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Y Arai

Publications and source records attributed to Y Arai.

At least 361 records · Page 20Linked to original sources

Developmental and aging changes in the expression of amyloid precursor protein in Down syndrome brains.

We studied immunohistochemically the expression of beta-amyloid precursor protein (APP) in the frontal lobes of 18 Down syndrome (DS) patients (20 gestation weeks (GW) to 50 years) and 15 controls (17 GW to 50 years) using six purified antibodies against the secretory forms (N-terminal, N-Amy and Amy540), the Kunitz-type protease inhibitor (KPI) domain, residues 1-28 of beta protein (Affi28), and the carboxyl-terminal fragment (Ac) of APP. In the cortex of fetuses, neonates and infants, immunoreactivity for N-Amy and Ac was observed in both neurons and glial cells, and that for Affi28 in glial cells in the subpial layer in both DS patients and controls suggesting the functioning role of APP was a growth factor. This immunoreactivity disappeared in childhood and reappeared in adulthood in only DS patients. The earlier reappearance of those in DS patients from a young adult age than in normal controls may result from a gene dosage effect, since APP is encoded on chromosome 21. The N-Amy, Amy540, Affi28 and Ac immunoreactivity in glial cells in the developing white matter in the both DS patients and controls may be associated with myelination glia. Immunoreactivity for KPI was noted on the tunica media of the arteries from the neonatal period to adulthood in only DS patients. In senile plaques in DS patients, N-terminal and Affi28 immunoreactivity became detectable at the age of 32 years. N-terminal immunoreactivity in the senile plaques was noted along the periphery of the senile plaques, while that for Affi28 was around the amyloid core. Thus, each fragment of APP exhibited a different localization and time course of immunohistochemical expression. The results indicated that APP plays a role in neuronal development and that its earlier reappearance in adult DS patients is associated with the regeneration process related to aging.

Adolescent↗

Developmental immunohistochemistry of growth inhibitory factor in normal brains and brains of patients with Down syndrome.

Growth inhibitory factor, a new metallothioneinlike protein, was investigated at postmortem examination in the brains of 18 patients with Down syndrome ranging in age from 18 weeks gestation to 50 years of age and in 20 age-matched normal controls by developmental immunohistochemistry. In the frontal cortex of both Down syndrome patients and controls, growth inhibitory factor immunoreactivity was localized in the cell bodies and processes of protoplasmic astrocytes from 18 weeks gestation, and these immunoreactive processes formed so dense a meshwork in the gray matter that they outlined neuronal perikarya as negative contours in the brain at age more than 16 years. The number of growth inhibitory factor-immunoreactive astrocytes exhibited a greater increase in layer 3 than in layer 2 in controls from 37 weeks gestation to 7 months of age, although there was no difference in the growth inhibitory factor-positive cell number between layers 2 and 3 in young Down syndrome patients. Therefore, growth inhibitory factor in astrocytes may be correlated with dendritic maturation of neurons. On the other hand, growth inhibitory factor-immunoreactive astrocytes in layer 2, where senile plaques are abundant, were smaller than those in layer 3 in adult Down syndrome patients from age 32 years. When senile plaques began to immunoreact with the amyloid precursor protein, the number of growth inhibitory factor-immunoreactive astrocytes decreased around senile plaques in elderly Down syndrome brains with the Alzheimer type of dementia. On the contrary, the number of glial fibrillary acidic protein-immunoreactive astrocytes around senile plaques increased. This loss of growth inhibitory factor around senile plaques may be correlated with neuronal loss or degeneration and lead to sprouting responses which may be involved in the formation of senile plaques.

Adolescent↗

A complete NotI restriction map covering the entire long arm of human chromosome 11.

