Biomedical subjects

Y Harada

Publications and source records attributed to Y Harada.

At least 55 records · Page 3Linked to original sources

PubMed2001

Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain.

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Alleles↗

PubMed2001

The relationship between alphaB-crystallin and neurofibrillary tangles in Alzheimer's disease.

AlphaB-crystallin is known as a small heat shock protein with a cytoprotective function. This study was undertaken to investigate the relationship between alphaB-crystallin and changes seen in Alzheimer's disease. The distribution and immunohistochemical characteristics of alphaB-crystallin positive neurones in the cerebral cortices of 4 patients with Alzheimer's disease were examined. AlphaB-crystallin positive neurones were mainly distributed in the limbic and paralimbic regions, namely parahippocampal gyrus, fusiform gyrus, cingulate cortex, middle and superior frontal gyrus, and insular cortex, which corresponded to commonly affected regions in Alzheimer's disease. Moreover, such neurones were present predominantly in the III or V layer of the cerebral cortex. The number of alphaB-crystallin positive neurones increased in parallel with the neuronal loss. Logistic regression analysis revealed a significant relation between the density of alphaB-crystallin positive neurones and that of extracellular neurofibrillary tangles (NFTs), with a correlation coefficient (r) of 0.57 and P < 0.0001 in 14 regions of the cerebral cortex. In contrast, the relation was not statistically significant between the density of alphaB-crystallin positive neurones and that of classical senile plaques, diffuse plaques or intracellular NFTs. Modified Gallyas-Braak (GB) staining on alphaB-crystallin positive neurone demonstrated several patterns of the structures: faint GB positive structures in the swollen perikaryon with straight neurites, fine granules compressed and contorted into fuzzy bundles, intensely GB positive filamentous structures together with fine granules and very intensely GB positive ring-like NFTs in a swollen perikaryon with curved neurites. In positive neurones, the density of ring-like NFTs correlated with that of atrophic perikaryon, or bent neurites and a decrease in the immunoreactivity of alphaB-crystallin. These data suggest that a close relationship exists between the appearance of alphaB-crystallin in neurones, extracellular NFTs, and neurofibrillary formation in alphaB-crystallin positive neurones in Alzheimer brain.

Aged↗

PubMed2001

Interventional treatment for fetus and newborn infant with congenital heart disease.

BACKGROUND: Catheter intervention has become popular not only in adult patients but in younger patients with congenital heart disease. The early neonatal catheter interventional treatment has also been attempted in conjunction with the development of prenatal diagnosis of the congenital heart disease. METHOD: Recent articles concerning several severe structural cardiac diseases in newborns, such as critical aortic stenosis, complete transposition of the great arteries, premature constriction of the ductus arteriosus, and pulmonary stenosis or atresia with intact ventricular septum are introduced with consideration. RESULTS: This study investigated our own experiences of early neonatal balloon valvuloplasty in a patient with critical aortic stenosis carried out immediately after the delivery following prenatal diagnosis. A case with prenatal diagnosis of premature constriction of ductus arteriosus which could prevent persistent pulmonary hypertension of the newborn by early delivery at 39 weeks and 1 day of gestation were reported. CONCLUSION: Several cardiac interventional treatments performed in the present time during the perinatal period and some prospects in the near future are described in the discussion.

Angioplasty, Balloon↗

PubMed2001

Urological management of cloacal anomalies.

BACKGROUND: A cloacal anomaly results from incomplete urorectal division and is frequently associated with genitourinary abnormalities. Experience of the urological reconstruction of this entity is reported. METHODS: Nine girls with cloacal malformation have been treated at the Osaka Medical Center in the past 9 years. Seven patients were detected by prenatal ultrasonography as having: megacystis (two patients); hydronephrosis (two patients); or hydrometrocolpos (three patients). Two patients underwent prenatal shunt placement between the enlarged bladder and the amniotic space. RESULTS: For neonatal urinary diversion, four patients received cystostomy. Six of seven patients with associated hydrocolpos required intermittent catheterization to decompress an enlarged vagina. Vesicoureteral reflux was detected in 12 ureters of seven patients. Antireflux surgery was indicated in four patients before definitive repair. Definitive reconstruction was performed on eight patients. The posterior sagittal approach was used in all patients. Vaginal reconstruction was done utilizing a perineal skin flap (one patient), a tubularized vaginal flap (three patients), distal rectum (three patients) and total urogenital mobilization (one patient). Postoperatively, urethrovaginal fistula was created in one patient and complete occlusion was seen in one patient. CONCLUSION: The anatomical variety of this entity determines the management options from in utero. It involves not only the creation of three perineal orifices, but also a continent, catheterizable urethra under the stabilization of renal function. Accomplishment of the definitive repair requires the combined expertise of experienced pediatric surgeons and pediatric urologists.

