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Biomedical subjects

T Kinoshita

Publications and source records attributed to T Kinoshita.

At least 163 records · Page 9Linked to original sources

Predictors of severity of behavioral disturbance among community-dwelling elderly individuals with Alzheimer's disease: a 6-year follow-up study.

To clarify which baseline factors, including apolipoprotein E (ApoE) genotyping and caregiver characteristics, predict the future severity of behavioral disturbance among community-dwelling elderly with Alzheimer's disease (AD), we conducted a longitudinal study for up to 6 years. Fourteen kinds of behavioral disturbance were evaluated. Analyses using data from 62 subjects with at least three annual assessments revealed that the baseline severity of behavioral disturbance was the strongest predictor of future severity, followed by baseline stage of dementia or use of support services. However, ApoE epsilon4 had only a marginal effect at most. The behavioral disturbances examined in the present study appear to be innately determined phenomena rather than merely representing stages of AD.

Aged↗

Application of short tandem repeat of genomic DNA and mitochondrial DNA for identification of mixed-up tissue specimens.

Deoxyribonucleic acid (DNA) typing methods, short tandem repeat of genomic DNA and mitochondrial DNA with the use of polymerase chain reaction amplification, were applied to formalin-fixed, paraffin-embedded tissues submitted for diagnosis, to identify and sort out mixed-up tissue specimens. These techniques were found to be reliable, reproducible and specific for personal identification, and thus to eliminate the need for further examinations and to prevent unnecessary surgery.

Aged↗

Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and ras pathways during hepatic development.

We recently demonstrated that oncostatin M (OSM) in the presence of glucocorticoid promotes development of fetal hepatic cells in a primary culture system. Our results also suggested that OSM transduces differentiation signals through gp130, a common subunit of the interleukin (IL)-6 family cytokine receptors. However, an essential downstream pathway required for hepatic development remains unknown. To address this issue, we expressed signal molecules by a retroviral expression vector in primary fetal hepatic cells and investigated a signaling pathway essential for OSM-mediated hepatic development. Expression of a dominant-negative form of STAT3 (DeltaSTAT3), but not DeltaSTAT5, suppressed differentiated phenotypes of hepatocytes induced by OSM. On the other hand, dominant-negative forms of Ras (RasN17) and SHP-2(C463A) rather augmented the expression of hepatic differentiation markers, suggesting that the Ras pathway negatively regulates hepatic development. Consistently, expression of a constitutively activated form of Ras (RasV12) inhibited cellular responses to OSM. Our results indicate that STAT3 is an essential signaling component for OSM-induced hepatic development, while activation of Ras appears to negatively regulate this process. Thus, retrovirus-mediated gene transfer is an effective means to analyze function of a gene in primary fetal hepatic culture.

Animals↗

Correlation of in vitro autofluorescence endoscopy images with histopathologic findings in stomach cancer.

BACKGROUND AND STUDY AIMS: There is increasing interest in the use of autofluorescence endoscopic imaging systems for the detection of malignancies in the gastrointestinal tract. The purpose of this study was to investigate the autofluorescent color of cancer lesions, and the detection rate of cancer areas using an autofluorescence endoscopic imaging system. Concurrent histopathologic examination was used for comparison. PATIENTS AND METHODS: This study involved a total of 50 stomach cancer patients (with a total of 61 lesions) undergoing surgery. Immediately after the resection, each lesion was observed using an autofluorescence endoscopic imaging system (LIFE-GI system, Light-Induced Fluorescence Endoscopy in the Gastrointestinal Tract). A total of 429 evaluation points in the specimens were selected according to tumor size. The images obtained in this way were assessed by comparison with histopathologic findings in terms of depth of invasion, thickness of the mucosa that had been invaded by cancer cells, and the histologic type of each cancer. RESULTS: Detection with the LIFE-GI system was possible in 58 of the 61 stomach cancer lesions (95.1%). When examined in detail with reference to sampling points, the detection rates of cancer areas according to depth of cancer cell invasion were 57.5 % for invasion to the mucosa, 74.3 % for invasion to the submucosa, and 88.1% for invasion to the muscularis propria or deeper. The detection rates increased as the depth of invasion increased, and they increased significantly as the mucosa invaded became thicker. Detection rates according to histologic type were 82% for differentiated cancer, and 61% for undifferentiated cancer. Most of the cancer areas appeared dark red. Light blue, brilliant red, and white areas were also observed. CONCLUSIONS: Mucosal thickening as a result of cancer cell invasion had a large impact on the detection rate of the LIFE-GI system. As a result, this method may not be useful for the detection of undifferentiated cancer, which may invade in a more dispersed manner, without altering the mucosal thickness.

