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Biomedical subjects

S Hayasaka

Publications and source records attributed to S Hayasaka.

At least 19 recordsLinked to original sources
PubMed2006

Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI.

OBJECTIVES: To test if arterial spin labeling (ASL) MRI could detect a pattern of hypoperfusion in frontotemporal dementia (FTD) vs cognitively normal (CN) control subjects; to determine the regional difference of perfusion between FTD and Alzheimer disease (AD); and to determine whether hypoperfusion in FTD correlates with cognitive impairment. METHODS: We included 21 patients with FTD, 24 patients with AD, and 25 CN subjects in this cross-sectional MRI study. All subjects had MRI scans including T1-weighted structural images and ASL-MR images. RESULTS: ASL-MRI detected a pattern of hypoperfusion in right frontal regions in patients with FTD vs CN subjects, similar to PET and SPECT. FTD had higher perfusion than AD in the parietal regions and posterior cingulate. Frontal hypoperfusion in FTD correlated with deficits in judgment and problem solving. Adding frontal perfusion to gray matter (GM) atrophy significantly improved the classification of FTD from normal aging to 74%, and adding parietal perfusion to GM atrophy significantly improved the classification of FTD from AD to 75%. Combining frontal and parietal lobe perfusion further improved the classification of FTD from AD to 87%. CONCLUSION: Frontotemporal dementia and Alzheimer disease display different spatial distributions of hypoperfusion on arterial spin labeling MRI. With further development and evaluation, arterial spin labeling MRI could contribute to the differential diagnosis between frontotemporal dementia and Alzheimer disease.

Adult↗
PubMed2001

Transport of 7-ethyl-10-hydroxycamptothecin (SN-38) by breast cancer resistance protein ABCG2 in human lung cancer cells.

Overexpression of breast cancer resistance protein (BCRP) ABCG2 reportedly confers cancer cell resistance to camptothecin-based anticancer drugs, such as topotecan and 7-ethyl-10-hydroxycamptothecin (SN-38: the active metabolite of irinotecan). We have recently shown that SN-38-selected PC-6/SN2-5H human lung carcinoma cells overexpressed BCRP with the reduced intracellular accumulation of SN-38 and SN-38-glucuronide (S. Kawabata et al., Biochem. Biophys. Res. Commun. 280, 1216-1223, 2001). In the present study, we have examined whether BCRP transports SN-38 and/or SN-38-glucuronide in vitro, by using plasma membrane vesicles from the parental PC-6 and resistant PC-6/SN2-5H cells, where SN-38 and SN-38-glucuronide accumulation in membrane vesicles was measured by HPLC. Both SN-38 and SN-38-glucuronide were ATP-dependently transported into membrane vesicles prepared from PC-6/SN2-5H cells, whereas no transport activity was observed in membrane vesicles from PC-6 cells. The kinetic parameters of the transport observed in PC-6/SN2-5H vesicles were K(m) = 4.0 microM, V(max) = 714 pmol/mg/min for SN-38 and K(m) = 26 microM, V(max) = 833 pmol/mg/min for SN-38-glucuronide. These findings suggest that BCRP expressed in PC-6/SN2-5H cells transports both SN-38 and SN-38-glucuronide with a higher affinity toward SN-38.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

Psychosocial characteristics of individuals with non-stage IV melanoma.

PURPOSE: Melanoma is the fastest growing solid tumor among men and women and accounts for 79% of skin cancer-related deaths. Research has identified that distress is frequently associated with a diagnosis of cancer and may slow treatment-seeking and recovery, increasing morbidity and even mortality through faster disease course. Given that the 5-year survival rates for individuals with melanoma are determined primarily by the depth and extent of spread, distress that interferes with seeking treatment has the potential to be life-threatening. PATIENTS AND METHODS: The current study was designed to identify levels of distress present in individuals seeking treatment at a large, Midwestern, multidisciplinary melanoma clinic. It also focused on determining the quality of life, level of anxiety, and coping strategies used by individuals with melanoma before treatment. Given that the course of treatment and outcome for patients with stage IV disease is vastly different from that of patients with stages I to III disease, they were excluded from the study. RESULTS: Results indicated that most individuals who are presenting to a melanoma clinic do not report a clinically significant level of distress. However, there is some variability in this, with 29% of patients reporting moderate to high levels of distress. Moreover, analyses suggest that distressed individuals are more likely to use maladaptive coping strategies, such as escape-avoidance coping, and to have poorer quality of life. CONCLUSION: Although most individuals do not present with significant levels of distress, a significant minority are distressed and rely more heavily on coping strategies that do not benefit them. Such individuals would likely benefit most from psychological intervention.

