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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 145 records · Page 8Linked to original sources
PubMed2001

Use of a monoclonal antibody against Lafora bodies for the immunocytochemical study of ground-glass inclusions in hepatocytes due to cyanamide.

AIMS: Ground-glass inclusions (GGIs) in hepatocytes are known to be associated with cyanamide treatment in patients with alcohol dependency. The purpose of this study was to assess the reactivity of a monoclonal antibody (MAb) raised against polyglucosan and to detect early events in GGI formation. METHODS AND RESULTS: Formalin-fixed paraffin-embedded liver tissues from four patients treated with cyanamide were used. Sections were stained with haematoxylin and eosin and periodic acid-Schiff with and without diastase digestion, and were immunohistochemically stained with the MAb. For electron microscopic study, routinely processed liver tissue from one patient was examined with conventional and immunoelectron microscopy with use of the MAb. All specimens from the four cyanamide-treated patients contained GGIs in the cytoplasm of hepatocytes, and these GGIs reacted intensely with the MAb. Fully developed GGIs contained various organelles, whereas early ones consisted primarily of glycogen granules and dilated smooth endoplasmic reticulum. In immunoelectron microscopic preparations, gold particles were located within GGIs, and the immunolabelled organelles appeared to be glycogen granules. CONCLUSIONS: This novel MAb is useful for the detection of GGIs caused by cyanamide. Our results support the idea that GGI formation may result from specific abnormalities in glucose metabolism.

Adult↗
PubMed2001

Differential neuropeptide responses to starvation with ageing.

During starvation, counterregulatory responses to loss of food (i.e. responses that lead to an increase in appetite) occur in the central nervous system (CNS). This study was designed to examine whether middle-aged rats show greater or smaller behavioural, peripheral and central hormonal responses during starvation compared to young rats. In experiment 1, refeeding following 4 days of starvation was measured in both middle-aged (72-week-old) and young (9-week-old) rats. The level of refeeding was similar to each prestarved level until 3 days after the end of starvation in both groups. From the 4th day, the level of refeeding in young rats increased and reached beyond the prestarved level, whereas refeeding in middle-aged rats remained similar to the prestarved level. Thus, overall refeeding throughout 7 days was greater in young rats than in middle-aged rats. In experiment 2, middle-aged and young rats were starved for 4 days and were killed in the morning. Middle-aged rats showed a smaller plasma corticosterone response than that of young rats. The magnitude of decreases in plasma glucose, insulin and leptin was similar in both groups. In the arcuate nucleus, the starvation-induced increase in neuropeptide Y (NPY) mRNA and the decrease in proopiomelanocortin (POMC) mRNA were smaller in middle-aged rats than in young rats. In contrast, the starvation-induced decrease in corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular nucleus was greater in middle-aged rats than young rats. The magnitude of decrease in type-2 CRH receptor mRNA in the ventromedial hypothalamus was similar in both groups. The results indicate that (a) ageing impaired refeeding response (b), middle-aged rats showed the same directional neuropeptide mRNA responses as seen in young rats during starvation and (c) the magnitude of these counterregulatory responses in the CNS in middle-aged versus young rats was not uniform, but rather was site-specific or neuropeptide-specific. This study suggests the importance of NPY and POMC responsiveness in the arcuate nucleus in the age-related differences resulting from starvation-induced refeeding.

Adrenocorticotropic Hormone↗
PubMed2001

Dexamethasone, but not IL-1 alone, upregulates acute-phase serum amyloid A gene expression and production by cultured human aortic smooth muscle cells.

Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrahepatic tissues; the site of synthesis of extrahepatic SAA remains to be clarified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated. A-SAA protein isoforms were detectable by immunoblot analysis in the culture medium of HASMC. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones including dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone, but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-alpha alone. Dex stimulation of A-SAA mRNA was time and dose dependent from 6 to 48 h. The threshold concentration for upregulation of A-SAA mRNA in HASMC by Dex was between 0.1 and 1 nM. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is possible that some of the A-SAA protein in the vascular wall (atherosclerotic plaques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle cell homeostasis within that, in a disease state, participates in the formation of atherosclerotic plaques.

Acute-Phase Reaction↗
PubMed2001

Role of protein kinase C, K(ATP) channels and DNA fragmentation in the infarct size-reducing effects of the free radical scavenger T-0970.

