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Biomedical subjects

T Sakaguchi

Publications and source records attributed to T Sakaguchi.

At least 19 recordsLinked to original sources
PubMed2006

Babesia parasites develop and are transmitted by the non-vector soft tick Ornithodoros moubata (Acari: Argasidae).

Ornithodoros moubata ticks were fed on blood infected with Babesia equi. However, the parasites were quickly cleared as evidenced by the disappearance of B. equi-specific ribosomal RNA from the ticks. We hypothesized that if the Babesia parasite can escape midgut-associated barriers a non-vector tick can become infected with Babesia. To test this hypothesis, B. equi parasite-infected blood from in vitro culture was injected into the haemocoel of ticks. B. equi-specific rRNA was surprisingly detected 45 days after injection even in the eggs. Babesia-free dogs were infested with O. moubata ticks that were infected by inoculation with B. gibsoni-infected red blood cells. Parasitaemia and antibody production against Bg-TRAP of B. gibsoni increased gradually. These results indicate that O. moubata may be a useful vector model for Babesia parasites and also a very important tool for studies on tick immunity against Babesia parasites and tick-Babesia interactions.

Animals↗
PubMed2006

Direct maxacalcitol injection into hyperplastic parathyroids improves skeletal changes in secondary hyperparathyroidism.

Direct maxacalcitol (OCT) injection into a parathyroid gland (PTG) ameliorates several important etiologic factors of resistance to medical treatments for secondary hyperparathyroidism (s-HPT): the upregulations of vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in PTGs and the regression of PTG hyperplasia by the induction of apoptosis. In this study, we evaluated the bone histomorphology on the basis of maintaining these effects in advanced s-HPT. Five/six nephrectomized Sprague-Dawley rats were fed a high-phosphorus and low-calcium diet for 8 weeks. These rats were divided into four treatment groups: (1) basic uremic (at the baseline), (2) direct OCT single injection into PTGs (DI-OCT) followed by OCT intravenous administration for 4 weeks (IV-OCT), (3) direct vehicle injection and IV-OCT, and (4) no treatment for an additional 4 weeks. The effects of these treatments on serum intact-parathyroid hormone (PTH) level, PTG weight, VDR and CaSR expression levels in PTGs, and bone histomorphometric parameters were investigated. In the DI-OCT+IV-OCT group, the significant decrease in serum intact-PTH level was maintained by the following IV-OCT. A significant decrease in PTG weight and the upregulations of VDR and CaSR expression levels in PTGs were also observed. Bone histomorphometric analysis showed significant improvements in osteitis fibrosa in both cancellous and cortical bones. However, these findings were not observed in the other groups. These results suggest that osteitis fibrosa caused by advanced s-HPT can be successfully reversed by a control of PTH at an appropriate level through the improvement of PTG hyperplasia as induced by DI-OCT+IV-OCT.

Animals↗
PubMed2006

Direct injection of calcitriol or its analog into hyperplastic parathyroid glands induces apoptosis of parathyroid cells.

Hyperplasia of the parathyroid gland (PTG) is associated not only with excessive secretion of parathyroid hormone (PTH) but also with changes in the parathyroid cell (PTC) characteristics (i.e. hyperproliferative activity, and low contents of vitamin D and calcium-sensing receptors). Control of PTG hyperplasia is most important in the management of secondary hyperparathyroidism, but the advanced stage of hyperplasia is considered irreversible. In the present study, dialysis patients with PTG hyperplasia underwent direct injection of calcitriol or maxacalcitol (OCT) into the PTG. Ultrasonography showed that this treatment had significantly reduced PTG volume and tissue analysis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method and DNA electrophoresis indicated that cellular apoptosis had been induced. The mechanism of apoptosis was evaluated in detail in uremic rats fed a high-phosphate diet. OCT or its vehicle was directly injected into the rats' PTGs. In the PTGs treated by OCT, there was a significantly increased number of TUNEL-positive PTCs and DNA electrophoresis revealed the characteristic ladder pattern of DNA fragmentation, both findings indicative of apoptosis. There was also a significant upregulation of both vitamin D and Ca-sensing receptors in the PTCs and a clear shift of the Ca-PTH response curve to the left and downward. None of these findings was observed in the PTGs treated by vehicle. This novel treatment is successful in causing regression of PTG hyperplasia. Thus, it is expected to significantly reduce the PTH level and ameliorate the abnormal bone turnover and mineral metabolism.

Animals↗
PubMed2005

Three novel polymorphisms in the beta globin gene.

