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Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 163 records · Page 9Linked to original sources

Local immunosuppression prolongs survival of RPE xenografts labeled by retroviral gene transfer.

PURPOSE: To determine whether local immunosuppression with Cyclosporin A can influence the survival of human fetal retinal pigment epithelium (RPE) xenografts in the rabbit's subretinal space. METHODS: Cultured human fetal RPE cells were transduced with the gene for green fluorescent protein (GFP) using a lentiviral vector. The RPE was transplanted into the subretinal space of rabbits that received intravitreal cyclosporine either by weekly injections (0. 25-0.5 mg) or by slow release (approximately 2 microg/d) from a capsule sutured into the vitreal cavity after prior cryopexy. The transplanted RPE was followed by GFP fluorescence scanning laser ophthalmoscopy and by histology of the transplant site. RESULTS: RPE xenografts in eyes receiving intravitreal cyclosporine survived longer (several months) than they did in control eyes without cyclosporine. Survival was as long with slow release capsules as it was with weekly intravitreal injections at much higher concentrations of cyclosporine. CONCLUSIONS: Local immunosuppression of the eye with cyclosporine prolongs the survival of RPE xenografts in the subretinal space of rabbits, implying that rejection involves activated T lymphocytes. Local immunosuppression with slow release capsules is as effective as weekly injections at much higher concentrations.

Animals↗

Regional variations in the number and subsets of intraepithelial lymphocytes in the mouse small intestine.

BACKGROUND AND PURPOSE: Regional variations in the intraepithelial lymphocytes (IELs) in the mouse small intestine were examined. METHODS: The small intestine was taken from six 12-week-old BALB/c mice and divided equally into three parts (proximal, middle, and distal). The IELs were isolated from each part of the intestine and analyzed by use of flow cytometry. RESULTS: The number of IELs in the distal part of the small intestine was significantly lower than that in the proximal and middle parts (P < 0.01). The distribution of IEL subsets was markedly different between the proximal and the distal parts, and that in the middle part had an intermediate pattern. The percentage of alphabetaT cells and expression of Thy-1.2 on the alphabetaT and gammadeltaT cells were higher in the distal part (P < 0.01). The percentage of CD8alphaalpha and of double-negative T cells were higher in the proximal part, whereas that of CD4CD8alphaalpha double-positive T cells was higher in the distal part (P < 0.01). Regional variations were found mainly in the extrathymically developed T cell subsets. CONCLUSION: Local development of IELs may differ between regions of the small intestine.

Animals↗

[Intra-arterial infusion chemotherapy with docetaxel for locally advanced breast cancer and inflammatory breast cancer].

From 1998 to 2000, we performed neoadjuvant intra-arterial infusion chemotherapy using docetaxel (60 mg/m2) a few times with 5 patients with local advanced breast cancer and inflammatory breast cancer. Therapeutic effects included 3 cases of PR among the breast tumor patients and downstaging was obtained 2 cases. No critical side effects were found due to this chemotherapy. We could perform mastectomy in all the cases. We consider intra-arterial infusion using docetaxel to be highly effective with few side effects in cases of advanced breast cancer.

Adenocarcinoma↗

Red swamp crawfish (Procambarus clarkii): an alternative experimental host in the study of white spot syndrome virus.

The pathogenicity of white spot syndrome virus (WSSV) for the red swamp crawfish (Procambarus clarkii) was investigated after infection by intramuscular (i.m.) injection and oral route. The cumulative mortality of crawfish injected i.m. with WSSV reached 100% in 5 days. After oral feeding WSSV-infected kuruma shrimp (Penaeus japonicus) muscle tissues to the crawfish the cumulative mortality of this host reached 100% in 11 days. On reinfection trials, all the crawfish fed WSSV-infected crawfish muscle tissues died in 9 days. All the shrimp injected with a filtrate of infected crawfish heart tissues died in 12 days with typical signs of white spot syndrome (WSS). Electron microscopy clearly demonstrated that WSSV propagated in the cells of the crawfish midgut. This study showed that the red swamp crawfish can be used as alternative experimental host in the study of WSSV.