Adaptation, Psychological↗
PubMed2001

Heterozygous 17-bp deletion in the forkhead transcription factor gene, FOXL2, in a Japanese family with blepharophimosis-ptosis-epicanthus inversus syndrome.

We examined mutations in the forkhead transcription factor gene, FOXL2, in three members a Japanese family with autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and in 100 healthy controls. The FOXL2 was analyzed by direct genomic sequencing. A novel 17-bp deletion at nucleotides 1092-1108 in FOXL2 was found in the three affected patients. No mutation was found in any of the 100 healthy controls. The 17-bp deletion in FOXL2 may be involved in the pathogenesis of BPES in Japanese patients.

Adult↗
PubMed2001

Aqueous flare elevation induced by transcorneal application of highly selective agonists for prostaglandin E2 receptor subtypes in pigmented rabbits: effect of tetramethylpyrazine.

We examined the disruptive effect of highly selective agonists for prostaglandin E2 receptor subtypes (EP1, EP2, EP3 and EP4) on the blood-aqueous barrier, and evaluated the inhibitory effect of tetramethylpyrazine, an active component of Ligusticum wallichii, on the elevation of aqueous flare induced by the EP agonists in pigmented rabbits. Highly selective EP agonists (ONO-DI-004, EP1 agonist; ONO-AE1-259-01, EP2 agonist; ONO-AE-248, EP3 agonist; ONO-AE1-329, EP4 agonist) at 12.5 to 250 microg/ml were transcorneally administered to the eyes of pigmented rabbits using a glass cylinder. Animals were pretreated intravenously with tetramethylpyrazine (10 or 30 mg/kg) 30 minutes before application of the EP2 or the EP4 agonist. Aqueous flare was measured using a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. After administration of ONO-AE1-259-01 or ONO-AE1-329, aqueous flare increased and then gradually decreased. ONO-DI-004 and ONO-AE-248 had almost no effect on aqueous flare elevation. The AUC of eyes in rabbits pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was significantly smaller than that of eyes in rabbits treated with ONO-AEI-259-01 alone. The AUC of eyes in rabbits pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was not significantly smaller than that of eyes in rabbits treated with ONO-AEI-329 only. The results indicated that EP2 and EP4 agonists induced aqueous flare elevation in pigmented rabbits, and that tetramethylpyrazine inhibited the aqueous flare elevation induced by the EP2 agonist but did not suppress the elevation induced by the EP4 agonist.

Animals↗
PubMed2001

Ocular changes after intravitreal injection of methanol, formaldehyde, or formate in rabbits.

We evaluated the effects of intravitreal injection of methanol, formaldehyde, or formate on rabbit eyes. One hundred microl of 1% methanol, 1% or 0.1% formaldehyde, or 1% formate was injected in the vitreous cavity of the right eyes of rabbits. The eyes were examined by biomicroscopy and ophthalmoscopy weekly. One month after injection, the eyes were enucleated and examined histologically. One week after treatment the animals that received 0.1% formaldehyde showed retinal vessel dilation, and the rabbits that received 1% formaldehyde showed mild posterior subcapsular cataract and retinal vessel dilation and haemorrhages. One month after treatment, the animals that received 0.1% or 1% formaldehyde developed mild posterior subcapsular cataract and retinal lesions. Animals that received 1% methanol or 1% formate showed nearly normal optical media and fundi. Histologically disorganized retina and optic nerve were seen in eyes that received 0.1% or 1% formaldehyde. Eyes that received 1% methanol or 1% formate appeared histologically normal. Our findings indicate that intravitreal injection of formaldehyde causes retinal and optic nerve damage, while methanol and formate are not or less toxic to ocular tissues.

Animals↗
PubMed2001

Effects of traditional Sino-Japanese herbal medicines on aqueous flare elevation after small-incision cataract surgery.

We evaluated prospectively the effects of traditional Sino-Japanese herbal medicines on elevation of aqueous flare. Fifty-four patients with age-related cataract undergoing phacoemulsification with intraocular lens implantation were studied. In the control group, 20 patients received no herbal medicine. In the treated groups, 14 patients were given Orengedoku- to (Huanglian-Jie-Du-Tang in Chinese) granules (7.5 g daily), 10 patients were given Kakkon-to (Ge-Gen-Tang in Chinese) granules (7.5 g daily), and 10 patients were given Sairei-to (Cai-Ling-Tang in Chinese) granules (9.0 g daily), for 3 days before surgery, the day of surgery, and for 7 days after surgery. Aqueous flare was measured before and after surgery. The differences in preoperative flare intensities among the four groups were not significant. In the control group, the flare was 29.4 photon counts/msec on day 1, and then gradually decreased. The flare intensities on days 1, 3, and 5 in the Orengedoku-to and Kakkon-to groups were significantly lower than in the control group. The flare intensities in the Sairei-to group were the same as those of the controls. Oral administration of Orengedoku-to and Kakkon-to decreased aqueous flare elevation after small-incision cataract surgery. Sairei-to had no effect on the elevation.

