours and risk for hypertension in Japanese male white collar workers.

STUDY OBJECTIVE: To evaluate the association of long working hours with the risk for hypertension. DESIGN: A five year prospective cohort study. SETTING: Work site in Osaka, Japan. PARTICIPANTS: 941 hypertension free Japanese male white collar workers aged 35-54 years were prospectively examined by serial annual health examinations. Men in whom borderline hypertension and hypertension were found during repeated surveys were defined as incidental cases of borderline hypertension and hypertension. MAIN RESULTS: 336 and 88 men developed hypertension above the borderline level and definite hypertension during the 3940 and 4531 person years, respectively. After controlling for potential predictors of hypertension, the relative risk for hypertension above the borderline level, compared with those who worked < 8.0 hours per day, was 0.63 (95% confidence intervals (CI): 0.43, 0.91) for those who worked 10.0-10.9 hours per day and 0.48 (95% CI: 0.31, 0.74) for those who worked > or = 11.0 hours per day. The relative risk for definite hypertension, compared with those who worked < 8.0 hours per day, was 0.33 (95% CI: 0.11, 0.95) for those who worked > or = 11.0 hours per day. The multivariate adjusted slopes of diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) during five years of follow up decreased as working hours per day increased. From the multiple regression analyses, working hours per day remained as an independent negative factor for the slopes of systolic blood pressure, DBP, and MABP. CONCLUSIONS: These results indicate that long working hours are negatively associated with the risk for hypertension in Japanese male white collar workers.

Adult↗

PubMed2001

Hours of work and the risk of developing impaired fasting glucose or type 2 diabetes mellitus in Japanese male office workers.

OBJECTIVE: To investigate the association between duration of overtime and the development of impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM). METHODS: A cohort of 1266 Japanese male office workers aged 35-59 years and free of IFG (fasting plasma glucose concentration 6.1-6.9 mmol/l), type 2 DM (fasting plasma glucose concentration of 7.0 mmol/l or more or taking hypoglycaemic medication), history of diabetes, or medication for hypertension were re-examined over 5 successive years after their initial examinations in 1994. RESULTS: 138 men developed IFG or type 2 DM during the 5736 person-years of follow up. After controlling for potential predictors of diabetes, the relative risks of IFG or type 2 DM, compared with those who worked <8.0 hours a day, were 0.82 (95% confidence interval (95% CI) 0.54 to 1.26), 0.69 (95% CI 0.38 to 1.26), 0.63 (95% CI: 0.37 to 1.09), and 0.50 (95% CI: 0.25 to 0.98) for those who worked 8.0-8.9, 9.0-9.9, 10.0-10.9, and of 11.0 hours or more a day, respectively (p for trend=0.020). 87 and 54 men developed IFG and type 2 DM during the 5817 and 5937 person-years of follow up, respectively. The multivariate adjusted relative risks of IFG tended to decrease with an increase in hours of overtime work a day, but did not reach significance (p for trend=0.202). On the other hand, the multivariate adjusted relative risks of type 2 DM significantly decreased with an increase in hours of overtime work a day (p for trend=0.014). CONCLUSION: Longer overtime is a negative risk factor for the development of IFG or type 2 DM in Japanese male office workers.

Adult↗

PubMed2001

Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor.

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac alpha-actin, skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.

Actins↗

PubMed2001

Induction of nuclear orphan receptor NGFI-B gene and apoptosis in rat vascular smooth muscle cells treated with pyrrolidinedithiocarbamate.