Clitoris↗

PubMed2001

Brachyury homolog (HpTa) is involved in the formation of archenteron and secondary mesenchyme cell differentiation in the sea urchin embryo.

Sea urchin Brachyury homolog (HpTa) is expressed exclusively in the vegetal plate and secondary mesenchyme cells in the embryos of sea urchin Hemicentrotus pulcherrimus. In order to gain insights into the role of HpTa during sea urchin development, we designed experiments to perturb the embryo by inducing ectopic overexpression of HpTa by injecting fertilized eggs with HpTa mRNA. The overexpression of HpTa resulted in suppression of the formation of vegetal plate and secondary mesenchyme cells. We assume that the interaction of HpTa with unknown factors is required for the activation of the HpTa target genes, and that the excess amount of HpTa proteins produced from injected HpTa mRNA depletes the co-factors. In consequence, the target genes of HpTa would be repressed by the overexpression of HpTa. We suggest that HpTa is involved in the formation of the vegetal plate and the differentiation of secondary mesenchyme cells.

Journal Article↗

PubMed2001

Comparison and evolution of the lagena in various animal species.

The structure of the vestibular organs of the teleost fish (bluegill), newts (Japanese fire-belly newt), frogs (black-spotted pond frog), snapping turtles and birds (chicks) was morphologically compared, with particular attention to the lagena macula, and the differences between animal species with relation to evolution were considered. Teleost fish had no striola on the lagena macula. The striola of newts were short and restricted to the central area of the macula, but those of frogs, snapping turtles and chicks extended from the anterior to posterior edges of the macula. This indicates that the frog is more highly evolved than the newt. The length of the kinocilium of sensory hairs was equal to that of the longest stereocilium in teleost fish and newts, but the kinocilia of frogs, snapping turtles and chicks were longer than the longest stereocilium. This indicates that the function of the lagena of teleost fish and newts is for hearing whilst in the other animals they are for posture. The diameter of the sensory hair bundles is small in teleost fish and frogs, but large in newts and snapping turtles. This indicates that the sensitivity of the sensory cells of the lagena towards outer force is low in teleost fish and frogs, high in newts and snapping turtles and intermediate in birds. The lagena of snapping turtles protrudes from the basilar papilla into the vestibule but the lagena of chicks lies on the tip of the long projecting basilar papilla. From observation of the locations of lagenae it is natural to speculate that there must have been some species of animal now extinct that had the evolving location of the lagena prior to that of chicks. In future it will be very interesting and useful to identify this extinct animal using DNA techniques.

Acoustic Maculae↗

PubMed2001

Clinical evaluation of human telomerase catalytic subunit in bladder washings from patients with bladder cancer.

PURPOSE: We examined the expression of mRNA of human telomerase reverse transcriptase (hTERT), a catalytic subunit of the telomerase complex, in bladder washings as a tumor marker for the detection of bladder cancer. MATERIALS AND METHODS: Bladder washings were obtained from 63 patients. We examined the expression of hTERT mRNA by the nested reverse transcription-polymerase chain reaction (RT-PCR) method and also measured the relative expressions of hTERT mRNA and beta(2)-microglobulin (beta(2)-MG) in these samples by RT-PCR analysis. Correlations between the relative expression of hTERT mRNA and clinical features were analyzed. We also compared the sensitivity of this assay with that of urinary cytology. RESULTS: By nested RT-PCR, we detected three false-positive cases (11%) in the control group. Therefore, the relative expression values of hTERT mRNA and beta(2)-MG correlated strongly with tumor size, but not with multiplicity or histologic grade. When the cut-off value of the expression was fixed at 0.27%, the sensitivity and specificity of this assay were 74% and 93%, respectively. This assay was more sensitive than urinary cytology for the detection of bladder cancer. CONCLUSION: These results suggest that the relative expression of hTERT mRNA in bladder washings is useful in screening for bladder cancer. Relative expression is of assistance in diagnosing bladder cancer.