Adult↗

Endoscopic surgery for a parathyroid functioning adenoma resection with the neck region-lifting method.

Recently, endoscopic surgery has been applied to cervical exploration. We have developed new techniques for endoscopic neck surgery. We reported on a 53-year-old Japanese man with functioning parathyroid adenoma resected by endoscopic surgery with a neck region-lifting method. A 10-mm midline trocar for the endoscope and two 5-mm lateral trocars were inserted from the anterior chest wall to avoid neck scars. There were no intraoperative complications. The incisions were completely covered by the patient's undergarments.

Adenoma↗

Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma.

BACKGROUND: Mass-forming type cholangiocarcinoma is a distinct from of cholangiocellular carcinoma, with pathologic and biologic behavior different from those of other types. The clinical consequences of these differences have never been clarified. METHODS: Fifty-two consecutive patients (32 men and 20 women, mean age 62 years) with mass-forming type cholangiocarcinoma that had been treated with curative surgical resection between 1980 and 1998 were retrospectively evaluated. Long-term survival and disease-free survival were calculated, and univariate and multivariate analysis of various prognostic factors was conducted. RESULTS: The 30-day postoperative mortality rate was 2%, and the overall and disease-free 5-year survival rates were 36% and 34%, respectively. Univariate analysis identified 5 significant risk factors for overall survival: surgical margin, lymph node metastasis, lymph node dissection, vascular invasion, and left-side location of the main tumor. Two risk factors were identified for disease-free survival: surgical margin and lymph node metastasis. Multivariate analysis confirmed that surgical margin, lymph node metastasis, and vascular invasion were independently significant variables for overall survival. CONCLUSIONS: This is the first reported study on the effectiveness of liver resection for the treatment of mass-forming type cholangiocarcinoma, showing that surgical therapy can prolong survival if local radicality can be achieved and lymph-node metastases are absent.

Adult↗

Intrahepatic inflow areas of the drainage vein of the gallbladder: analysis by angio-CT.

BACKGROUND: The drainage veins of the gallbladder (cystic veins) are important hepatic metastatic routes of gallbladder cancer. We studied the cystic vein inflow portions of the intrahepatic vessels by computed tomography during angiography (angio-CT). METHODS: The subjects were 27 unoperated pancreatic-biliary patients. After superselective catheterization of the cystic artery, angio-CT was performed, and cystic veins and sinusoidal filling were visualized. We identified the cystic vein inflow routes and the vessels they fed. RESULTS: We found 72 cystic veins in 26 patients. All cystic veins flowed into the intrahepatic portal branches or sinusoids. The cystic veins took either of two routes: one into the liver through the hepatic hilum (17 patients, 21 veins), taken mainly by the portal branch for subsegment 4a (P4a), the anterior portal branch, and the umbilical portion of the portal branch; and the other through the hepatic bed (23 patients, 51 veins), taken mainly by S4a sinusoid, S5 sinusoid, P4a, and P5. CONCLUSIONS: Angio-CT is useful for detecting the cystic vein inflow portions of the intrahepatic vessels. It makes possible identification of areas where there is a possibility for micrometastasis of the gallbladder cancer.

Adult↗

Gaa1p and gpi8p are components of a glycosylphosphatidylinositol (GPI) transamidase that mediates attachment of GPI to proteins.