BACKGROUND: Human chromosome 11 is one of the autosomes on which many disease genes have been mapped. Many different types of map, including a radiation hybrid map, a genetic map, and an STS-content YAC map, have been constructed for the chromosome. However, a physical map providing accurate physical distances has not yet been established. A chromosome-wide NotI restriction map was constructed to understand the overall feature of the genome organization and to facilitate the positional cloning of disease genes. RESULTS: A complete NotI restriction map of the entire long arm of human chromosome 11 was constructed using linking-clone mapping. This physical map covers 77.6Mb, from a pericentromeric NotI site to the terminus, and provides the most accurate ordering and distance estimation to date. We also mapped 138 sequence markers in the q13 region that have been poorly mapped previously. CONCLUSIONS: The restriction map of the entire long arm of human chromosome 11 is the longest restriction map of the human genome. This mapping has disclosed unique features regarding the organization of the chromosome, indicating that restriction sites of NotI, a CpG-recognition enzyme, are primarily distributed in R (or T) bands and that genetic distance is considerably longer in R (or T) bands than in G bands. The mapping, as well as the dense concentration of mapped markers within the q13 region, should help with positional cloning of the genes associated with various diseases.

Bacteriophage P1↗

The first exon of the rat aldolase C gene is essential for restoring the chromatin structure in transgenic mice.

A 13-kb fragment of the rat aldolase C gene contains sufficient information for gene expression. Transgenic mice carrying the 13-kb fragment showed restoration of chromatin structure and tissue-specific, copy number-dependent expression. To localize the regulatory elements responsible for restoring chromatin structure, several mutated constructs were used to produce transgenic mice. Three activities were examined: recreation of DNase hypersensitive sites, restoration of methylation status, and copy number-dependent expression. Deletions of the 3'-flanking region did not affect those activities. Deletion of seven introns affected the mRNA levels but not the restoration of the chromatin structure. The insertion of the LacZ gene into the first exon of the transgene interfered with both the restoration of the chromatin structure and the copy number-dependent expression in transgenic mice. DNase I footprinting assays revealed that brain-specific factors bind to the sequence disrupted by the LacZ insertion. These results suggest that the sequence in the first exon is essential for restoring the chromatin structure of the rat aldolase C gene.

Animals↗

Prospective evaluation of prostate specific antigen density and systematic biopsy for detecting prostate cancer in Japanese patients with normal rectal examinations and intermediate prostate specific antigen levels.

PURPOSE: To improve the specificity of cancer detection in patients with normal digital rectal examination and intermediate prostate specific antigen (PSA) level, PSA density has been recommended, with biopsy based on a PSA density of 0.15 or more. PSA density is reportedly higher in Japanese men than in white men, because of physiological differences between the 2 races. We prospectively evaluated PSA density as a discriminator of prostate cancer in Japanese men. MATERIALS AND METHODS: We evaluated prospectively 60 consecutive men with normal digital rectal examinations and serum PSA levels of 4.1 to 10.0 ng./ml. enrolled during a 17-month period. All patients underwent transrectal ultrasound guided sextant biopsies, regardless of calculated PSA density and transrectal ultrasound findings. Serum PSA levels were determined by IMx assay. RESULTS: Overall, 8 of 60 men (13%) had prostate cancer. There was no significant difference in mean PSA between those with positive and those with negative biopsies, but the difference was significant in the mean PSA density (mean 0.24 and 0.15, respectively, p < 0.01). Receiver operating characteristics curves for PSA and PSA density demonstrated superior benefit for PSA density in this patient population. A reference PSA density value of 0.19 was chosen because it showed the highest sum of sensitivity and specificity, which gave a sensitivity of 75%, a specificity of 87%, a positive predictive value of 46% and a negative predictive value of 96%. CONCLUSIONS: The results suggest that PSA density improves the specificity of cancer detection in men with a normal digital rectal examination and an intermediate PSA level. Although further study with a larger patient population is needed to obtain a best-fit value, an optimal PSA density cutoff seems to be higher than that recommended in the literature from western countries. Because of possible racial differences in serum PSA and prostate volume, the role of PSA density in Asian men should be studied independently.

Aged↗

Reliability and validity of the Japanese version of the Zarit Caregiver Burden interview.

