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M Arai

Publications and source records attributed to M Arai.

825 records · Page 46Linked to original sources

Ground-glass hepatocytes in fibrinogen storage disease in Japanese Black calves.

This paper reports the occurrence of large intracytoplasmic inclusions observed in the hepatocytes of six Japanese Black calves showing clinical illness. These inclusions were round to elongated polyhedral in shape, with a consistently homogeneous glassy appearance. Hepatocytes with the inclusions had a ground-glass appearance. The inclusions were negative for the periodic acid-Schiff reaction and methenamine silver stain. Immunohistochemically, they were strongly positive for fibrinogen. Electron microscopy revealed that the inclusions consisted of granular material, showing moderate electron density and bounded by a unit membrane. On the external surface of the unit membrane, there were direct connections to cellular organelles, including the ribosomes and rough-surfaced endoplasmic reticulum. The results showed these inclusions to be entirely consistent with fibrinogen inclusions described in man. Hepatocellular fibrinogen storage disease, as identified in this study, has not previously been described in animals.

Animals↗

Characterization of a mouse beta 1-adrenergic receptor genomic clone.

A beta 1-adrenergic receptor (beta 1AR) clone, designated Clone 5, was isolated from a BALB/c mouse liver genomic library screened at low stringency with a human brain beta 2 AR cDNA probe. Sequence analysis of Clone 5 revealed a 1,395-bp open reading frame encoding a 464-amino-acid polypeptide. The predicted protein exhibited structural features characteristic of members of the G-protein-coupled receptor family including seven hydrophobic segments corresponding to putative transmembrane domains, a potential N-linked glycosylation site near the amino-terminus, and multiple potential phosphorylation sites in the third cytoplasmic loop and carboxy-terminal cytoplasmic tail. The sequence of the Clone 5-encoded protein was nearly identical to those previously reported for the rat and human beta 1 ARs. Potentially important differences were noted in the third cytoplasmic loop and carboxy-terminal cytoplasmic tail. Reverse transcription-primer extension studies of adult mouse brain RNA demonstrated the predominant transcriptional start site to be 415 nucleotides upstream of the translational start site. A GC-box precedes the transcriptional start site by 40 nucleotides. No consensus TATA or CAAT box sequences were identified in this region. Southern blot analysis of a Chinese hamster x mouse somatic cell hybrid panel and of the progeny of an inter-subspecies backcross mapped the Clone 5-encoded gene to mouse chromosome 19, the localization previously determined for the mouse homolog of the human beta 1AR gene. Binding studies of transient COS-7 transfectants and stable L-cell transfectants confirmed that Clone 5 encodes a beta AR of the beta 1 subtype. A probe derived from Clone 5 selectively hybridized in Northern blot studies to mRNA isolated from adult mouse cerebrum, lung, and heart. These data should serve as the basis for further studies of the regulation and function of the beta 1AR.

Amino Acid Sequence↗

Ontogenic development of neurotensin-like immunoreactivity in the gastrointestinal tract and the influence of dietary changes in rats.

The ontogenic development of neurotensin-like immunoreactivity (NTLI) in the gastrointestinal tract was studied in three groups of male rats on different diets. Group I rats were weaned physiologically. Group II rats received only mother's milk until 25 days of age. Group III rats were fed mother's milk alone for 20 days and then switched abruptly to laboratory chow. The NTLI concentration in the gastrointestinal tract from the esophagus to the small intestine was almost the same as that in adult rats before weaning. It increased after weaning to a peak on day 20 or 25, and then decreased to the adult level. The NTLI concentration in the cecum and large intestine, however, decreased from high neonatal level, reaching the adult level on day 20 or 25, and it remained constant thereafter. Prolonged mother's milk feeding alone enhanced neurotensin production in the esophagus and postponed the physiological decrement of NTLI concentrations in the duodenum and small intestine. The sudden change from mother's milk to laboratory chow accelerated the decrement of intestinal NTLI concentrations.

Animals↗

Small-cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases.