Biomarkers, Tumor↗

PubMed2001

Loss of p73 induction in a cisplatin-resistant bladder cancer cell line.

BACKGROUND: Cisplatin (CDDP) plays an important role in the treatment of transitional-cell carcinoma (TCC), but resistance develops. The mechanism is not entirely understood. METHODS: To assess acquired resistance to CDDP, we established a CDDP-resistant subclone, CL8-2, of T24, which is a bladder cancer cell line. We examined the changes in the various pathways leading to apoptosis in the parent line and CL8-2. RESULTS: The drug caused apoptosis of T24 cells but not CL8-2 cells. The CL8-2 cells were 6.4 times more resistant to CDDP than was T24. In both cell lines, the mismatch repair genes hMLH-1 and hMSH-2 were expressed at high levels. The p53 protein was not detected in either cell line but p73 protein was induced by CDDP treatment in T24 cells, which was followed by activation of caspases 3, 8, and 9. This phenomenon was not observed in CL8-2 cells. CONCLUSION: These results suggest that loss of p73 induction may lead to CDDP resistance of TCC.

Antineoplastic Agents↗

PubMed2001

Efforts toward creating unnatural base pairs for an expanded genetic code.

A series of unnatural base pairs was designed and examined for the expansion of the genetic alphabet and for a better understanding of the mechanism of nucleic acid biosyntheses. To improve the shape complementarity of the previously developed unnatural base pairs, 2-amino-6-(N,N-dimethylamino)purine (x)--pyridon-2-one (y) and 2-amino-6-(2-thienyl)purine (s)--y, the pyrimidine analogue, y, was replaced by a five-member ring, 4-imidazolin-2-one (z), and the s-z pairing in replication was examined. Unnatural bases based on the five-member ring were also applied to the development of non-hydrogen-bonded base pairs.

Base Pairing↗

PubMed2001

Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment.

OBJECTIVES: To investigate the actual time of onset of osteonecrosis (ON) after high dose corticosteroid treatment in systemic lupus erythematosus (SLE). METHODS: 72 patients with active SLE, who received high dose corticosteroid for the first time, for the development of ON at hips and knees were monitored by magnetic resonance imaging for at least 12 months. RESULTS: ON lesions were detected in 32/72 patients (44%) between one and five months (3.1 months on average) after starting high dose corticosteroid treatment. No osteonecrotic lesion was newly detected from the sixth month of treatment until the end of the follow up period. CONCLUSION: The findings suggested that the actual time of onset of ON in SLE is within the first month of high dose corticosteroid treatment.

Adolescent↗

PubMed2001

Oral combination of cyclophosphamide, uracil plus tegafur and estramustine for hormone-refractory prostate cancer.

OBJECTIVE: To evaluate the clinical usefulness of an oral combination of cyclophosphamide, uracil plus tegafur (UFT) and estramustine in the treatment of patients with hormone-refractory prostate cancer (HRPC). METHODS: Twenty-one patients were treated with oral administration of cyclophosphamide (100 mg/day), UFT (400 mg/day) and estramustine phosphate (560 mg/day). The median age of the patients was 70 years. Twelve patients had symptomatic bone metastasis, 6 had asymptomatic bone metastasis, 5 had lymph node metastasis, while 2 had only biochemical progression evaluated by prostate-specific antigen (PSA). RESULTS: Twelve (57%) out of 21 patients showed a PSA decline of 50% or greater. The median response duration was 7 months (range 2-15 months). Among the 20 patients assessable for bone pain, 2 (10%) improved, 12 (60%) remained stable and 6 (30%) progressed. Among the 10 patients assessable for bone metastasis, 1 (10%) improved, 5 (50%) were stable and 4 (40%) progressed on bone scan. Among 3 patients assessable for measurable disease (lymph node metastasis), 2 (67%) showed partial response and 1 (33%) progression. Most toxicities were mild. CONCLUSIONS: The combination of cyclophosphamide, UFT and estramustine is an active and well-tolerated regimen for HRPC. To evaluate the survival benefit, further randomized studies are required.