Administration, Oral↗
PubMed2001

Peroral infectivity of non-occluded viruses of Bombyx mori nucleopolyhedrovirus and polyhedrin-negative recombinant baculoviruses to silkworm larvae is drastically enhanced when administered with Anomala cuprea entomopoxvirus spindles.

Non-occluded viruses (NOVs) of Bombyx mori nucleopolyhedrovirus (BmNPV) are poorly infectious to silkworm larvae when administered by peroral inoculation, although they are highly infectious when injected into the insect haemocoel. In the present study, it is demonstrated that NOVs of BmNPV became highly infectious even through peroral inoculation when administered with spindles (proteinaceous structures) of Anomala cuprea entomopoxvirus (AcEPV). Marked enhancement of peroral infectivity of NOVs by AcEPV spindles (nearly 1000-fold higher in the strongest case) was observed in all growth stages of silkworm larvae tested (2nd to 5th instar). Similarly, peroral infectivity of polyhedrin-negative recombinants of BmNPV, which do not produce polyhedra, was also enhanced remarkably by AcEPV spindles. In contrast, spheroids (proteinaceous structures containing AcEPV virions) did not enhance the peroral infectivity of either NOVs or the recombinant BmNPV in silkworm larvae.

Animals↗
PubMed2001

Effects of Orengedoku-to and Senkanmeimoku-to, traditional herbal medicines, on the experimental elevation of aqueous flare in pigmented rabbits.

We investigated the effects of Orengedoku-to (Huanglian-Jie-Du-Tang in Chinese) and Senkanmeimoku-to (Xygan-Ming-Mu-Tang in Chinese), traditional herbal medicines, on experimantal elevation of aqueous flare in pigmented rabbits. To produce the elevation of aqueous flare in rabbits, prostaglandin E2 (PGE2) was applied to the cornea with use of a glass cylinder, or lipopolysaccharides (LPS) were injected into the ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.7%, 0.2% or 0.07% (w/w) Orengedoku-to, or 2%, 0.6% or 0.2% (w/w) Senkanmeimoku-to for 5 days. Aqueous flare was measured with a laser flare-cell meter. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% Senkanmeimoku-to did suppress significantly (P < 0.05) elevation of aqueous flare induced by PGE2. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% or 0.6% Senkanmeimoku-to significantly suppressed (P < 0.001) elevation of aqueous flare induced by LPS. It is possible that Orengedoku-to and Senkanmeimoku-to may migrate some forms of uveitis.

Animals↗
PubMed2001

Expression of ZAKI-4 messenger ribonucleic acid in the brain during rat development and the effect of hypothyroidism.

We identified ZAKI-4 (also designated as DSCR1L1) as a thyroid hormone responsive gene in cultured human skin fibroblasts. Recently it has been reported that ZAKI-4 belongs to an evolutionary conserved family of proteins that function as calcineurin inhibitor. In human, ZAKI-4 and calcineurin are highly expressed in brain, where thyroid hormones play essential roles in the development during fetal and neonatal periods. In the present study, we examined the temporal and spatial expression patterns of ZAKI-4 messenger RNA (mRNA) in control and hypothyroid rat brains. Northern blot analysis revealed that ZAKI-4 mRNA was detected in both cerebral cortex and cerebellum as early as embryonic day (E)18. In the cerebral cortex, the expression level gradually increased with age, reaching a plateau at postnatal day (P)7 and remained constant thereafter until P30. A similar pattern of increase with age was also observed in hypothyroid rats; however, the magnitude of the increase was significantly reduced. In control rats, the fold increase in ZAKI-4 mRNA level from E18 to P17 was 10.8; whereas in hypothyroid rats, it was 7.4. In cerebellum the expression level did not change with age or by thyroid status. In situ hybridization revealed that ZAKI-4 mRNA is widely expressed in neurons throughout the brain. It is noteworthy that the expression in the neurons of layer VI of the cerebral cortex was more evident in control rats than that in hypothyroid rats from P17 to P30. Though not influenced by hypothyroidism, there were several regions of the brain in which ZAKI-4 mRNA was strongly expressed. These regions were the mitral cell layer of the olfactory bulb, the substantia nigra, and the hippocampus, where calcineurin is also abundantly expressed. Therefore, it may be hypothesized that ZAKI-4 plays an important role in the development and function of the brain by modulating calcineurin function; and decrease in ZAKI-4 mRNA expression in the specific brain areas may explain, in some parts, the mechanism of abnormal brain development by hypothyroidism.