1. In the present study, we investigated the effect of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl) urea hydrocloride (T-0970), a novel water-soluble low-molecular weight free radical scavenger, on the generation of hydroxyl radicals in vivo and on myocardial infarct size in an in vivo model of myocardial infarction in rabbits. 2. T-0970 scavenged hydroxyl radicals generated in the myocardium during reperfusion, as assessed by using a microdialysis technique and HPLC in an in vivo model with 30 min coronary occlusion and 30 min reperfusion in rabbits. 3. Another group of rabbits was subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with saline for 190 min from 10 min before occlusion to 180 min after reperfusion. The treatment group (T-0970 group; n = 10) was injected with a bolus 2.5 mg/kg T-0970 and then infused with T-0970 for 190 min from 10 min before reperfusion to 180 min after reperfusion at a rate of 100 microg/kg per min. The T-0970 + CHE group (n = 5) was given chelerythrine (CHE; a selective inhibitor of protein kinase C (PKC); 5 mg/kg, i.v.) 10 min before the administration of T-0970. The T-0970 + 5-HD group (n = 5) was given 5-hydroxydecanoate (5-HD; an inhibitor of mitochondrial K(ATP) channels; 5 mg/kg, i.v.) 10 min before the administration of T-0970. The CHE and 5-HD groups were given CHE (5 mg/kg, i.v.) and 5-HD (5 mg/kg, i.v.) 20 min before reperfusion, respectively. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of the area at risk (AAR). In another series of experiments, the control (n = 5) and T-0970 (n = 5) groups were killed 4 h after reperfusion following 30 min coronary occlusion and DNA fragmentation in myocytes was assessed using in situ dUTP nick end-labelling (TUNEL) at the light microscopic level. 4. Infarct size, as a percentage of AAR, in the T-0970 group was significantly reduced compared with the control group (21+/-4 vs 41+/-4%, respectively; P<0.05). This reduction of infarct size by T-0970 was abolished by pretreatment with CHE and 5-HD. Neither CHE nor 5-HD alone had any effect on infarct size. The percentage of infarcted myocytes with DNA fragmentation by TUNEL in the T-0970 group was significantly reduced compared with the number in the control group (4.0+/-1.5 vs 10.7+/-1.9%, respectively; P<0.05). 5. T-0970, a free radical scavenger, improved reperfusion injury. This effect seemed to be mediated by activation of PKC, the opening of mitochondrial K(ATP) channels and inhibition of DNA fragmentation.

ATP-Binding Cassette Transporters↗
PubMed2001

Troglitazone enhances glucose uptake induced by alpha-adrenoceptor stimulation via phosphatidylinositol 3-kinase in rat heart.

1. Thiazolidinedione-derived agents have been reported to act as insulin sensitizers by augmenting insulin-dependent stimulation of phosphatidylinositol 3-kinase (PI3K) activity in a specific manner. It has been suggested that alpha-adrenoceptor stimulation mediates glucose uptake through PI3K in the heart. 2. To elucidate whether the thiazolidinedione-derived agent troglitazone (TRO) affects glucose uptake induced by alpha-adrenoceptor stimulation through PI3K, the rate of glucose uptake was quantified from the rate of accumulation of sugar phosphate (d[SP]/dt) using [(31)P] nuclear magnetic resonance spectroscopy after substitution of glucose with 2-deoxyglucose in rat perfused heart. Hearts were stimulated with 100 micromol/L phenylephrine plus 10 micromol/L propranolol (alpha-adrenoceptor stimulation), or 1 micromol/L isoproterenol plus 10 micromol/L phentolamine (beta-adrenoceptor stimulation). 3. The d[SP]/dt in the alpha- and beta-adrenoceptor-stimulated groups (0.45 +/- 0.06 and 0.42 +/- 0.04 micromol/min per g, respectively) was higher than that of the control group (0.27 +/- 0.02 micromol/min per g; P < 0.01). The addition of 2 microg/mL troglitazone to alpha-adrenoceptor stimulation augmented d[SP]/dt (0.72 +/- 0.08 micromol/min per g; P < 0.05 vs the alpha-adrenoceptor-stimulated group), which was effectively blocked by 3 micromol/L wortmannin (0.35 +/- 0.06 micromol/min per g; P < 0.01 vs troglitazone + alpha-adrenoceptor stimulation group). However, addition of troglitazone to beta-adrenoceptor stimulation did not alter d[SP]/dt (0.33 +/- 0.02 micromol/min per g; P = NS vs the beta-adrenoceptor-stimulated group). 4. These results indicate that troglitazone acutely enhances alpha-adrenoceptor stimulation on glucose uptake through a PI3K-dependent pathway, thus possibly improving glucose utilization in a catecholamine-released state.