Administration, Oral↗

PubMed2001

Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758.

Synthesis and in vitro antifungal activities of a novel triazole antifungal agent CS-758 (former name, R-120758) are described. The minimum inhibitory concentrations (MICs) of a series of dioxane-triazole compounds related to R-102557 were examined. Variation of the length of the chain between the dioxane ring and the phenyl ring revealed that the linkage with two double bonds is the most preferable. When a cyano group was introduced to the C4 position on the benzene ring, MICs improved further. A fluorine atom was introduced to obtain CS-758. The MICs of CS-758 surpassed those of fluconazole and itraconazole against Candida, Aspergillus and Cryptococcus species. The precursor (E,E)-aldehyde was synthesized stereoselectively from 3-fluoro-4-methylbenzonitrile using the Horner-Wadsworth-Emmons reaction.

Antifungal Agents↗

PubMed2001

Balloon aortic valvuloplasty in children: a multicenter study in Japan.

A questionnaire was used to survey the experience of 8 Japanese institutions with percutaneous transluminal aortic valvuloplasty (PTAV) in children. Among 99 procedures reported in 88 patients, sufficient data for analysis was obtained from 76 procedures in 72 patients. In those 76 procedures the pressure gradient decreased significantly from 68+/-25 (20-140) to 33+/-22 (0-100) mmHg (p<0.01), whereas aortic regurgitation (AR) increased at least one grade in 26 cases (34%). None of the parameters analyzed in this study were predictors of an increase in AR. The reduction in pressure gradient was judged as good in 44 of the 76 procedures (58%). A larger ring diameter, larger balloon diameter and larger ratio balloon diameter/the normal predicted diameter of the aortic valve ring significantly contributed to an effective reduction of pressure gradient. Follow up data (mean interval, 4 years) was available for 26 of 39 clinically effective procedures. AR progressed at least 1 grade in 11 (42%), and the pressure gradient re-developed to more than 50mmHg in 2 cases (8%). In Japan, PTAV has been accepted as a useful procedure for valvular aortic stenosis in children, but progressive AR or re-development of the pressure gradient is not uncommon even after clinically effective PTAV.

Adolescent↗

PubMed2001

Differential effects of oxidised and non-oxidised polyethylene particles on human monocyte/macrophages in vitro.

Sterilisation by gamma irradiation in the presence of air causes free radicals generated in polyethylene (PE) to react with oxygen, which could lead to loss of physical properties and reduction in fatigue strength. Tissue retrieved from failed total hip replacements often has large quantities of particulate PE and most particles associated with peri-implant osteolysis are oxidised. Consequently, an understanding of the cellular responses of oxidised PE particles may lead to clarification of the pathogenesis of osteolysis and aseptic loosening. We have used the agarose system to demonstrate the differential effects of oxidised and non-oxidised PE particles on the release of proinflammatory products such as interleukin-1beta (IL-1beta), IL-6, and tumour necrosis factor-alpha (TNF-alpha) from monocytes/macrophages (M/M). Oxidised PE particles were shown to stimulate human M/M to phagocytose and to release cytokines. Oxidation may alter the surface chemistry of the particles and enhance the response to specific membrane receptors on macrophages, such as scavenger-type receptors.

Cells, Cultured↗

PubMed2001

Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by acting on the various cellular reactions in the fracture callus.

Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1-8; Ph-2, days 9-16; Ph-3, days 17-24; throughout [T], days 1-24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (muCT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) muCT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling.

Animals↗

PubMed2001

Sink-limitation and the size-number trade-off of organs: production of organs using a fixed amount of reserves.

