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Biomedical subjects

K Araki

Publications and source records attributed to K Araki.

At least 73 records · Page 4Linked to original sources

Temporal order of sleepiness, performance and physiological indices during 19-h sleep deprivation.

Nineteen-hour variation of subjective sleepiness, performance and physiological indices were assessed during sleep deprivation. Longitudinal data of each index had its characteristic curve through which the values changed from day level to night level. A comparison of the time when each curve crossed its mid-range (50% value of its range) showed that those of subjective sleepiness and heart rate were significantly earlier than those of tracking error and coefficient of variation of R-R interval (CV(R-R)), P<0.01. That of rectal temperature was located at between 1:00 and 4:00 am. These temporal relationships were reproducible under two lighting conditions. These results will be useful in considering the occurrence of human errors by night-time workers in the early morning.

Adult↗

Regulation of melanogenesis through phosphatidylinositol 3-kinase-Akt pathway in human G361 melanoma cells.

The involvement of the phosphatidylinositol 3-kinase pathway in the regulation of melanogenesis was examined using human G361 melanoma cells. In the cells treated with wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, the melanin content increased concomitant with the elevated protein level of tyrosinase, a key enzyme in melanogenesis. Northern blot analysis revealed that the mRNA level of tyrosinase increased transiently on treatment of the cells with the phosphatidylinositol 3-kinase inhibitor. When the cells were infected with the adenovirus vector encoding the mutant adapter subunit of phosphatidylinositol 3-kinase, which acts as a dominant negative of phosphatidylinositol 3-kinase, both the melanin content and the expression of tyrosinase increased. In cells infected with the adenovirus vector encoding the constitutively active mutant of the lipid kinase, a decrease in melanin content as well as reduced expression of tyrosinase was observed. In cells expressing the constitutively active mutant of the serine-threonine protein kinase Akt, one of the downstream targets of phosphatidylinositol 3-kinase, the melanin content decreased as in the cells overproducing the constitutively active mutant of phosphatidylinositol 3-kinase. These results indicate that phosphatidylinositol 3-kinase regulates melanogenesis by modulating the expression of tyrosinase, and that activation of Akt is sufficient for suppression of melanin production in G361 melanoma cells.

Androstadienes↗

Sensorless controlling method for a continuous flow left ventricular assist device.

We originated a novel control strategy for a continuous flow left ventricular assist device (LVAD). We examined our method by acute animal experiments to change the left ventricular (LV) contractility or LV end-diastolic pressure (LVEDP). To estimate the pump pulsatility without any specific sensor, we calculated the index of current amplitude (ICA) from motor current waveform. The ICA had a peak point (t-i point) that corresponded closely with the turning point from partial to total assistance, and a trough (s-i point) that corresponded with the beginning point of ventricular collapse. The pump flow at the t-i point (Qt-i) had no component of flow regurgitation. In the evaluation of the effects of preload LVEDP, afterload (mAoP), and contractility (max LV dp/dt), we found that preload was the only parameter that significantly influenced Qt-i. We concluded that our method could well control continuous flow LVAD by preventing reversed flow and ventricular collapse.

Animals↗

Control strategy for biventricular assistance with mixed-flow pumps.

A left ventricular assist device (LVAD) is an effective method to rescue severe heart failure. Although some require a biventricular assist, the control method for the biventricular assist device (BVAD) with a rotary pump is rarely shown. The objective of this study was to investigate the strategy for controlling BVAD with rotary pumps by in vivo studies. Using 5 piglets, we set a BVAD through a left thoracotomy and made global ischemia for 30 min by clamping the base of the ascending aorta. After unclamping, the analysis of pumping performance acted for 6 h reperfusion. We set the target flow of the LVAD and set the right ventricular assist device (RVAD) speed limit as less than when the atrial collapse occurs. To detect the ventricular collapse without any specific sensor, we calculated the index of current amplitude from motor current waveform and simultaneous mean current value. In all cases, over 6 h of observation was performed, and the RVAD was weaned almost automatically.

Analysis of Variance↗

Alcohol consumption and cigarette smoking in relation to high frequency of p53 protein accumulation in oesophageal squamous cell carcinoma in the Japanese.

We investigated levels of p53 protein expression in Japanese patients with oesophageal squamous cell carcinoma. A significantly larger proportion of heavy alcohol drinkers and cigarette smokers was evident in the p53-positive group. The combination of drinking and smoking was associated with a high frequency of p53 protein accumulation.

Alcohol Drinking↗

Prognostic factors in patients with submucosal carcinoma of the oesophagus.