Many eukaryotic cell surface proteins are anchored to the membrane via glycosylphosphatidylinositol (GPI). The GPI is attached to proteins that have a GPI attachment signal peptide at the carboxyl terminus. The GPI attachment signal peptide is replaced by a preassembled GPI in the endoplasmic reticulum by a transamidation reaction through the formation of a carbonyl intermediate. GPI transamidase is a key enzyme of this posttranslational modification. Here we report that Gaa1p and Gpi8p are components of a GPI transamidase. To determine a role of Gaa1p we disrupted a GAA1/GPAA1 gene in mouse F9 cells by homologous recombination. GAA1 knockout cells were defective in the formation of carbonyl intermediates between precursor proteins and transamidase as determined by an in vitro GPI-anchoring assay. We also show that cysteine and histidine residues of Gpi8p, which are conserved in members of a cysteine protease family, are essential for generation of a carbonyl intermediate. This result suggests that Gpi8p is a catalytic component that cleaves the GPI attachment signal peptide. Moreover, Gaa1p and Gpi8p are associated with each other. Therefore, Gaa1p and Gpi8p constitute a GPI transamidase and cooperate in generating a carbonyl intermediate, a prerequisite for GPI attachment.

Acyltransferases↗

Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma.

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.

Aged↗

Cervical pedicle screw insertion: assessment of safety and accuracy with computer-assisted image guidance.

We used a commercially available computer-assisted image-guidance system for cervical pedicle screw insertion in both the laboratory and in a preliminary clinical setting. Nine plastic cervical spine models (C2-C7) were used in the laboratory test. The StealthStation was used to create the preoperative plan for each screw such that it would be inserted down the center of the pedicle, parallel to the long axis. Using a light-emitting diode-equipped drill guide, 2-mm holes were drilled in 108 pedicles. A total of 108 pedicle holes were drilled. The mean trajectory deviation from the surgical plan in the axial plane was 1.7+/-1.7 degrees (range, 0 to 8 degrees), and the mean deviation of the position of the hole was 1.7+/-0.6 mm (range, 0.1 to 2.9 mm). Eighty-three drill holes (76.9%) were contained within the pedicles, whereas partial cortical perforation was noted in 25 pedicles (23.1%). In the clinical setting, 36 cervical pedicle screws were inserted in nine patients using the image-guided system. Within the limits of imaging artifact, all 36 pedicle screws appear to have been inserted accurately by postoperative computed tomographic examination. No neurologic or vascular complications were encountered.

Aged↗

Thoracic epidural desmoplastic fibroma.

Desmoplastic fibroma is a relatively uncommon tumor and rarely involves the spine. The authors describe a 20-year-old woman with a thoracic epidural desmoplastic fibroma treated by complete resection and posterior spinal fusion. Four years after surgery, neither the tumor nor clinical symptoms have recurred. Thus, complete resection is considered necessary to treat this tumor.

Adult↗

Regional differences in cerebral vascular response to PaCO2 changes in humans measured by positron emission tomography.

Hypercapnia and hypocapnia produce cerebral vasodilation and vasoconstriction, respectively. However, regional differences in the vascular response to changes in Paco2 in the human brain are not pronounced. In the current study, these regional differences were evaluated. In each of the 11 healthy subjects, cerebral blood flow (CBF) was measured using 15O-water and positron emission tomography at rest and during hypercapnia and hypocapnia. All CBF images were globally normalized for CBF and transformed into the standard brain anatomy. t values between rest and hypercapnia or hypocapnia conditions were calculated on a pixel-by-pixel basis. In the pons, cerebellum, thalamus, and putamen, significant relative hyperperfusion during hypercapnia was observed, indicating a large capacity for vasodilatation. In the pons and putamen, a significant relative hypoperfusion during hypocapnia, that is, a large capacity for vasoconstriction, was also observed, indicating marked vascular responsiveness. In the temporal, temporo-occipital, and occipital cortices, significant relative hypoperfusion during hypercapnia and significant relative hypoperfusion during hypocapnia were observed, indicating that cerebral vascular tone at rest might incline toward vasodilatation. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve by hypercapnia and in the correction of CBF measurements for variations in subjects' resting Paco2.