Animals↗
PubMed2001

The human homolog of Diminuto/Dwarf1 gene (hDiminuto): a novel ACTH-responsive gene overexpressed in benign cortisol-producing adrenocortical adenomas.

To elucidate the molecular mechanism of the pathogenesis of benign functioning adrenocortical adenomas causing Cushing's syndrome, we employed suppression PCR-based cDNA subtractive hybridization to identify novel genes that are differentially expressed in the adenoma. In this report we describe the adenoma-specific overexpression of the human homolog of the Diminuto/Dwarf1 (hDiminuto) gene. Northern blot analysis revealed that hDiminuto mRNA was overexpressed in the adenoma tissue of 14 patients with Cushing's syndrome in comparison to the adjacent nontumorous adrenal gland. In situ hybridization using hDiminuto cRNA probe showed its abundant expression in the tumor cells, whereas the nontumorous cells showed a low level of expression. As the atrophic adjacent gland may not represent the normal architecture, we examined the expression pattern of hDiminuto mRNA in normal human adrenal cortex. In situ hybridization revealed that it was expressed in all layers of the normal adrenal cortex. In situ apoptosis detection by the TUNEL method revealed that a low level of hDiminuto expression in the atrophic, adjacent gland was associated with numerous TUNEL-positive cells in all layers of cortex. In contrast almost no apoptotic cell was detected in the tumor or in the normal adrenal cortex where hDiminuto expression was abundant. These results are compatible with a recent report that hDiminuto acts as an antiapoptotic factor in neurons. The expression of hDiminuto in the normal adrenal cortex was most abundant in the zona fasciculata, suggesting its possible regulation by ACTH/cAMP. Indeed, forskolin treatment of H295R human adrenocortical cells resulted in a significant induction of the mRNA in a time- and dose-dependent manner. To further demonstrate the physiological regulation, an in vivo experiment was carried out in dexamethasone-treated rats. ACTH administration to these rats increased the mRNA expression. These results led us to speculate that the overexpression of hDiminuto in the adenoma could be due to the abundant expression of ACTH receptor, as we previously described. Diminuto is involved in steroid synthesis and cell elongation in plants. We, therefore, hypothesize that hDiminuto might be involved in the molecular events of adrenocortical tumorigenesis by facilitating steroid synthesis and cell growth.

Adenoma↗
PubMed2001

Overexpression of glutathione-S-transferase A1 in benign adrenocortical adenomas from patients with Cushing's syndrome.

Benign adrenocortical adenoma is a major primary cause of Cushing's syndrome. Although numerous studies have been performed, the molecular mechanism of adrenocortical adenoma is yet to be elucidated. In this study we endeavored to identify genes differentially regulated in adrenocortical adenoma by suppression PCR-based complementary DNA (cDNA) subtractive hybridization. The cDNA population in atrophied nontumorous adrenal gland adjacent to the adenoma was subtracted from that in the adenoma. Then adenoma-specific cDNAs were amplified by PCR. We cloned several cDNAs that are selectively up-regulated in the adenoma, one of which was identified to encode glutathione-S-transferase A1 (GSTA1). Northern blot analysis revealed that GSTA1 messenger ribonucleic acid was abundantly expressed in the adenoma compared with that in the adjacent atrophied nontumorous gland. Western blot analysis and immunohistochemistry showed high expression of GSTA1 also at the protein level. In concordance with this finding, GST activity was significantly higher in the adenoma than in the adjacent atrophied nontumorous gland. To clarify the role of GSTA1 in adrenocortical cells, GST activity in the H295R human adrenocortical cell line was inhibited by ethacrynic acid. Inhibition of GSTs interfered with proliferation of the cells. We, therefore, hypothesize that overexpression of GSTA1 in adrenocortical adenomas might be involved in the growth of tumor cells. We also speculate that this overexpression might be an adaptive response to excess cortisol production.

Adenoma↗
PubMed2001

Histological characteristics of the pelage skin of rough fur mice (C3H/HeJ- ruf/ruf).