We report the clinical profiles and immunohistochemical features of small-cell carcinoma of the uterine cervix. Eleven cases that we have encountered at the Department of Gynecology, Kitasato University Hospital, between 1971 and 2003 are presented. Of 1370 invasive carcinomas of the uterine cervix, the incidence of small-cell carcinoma was 0.8%. Patient ages ranged between 32 and 65 years, with a mean age of 46.3 years. The clinical stages at diagnosis were Ib in four patients, IIb in three, IIIb in three, and IVb in one. All patients presented with abnormal vaginal bleeding. Two patients who are alive with no evidence of disease for 12 years and 3 years 6 months, while eight patients died of primary carcinoma between 4 and 25 months after treatment. Histopathologic findings showed solid nests with marked peripheral palisading pattern and rosette formation. Small tumor cells with scant cytoplasm demonstrated a very high nuclear/cytoplasm ratio and indistinct cell borders. The nuclei were round to oval and demonstrated increased but fine granular chromatin. Nucleoli were indistinct in all cases. Immunohistochemical findings were positive in 81.8% each for neuron-specific enolase and protein gene product 9.5, 72.7% for synaptophysin, 63.6% for chromogranin A, and 54.5% for neural cell adhesion molecule. All specimens were positive for at least one of the above. In conclusion, small-cell carcinoma of the uterine cervix revealed poor prognosis. Making an accurate diagnosis of small-cell carcinoma before performing treatment is of great significance but often difficult. Immunohistochemical analysis using several kinds of neuroendocrine markers is helpful in establishing the correct diagnosis in addition to focusing on characteristic histo- and cytopathologic features.

Adult↗

gamma-Glutamyl transpeptidase activity in liver of alcoholics and its localization.

The activity and the histochemical localization of gamma-GTP in the liver of chronic alcoholics were investigated. Mean serum gamma-GTP activity in alcoholics was 542.5 +/- 337.9 milliunits/ml, and that of patients with nonalcoholic liver disease was 34.3 +/- 22.6 milliunits/ml. Hepatic gamma-GTP activity in alcoholics was significantly increased compared to that in control patients (15.62 +/- 9.29 versus 4.04 +/- 2.67 units/g of liver; p less than 0.001). A significant correlation was observed between hepatic and serum gamma-GTP activity. Light microscopically, a marked gamma-GTP activity was found in the bile canaliculi and a diffuse activity in the cytoplasm in alcoholic livers. By contrast, in the livers of nonalcoholic patients, only slight activity was observed in the bile canaliculi. The electron micrographs showed the enzyme was localized in the microvilli of both the bile canalicular and plasma membranes and the endoplasmic reticulum near the mitochondria in alcoholics. But a very low activity was demonstrated in the plasma membranes in the livers of nonalcoholic patients.

Bile Canaliculi↗

Relationships among the expression of epidermal growth factor receptor, proliferating cell nuclear antigen labeling index, and lymph node metastasis in gastric cancer.

The expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and the labeling index of proliferating cell nuclear antigen (PCNA LI) were examined immunohistochemically in 288 gastric cancer patients, and the relationships between these results and the lymph node metastasis were studied. To investigate the relation between the expression of EGFR and PCNA LI, we divided the patients into the following three groups according to the immunohistochemical findings: group A, EGFR (+); group B, EGFR (-), and EGF(+) or TGF alpha(+); group C, EGFR(-), EGF(-) and TGF alpha(-). In the cancers invading submucosal or proper muscle layer, high-PCNA tumors (PCNA LI > or = 70) in both groups A and B had more frequent lymph node metastasis than in the intermediate-(40-69) and low- (< or = 39) PCNA tumors. In the cancers invading subserosal layer or further, the frequency of metastasis in group A was over 78% and was not related to the PCNA range. In group B, metastasis was more frequent in high- and intermediate-PCNA tumors (about 80%) than in low-PCNA tumors (44%). These results suggest that growth regulation by EGFR is related to lymph node metastasis in gastric cancer, and the higher the PCNA LI of cancer cells becomes, the more frequent the occurrence of lymph node metastasis.

Adult↗

Usefulness of endometrial aspiration cytology for the preoperative diagnosis of ovarian carcinoma.

OBJECTIVE: To evaluate the usefulness of endometrial aspiration cytology for the preoperative diagnosis of ovarian carcinoma. STUDY DESIGN: A total of 210 patients with ovarian carcinoma were investigated by endometrial aspiration cytology. RESULTS: Fifty-five of 210 patients (26.2%) had positive endometrial aspiration cytology. The positive rates of endometrial cytology were 3.9% in stage I, 23.8% in stage II, 36.5% in stage III and 53.3% in stage IV. When classified by histologic type, the positive rates of endometrial cytology in patients with serous adenocarcinoma, mucinous adenocarcinoma, clear cell adenocarcinoma, undifferentiated carcinoma and yolk sac tumor were 38.9%, 11.8%, 21.1%, 16.7% and 16.7%, respectively. One hundred twenty-eight of 210 patients (61.0%) were positive on peritoneal cytology, and 54 of these 128 cases (42.2%) were also positive on endometrial cytology. The positive rates of endometrial cytology were especially high in patients with serous adenocarcinoma (51.2%) and those with clear cell adenocarcinoma (40.0%) among those who were positive on peritoneal cytology. Of 74 patients who were negative on peritoneal cytology, only one (1.4%) with mucinous adenocarcinoma had positive endometrial cytology. Hysterectomy was performed on 130 patients, and the positive rate of endometrial cytology was 100% in 4 patients with endometrial invasion and 15.9% in 126 cases without invasion. CONCLUSION: Endometrial aspiration cytology can detect ovarian carcinoma cells not only in patients with endometrial involvement but also in patients with positive peritoneal cytology. Endometrial aspiration cytology appears to be useful for the preoperative diagnosis of ovarian carcinoma.