Aged↗

Mutations in the FIE and MEA genes that encode interacting polycomb proteins cause parent-of-origin effects on seed development by distinct mechanisms.

In flowering plants, two cells are fertilized in the haploid female gametophyte. Egg and sperm nuclei fuse to form the embryo. A second sperm nucleus fuses with the central cell nucleus, which replicates to generate the endosperm, a tissue that supports embryo development. The FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) and MEDEA (MEA) genes encode WD and SET domain polycomb proteins, respectively. In the absence of fertilization, a female gametophyte with a loss-of-function fie or mea allele initiates endosperm development without fertilization. fie and mea mutations also cause parent-of-origin effects, in which the wild-type maternal allele is essential and the paternal allele is dispensable for seed viability. Here, we show that FIE and MEA polycomb proteins interact physically, suggesting that the molecular partnership of WD and SET domain polycomb proteins has been conserved during the evolution of flowering plants. The overlapping expression patterns of FIE and MEA are consistent with their suppression of gene transcription and endosperm development in the central cell as well as their control of seed development after fertilization. Although FIE and MEA interact, differences in maternal versus paternal patterns of expression, as well as the effect of a recessive mutation in the DECREASE IN DNA METHYLATION1 (DDM1) gene on mutant allele transmission, indicate that fie and mea mutations cause parent-of-origin effects on seed development by distinct mechanisms.

Arabidopsis↗

Crystallization and preliminary X-ray analysis of cephalosporin C acylase from Pseudomonas sp. strain N176.

Cephalosporin C acylase from Pseudomonas sp. strain N176, a heterodimer of 25 and 58 kDa, has been crystallized using polyethylene glycol 6000 as precipitant. The crystals are orthorhombic and have unit-cell parameters a = 141.41, b = 192.10, c = 80.75 A. They belong to space group P2(1)2(1)2(1) and diffract to at least 2.7 A resolution. Calculations indicate that there are two heterodimers in the asymmetric unit. The structure is being solved by molecular replacement using penicillin G acylase from Escherichia coli as a search model and by multiple isomorphous replacement.

Crystallization↗

Effects of artefacts on scanning laser polarimetry of retinal nerve fibre layer thickness measurement.

AIMS: To investigate the effects of artefacts on scanning laser polarimetry of the retinal nerve fibre layer. METHODS: Six eyes of six normal volunteers and an artificial nerve fibre layer were examined using the nerve fibre analyser II. The retinal nerve fibre layer thickness (RNFLT) was measured in each of four 90 degree quadrants, superior (S), temporal (T), inferior (I), and nasal (N), at 1.5 disc diameters from the disc margin. Study 1: Measurement in normal eyes. The amount of maximum error in RNFLT measurements was investigated as follows: (1) the intensity setting of the laser beam was changed to be as weak as possible or to be as strong as possible; (2) the intentional offsets of the laser beam axis in relation to the pupil were made in four directions; (3) the eye was rotated by shifting the head 45 or 90 degrees; (4) the right eye was measured by moving it to the left eye position on the head rest. Study 2: Measurements on an artificial nerve fibre layer. The birefringence measurements were confirmed with a plastic disc, which has a radial arrangement of birefringence. The plastic disc with black paper was fixed at the right eye position or the left eye position on the head rest. The retardation of the laser beam by the plastic disc on the black paper was measured. The retardation of the plastic disc was checked by an automatic birefringence evaluation system (ABR-10A, Uniopt Co, Ltd, Shizuoka). RESULTS: Study 1: The effects of the rotated eye and the measurement of the opposite eye position were significant. The eyes rotated 90 degrees showed quite a different pattern in which the thicker and thinner locations of the RNFLT are switched. The nasal RNFLT of the baseline and the 90 degree rotated eye are 41.9 (SD 6.0) microm and 122.5 (11.2) microm, respectively (p<0.0001, Scheffe multiple comparison test). Study 2: The uniform retardation of the plastic disc was observed with the ABR-10A. The NFA detects the retardation of the plastic disc which the retardation map showed as a double humped pattern. CONCLUSIONS: Study 2 indicated that the amount of corneal compensation was not small. The cause of significant influences by the rotated eyes and right eyes measurement in left eye position were thought to be incorrect corneal compensation. To increase the diagnostic ability of SLP, an improved compensation of the cornea is thought to be important.