Pelage skin of C3H/HeJ mice homozygous at an autosomal recessive mutant locus, rough fur (ruf) which is located on chromosome 9, was histologically analyzed. Sebaceous glands synthesizing lipids were larger in the mutant mice than in controls in an examination by Sudan IV staining. Electron microscopic analysis of the sebaceous gland showed that lipid droplets were denser in mutant mice than in control mice, and that they were irregular in shape in ruf mice while those of controls were round. Our results suggested that rough fur (ruf) mice might be an animal model for hyperlipogenesis of the pelage skin.

Animals↗
PubMed2001

Accidents associated with bathing in home care services for the aged in Japan.

OBJECTIVES: To reveal what kinds of accidents happen associated with bathing in home care services for the aged in Japan. METHODS: The study was cross-sectional in design. In November 1999, a postal questionnaire survey was conducted of 828 councils selected from the list of the National Council of Social Welfare of Japan by a systematic sampling method (extraction rate was 25%). The main outcome measures were characteristics of cases of accidents associated with bathing service for the aged, including patient age, sex, time of occurrence, symptoms, and results of accidents. RESULTS: Replies were received from 683 (82%) councils. Of the councils that replied, 430 (63%) reported providing bathing service for the aged. Of these 430 councils, 108 (25%) have experienced accidents, and 130 cases were analyzed. Affected patients had a mean age of 80.7 years (SD: 9.0 years), and 71 were females (55%). Sixty-two (48%) had symptoms of a disease or had accidents after bathing, and 42 (32%) presented with loss of consciousness. In results of accidents, 14 (11%) were reported to have died. CONCLUSION: This study revealed that there were not a few accidents associated with bathing in home care services for the aged in Japan, the most frequent symptom was loss of consciousness, most accidents occurred after bathing, and that some patients died as a result of bathing provided by home care services.

Accidents, Home↗
PubMed2001

Lack of association of prostate carcinoma nuclear grading with prostate specific antigen recurrence after radical prostatectomy.

PURPOSE: Grading prostate cancer using the Gleason system relies only on architectural tumor growth, in contrast to other systems, such as the WHO system, which grade prostate carcinoma based on nuclear features as well as architectural patterns. The prognostic significance of nuclear grading remains controversial since most studies were performed before prostate specific antigen (PSA) screening became widely available. We evaluated the significance of nuclear grade for predicting PSA recurrence in a contemporary cohort of patients treated with radical prostatectomy for clinically localized prostate carcinoma. MATERIALS AND METHODS: Nuclear grades 1 to 3 were determined in 141 consecutive radical prostatectomies in 1995. Predominant and worst nuclear grade was determined by a consensus of 3 pathologists. Statistical analysis compared nuclear grade with Gleason score using the chi-square test. The Cox proportional hazards analysis was performed to calculate the ability of nuclear grade, Gleason score and other variables to predict PSA recurrence. RESULTS: We identified a significant association of Gleason score with worst nuclear grade (p = 0.007). All 6 cases with a Gleason score of 8 or greater had a worst nuclear grade of 3, in contrast to 36 of 60 (60%) with a score 6 or less, in which the worst nuclear grade was 3. Of the 141 patients 31 (21.9%) had PSA recurrence at a median followup of 3.7 years. The univariate Cox model revealed significant associations of PSA recurrence with Gleason score 8 or greater (hazards ratio 5.5, p = 0.005), extraprostatic extension (hazards ratio 3.4, p = 0.001), positive surgical margin (hazards ratio 2.6, p = 0.009), seminal vesicle involvement (hazards ratio 7.3, p <0.001), preoperative serum PSA (hazards ratio 1.03, p = 0.007), tumor stage (hazards ratio 3.6, p = 0.001) and maximal tumor dimension (hazards ratio 2.4, p <0.001). However, overall and worst nuclear grade did not predict PSA recurrence (p = 0.89 and 0.13, respectively). Nuclear grade did not fit any multivariate model tested, which otherwise included Gleason score, log(PSA), surgical margin status, extraprostatic extension, seminal vesicle status, tumor size and pathological stage. By varying sample fixation time we also showed that benign prostate tissue in the same section as prostate carcinoma had grade 2 or 3 nuclear changes, that is moderate to marked anaplasia. CONCLUSIONS: High nuclear grade is associated with high Gleason score. However, prostate carcinoma with a Gleason score of 6 or less shows extreme variability. Nuclear grade determined by light microscopy failed to predict PSA recurrence in a contemporary series of men with clinically localized prostate cancer treated with radical prostatectomy. Nuclear morphology is subject to tissue fixation and processing artifact. Any nuclear morphometric study must consider this artifact.

Adult↗