Adenocarcinoma, Clear Cell↗

Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca(2+)-ATPase gene transcription.

Doxorubicin (DOX)-induced cardiomyopathy has been found to be associated with impaired Ca(2+) handling in the sarcoplasmic reticulum (SR), leading to reduced cardiac function. We have recently demonstrated that expression of mRNA encoding sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2), a major Ca(2+) transport protein in SR, is markedly decreased in DOX-treated hearts. To extend this observation, we have dissected the molecular mechanisms by which DOX downregulates SERCA2 gene transcription. Using cultured rat neonatal cardiac myocytes, we found that the antioxidant N-acetylcysteine blocked the DOX-induced decrease in SERCA2 mRNA levels, as well as the DOX-induced increase in H(2)O(2) concentration; thus, H(2)O(2) is an intracellular mediator of DOX activity. Using a luciferase reporter assay, we found that the sequence from -284 to -72 bp in the 5' flanking region of the SERCA2 gene has a DOX-responsive element. Although several transcription factors have putative binding motifs in this region of the SERCA2 gene, only the expression of Egr-1 mRNA and the binding of Egr-1 protein to the 5' regulatory sequence of SERCA2 gene increased markedly after DOX administration. We also found that overexpression of Egr-1 was associated with a significant reduction in SERCA2 gene transcription. In addition, Egr-1 antisense oligonucleotides blocked the DOX-induced reduction in SERCA2 mRNA, suggesting that Egr-1 is a transcriptional inhibitor of the SERCA2 gene in DOX-induced cardiomyopathy. We observed activation of 3 mitogen-activated protein kinases (MAPKs), p44/42 MAPK, p38 MAPK, and stress-activated MAPK/Jun N-terminal kinase, by DOX, but only a specific inhibitor of the p44/42 MAPK kinase suppressed the effects of DOX on Egr-1 and SERCA2 mRNA expression. These findings indicate that reactive oxygen intermediates, the transcription factor Egr-1, and p44/42 MAPK are critical elements in the transcriptional regulation of the SERCA2 gene in response to DOX.

Animals↗

Recurrent pyogenic vertebral osteomyelitis associated with type 2 diabetes mellitus.

We report a case of recurrent pyogenic vertebral osteomyelitis associated with type 2 diabetes mellitus. A 51-year-old male was admitted to our hospital because of lumbago and general fatigue, with multiple ulcers on the soles of his feet. Staphylococcus aureus was isolated from peripheral blood and the foot ulcers, and 67Gallium scintigram showed abnormal isotope uptake, accumulated at the lower thoracic spine. Antibiotics were administered and the patient underwent intensive insulin therapy. Magnetic resonance imaging (MRI), performed after the levels of C-reactive protein decreased to 0.0 mg/dl, indicated old inflammatory changes at the Th8-Th9 spine and antibiotics were stopped. Unexpectedly, 8 days later the patient complained of lumbago with fever again, and MRI showed acute inflammatory changes at the same lesion site. This case report suggests that it is important for complementary antibiotic therapy to continue after signs of inflammation have disappeared in cases of pyogenic vertebral osteomyelitis.

Diabetes Mellitus, Type 2↗

Caudal left hepatic duct in relation to the umbilical portion of the portal vein.

BACKGROUND/AIMS: Intrahepatic ducts from the left lateral segment of the liver are generally considered to run from the cranial to the umbilical portion of the left portal vein. This understanding often limits surgical exploration of the left hepatic ducts during both curative and palliative surgical procedures. The prevalence of ducts from the lateral segment running caudally to the umbilical portion was studied retrospectively on computed tomography (CT) films, and its clinical implications were evaluated. METHODOLOGY: One hundred and sixty-six DIC (drip infusion cholangiography) CT and 30 post-PTCD (percutaneous transhepatic cholangio-drainage) CT films taken during 4 consecutive years were reviewed giving special consideration to whether the ducts from the left lateral segment of the liver run caudal to the umbilical portion of the left portal vein. RESULTS: Corresponding variation was found in 3.6% of the DIC-CT examinations and in 3.3% of the CT examination after PTCD, respectively. CONCLUSIONS: The incidence of caudal left hepatic ducts with respect to the umbilical portion of the left portal vein was higher than expected from clinical experience. These results emphasize that more careful planning is necessary prior to hepatobiliary surgery.

Biliary Tract Surgical Procedures↗

Primary hepatic choriocarcinoma--a case report.