To clarify the prognostic factors in patients with submucosal carcinoma of the oesophagus, we examined the results of surgical treatment for 78 cases over the last decade. The clinicopathological factors including age, sex, location of the tumour, length of the tumour, histological differentiation, subclassification of depth, lymphatic or blood vessel invasion, intramural metastasis and lymph node metastasis were all analysed. Then the correlation between these factors and prognosis was investigated. As a result, significant differences were observed in the survival rates between the groups regarding lymphatic vessel invasion (P = 0.0003), intramural metastasis (P = 0.0051) and lymph node metastasis (P = 0.0026). According to a multivariate analysis, intramural metastasis (P = 0.0038, relative risk 9.17), vessel invasion (P = 0.0033, relative risk 6.25) and lymph node metastasis (P = 0.0187, relative risk 3.62) were found to be independent prognostic factors. The prognosis of the patients with at least one of these factors was significantly poorer than that without. The five-year survival rate of the patients without these factors was as good as that with mucosal carcinoma of the oesophagus. Based on our findings, vessel invasion, intramural metastasis and lymph node metastasis are thus considered to be significant prognostic factors in patients with submucosal carcinoma of the oesophagus.

Age Factors↗

Molecular characterization of a novel gamma-glutamyl transpeptidase homologue found in rat brain.

A cDNA clone for a novel homologue to gamma-glutamyl transpeptidase (gamma-GTP), termed GTPH, was isolated from a rat brain expression cDNA library using antisera against total brain synaptosomal fractions. The cloned GTPH consists of 641 amino acid residues (78 kDa) and exhibits structural similarity with a conventional type of gamma-GTP that is predominantly expressed in the liver: They share significant amino acid homology (33% identity, 73% similarity) spanning over the entire sequence. RNA analyses revealed that GTPH mRNA expression is found only in the nervous system, including all brain regions, eyes and peripheral ganglia, and increases during development. Endogenous GTPH protein is a membrane-bound glycoenzyme and migrates as 90-100 kDa in polyacrylamide gels. Taken together, GTPH is a novel form of a gamma-GTP-like molecule expressed exclusively in the nervous system.

Amino Acid Sequence↗

Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan.

Hantaviral antibodies were detected in the sera from patients with hepatic disease of unknown etiology in Japan by several different serological diagnostic methods. A total of 105 sera from diseased patients which were negative to A-G hepatitis virus infections in the Tokyo area were tested. Among them, 3 out of 73 sera from patients with chronic hepatic disease were positive to hantaviral antibody by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescent antibody assay (IFA) and Western blot analysis (WB). Neutralizing antibody titers of the 3 sera to Seoul virus (SEO) were 4 to 8 times higher than those to Hantaan virus (HTN). However, all of the 32 sera from patients with acute hepatitis were negative for hantaviral antibody. Among the 60 patients with chronic hepatitis in Hokkaido which were serologically negative to B and C hepatitis virus infection, one was positive for hantaviral antibody by ELISA and WB. In contrast, the sera from healthy adults in Japan, 550 from the Honshu and Kyushu regions, and 1,000 from the Hokkaido region, were negative for hantavirus antibody. These results show that hantaviral antibodies are more frequently detected in patients with hepatic disease than in healthy adults. However, the observation that no positive sera were detected from patients with acute hepatitis implies that hantavirus might not be directly related to hepatitis.

Acute Disease↗

Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes.

We report a Japanese man with Hermansky-Pudlak syndrome, having oculocutaneous albinism with a bleeding diathesis. Gene analysis of the patient's peripheral blood cells revealed that he was a compound heterozygote for HPS1 gene mutations. One of the mutations was a novel frameshift mutation at codon 321 (a G insertion) in exon 11 ( approximately 962-963insG), and the other was a 5' splice-junction mutation of IVS5 (IVS5 + 5G-->A). The content of eumelanin in the patient's hairs was significantly reduced. Histological analysis using light and electron microscopy revealed that melanocytes in the patient's epidermis contained an appreciable number of giant melanosomes. Cultured melanocytes from the patient's skin also contained giant melanosomes. Our finding of mutations in the HPS1 gene in relation to abnormalities in melanosome morphology and melanin production shed light on the role and function of the HPS1 gene product in the synthesis of melanosomes and melanin pigment.

Adult↗

[Molecular investigation of pathogenic factors of suspected-diarrheogenic Escherichia coli isolates from patients feces].