To analyze the nature of size-number trade-off of organs, we develop models in which the effects of sink-limitation in the growth of organs and the loss of resources by maintenance respiration are taken into consideration. In these models, the resource absorption rate of an organ is proportional to either its absolute size or its surface area and either the initial size of an organ or the total initial size of the organs produced is fixed. In all models, organs are produced using a fixed amount of reserved resources and no additional resources become newly available for their growth. We theoretically show that size-number trade-offs are nonlinear if the resource absorption rate of an organ is proportional to the absolute size of the organ and the initial size of the individual organs is fixed or if the resource absorption rate of an organ is proportional to the surface area of the organ. In these nonlinear size-number trade-offs, the size of individual organs increases less rapidly than in linear trade-offs with a decrease in the number of organs and the total size of organs is an increasing function of the number of organs produced. This implies that increasing the number of organs produced is advantageous in terms of resource-use efficiency. In contrast, size-number trade-off is linear if the resource absorption rate of an organ is proportional to the absolute size of the organ and there is a linear trade-off between the initial size of organs and their number. To exemplify the effects of those size-number trade-offs on the life-history evolution, we calculate the optimal offspring sizes that maximize the number of offspring successfully being established. In the case of nonlinear size-number trade-offs, the optimal offspring sizes are smaller than the optimal offspring size in the case of linear size-number trade-offs, namely, that in the model of Smith and Fretwell (1974). Our optimal offspring size depends on the metabolism of organ development; the optimal offspring size decreases with an increase in maintenance respiration rate relative to the growth coefficient of organs.

Absorption↗

PubMed2001

Concentration of nitric oxide (NO) in spinal fluid of chronic spinal disease.

We studied total nitric oxide (nitrite + nitrate) (NO) levels in cerebrospinal fluid (CSF) of chronic spinal diseases in nonsmokers (133 patients: 76 men and 57 women; mean age, 63 years; range, 15-92 years) by the Griess method to clarify the role of NO in different spinal diseases. The extent of compression in terms of numbers of disc level at the compressed spinal nerve and neurological evaluation were also assessed according to the Japanese Orthopaedic Association scores. The spinal diseases included cervical myelopathy and radiculopathy (cervical disease group), ossification of yellow ligament (thoracic disease group), and lumbar disc herniation, lumbar canal stenosis and lumbar spondylolisthesis (lumbar disease group). NO levels in the spinal disease groups (4.98+/-2.28 micromol/l: mean +/- SD) were significantly higher than that in the control group (2.53+/-0.94 micromol/l). An inverse correlation was detected between the elevated levels of NO and the grade of clinical symptoms in the cervical disorders. The number of disc level at the compressed spinal nerve was positively correlated with elevated NO levels in CSF in the cervical and lumbar disorder groups. These results indicate that nerve compression may elevate NO levels in CSF, and that NO concentration in the CSF might be a useful marker of damage to nervous system in spinal disorders.

Adolescent↗

PubMed2001

Relationship between sprint performance and muscle fascicle length in female sprinters.

The purpose of this study was to investigate the relationship between sprint performance and architectural characteristics of leg muscles in 26 female 100-m sprinters. Pennation angle and muscle thickness of the vastus lateralis (VL) and gastrocnemius medialis (GM) and lateralis (GL) muscles were measured by B-mode ultrasonography, and fascicle length was estimated. Sprinters had a significantly lower VL pennation angle, but GM and GL pennation angle was similar between sprinters and female control subjects (N = 22). There was no significant correlation between pennation angle and 100-m personal best performance. Sprinters had significantly greater absolute fascicle length in VL and GL than controls, which significantly correlated to 100-m best-record (r = -0.51 and r = -0.44, respectively). Relative fascicle length (VL and GL) were also significantly greater in sprinters than controls. However, there were no significant correlation between relative fascicle length and 100-m best-record (r = -0.36 and r = -0.29, respectively). No relationship was found between the sprint performance and fat-free mass (r = -0.26) or body mass index (r = -0.03). However, there was a significant correlation between percent (%) body fat and 100-m best-record (r = 0.62, p < 0.01). Adjusting the confounding effect of % fat, significant correlations were seen between relative fascicle length and 100-m best-record (VL; r = -0.39 and GL; r = -0.40). Absolute and relative fascicle length were similar in elite female sprinters compared with previous reported values for elite male sprinters (Kumagai et al., 2000). It was concluded that longer fascicle length is associated with greater sprinting performance in sprinters, but there is no gender differences in fascicle length for elite sprinters.

Adult↗