Despite a rapid increase in disabled elderly in Japan, the burden of the caregiver has not been properly assessed due to a lack of objective measurements. Our study was aimed at adapting and validating the Zarit Caregiver Burden Interview (ZBI) in Japan, which is one of the most widely used measurements for caregivers' burden in the United States. Sixty-six caregivers answered the self-administered questionnaire, involving the Japanese version of the ZBI and questions regarding their caregiving situation. Our study demonstrated that the Japanese version of the ZBI had equally as high reliability and validity as the original version. The Japanese ZBI had a high test-retest reliability (r = 0.76) and internal consistency (Cronbach's alpha = 0.93). The total score of the ZBI was highly correlated with the caregivers' score of the Center for Epidemiologic Studies Depression Scale (CES-D) score (r = 0.50), as well as a single global rating of burden (r = 0.71). It was also shown that demographic distribution of the score of the Japanese version had a similar trend to that of the original version. Caregivers who looked after patients with behavioral disturbances were found to have a significantly higher ZBI score than those who looked after patients without behavioral disturbances, which is consistent with previous findings. It is concluded that the Japanese version of the ZBI can be used to measure feelings of burden of caregivers in the Japanese population and can be used for cross-cultural comparison.

Activities of Daily Living↗

Urinary reconstruction using appendix as a urinary and catheterizable conduit in 12 patients.

BACKGROUND: The appendix vermiformis can provide an excellent urinary conduit or a catheterizable outlet in continent urinary reservoirs in selected cases. We report our clinical experience using the appendix in urinary reconstruction in adult patients. METHODS: A total of 12 patients underwent urinary reconstruction using the appendix. The indications were pelvic malignancies except for 1 patient with neurogenic bladder and difficulty in self-catheterization via urethra. The appendix was used as a catheterizable conduit in 8 patients, and as a urinary conduit in 4 patients. The in situ submucosally embedded method was used in 6 patients and the Mitrofanoff method was used in 2 patients. Follow-up ranged from 3 to 41 months (mean, 22). RESULTS: Early complications occurred in 3 patients (wound infection, false passage and intestinal anasotomotic leak). Late complications occurred in 3 (slight hydronephrosis, ileus, stomal stenosis). Emergent colostomy and pouchstomy with resection of the appendix was performed in the patient with anastomotic leak. The isoperistaltic Kock nipple valve was reconstructed for continence in this case. Prolonged ileus in 1 patient was treated by open surgery. Other complications were managed conservatively. End results were excellent in 8 patients, good in 3, and poor in 1. CONCLUSIONS: The appendix can be used advantageously as an outlet of continent urinary reservoirs or for a urinary conduit when the ureter is too short to reach the skin. Complete continence and easy catheterization can be obtained, and the appendix construction can be used as a urinary conduit instead of the ileal conduit in poor risk patients.

Aged↗

Vitamin B12 deficiency in patients with urinary intestinal diversion.

BACKGROUND: Because vitamin B12 is absorbed exclusively by the terminal ileum, we investigated vitamin B12 deficiency as a potential metabolic complication after urinary intestinal diversion. METHODS: We measured serum levels in patients with Kock pouches (n = 35); Indiana pouches (n = 27); and ileal conduits (n = 25). Serial determinations of serum B12 levels were obtained in 19 patients with kock pouches and 14 patients with Indiana pouches. The dual-isotope Schilling test was performed in 9 patients with Kock pouches and 6 patients with Indiana pouches. RESULTS: No patient had an abnormally low serum B12 level (< 200 pg/mL). Mean (+/-SD) serum B12 levels in patients with the Kock pouch (506 +/- 202 pg/mL) and the Indiana pouch (536 +/- 249 pg/mL) were lower than that in patients with the ileal conduit (727 +/- 391 pg/mL). The mean serum B12 level was not significantly different between patients with and without preoperative irradiation. Serial determinations showed that serum B12 levels in some patients with continent urinary reservoirs were persistently near the lower normal limit, or became progressively lower. Three of the 9 patients (33%) with Kock pouches and 4 of the 6 patients (67%) with Indiana pouches were B12 malabsorbers, although no patients had megaloblastic anemia or neurologic symptoms. CONCLUSIONS: Some patients with continent urinary reservoirs are at risk for vitamin B12 deficiency due to malabsorption. Routine evaluation of serum B12 levels is recommended for all patients with continent urinary reservoirs, and a Schilling test for those with subnormal serum B12 levels.