Adenosine Triphosphate↗
PubMed2001

Pancreatic granular cell tumor combined with carcinoma in situ.

A 58-year-old man was treated for a granular cell tumor (GCT) of the pancreas; a very rarely occurring tumor. The patient, who had been followed for 6 years due to alcoholic hepatitis, chronic pancreatitis and elevated carcinoembryonic antigen (CEA) levels from smoking, was admitted to our hospital for evaluation of back pain, diarrhea and constipation. The patient was diagnosed as having pancreatic head cancer using clinical imaging studies, and a pylorus-preserving pancreatico-duodenectomy was done. In the resected specimen, a white tumor measuring 13 mm in diameter was observed at the pancreatic head, and there was marked fibrous change surrounding the tumor. The microscopic appearance of the pancreas showed atrophy of acinar cells, fibrosis, and dilatation of the main pancreatic duct (MPD). Within the tumor were oval cells with low-grade atypia and an increased number of diffuse eosinophilic granules. Neither mitosis nor invasive findings were observed. Periodic acid-Schiff staining and immunohistochemical staining for the S-100 protein were positive, thus the tumor was diagnosed as a benign GCT. In addition, carcinoma in situ was found at the dilated MPD. Therefore, this patient was diagnosed as having GCT with carcinoma in situ of the pancreas. To the best of our knowledge, this is only the fourth case of GCT of the pancreas to be reported.

Biomarkers, Tumor↗
PubMed2001

Contact pressure distribution in the supine position in low-birth weight infants analyzed by a photoelastic method.

BACKGROUND: Contact pressure distribution patterns in the supine position in low-birth weight (LBW) neonates were analyzed by the use of a photoelastic method. METHODS: A total of 61 subjects (LBW neonates, mature (bodyweight > 2,500 g at birth) neonates, normal infants and Down syndrome (DS) infants) were selected for the study. Infants were placed on a photoelastic measuring table. Photoelastic images generated in the contact regions of the body were photographed with a camera and printed on monochrome paper. The coefficient of variation in the pressure distribution value (PcV) and the top and bottom ratio (mu) of the trunk at the center of pressure were calculated. RESULTS: The Pcv value was significantly lower in DS than LBW (P < 0.001), mature (P < 0.002) and normal infants (P < 0.01). The mu value in LBW and mature neonates was 48.9 and 50.2%, respectively. Normal infants had a mu value of 44.0%, which was significantly lower than that in LBW neonates. However, there was no significant difference between LBW and DS infants. CONCLUSIONS: Neurological impairment specifically affects the data obtained by photoelastic analysis.

Body Weight↗
PubMed2001

Correlation between neuroimaging and neurological outcome in periventricular leukomalacia: diagnostic criteria.

BACKGROUND: Periventricular leukomalacia (PVL) is the most important factor in cerebral palsy in preterm infants. METHODS: In the present study, we investigated 747 preterm infants of less than 36 weeks gestation who were repeatedly examined by cranial ultrasonography and computed tomography (CT) scanning at around 40 weeks of corrected post-menstrual age. The clinical course of these infants was followed for more than 3 years and they were examined by magnetic resonance imaging (MRI) between 12 and 18 months of age. RESULTS: Single examinations in early infancy were not sufficient to diagnose PVL, but the combination of ultrasonography, CT and MRI examinations allowed the clinical diagnosis of PVL. In preterm infants, clinical PVL could be predicted from cystic PVL and periventricular echogenicity (PVE) 3 or PVE 2 prolonged over 3 weeks on ultrasonography and confirmed by MRI after 11 months of corrected age. CONCLUSIONS: We tried to determine diagnostic criteria for PVL by neuroimaging. Such criteria from neuroimaging for PVL may be useful for determining the exact occurrence rate of and clinical risk factors for PVL.

Cerebral Palsy↗
PubMed2001

Iron deposition in renal biopsy specimens from patients with kidney diseases.