One hundred fifty-one O serotypable Escherichia coli strains which were assumed diarrheogenic E. coli among 2,240 strains of E. coli isolated from the in- and outpatients stools with or without gastrointestinal symptoms at Kyorin University Hospital from February 1994 to September 1996 were examined for the relationship between the possession of eight pathogenic factor-related genes and gastrointestinal symptoms of the patients using the polymerase chain reaction (PCR) for these strains. The rate of possession of pathogenic factor-related genes in the E. coli examined was 20.5% (31 strains) and gastrointestinal symptoms were found in all the patients with these strains except one. In the patients without gastrointestinal symptoms, E. coli isolates that possesses these genes was detected in only one case during 61 cases. The respective genes detected were eaeA and astA in each 14 strains, VT1 in 6, VT2 in 5, ST1b in 4, aggR in 3 and LT in 2, ST1a and invE gene was not detected. In particular, the O157 strains were found in 55.6% (5/9 strains) for these genes, and individual strains had VT1, VT2, eaeA and astA genes simultaneously. In contrast, none of these related genes was found in 9 strains of enteroinvasive serotype but enteropathogenic E. coli-related genes were found in 3 strains. The rate of possession of the genes related to enterotoxigenic E. coli, O159 which was most frequently isolated was low as 2.3% (1/43 strains, astA gene) and there were strains showing low correlation to the state of possession of the genes with the O serotype. Since the prevalence of the gastrointestinal symptoms is clearly high for the case which possesses the strain of which the pathogenic factor-related gene was detected, it was suggested that detection of pathogenic factor-related genes in E. coli isolates from feces using the PCR could be an effective means to decide whether the bacteria concerned was a causal bacteria or not in clinical practice.

Diarrhea↗

Development of a highly specific recombinant Toxocara canis second-stage larva excretory-secretory antigen for immunodiagnosis of human toxocariasis.

The specificity of the recombinant Toxocara canis antigen developed for the immunodiagnosis of human toxocariasis was compared with that of the excretory-secretory antigen from T. canis second-stage larvae (TES) by enzyme-linked immunosorbent assay. A total of 153 human serum samples from patients infected with 20 different helminths, including 11 cases of toxocariasis, were examined. No false-negative reactions were observed for the toxocariasis cases. When the TES was used at concentrations of 0.5 and 0.125 microg/ml, cross-reactions were observed in 79 (55.6%) and 61 (43.0%) of 142 cases, respectively. In contrast, when the recombinant antigen was tested at a concentration of 0.5 microg/ml, cross-reactions were observed in 19 (13.4%) of 142 cases. At a concentration of 0.125 microg/ml, however, the cross-reaction rate decreased sharply to only 2.1%, corresponding to 3 of 142 cases. The cross-reactions occurred with one case each of gnathostomiasis, paragonimiasis with Paragonimus miyazakii, and spirometriasis, in which high antibody titers were detected. In addition, the recombinant antigen showed negative reactions with serum samples from patients infected with Ascaris and hookworms, which are the most common parasites in the world. These findings are also supported by experiments with animals infected with Ascaris and hookworm. From these results, the recombinant antigen is highly specific for toxocariasis and may provide more reliable diagnostic results than other methods.

Animals↗

Pathogenicity of Hantaan virus in newborn mice: genetic reassortant study demonstrating that a single amino acid change in glycoprotein G1 is related to virulence.

Two Hantaan virus strains, clone 1 (cl-1), which is virulent in newborn mice, and its attenuated mutant (mu11E10), were used to examine the pathogenesis of Hantaan virus infection in a mouse model and identify virus factors relating to virulence. After subcutaneous inoculation of newborn BALB/c mice, cl-1 caused fatal disease with high viral multiplication in peripheral organs, but mu11E10 produced nonfatal infection with a low level of virus multiplication. Intracerebral inoculation of either strain caused fatal disease. Histopathological changes in the dead animals were prominent in the brain, indicating that the brain is the target organ and produces the fatal outcome. These results indicate that mu11E10 has a generally less virulent phenotype, and because of decreased multiplication in peripheral tissues, neuroinvasiveness is also decreased. An experiment with genetic reassortant viruses showed that in newborn mice the M segment is the most related to virulence and the L segment is partly related. Sequence comparison detected a single deduced amino acid change (cl-1 Ile to mu11E10 Thr) at amino acid number 515 in glycoprotein G1. One nucleotide change, but no amino acid substitution, was observed in the noncoding region of the L segment. In mouse brain microvascular endothelial cells in vitro, viruses possessing a cl-1-derived M segment grew more rapidly than viruses containing a mu11E10-derived M segment. These results suggest that the single amino acid change in the glycoprotein alters peripheral growth, which affects invasion of the central nervous system in mice.

Amino Acid Substitution↗

Role of E-selectin in bleomycin induced lung fibrosis in mice.