Absorption↗

Nerve-sparing retroperitoneal lymph node dissection for metastatic testicular cancer.

BACKGROUND: Nerve-sparing techniques are used during retroperitoneal lymph node dissection (RPLND) in patients with early stage testicular cancer to preserve postoperative ejaculatory function. Indications for the procedures have been extended to patients with a postchemotherapy retroperitoneal residual mass without compromising the efficacy of surgery. We report 6 cases diagnosed with metastatic testicular cancer who underwent nerve-sparing RPLND. METHODS: Between January 1994 and March 1996, 6 patients with metastatic testicular cancer underwent nerve-sparing RPLND. Five of these patients received primary chemotherapy and a retroperitoneal residual mass. Four patients underwent complete bilateral RPLND and 2 underwent unilateral template surgery. RESULTS: After a mean follow-up of 18.7 months (range, 8 to 34), there have been no local recurrences and 5 (83%) patients report antegrade ejaculation. CONCLUSION: Nerve-sparing RPLND is applicable for selected patients with metastatic testicular cancer without increasing the risk of local recurrence. Ejaculatory function is preserved in the majority of patients, contributing to the improvement of the quality of life in men who require such surgery.

Adolescent↗

Value of systematic transition zone biopsy in the detection of prostate cancer.

BACKGROUND: We evaluated routine transition zone biopsies for the detection of prostate cancer. METHODS: Systematic sextant transrectal biopsies, including 2 systematic transition zone biopsies (sextant biopsy group), were performed on 196 consecutive patients. Biopsies were based on indications from digital rectal examination and/or a serum PSA level greater than 4.0 ng/mL. During the same period, 21 patients with persistently elevated PSA levels and earlier negative systematic biopsies also had the sextant biopsy (re-biopsy group). The sextant biopsy group was compared with 124 cases in our previous cancer detection program who had systematic quadrant biopsies targeted to the peripheral zone (quadrant biopsy group). RESULTS: Between the sextant and quadrant biopsy groups, the difference in rate of cancer detection was not significant statistically. Of the sextant biopsy group, 64 (33%) demonstrated malignancy, including 9 (4.6%) with cancer found exclusively in the peripheral zone and 55 (28%) both in the peripheral and transition zones. No cancer was found exclusively in the transition zone. Of the re-biopsy group, all 4 cancers (19%) were detected in the transition zone, 2 of them exclusively in the transition zone. CONCLUSION: Routine transition zone biopsies did not increase the detection rate of prostate cancer. Systematic transition zone biopsies proved useful to the patients with persistently elevated PSA values and negative results in previous systematic peripheral zone biopsies.

Aged↗

Sexuality and fertility in long-term survivors of testicular cancer.

PURPOSE: We assessed the impact of different treatment modalities on sexuality and fertility in long-term survivors of testicular cancer. MATERIALS AND METHODS: The sample consisted of 85 testicular cancer patients, of whom 19 had undergone chemotherapy with retroperitoneal lymph node dissection (RPLND), 15 had received chemotherapy only, 42 had received infradiaphragmatic radiotherapy, and nine had received surveillance therapy. The questionnaire reported sexual function, marital status, and issues related to fertility and childbearing. RESULTS: One fourth to one half reported some type of sexual impairment in each group. The only significant difference was that approximately 70% of men with RPLND reported inability of ejaculation and a greater decline in semen volume, which is expected. The most striking finding is that the rates and nature of sexual dysfunction of surveillance patients were similar to other treatment groups, except for ejaculatory function. The highest rates of infertility distress were observed in chemotherapy patients. CONCLUSION: These data suggest that sexual dysfunction and infertility represent the major persisting side effects, even years after diagnosis. The hypothesis that surveillance patients have fewer sexual problems is not upheld in this study.

Adult↗

[Effect of a novel tachykinin NK-2-receptor antagonist, TAC-363, on bronchoconstriction and airway hyperresponsiveness in guinea pigs].