Animals↗

Effects of hypergravity on morphology and osteopontin expression in the rat otolith organs.

Recovery from balance disorders after spaceflight is supposed to reflect the process of readaptation to normal gravitational environment (1G) from microgravity. Linear acceleration including gravity is perceived by otolith pathways, therefore, it could be assumed that possible plastic changes in any part of otolithic pathways from the level of the vestibular periphery to the central vestibular system might be responsible for adaptive mechanisms to an altered gravitational environment. In the present study, to elucidate a role of otoconia in adaptation to altered gravity, we examined the effects of hypergravity (2G) on morphology and synthesis of saccular and utricular otoconia in young adult rats. Morphology of otoconia was examined by scanning electron microscopy. Otoconial synthesis was assessed by mRNA expression of osteopontin, a matrix protein of otoconia, in otolithic maculae as a marker of otoconial genesis determined by a real-time quantitative PCR method. The present results showed that neither otoconial morphology nor otoconial synthesis was affected by up to one week exposure to hypergravity. These findings suggest that changes in neurotransmission at the synapses of the peripheral and/or central vestibular system rather than the changes in otoconial morphology and synthesis may be involved in adaptive mechanisms to an altered gravitational environment.

Animals↗

Sequencing by hybridization in the presence of hybridization errors.

DNA sequencing is a very important problem in genomics. Several different sequencing methods are currently utilized. One promising method uses a sequencing chip to obtain information about the presence of subsequences in DNA. This paper deals with sequencing of hybridization data from a sequencing chip, called Sequencing by Hybridization (SBH). Preparata et al. proposed a new sequencing chip using universal bases, together with a new sequencing algorithm, and showed that its performance is significantly better than the standard scheme based on oligomer probes. However, the presence of errors in the sequencing chip was not considered, and the method of Preparata et al. cannot be used directly in practice. This paper proposes sequencing algorithms in the presence of hybridization errors for their sequencing chip and applies these algorithms to random data in the presence of random errors. Computational results show that false negative errors have larger effects on the rates of correct reconstruction than do false positive errors. Our extended sequencing algorithms are useful when there are a few hybridization errors.

Algorithms↗

Operative results of canal-expansive laminoplasty for cervical spondylotic myelopathy in elderly patients.

STUDY DESIGN: The study involved elderly patients (age > or = 65), who underwent treatment for cervical spondylotic myelopathy by canal-expansive laminoplasty. OBJECTIVES: To determine the factors that influence the operative results of canal-expansive laminoplasty for treatment of cervical spondylotic myelopathy in elderly patients. SUMMARY OF BACKGROUND DATA: Although there have been previous reports of many operative procedures, to the authors' knowledge there are no reports on the results of surgical treatment for cervical spondylotic myelopathy in elderly patients, treated by a unified surgical procedure. To date, no attempts have been made to predict the results of these procedures. METHODS: Forty-seven patients (age > or = 65) who underwent canal-expansive laminoplasty were reviewed in this study. The severity of the clinical picture and the quality of operative results were graded according to the Japanese Orthopaedic Association scoring system. RESULTS: Of the 13 patients whose period of disability persisted for less than 3 months before the operation, 12 were able to walk after surgery. The operative results of patients more than 80 years of age were not significantly different from those of patients aged between 65 and 79 years. Results of multiple regression analysis indicate that the predictive probability of the postoperative motor function score of the lower extremities was 70%. CONCLUSIONS: The severity of the clinical picture and the duration of symptoms influenced the outcome of the operation. Despite the advanced age of some patients (> 80), the operation increased the chance of recovery from the disease.

Aged↗

Differential modulation of nitric oxide and prostacyclin release in senescent rat heart stimulated by angiotensin II.