This study was performed to investigate the correlation between clinical parameters and grading of iron deposition in renal biopsy specimens from 102 patients with various kidney diseases. Iron deposition in renal tissues was detected by Berlin blue staining. The extent of iron staining was semiquantitatively graded as negative (Fe(-)), grade 0, or positive (Fe(+)), including faint, grade 1; moderate, grade 2; or severe, grade 3, by light microscopy. Thirty-four of 102 patients (33%) showed positive iron staining. Fe(+) patients had various renal diseases, mainly consisting of 12 patients with immunoglobulin A nephropathy and 5 patients with benign nephrosclerosis. Mean arterial pressure (MAP), serum creatinine (sCr) levels, incidence of hematuria, and urinary N-acetylbeta-D-glucosaminidase (u-NAG) levels in Fe(+) patients were significantly greater than those in Fe(-) patients, and u-NAG levels correlated positively with the extent of iron deposition. Study patients were tentatively divided into two groups according to the extent of iron deposition: group A, patients with grades 2 and 3 staining, and group B, patients with grades 0 and 1 staining. In group A, MAP, sCr level, urinary protein excretion, and the incidence of hematuria were significantly greater than in group B. Our results suggest that the amount of iron deposition in renal tissue may contribute to the progression of chronic renal disease and may be an early and sensitive indicator of renal damage in certain renal diseases.

Acetylglucosaminidase↗
PubMed2001

Superior hepatic mitochondrial oxidation-reduction state in normothermic cardiopulmonary bypass.

OBJECTIVE: This study is the first comparative investigation of hepatic blood flow and oxygen metabolism during normothermic and hypothermic cardiopulmonary bypass. METHODS: Twenty-four patients undergoing coronary bypass operations were randomly divided into 2 groups according to their perfusion temperatures, either normothermia (36 degrees C) or hypothermia (30 degrees C). The clearance of indocyanine green was measured at 3 points. Arterial and hepatic venous ketone body ratios (an index of mitochondrial redox potential) and hepatic venous saturation were measured. RESULTS: Hepatic blood flow in both groups was identical before, during, and after cardiopulmonary bypass (normothermia, 499 +/- 111, 479 +/- 139, and 563 +/- 182 mL/min, respectively; hypothermia, 476 +/- 156, 491 +/- 147, and 560 +/- 202 mL/min, respectively). The hepatic venous saturation levels were significantly lower during cardiopulmonary bypass in the normothermic group (normothermia, 41% +/- 13%; hypothermia, 61% +/- 18%; P <.01), indicating a higher level of oxygen extraction use. The arterial ketone body ratio in the hypothermic group decreased severely after the onset of cardiopulmonary bypass (P <.01) and did not return to its subnormal value (>0.7) until the second postoperative day. However, the reduction in arterial ketone body ratio was less severe in the normothermic group. The difference in hepatic venous ketone body ratios was more obvious, and the hepatic venous ketone body ratios in the normothermic group were statistically superior to those of the hypothermic group throughout the course (P <.05-.01). CONCLUSIONS: Normothermic cardiopulmonary bypass provides adequate liver perfusion and results in a better hepatic mitochondrial redox potential than hypothermic cardiopulmonary bypass. Because arterial ketone body ratios reflect hepatic energy potential, normothermia was considered to be physiologically more advantageous for hepatic function.

Aged↗
PubMed2001

Co-overexpression of DEAD box protein rck/p54 and c-myc protein in human colorectal adenomas and the relevance of their expression in cultured cell lines.

The RCK gene was cloned through a study of the breakpoint of the t(11;14)(q23;q32) chromosomal translocation observed in a human B-cell lymphoma and overexpression of the protein (rck/p54) due to the translocation was shown to be associated with malignant transformation. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions such as translation initiation, pre-mRNA splicing and ribosome assembly. It is considered that rck/p54 protein may have significant effects on the mRNA structure of genes associated with cell proliferation, facilitating protein synthesis. Expression of rck/p54 in colorectal adenomas, which are a premalignant lesion of colorectal cancer, was examined by Western blot analysis and immunohistochemistry. The rck/p54 protein was found to be overexpressed in tumor tissues resected from 17 of 26 cases (65.4%) of colorectal adenomas and 13 of 14 c-myc-positive cases (92.8%) also co-overexpressed rck/p54 protein. Thus, a significant correlation between rck/p54 and c-myc co-overexpression was found (Spearman's rank correlation, P = 0.0018). We demonstrate that overexpression of rck/p54 in two different cell lines, COS 7 and human colorectal cancer cell line SW480, caused an increase in c-myc protein levels by enhancement of its translation efficiency and/or stabilization of its mRNA. These results suggest that rck/p54 of the DEAD box protein/RNA helicase family may contribute to cell proliferation and carcinogenesis in the development of human colorectal tumors at the translational level by increasing synthesis of c-myc protein.