We examined the effect of a novel tachykinin NK-2-receptor antagonist, N alpha-(tert-Butylcarbamoyl)-L-glutaminyl-L-tryptophyl-alpha-aza- phenylalanine 2-benzyloxyethylamide (TAC-363), on hyperventilation- and citric acid-induced bronchoconstriction and neurokinin A (NKA)-, capsaicin- and antigen-induced airway hyperresponsiveness in guinea pigs. The i.v. administration of TAC-363 at doses of 0.01-1 mg/kg inhibited hyperventilation- and citric acid-induced bronchoconstriction in a dose-dependent manner, while FK-888, a tachykinin NK-1-receptor antagonist, did not inhibit hyperventilation-induced bronchoconstriction. NKA-induced airway hyperresponsiveness to acetylcholine was attenuated by i.v. injection of TAC-363, but not by the thromboxane A2 synthetase inhibitor ozagrel and the mast cell stabilizer DSCG. Furthermore, TAC-363 prevented the occurrence of capsaicin- and antigen-induced airway hyperresponsiveness to acetylcholine, while FK-888 did not prevent occurrence of capsaicin-induced airway hyperresponsiveness. In summary, TAC-363 inhibits bronchoconstriction and airway hyperresponsiveness induced by various stimuli. These results suggest that NKA mediates bronchoconstriction and airway hyperresponsiveness. Thus, TAC-363 is expected to be useful in the treatment of airway diseases such as asthma.

Animals↗

The case fatality rate of methicillin-resistant Staphylococcus aureus (MRSA) infection among the elderly in a geriatric hospital and their risk factors.

From April 1991 to March 1993, there were 49 elderly patients with methicillin-resistant Staphylococcus aureus (MRSA) infection in a geriatric hospital in Fukuoka, Japan. The retrospective study was carried out in order to evaluate the various factors which may influence the case fatality rate of MRSA infection among the elderly. Among them, 33 patients (67.3%) died while only 16 patients became culture-negative for MRSA and discharged after recovering from MRSA infection. A univariate analysis revealed that male sex (odds ratio [OR] = 12.25, 95% confidence interval [CI] = 2.80-53.55), hypoalbuminemia (OR = 3.83, 95% CI = 1.11-13.21) and an excessive usage of antibiotics (OR = 6.67, 95% CI = 1.70-26.09) were risk factors for death among the patients with MRSA infection. In a multivariate analysis, male sex and an excessive usage of antibiotics were still risk factors while hypoalbuminemia was not. However, hypoalbuminemina was more common in male patients than female patients (78.3% vs. 42.3%, p < 0.05). These findings suggest that the case fatality rate of MRSA infection may be high and also suggest that the elderly with MRSA infection who had hypoalbuminemia and/or received many antibiotics may have a poor prognosis.

Aged↗

Methicillin-resistant Staphylococcus aureus (MRSA) isolation from pharyngeal swab cultures of Japanese elderly at admission to a geriatric hospital.

The isolation rate of the methicillin-resistant Staphylococcus aureus(MRSA) from pharyngeal swab cultures in Japanese elderly was studied at admission to a geriatric hospital. The subjects were 233 consecutive patients admitted to Kitakyushu Tsuyazaki Hospital from April 1994 to March 1996. The isolation rate of MRSA was 3.0% in the patients admitted from their own homes, 9.7% in those transferred from nursing homes and 14.0% in those transferred from other hospitals. The patients from their own homes were younger than those from nursing homes, the latter being older than those transferring from other hospitals. The patients from their own homes had better activities of daily living(ADL), higher levels of hemoglobin and serum albumin than those from nursing homes or other hospitals. The white blood cell counts, and the proportion of patients with positive c-reactive protein or with fever did not differ among the three groups. Multiple logistic regression analysis revealed that fever and ADL disability were independent risk factors for the isolation of MRSA, and hypoalbuminemia was a risk factor for MRSA isolation in the model using serum albumin instead of ADL score. These results suggest that the lower isolation rate MRSA among patients from their own homes may be partly due to better ADL and nutritional status compared with those from nursing homes or other hospitals.

Aged↗

Localization of heat shock protein in osteoarthritic cartilage.