To elucidate the mechanism of age-related changes in the cardiovascular function stimulated with angiotensin II, we examined the effects of angiotensin II on the coronary flow, production of nitric oxide (NO) and prostacyclin, and on the cardiac function in the Langendorff-perfused young and aged rats' hearts. Angiotensin II decreased coronary flow, left ventricular dP/dt and heart rate. These effects were more pronounced in aged rats. Pretreatment with a NO synthase inhibitor, N(G)-nitro-L-arginine, significantly increased the angiotensin II-induced vasoconstriction in young rats. Angiotensin II increased the concentration of NO in the coronary effluent in young but not in aged rats. In contrast, angiotensin II stimulated the release of prostacyclin to a much greater extent in aged rats than in young rats. These results suggest that impaired production of NO may contribute to the greater constrictor effect of angiotensin II in the aged rat, although aging modulated the production of prostacyclin in a different manner. This age-related endothelial dysfunction may alter the physiological regulation of coronary flow and cardiac function stimulated with angiotensin II.

Acetylcholine↗

Three novel connexin26 gene mutations in autosomal recessive non-syndromic deafness.

Since the first identification of an association between mutations in the connexin26 (Cx26) gene and autosomal recessive non-syndromic deafness it has been shown that several mutations in this gene cause recessive, sporadic, and dominant non-syndromic deafness. Three novel mutations in the Cx26 gene were identified in four of 20 Japanese families with autosomal recessive non-syndromic deafness. Seven of 40 chromosomes contained a 233delC allele, while Tyr136Stop (408C-->A) and Gly45Glu (134G-->A) were detected in two of 40 chromosomes, respectively. These mutations were not found in chromosomes in cases of sporadic congenital deafness (0/60) or in control groups (0/100). This indicates that 27.5% (11/40 chromosomes) of cases of autosomal recessive non-syndromic deafness among the Japanese are caused by mutations in the Cx26 gene.

Alleles↗

A pitch glide activates an intermediate response between auditory N1 and mismatch negativity.

Pitch glides of a continuous tone elicit auditory N1-like responses. However, their characteristics have not well been investigated, and it remained unclear whether the response is an auditory true N1 or the mismatch negativity (MMN). We found here that a rapid pitch glide activates almost the same response as a true N1. On the contrary, as the rate of the pitch glide decreases, the response continuously varies the characteristics from true N1 to MMN. This suggests that there would exist intermediate responses between auditory N1 and MMN.

Acoustic Stimulation↗

Hepatic cytochrome P450 and flavin-containing monooxygenase in male Nts:Mini rat, a transgenic rat carrying antisense RNA transgene for rat growth hormone.

We investigated the characteristics of hepatic cytochrome P450s and flavin-containing monooxygenase 1 (FMO1) in male Nts:Mini rats, a Wistar/Jcl-derived transgenic rat strain showing less plasma GH concentration than the parental strain. The total hepatic P450 contents of Mini rats were significantly reduced. A suppression was observed in the activities and protein expression of male-specific P450s (CYP3A and CYP2C11) and was speculated to be a potential cause of the reduction in total P450 contents. The activity and protein expression of CYP2B1 were suppressed and those of CYP2E1 and CYP2B2 were enhanced. With the exception of our data on CYP2B1, these results largely agreed with previous reports concerning GH-depletion rat models (hypophysectomized rats, rats neonatally treated with glutamate, and dwarf rats), implying that the changes in Mini rats were caused by GH insufficiency. The liver FMO1 protein expression in Mini rats was higher than that in Wistar rats but the activity was comparable, suggesting that GH is not a positive regulator of FMO expression. With their insufficient but not depleted levels of plasma GH, Mini rats may thus become another candidate for use in the investigation of GH regulation of hepatic mixed-function monooxygenases.

Animals↗

Application of temporal subtraction for detection of interval changes on chest radiographs: improvement of subtraction images using automated initial image matching.

