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Biomedical subjects

Y Shinohara

Publications and source records attributed to Y Shinohara.

At least 73 records · Page 4Linked to original sources
PubMed2000

Impaired interleukin-2 response of mononuclear cells in Guillain-Barré syndrome.

We studied the production of and response to interleukin-2 (IL-2) by cultured peripheral blood mononuclear cells (PBMC) and the soluble IL-2 receptor levels in 10 patients with GBS (eight men and two women) aged 23-67 years. The first blood sample was obtained within seven days of the onset of neuropathic symptoms, and blood samples were collected serially after treatment with plasma exchange. PBMC from GBS patients were found to produce little IL-2 and to have a low response to IL-2 soon after the onset, but marked improvement was seen within one month, concomitantly with improvement of neuropathic symptoms. Serum soluble IL-2 receptor levels were increased at the onset, but gradually decreased thereafter. Our findings suggest that primary immune response in acute-stage GBS may be downregulated via a decrease in the function of PBMC that had previously been activated by interacting with the antigen.

Adult↗
PubMed2000

Detection of telomerase activity in biopsy specimens for diagnosis of biliary tract cancers.

BACKGROUND: Telomerase activity is detectable in more than 85% of primary cancers. We determined telomerase activity in biopsy specimens obtained from biliary tract cancers to evaluate the clinical application of telomerase activity detection in combination with p53 immunostaining and routine histologic examination. METHODS: Biopsy specimens obtained during percutaneous transhepatic cholangioscopy from 13 patients with cholangiocarcinoma, 3 patients with gallbladder carcinoma, and 4 patients with intrahepatic bile duct stones were evaluated by routine histologic examination, p53 immunostaining, and telomerase activity. Semiquantitative determination of telomerase activity was performed using a fluorescence-based telomeric repeat amplification protocol. RESULTS: Thirteen of 16 specimens of malignant tissue had detectable telomerase activity, whereas no specimen of nonmalignant tissue had detectable telomerase activity. A p53 overexpression was recognized by immunostaining in 9 of 16 samples with cancers. Combining both telomerase activity and p53 overexpression resulted in the detection of all cancer with a sensitivity of 100%. There were no false-positive results by either modality (specificity 100%). CONCLUSIONS: The detection of telomerase activity in biopsy specimens and p53 overexpression in combination with routine histologic examination may improve the diagnosis of biliary tract cancers. (Gastrointest Endosc 2000;52:380-6).

Aged↗
PubMed2000

Irreversible extrusion of the first loop facing the matrix of the bovine heart mitochondrial ADP/ATP carrier by labeling the Cys(56) residue with the SH-reagent methyl methanethiosulfonate.

The effect of the SH-reagent methyl methanethiosulfonate (MMTS) on the ADP/ATP carrier of bovine heart mitochondria was studied under various conditions. MMTS labeled predominately Cys(56) in the first loop facing the matrix (loop M1), and the labeling inhibited ADP transport via the carrier. The transport inhibition was found to be due to fixation of the carrier in the m-state conformation. MMTS labeling was suggested not to affect ADP binding to its major binding site. These features were the same as those of another commonly used SH-reagent, N-ethylmaleimide (NEM). Although the van der Waals volume of the non-hydrogen-bondable methylthio group of MMTS is much smaller than that of the ethylsuccinimide group of NEM, modification of Cys(56) inhibited the interconversion between the m- and c-state conformation. The mechanism by which MMTS inhibited the transport activity is discussed in terms of stabilization of conformation of the loop M1.

Adenosine Diphosphate↗
PubMed2000

Evaluation of pathologic abnormalities of clubfoot by magnetic resonance imaging.

Three-dimensional analyses of clubfoot in infants younger than 1 year of age were done using magnetic resonance imaging in an in vivo study. Twenty-one patients (31 feet) with congenital clubfoot were examined. The average age at examination was 8.6 months (range, 4-12 months). All patients originally were treated using corrective casts. Seventeen feet required complete subtalar release operations and the remaining 14 feet were treated conservatively with various orthoses. Four measurements using magnetic resonance imaging were performed in the transverse and coronal planes as follows: the calcaneus adduction angle, to define the degree of medial rotation of the calcaneus in the transverse plane; the navicular angle, to define the degree of medial displacement of the navicular; the talus neck angle, to define the degree of medial angulation of the talus; and the calcaneus shift index, to define the degree of medial shift of the calcaneus beneath the talar head in the coronal plane. In the results, all four measurements of clubfoot on magnetic resonance imaging were statistically different from those of normal feet. In the surgical group there were statistical differences in the calcaneus adduction angle, the navicular angle, and the calcaneus shift index (including two feet of patients whose parents had rejected proposed treatment), compared with the conservative group, but there was no statistical difference in the talus neck angle. Magnetic resonance imaging could delineate the three-dimensional abnormalities of the tarsal bones in clubfoot and quantitatively evaluate the severity of clubfoot.