Adenoma↗
PubMed2001

A study of apoptosis in Merkel cell carcinoma: an immunohistochemical, ultrastructural, DNA ladder, and TUNEL labeling study.

We performed immunohistochemical, ultrastructural, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), and DNA ladder studies of apoptosis in nine cases of Merkel cell carcinoma (MCC). None of the cases showed spontaneous regression as has been reported in several MCCs. Neuron-specific enolase was demonstrated by immunohistochemistry (8/8 MCCs), and staining for cytokeratin 20 was positive (2/8 MCCs). Ultrastructural examination revealed many cytoplasmic dense-cored granules, desmosome-like structures, and intermediate filaments. The granules were seen along the plasma membrane or around perinuclear centrioles. We found various stages of development of apoptotic bodies. Apoptosis resulted in vacuolization and fragmentation of nuclei and phagocytosed bodies in tumor cells. Apoptotic cells were also detected by TUNEL, DNA ladder, and immunostaining using the antibody against Fas (Apo- 1/CD95) antigen. It seems that a high apoptotic rate is a common finding in MCC, although spontaneous regression is an exceedingly rare event. It is thus unlikely that apoptosis alone would explain spontaneous regression.

Aged↗
PubMed2001

Epinephrine increases the neurotoxic potential of intrathecally administered lidocaine in the rat.

BACKGROUND: Epinephrine is commonly added to lidocaine solutions to increase the duration of spinal anesthesia. Despite this common usage, the effect of epinephrine on the neurotoxic potential of this anesthetic is not known. The current experiments investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat. METHODS: Eighty rats were divided into four groups to receive an intrathecal injection of normal saline containing either 5% lidocaine, 5% lidocaine with 0.2 mg/ml of epinephrine, 0.2 mg/ml of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail-flick test administered 4 and 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. RESULTS: Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls. CONCLUSIONS: The neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine.

Anesthesia, Spinal↗
PubMed2001

Small graft for living donor liver transplantation.

OBJECTIVE: To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement. SUMMARY BACKGROUND DATA: Although the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown. METHODS: A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated. RESULTS: The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group. CONCLUSIONS: Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate.

Adult↗
PubMed2001

Electropharmacologic effects of a new phosphodiesterase III inhibitor, toborinone (OPC-18790), assessed in an in vivo canine model.

Electropharmacologic effects of a new phosphodiesterase (PDE) III inhibitor toborinone (OPC-18790) were assessed in a halothane-anesthetized, closed-chest canine model. Toborinone, 0.03 mg/kg, increased ventricular contractility, decreased total peripheral resistance, and inhibited intraventricular conduction without changing other cardiovascular parameters. A clinically relevant dose of 0.3 mg/kg increased heart rate, systolic blood pressure, and cardiac output, decreased preload to the left ventricle, enhanced atrioventricular nodal conduction, and shortened repolarization and the vulnerable period of the ventricle, in addition to enhancing the effects observed after the low dose. A high dose of 3 mg/kg of toborinone decreased systolic, mean, and diastolic pressures and prolonged the effective refractory period (ERP) in addition to the effects observed after the middle dose. No further change was detected in ventricular repolarization. Most of the cardiohemodynamic effects can be explained by the PDE III inhibition by toborinone. With regard to electrophysiologic properties, the prolongation of intraventricular conduction time and ERP by toborinone suggests sodium channel inhibition. The lack of the prolongation of ventricular repolarization suggests that previously demonstrated inhibition of I(Kr) and I(K1) and increased I(Ca-L) by toborinone might be counteracted by factors such as the cyclic AMP-dependent outward currents, I(Ks) and I(C1).

3',5'-Cyclic-AMP Phosphodiesterases↗