The authors developed a temporal subtraction scheme based on a nonlinear geometric warping technique to assist radiologists in the detection of interval changes in chest radiographs obtained on different occasions. The performance of the current temporal subtraction scheme is reasonably good; however, severe misregistration can occur in some cases. The authors evaluated the quality of 100 chest temporal subtraction images selected from their clinical image database. Severe misregistration was mainly attributable to initial incorrect global matching. Therefore, they attempted to improve the quality of the subtraction images by applying a new initial image matching technique to determine the global shift value between the current and the previous chest images. A cross-correlation method was employed for the initial image matching by use of blurred low-resolution chest images. Nineteen cases (40.4%) among 47 poor registered subtraction images were improved. These results show that the new initial image matching technique is very effective for improving the quality of chest temporal subtraction images, which can greatly enhance subtle changes in chest radiographs.

Humans↗

Comparison of the quality of temporal subtraction images obtained with manual and automated methods of digital chest radiography.

The authors have been developing a fully automated temporal subtraction scheme to assist radiologists in the detection of interval changes in digital chest radiographs. The temporal subtraction image is obtained by subtraction of a previous image from a current image. The authors' automated method includes not only image shift and rotation techniques but also a nonlinear geometric warping technique for reduction of misregistration artifacts in the subtraction image. However, a manual subtraction method that can be carried out only with image shift and rotation has been employed as a common clinical technique in angiography, and it might be clinically acceptable for detection of interval changes on chest radiographs as well. Therefore, the authors applied both the manual and automated temporal subtraction techniques to 181 digital chest radiographs, and compared the quality of the subtraction images obtained with the two methods. The numbers of clinically acceptable subtraction images were 147 (81.2%) and 176 (97.2%) for the manual and automated subtraction methods, respectively. The image quality of 148 (81.8%) subtraction images was improved by use of the automated method in comparison with the subtraction images obtained with the manual method. These results indicate that the automated method with the nonlinear warping technique can significantly reduce misregistration artifacts in comparison with the manual method. Therefore, the authors believe that the automated subtraction method is more useful for the detection of interval changes in digital chest radiographs.

Humans↗

Down regulation of peroxisome proliferator-activated receptorgamma expression by inflammatory cytokines and its reversal by thiazolidinediones.

AIMS/HYPOTHESIS: Previous studies show that inflammatory cytokines play a part in the development of insulin resistance. Thiazolidinediones were developed as insulin-sensitizing drugs and are ligands for the peroxisome proliferator-activated receptory (PPARgamma). We hypothesized that the anti-diabetic mechanism of thiazolidinediones depends on the quantity of PPARgamma in the insulin resistant state in which inflammatory cytokines play a part. METHODS: We isolated rat PPARgamma1 and gamma2 cDNAs and examined effects of various cytokines and thiazolidinediones on PPARgamma mRNA expression in rat mature adipocytes. RESULTS: Various inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6 and leukaemia inhibitory factor decreased PPARgamma mRNA expression. In addition, hydrogen peroxide, lysophosphatidylcholine or phorbol 12-myristate 13-acetate also decreased the expression of PPARgamma. The suppression of PPARgamma mRNA expression caused by 10 nmol/l of TNF-alpha was reversed 60% and 55% by treatment with 10(-4) mol/l of troglitazone and 10(-4) mol/l of pioglitazone, respectively. The suppression of glucose transporter 4 mRNA expression caused by TNF-alpha was also reversed by thiazolidinediones. Associated with the change of PPARgamma mRNA expression, troglitazone improved glucose uptake suppressed by TNF-alpha. CONCLUSION/INTERPRETATION: Our study suggests that inflammatory cytokines could be factors that regulate PPARgamma expression for possible modulation of insulin resistance. In addition, we speculate that the regulation of PPARgamma mRNA expression may contribute to the anti-diabetic mechanism of thiazolidinediones.

Adipocytes↗