Clubfoot↗
PubMed2000

A case of hemangioma accompanied by inflammatory pseudotumor of the spleen.

Both hemangioma and inflammatory pseudotumor (IPT) of the spleen are rare benign mass lesions. Moreover, a splenic hemangioma accompanied by IPT is extremely rare. A 61-year-old woman who suffered from liver cirrhosis had a splenic cavernous hemangioma surrounded by granuloma. The literature on IPT of the spleen has described several possibilities of its causes; however, it is still unknown. This case was accompanied by portal hypertension due to liver cirrhosis, which may cause microrupture of hemangioma resulting in an IPT.

Female↗
PubMed2000

Lymphocyte subset proportions in Guillain-Barré syndrome patients treated with plasmapheresis.

We examined the changes in the proportions of certain T cell subsets in 18 Guillain-Barré syndrome patients treated with plasmapheresis (PP). PP was performed within 8 days after the onset using a continuous-flow blood cell separator or immunoadsorption. The proportions of CD3+, CD4+ and CD4+CD45RA+ cells at the onset were decreased and that of CD19+ was increased compared with those of 25 normal controls. However, the proportions of CD4+CD45R-, CD4+HLADR+, CD4+CD25+ cells and the CD8+ subpopulations were similar in patients and controls. After PP, the altered subsets tended to normalize, particularly in the group that improved after PP.

Adolescent↗
PubMed2000

Stereoselective internal acyl migration of 1beta-O-acyl glucuronides of enantiomeric 2-phenylpropionic acids.

Internal acyl migration reactions of 1beta-O-acyl glucuronides of 2-arylpropionic acids (profens) are of interest because of their possible role in covalent binding to serum proteins and consequent allergic reactions. The stereoselective degradation of 1beta-O-acyl glucuronides of enantiomeric 2-phenylpropionic acids (PAs), the basic structures of profens, in phosphate buffer (pH 7.4) at 37 degrees C, has been investigated using HPLC. Apparent first-order degradation of 1beta-O-acyl glucuronide and the sequential appearance of 2-, 3- and 4-O-acyl isomers were observed for each enantiomer. Acyl migration was observed to predominate over hydrolysis as in the other profen glucuronides. All the positional isomers and anomers were characterized using NMR and HPLC-NMR. The overall degradation half-life of (R)- and (S)-PA glucuronides was 1.8 and 3.3 h, respectively. These results suggest that (R)-PA glucuronide could be more susceptible to covalent binding to proteins via acyl migration than the corresponding antipode. The lability of the (R)-diastereomer over the antipode is consistent with previous reports on other profen glucuronides. Thus, the diastereomeric PA glucuronides are considered to be the best model compounds for the computation of structural physicochemical parameters to control the stereoselective internal acyl migration of profen glucuronides because PA has the simplest chemical structure of all the profens.

Acylation↗
PubMed2000

[Identification and characterization of hexokinase isozyme predominantly expressed in malignant tumor cells].

Tumor cells show a higher glycolytic rate than normal cells. Of glycolytic enzymes, the activity of hexokinase, known as a rate limiting enzyme in glycolysis, is amazingly high in malignant tumor cells. In mammals, four isozymes of hexokinase are expressed but the question which isozyme is responsible for the high hexokinase activity observed in tumor cells was not yet clearly answered. By Northern blot analysis, we found that the type II isozyme, which is only slightly expressed in normal heart, muscle and adipose tissue, was remarkably expressed in malignant tumor cells. We next tried to understand how the expression of type II hexokinase gene is regulated in tumor cells. For this purpose, we first isolated the type II hexokinase gene and characterized its structural features. We further investigated the regulatory mechanisms of the expression of type II hexokinase in tumor cells. Results indicate the potential involvement of a serum responsive factor in the regulation of the expression of type II hexokinase in tumor cells. In addition to the remarkable expression, binding of the type II hexokinase to mitochondria is another characteristic of tumor cells, however, the physiological meaning of hexokinase binding to mitochondria was not yet fully understood. Our results clearly showed that the mitochondria-bound hexokinase utilize mitochondrially generated ATP more preferentially under normal conditions. However, when the rate of extramitochondrial ATP generating system (glycolysis) exceed that of mitochondrial ATP generating system (oxidative phosphorylation), the mitochondria-bound hexokinase utilize extramitochondrial ATP. This result indicates that the hexokinase binding enables a cross talk between oxidative phosphorylation and glycolysis.

Adenosine Triphosphate↗
PubMed2000

Global reduction of cerebral glucose metabolism in persons with symptomatic as well as asymptomatic lacunar infarction.