Adult↗

Effect of acute hypoxia on vasopressin release and intravascular fluid during dynamic exercise in humans.

To test the hypothesis that acute hypoxia does not modify the relationship between plasma vasopressin concentration ([AVP](p)) and plasma osmolality (P(osmol)) during exercise and that the increase in [AVP](p) during exercise is due mainly to the exercise intensity-dependent increase in P(osmol), we examined [AVP](p) during a graded exercise in a hypoxic condition (13% O(2), N(2) balance) in seven healthy male subjects. A graded exercise in a normoxic condition on a separate day served as the control. Hypoxia reduced peak aerobic power (VO(2 peak)) by 32.4 +/- 2.7%. Blood samples obtained during rest and at around 25, 45, 65, 80, and 100% of VO(2 peak) of each of the respective conditions were used for analyses of intravascular water and electrolyte balance. The pattern of the changes in fluid and electrolyte balance in response to percent VO(2 peak) was similar between the two conditions. Plasma volume decreased linearly as percent VO(2 peak) increased while P(osmol) increased in a curvilinear fashion with a steep increase occurring at above approximately 66% VO(2 peak). Above this relative exercise intensity, plasma sodium, potassium, and lactate concentrations also increased, whereas plasma bicarbonate concentration decreased. Thus transvascular fluid movement at above approximately 66% VO(2 peak) was due to the net efflux of hypotonic fluid out of the vascular space in both conditions. The relationship between [AVP](p) and P(osmol) during exercise in response to relative exercise intensity was similar between the two conditions. The results indicate that acute mild hypoxia itself has no direct effect on vasopressin release, and it does not modify the relationship between [AVP](p) and P(osmol) during exercise. The results also support the hypothesis that exercise-induced vasopressin release is primarily stimulated by increased P(osmol) produced by hypotonic fluid movement out of the vascular space in a relative exercise intensity-dependent manner.

Acute Disease↗

Assessment of lacunar hemorrhage associated with hypertensive stroke by echo-planar gradient-echo T2*-weighted MRI.

BACKGROUND AND PURPOSE: Echo-planar gradient-echo T2*-weighted MR imaging (GRE-EPI) may detect hypointense lesions representing microhemorrhages with high sensitivity. The aim of this study was to evaluate the effectiveness of GRE-EPI for detecting old lacunar hemorrhages in hypertensive patients with stroke. METHODS: GRE-EPI was performed with a 1.5-T MRI system in 198 hypertensive patients with stroke (130 patients with hemorrhagic stroke and 68 patients with multiple lacunar stroke) and 66 age-matched healthy elderly individuals. RESULTS: Concomitant hypointense foci were found in 84 (66%) patients with hemorrhagic stroke, 46 (68%) patients with multiple lacunar stroke, and 3 (5%) healthy elderly individuals. These hypointense foci were noted in the lentiform nucleus in 61 (47%) patients with hemorrhagic stroke, in the caudate nucleus in 9 (7%) patients, in the thalamus in 54 (42%) patients, in the corticosubcortical region in 57 (44%) patients, in the brain stem in 40 (34%) patients, and in the cerebellum in 32 (25%) patients. CONCLUSIONS: GRE-EPI is effective for the detection of lacunar hemorrhages induced by hypertension.

Acute Disease↗