In osteoarthritic (OA) chondrocytes, expression of 70 kD heat shock protein (HSP70) is enhanced under stress. The HSP70 level is also related to OA severity in humans. In the present study, specimens of OA cartilage were obtained from 14 surgically treated female patients. Their disease severity was evaluated according to Mankin's histological/histochemical grading scores. The ratio of HSP70-positive cells was examined by using immunohistochemistry. As OA became more severe, the ratio of HSP70-positive cells increased in deeper areas from the surface, and there was a positive correlation between the grade and the ratio. Distribution of cells expressing HSP70 mRNA detected by in situ hybridization was similar to the distribution of positive cells in the immunohistochemistry. It was presumed that HSP70 plays a role in cell protection from stress, and that mechanical and biological factors which are related to the enhancement of HSP70 expression, have a considerable influence on OA progressions.

Aged↗

[Lipid and lipoprotein profile of Japanese centenarians--high prevalence of hypo beta lipoproteinemia].

To study the relationship between lipids and longevity, we examined the level of serum lipids and apolipoproteins, and the susceptibility of low density lipoprotein (LDL) to oxidation of 45 centenarians (15 men, 30 women, mean age 101.1 +/- 1.4) living in the Tokyo metropolitan area. The average levels of total cholesterol (TC), of LDL-C of high-density lipoprotein cholesterol (HDL-C), and of apolipoproteins A1 and B were significantly lower in centenarians than in healthy middle-aged controls. The frequency of hypobeta-lipoproteinemia (apoB < 60 mg/dl) in centenarians was almost ten times as high as in controls. The time course of copper-mediated LDL, oxidation (assessed by monitoring 234 nm diene absorption (lag time)) did not significantly differ between the two groups. Analysis of LDL subfractions by non-denaturated gradient-gel electrophoresis showed a predominance of large, buoyant LDL particles (pattern A) in 75%, and a predominance of small dense LDL particles (pattern B) in 25% of centenarians. We also assessed activities of daily living (ADL) and cognitive function in the centenarians. Centenarians were divided into two groups according to the median ADL score, and were classified into five groups with a scale clinical dementia. In subjects with good ADL scores, the mean concentration of HDL-3-C was significantly higher than in those with poor ADL scores. Average levels of HDL-C were also significantly lower in subjects with moderate or severe dementia than in those with normal cognitive function. These findings suggest that centenarians have protective phenotypes of lipids and lipoproteins that protect them from atheroscierosis.

Activities of Daily Living↗

[Tokyo Centenarian Study. 4. Apolipoprotein E phenotype in Japanese centenarians living in the Tokyo Metropolitan area].

To examine the relationship between apolipoprotein E (apoE) phenotype and life span, we measured the frequently of the apoE phenotype and allele in 54 Japanese centenarians who lived in the Tokyo metropolitan area in 1994, 1995, and 1996. The control group consisted of 973 subjects, 883 healthy volunteers who were described previously and 90 healthy people who came to the Keio health consulting center. The apoE phenotypes in the centenarians was 2 E2/E2 (3.7%), 5 E2/E3 (9.3%), 38 E3/E3 (70.4%), and 9 3E/E4 (16.7%). No other phenotype was observed. In the control group, the phenotypes were 2 E2/E2 (0.2%), 57 E2/E3 (5.9%) 712 E3/E3 (73.2%), and 179 E3/E4 (18.4%). The frequency of E2 was higher in the centenarians. The frequencies of the apoE allele in the centenarians and the control subjects were epsilon 2 8.3% vs. 3.5%, epsilon 3 83.3% vs. 85.4%, and epsilon 4 8.3% vs. 10.9%. The frequency of the apoE allele differed significantly between centenarians and control subjects (chi 2 = 6.84, p = 0.033). Levels of serum cholesterol and apolipoprotein B were significantly lower in the E2/E2 + E2/E3 centenarians. Studies of the frequency of the apoE allele in Japanese, French, and Finnish subjects showed that epsilon 2 is more frequent and epsilon 4 is less frequent in centenarians. These data show the apoE phenotype may affect life span: epsilon 2 is positively and epsilon 4 is negatively associated with longevity.

Aged↗