To clarify the hemodynamic changes in lacunar infarction, we evaluated cerebral glucose metabolism by using positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in patients with asymptomatic and symptomatic lacunar infarction and in persons without cerebral infarction on MRI. Subjects in this study were 27 patients with symptomatic lacunar infarction (SCI group), 73 subjects with asymptomatic lacunar infarction (ACI group), and 134 persons without infarction (NC group). CMRgl in the ACI group was significantly lower than that in the NC group in the cerebral cortex (P < 0.05) and thalamus (P < 0.05). CMRgl in the SCI group was significantly reduced from that in the NC group in the cerebral cortex (P < 0.005), basal ganglia (P < 0.001), thalamus (P < 0.05) and white matter (P < 0.005). The reduction in CMRgl in the SCI group was more severe than that in the ACI group in basal ganglia (P < 0.05) and thalamus (P < 0.05). Our results indicated that glucose metabolism in patients with asymptomatic lacunar infarction is reduced throughout the whole brain as compared with non-infarcted elderly persons. Follow-up and treatment of risk factors if present, may be necessary in such patients.

Aged↗
PubMed2000

Assessment of the metabolic chiral inversion of D-leucine in rat by gas chromatography-mass spectrometry combined with a stable isotope dilution analysis.

The stereoselective pharmacokinetics of leucine enantiomers in rats has been investigated to evaluate the inversion of D-leucine to L-enantiomer. After a bolus i.v. administration of D- or L-[2H7]leucine to rats, blood samples were obtained over 6 h after administration and analyzed by a stereoselective gas chromatography-mass spectrometry method. Racemic [2H3]leucine was used as an internal standard. The method involved methyl esterification and subsequent chiral derivatization with (+)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride to form the diastereomeric amide. The derivatization made possible the separation of leucine enantiomers with good gas chromatographic behavior. Plasma concentration of both D- and L-[2H7]leucine declined biexponentially, with elimination half-lives of 60 and 14 min, respectively. In contrast to the L-enantiomer, the D-enantiomer had a lower systemic clearance. When D-[2H7]leucine was administered, the L-enantiomer was found to rapidly appear in plasma. About 30% of an administered dose of the D-isomer was stereospecifically inverted to the L-enantiomer. There was no measurable inversion of the L- to D-enantiomer. This methodology has made it possible to evaluate the pharmacokinetics of each enantiomer of amino acids and estimate of chiral inversion after administration of D-amino acids.

Animals↗
PubMed2000

[An autopsy case of juvenile neuronal ceroid-lipofuscinosis with dilated cardiomyopathy].

We reported an autopsy case of neuronal ceroid-lipofuscinosis (NCL3) with dilatated cardiomyopathy. A 29-year-old male patient first noticed night-blindness at the age of four years. He was pointed out retinitis pigmentosa at the age of six years and developed ataxia, mental retardation, epilepsy and myoclonus, thereafter. T1 weighted MRI showed diffuse atrophy of the cerebellum, brainstem, and cerebrum, and dilatation of the ventricular system and T2-weighted MRI showed mild high signal intensity in the white matter around the trigones of the lateral ventricles. Autopsy findings showed an abundant accumulation of ceroid-lipofuscin-like lipopigments in most neurons in the central nervous system, and curvilinear bodies and lipofuscin like granules were confirmed by electron microscopy. The heart muscle showed an increase in the accumulation of ceroid-lipofuscin-like lipopigments, severe fibrosis and fatty infiltration in the myocardium. The peculiar point of this case is NCL3 with dilated cardiomyopathy.

Adult↗
PubMed1999

Simultaneous determination of the enantiomers of leucine and [2H7]leucine in plasma by capillary gas chromatography-mass spectrometry.

A method for the stereoselective assay of D- and L-enantiomers of both leucine and [2H7]leucine in rat plasma was developed using gas chromatography-mass spectrometry-selected-ion monitoring. DL-[2H3]leucine was used as an internal standard. The method involved purification by cation-exchange chromatography using BondElut SCX cartridge and derivatization with hydrochloric acid in methanol to form methyl ester followed by subsequent chiral derivatization with (+)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride to form diastereomeric amide. The derivatization made the separation of the leucine enantiomers possible with good gas chromatographic behavior. Quantitation was performed by selected-ion monitoring of the quasi-molecular ions of the diastereomers on the chemical ionization method. The sensitivity, specificity, accuracy and reproducibility of the method were demonstrated to be satisfactory for application to pharmacokinetic studies of leucine enantiomers.

Animals↗
PubMed1999

Functional expression of the tandem-repeated homodimer of the mitochondrial ADP/ATP carrier in Saccharomyces cerevisiae.

The mitochondrial ADP/ATP carrier (AAC) is believed to function as a dimer. To characterize the oligomeric state of the yeast type 2 AAC (yAAC2), we tried to express its tandem-repeated homodimer, in which the C-terminus of the first repeat was fused to the N-terminus of the second repeat, in yeast mitochondria. The tandem dimer was expressed in the mitochondrial membrane at the same level as that of yAAC2, being inserted into the mitochondrial membrane as in yAAC2, and it showed very similar transport activity to that of yAAC2. It was suggested that the two carrier molecules in a dimeric form are located in the membrane facing each other in the same orientation.

Dimerization↗