BACKGROUND: Bleomycin (BLM), a well known anti-cancer drug, often causes acute lung injury and fibrosis by mechanisms that are not well understood. It is suspected that some proteases and active oxygen species generated from inflammatory cells cause the lung injury and subsequent lung fibrosis. It was therefore hypothesised that inhibition of adhesion of inflammatory cells to the endothelium might prevent these developments. METHODS: BLM (100 mg/kg) was injected into the tail veins of ICR mice to evaluate the induction of E-selectin, an adhesion molecule known to induce neutrophil attachment on endothelial cells. E-selectin mRNA induction was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The myeloperoxidase (MPO) activities in the lung tissues of BLM treated and control mice were compared to evaluate neutrophil infiltration. Pathological changes in the lungs of soluble E-selectin transgenic mice (TG) and their TG negative (non-TG) littermates after BLM treatment were also compared. Serum samples of TG mice and non-TG mice were tested for their ability to block the binding of sialyl Lewis(x) to recombinant E-selectin in vitro. RESULTS: E-selectin mRNA was maximally induced at six hours after BLM treatment in the ICR mice. The soluble form of E-selectin which can competitively inhibit the binding of sialylated antigens on inflammatory cells to E- and P-selectins on the endothelium was detected in the serum of TG mice. BLM induced lung fibrosis occurred in non-TG mice but not in TG mice. This result confirms the finding that the serum of TG mice inhibits the binding of sialyl Lewis(x) to E-selectin in vitro. CONCLUSION: E-selectin plays an essential role in BLM induced lung fibrosis through the induction of neutrophil and other inflammatory cell accumulation, and soluble E-selectin may be of use in the prophylactic treatment of lung fibrosis.

Animals↗

A discrepant finding between magnetic resonance imaging and other imaging modalities suggests a microcystic serous cystadenoma of the pancreas.

BACKGROUND: Serous cystadenoma of the pancreas is generally considered as having no malignant potential. Thus, of clinical importance is a differential diagnosis of this neoplasm from other solid tumors that are often malignant. RESULTS: We report a case of microcystic serous cystadenoma of the pancreas. Abdominal ultrasonography, computed tomography, and endoscopic ultrasonography showed a solid mass in the body of the pancreas with a diameter of 15 mm, but magnetic resonance imaging revealed it as a unilocular cystic lesion. Histological examinations on the surgically resected tissue specimen showed a honeycombed tumor with innumerable tiny cysts appearing grossly as a solid mass. The discrepant finding between magnetic resonance imaging and other imaging modalities observed in this case is suggestive of and might be specific to microcystic serous cystadenoma of the pancreas. CONCLUSIONS: Magnetic resonance imaging is a mandatory modality to identify pancreatic serous cystadenoma that contains no visible cystic compartments on computed tomography and ultrasonography.

Cystadenoma, Serous↗

A boy with normal growth in spite of growth hormone deficiency after resection of a suprasellar teratoma.

We reported a boy with panhypopituitarism after removal of a suprasellar teratoma and pituitary stalk transection at the age of 3 months. His growth was accelerated after 5 years of age without growth hormone (GH) therapy, although he had poor height growth until age 4 under treatment with hydrocortisone, levothyroxine sodium, and desamino-D-arginine vasopressin (DDAVP). Hyperphagia and obesity developed after surgery. Endocrinological examination revealed no GH response to glucagon, low serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3). Serum prolactin was normal, but serum insulin was high. Some patients who received an operation for craniopharyngioma were reported to achieve normal growth without GH secretion, but the mechanism is still unknown. High serum levels of prolactin or insulin can be associated with normal IGF in GH deficient patients. This patient had obesity and high serum insulin, which may be related to growth without GH secretion.

Growth↗

Thin molecular films of supramolecular porphyrins.

A relevant series of symmetric supramolecular porphyrins has been obtained by attaching four [RuII(bipy)2Cl] groups to the pyridyl substituents of meso-tetra(4-pyridyl)porphyrin and its metallated derivatives. These compounds display a rich electrochemistry and versatile catalytic, electrocatalytic and photochemical properties, associated with the ruthenium-bipyridine and the porphyrin complexes. These properties can be transferred to the electrodes by attaching thin molecular films of the compounds, by dip-coating, electrostatic assembly or electropolymerization. In this way, the interesting properties of those supermolecules and supramolecular assemblies can be used to prepare molecular devices and sensors.

Biosensing Techniques↗

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Adult↗

[Multiple endocrine neoplasia type 2; MEN 2].

Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disorder as an autosomal dominant trait, characterized by medullary thyroid carcinoma (MTC). MEN 2 is classified with associated diseases into three subtypes: MEN 2A, MEN 2B and familial MTC. It has recently been shown to be associated with germline mutation in the RET proto-oncogene. Genetic testing allows easily for accurate diagnosis of presymptomatic gene carriers and surgical treatment at an early stage of the disease. In this review we delivered the classification, clinical feature, mutation in RET, mutation analysis, and management of MEN 2, and we discuss recent progress of research on the molecular basis and how genetic testing could be used for clinical management of affected patients or individuals in at-risk families.

Carcinoma, Medullary↗