NGFI-B is one of the orphan nuclear receptors, and its gene is implicated in the apoptosis of T cells. The aim of this study was to investigate the expression and the role of NGFI-B in vascular smooth muscle cells (VSMCs). Pyrrolidinedithiocarbamate (PDTC) is a modulator of an oxidative state and is reported to induce apoptosis only when the density of VSMCs is low. Under low VSMC density (10 000 cells/cm(2)), addition of PDTC (0.1 to 10 micromol/L) caused apoptosis of VSMCs, which was confirmed by Hoechst 33258 staining under fluorescence microscopy. At low VSMC density, expression of NGFI-B mRNA was induced 1 hour after the addition of PDTC, peaking at 6 hours, and persisted for up to 12 hours. The protein level of NGFI-B was increased 4 hours after PDTC addition and persisted for up to 12 hours. Under low VSMC density, PDTC-induced expression of NGFI-B mRNA was correlated with the magnitude of apoptosis, which was quantified by enzyme immunoassay for histone-associated DNA fragments. In contrast, when the density of VSMCs was high (50 000 cells/cm(2)), PDTC did not induce apoptosis, and the expression of NGFI-B was only transient. This transient expression pattern was also seen when VSMCs were treated with phorbol ester, calcium ionophore, hydrogen peroxide, or angiotensin II, even at low cell density. We next investigated whether the NGFI-B gene may act as a transcription factor under treatment with PDTC by measuring the promoter activity of luciferase reporter plasmids that contained typical NGFI-B-responsive elements. The PDTC-induced transcriptional activity of NGFI-B was 2-fold higher at low cell density than at high cell density. These data demonstrate that NGFI-B can be induced in VSMCs and suggest that NGFI-B may play a role in PDTC-induced VSMC apoptosis.

Animals↗

PubMed2000

Tor-mediated induction of autophagy via an Apg1 protein kinase complex.

Autophagy is a membrane trafficking to vacuole/lysosome induced by nutrient starvation. In Saccharomyces cerevisiae, Tor protein, a phosphatidylinositol kinase-related kinase, is involved in the repression of autophagy induction by a largely unknown mechanism. Here, we show that the protein kinase activity of Apg1 is enhanced by starvation or rapamycin treatment. In addition, we have also found that Apg13, which binds to and activates Apg1, is hyperphosphorylated in a Tor-dependent manner, reducing its affinity to Apg1. This Apg1-Apg13 association is required for autophagy, but not for the cytoplasm-to-vacuole targeting (Cvt) pathway, another vesicular transport mechanism in which factors essential for autophagy (Apg proteins) are also employed under vegetative growth conditions. Finally, other Apg1-associating proteins, such as Apg17 and Cvt9, are shown to function specifically in autophagy or the Cvt pathway, respectively, suggesting that the Apg1 complex plays an important role in switching between two distinct vesicular transport systems in a nutrient-dependent manner.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Prostanoids regulate proliferation of vascular smooth muscle cells induced by arginine vasopressin.

The aim of the present study was to investigate the effect of arginine [Arg(8)]vasopressin (vasopressin) on proliferation of vascular smooth muscle cells and the mechanisms underlying the action of vasopressin. To clarify these issues, we used two different types of vascular smooth muscle cells, cultured adult rat aortic smooth muscle cells and A10 cells, a cell line derived from fetal rat aorta. Vasopressin (10(-8) to 10(-6) M) significantly stimulated the proliferation of rat aortic smooth muscle cells in a dose-dependent manner. In contrast, vasopressin significantly inhibited the proliferation of A10 cells. This inhibition was abolished when A10 cells were treated with indomethacin. Vasopressin stimulated the production of prostanoids several-fold in A10 cells but not in rat aortic smooth muscle cells. These effects were completely blocked by the vasopressin V(1) receptor antagonist, 1-¿1-[4-(3-acetylamino-propoxy)benzoyl]4-piperidyl¿-3, 4-dihydro-2(1H)-quinolinone (OPC21268), but not by the vasopressin V(2) receptor antagonist, (+/-)-5-dimethylamino-1-[4-(2-methylbenzoylamino)benzol]-2, 3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC31260). These results indicate that vasopressin has diverse effect on proliferation of vascular smooth muscle cells through the vasopressin V(1) receptor, depending on the production of growth regulatory prostanoids.