A 65-year-old man experienced anorexia and abdominal enlargement and died suddenly 45 days after admission. Multiple necrotic and hemorrhagic tumors were present in the liver (6 kg). The fragile tumor ruptured and a large amount of blood accumulated in the peritoneal cavity. The tumor was composed of cytotrophoblast and syncytiotrophoblast cells. Neoplastic cells were positive for human chorionic gonadotropin and negative for alpha-fetoprotein and carcinoembryonic antigen. The huge tumor directly invaded the entire antrum of stomach. Neoplastic trophoblastic cells proliferated mainly in the serosa and propria muscular layer of the stomach, and tiny cancer nests were observed in many vessels of the submucosa and propria mucosa. The serum alpha and beta human chorionic gonadotropin subunits showed a very high level; 51 ng/mL and 820 ng/mL, respectively. No tumor, cyst or scar was observed in the testes, mediastinum and retroperitoneum, macroscopically and microscopically. Based on these autopsy findings, we diagnosed this patient as having primary hepatic choriocarcinoma.

Aged↗

Interleukin-18 in patients with congestive heart failure: induction of atrial natriuretic peptide gene expression.

Activated inflammatory responses appear to play a role in the development of congestive heart failure (CHF). We investigated interleukin-18 (IL-18), which is a cytokine synthesized by activated macrophage, changes in patients with CHF. We evaluated 11 Japanese patients with angina pectoris (n=4) or CHF (n=7). Blood was sampled immediately after admission and at 1, 2, 3, 6, and 9 hours after admission and then every 12 hours until 5 days after admission. Plasma IL-18 concentrations were measured by an enzyme-linked immunosorbent assay. Expression of atrial natriuretic peptide (ANP) mRNA and protein synthesis was examined in cardiac myocyte by stimulation of IL-18. Plasma IL-18 concentration was significantly higher in patients with CHF than in 15 healthy volunteers (51+/-21 pg/mL, and 28+11 pg/mL, respectively, P<0.05). Increased expression of ANP mRNA was demonstrated in IL-18 treated myocytes. Protein synthesis in myocytes was increased by IL-18 in a dose-dependent manner. Increased secretion of IL-18 is induced in patients with CHF and correlates with the severity of myocardial damage and dysfunction.

Adult↗

Cardiac sympathetic nerve function assessed by [131I]metaiodobenzylguanidine after ischemia and reperfusion in anesthetized dogs.

BACKGROUND: Accumulation of 131I-labeled metaiodobenzylguanidine ([131I]MIBG), a radiolabeled norepinephrine analog, is reduced in infarcted myocardium, suggesting loss of cardiac sympathetic nerve viability. Histopathologic studies, however, indicate that the nerve endings ae morphologically intact. Experiments were therefore designed to determine the mechanism of reduced MIBG accumulation. METHODS AND RESULTS: Desipramine, a specific blocker or neuronal norepinephrine reuptake, was used to separate the portions of total myocardial [131I]MIBG accumulation attributable to neuronal and nonneuronal uptake mechanisms. Sixteen dogs underwent circumflex coronary artery occlusion for 60 minutes followed by a 5-hour reperfusion. [131I]MIBG was injected intravenously 1 hour after reperfusion. The left ventricle was removed and incubated in triphenyltetrazolium chloride to identify infarcted and viable myocardium within the zone at risk. Preliminary studies in sham-operated dogs showed that pretreatment with desipramine (5 mg/kg) reduced [131I]MIBG accumulation 4 hours after injection to 38.9% of untreated controls. Chemical sympathectomy by topical phenol resulted in a similar decrease in [131I]MIBG accumulation (to 45.7% of normal), and desipramine did not produce further inhibition of [131I]MIBG accumulation over that produced by phenol alone, indicating that the inhibitory effect of desipramine on neuronal accumulation of [131I]MIBG was essentially complete. In dogs undergoing ischemia-reperfusion, myocardial samples from infarcted and viable postischemic areas showed 64.5% +/- 11.85 and 84.7% +/- 9.1% of normal [131I]MIBG activity, respectively (both, p < 0.01 vs normal area, n = 9). With desipramine pretreatment (n = 7), accumulation of [131I]MIBG decreased in all areas. Neuronal accumulation was reduced uniformly in infarcted, viable postischemic, and normal areas by 30% to 35% compared with sham-operated controls. In contrast, nonneuronal accumulation was only 39.3% in infarcted areas and 84.6% in viable postischemic areas compared with normal areas, and these decreases accounted entirely for the reduced total [131I]MIBG accumulation. CONCLUSIONS: Reduced [131I]MIBG accumulation in infarcted myocardium after 60 minutes of ischemia and 5 hours of reperfusion is attributable to a deficit in nonneuronal accumulation and not to decreased accumulation by sympathetic nerves.

3-Iodobenzylguanidine↗