6-Ketoprostaglandin F1 alpha↗

PubMed2000

Clinico-radiological study of total knee arthroplasty after high tibial osteotomy.

The results of total knee arthroplasty (TKA) after high tibial osteotomy (HTO) and problems encountered during the operation were investigated in 23 patients (28 knees). HTO was performed by Coventry's method in 18 knees and by Maquet's method in 10 knees. The mean interval from HTO to TKA was 86 months (range, 3 to 288 months) and the mean follow-up period after TKA was 25 months (range, 6 to 116 months). Radiological evaluation showed that the proximal part of the tibia was shifted and tilted lateroinferiorly after HTO. Thus, a tendency to patella infera was observed. Lateral shift of the proximal part of the tibia was more marked with Maquet's method than with Coventry's method (P < 0.01). Posterior inclination of the tibial articular surface before TKA was smaller in the patients who gained a range of motion of 90 degrees or more after TKA than in those with less than 90 degrees (P < 0.05). In patients with 70 points or more on the three-university score after TKA, there was no change in the joint line level between before and after TKA, while the joint line was significantly lower after TKA in those with less than 70 points (P < 0.01). When TKA is done after HTO, various technical problems may influence the outcome, such as correction of the soft tissue imbalance, in addition to difficulties with patellar eversion and exposure of the proximal part of the tibia. The clinical results of TKA after HTO tend to be slightly inferior to those of primary TKA, probably because of such technical problems.

Aged↗

PubMed2000

Massive bleeding from a gastric erosion after transcatheter arterial chemoembolization for hepatocellular carcinoma in a patient with mild haemophilia A.

We observed massive bleeding from a gastric erosion following transcatheter arterial chemoembolization (TAE) in a patient with mild haemophilia A. A 78-year-old haemophiliac (factor VIII level over 60%) received TAE with farmorubicin and spongel. Haematemesis and melena with loss of consciousness occurred 3 days [corrected] after TAE, and endoscopy revealed superficial erosions with oozing. Toxic effects of the anticancer drug in conjunction with the bleeding disorder may have caused the massive bleeding. We should always consider the possibility of unexpected complications in patients with bleeding disorders; gastrointestinal bleeding can develop during treatment for liver tumours.

Aged↗

PubMed2000

Growth factor-induced promoter activation of murine phospholipase C delta4 gene.

Phospholipase C delta4 (PLCdelta4) is one of the delta-type PLC isozymes, the expression of which is induced in nuclei by treatment with serum and also in some cancer cells. We isolated and analyzed a promoter region of the murine PLCdelta4 gene. DNA sequence analysis showed that this region is GC-rich and has no TATA box, and the region from -143 to -127 was found, by luciferase activity and gel mobility-shift assay, to be essential for transcription of PLCdelta4. We also found that the promoter activity of PLCdelta4 was stimulated by treatment with growth factors such as bradykinin, lysophosphatidic acid, and Ca2+ ionophore in addition to serum. In parallel, we detected PLCdelta4 mRNA induction and an increase in complex formation of the promoter region and nuclear protein from HeLa cells on stimulation with these growth factors. Finally, we found that trapping the growth factor-induced cytoplasmic Ca2+-inhibited activation of the promoter activity and protein induction in nuclei. These results show that PLCdelta4 may have an important role in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+.

Animals↗

PubMed2000

[Anesthetic management in a patient with severe acute pancreatitis during pregnancy].

Continuous epidural anesthesia was used in a 34 year-old pregnant woman with acute pancreatitis related to hypertriglyceridemia. She underwent an emergency cesarean section due to severe pancreatitis under spinal anesthesia. After delivery, extended incision was made to examine the pancreas and to perform drainage. Epidural infusion using 1% mepivacaine and buprenorphine was started to reduce pain and improve microcirculation. After starting epidural infusion with other therapies, clinical feature and data improved. This case suggests that reduction of severe pain and improvement of microcirculation are important in therapies of severe pancreatitis.

Acute Disease↗