We report on three novel polymorphisms in and around the beta globin gene. Two of them are intronic (IVS2) polymorphisms (IVS 2 nt 200-203 (-CTTT) and IVS2 82-83 (-AG)). The third is a novel G-->C substitution at nt +1707 related to the beta globin cap site. This +1707 G-->C polymorphism was detected in 23.5% of chromosomes among 140 samples from India. It seems to be a novel but common polymorphism among Indians. There was no linkage between these novel polymorphisms and any beta thalassemia mutation.

Adult↗
PubMed2005

Isolated colonic hernia through the esophageal hiatus.

We report on a 75-year-old woman with an isolated colonic hernia through the esophageal hernia. The patient had suffered from cough, palpitation and dyspnea. A chest X-ray showed a colon loop gas in the mediastinum. Simultaneous barium swallow and enema showed the herniation of the only transverse colon into the mediastinum and displacement of the distal esophagus by the migrated colon. The patient underwent an open-mesh cruroplasty and a Hill's posterior gastropexy. The postoperative clinical course was uneventful. The patient has cessation of the symptoms. To our knowledge, there are only five reports presenting patients with isolated colonic hernia through the esophageal hiatus, including our case.

Aged↗
PubMed2004

Large-scale isolation of ESTs from medaka embryos and its application to medaka developmental genetics.

The medaka is becoming an attractive model organism for the study of vertebrate early development and organogenesis and large-scale mutagenesis projects that are aimed at creating developmentally defective mutants are now being conducted by several groups in Japan. To strengthen the study of medaka developmental genetics, we have conducted a large-scale isolation of ESTs from medaka embryos and developed tools that facilitate mutant analysis. In this study, we have characterized a total of 132,082 sequences from both ends of cloned insert cDNAs from libraries generated at different stages of medaka embryo development. Clustering analysis with 3-prime sequences finally identified a total of 12,429 clusters. As a pilot analysis, 924 clusters were subjected to in situ hybridization to determine the spatial localization of their transcripts. Using EST sequence data generated in the present study, a 60-mer oligonucleotide microarray with 8,091 unigenes (Medaka Microarray 8K) was constructed and tested for its usefulness in expression profiling. Furthermore, we have developed a rapid and reliable mutant mapping system using a set of mapped EST markers (M-marker 2003) that covers the entire medaka genome. These resources will accelerate medaka mutant analyses and make an important contribution to the medaka genome project.

Animals↗
PubMed2004

An interplay of alleviating mutations in the clinical phenotype of beta-thalassaemia intermedia.

Prediction of a beta-thalassaemia major phenotype from the beta-genotype is generally relatively straightforward. However, despite the ability to accurately define the beta-thalassaemia mutations, prediction of a beta-thalassaemia intermedia phenotype from the genotype sometimes remains problematic and this has important implications in genetic counselling and prenatal diagnosis. We report a 11-year-old Indian male child with a thalassaemia intermedia phenotype. beta-Globin gene analysis of the family showed that he was a compound heterozygote with the -88 (C-->T) beta+-mutation and the IVS1 nt 130 (G-->C) beta0-mutation. Both these mutations are rare among Indians. The propositus was also found to be heterozygous for the XmnI polymorphism and had a normal alpha-genotype. In this family interplay of two alleviating mutations (a milder promoter mutation along with a gene for raised HbF) might have synergistically compensated for lack of globin chains in the patient. Hence, the nature of the beta-genotype as well as the knowledge of the presence or absence of alleviating factors will help the clinician to decide whether early commencement of a regular transfusion regime is necessary.

Child↗
PubMed2004

T-shaped re-anastomosis of graft for outlet obstruction after free jejunal graft.

We experienced three patients with persistent outlet obstruction after free jejunal graft and performed T-shaped re-anastomosis for relief of this symptom. Two patients underwent a laryngopharyngectomy for hypopharyngeal cancer and the other patient underwent a laryngopharyngectomy and total esophagectomy for concurrent hypopharyngeal cancer and esophageal cancer. We reconstructed alimentary conduit by a free jejunal reconstruction without using surgical microscopes. In brief, a graft vein and the internal jugular vein were anastomosed and a graft artery and the carotid artery were anastomosed. Then, the anastomosis of pharyngojejunostomy was carried out in a side-to- end fashion, followed by an end-to- end jejunesophagostomy. In a T-shaped re-anastomosis, the flexure of the transplanted jejunum was separated by GIA (US Surgical Corporation, Norwalk, CT, USA). In cases where the efferent part was redundant, the proximal or distal site was resected and straightened in order to avoid outlet stasis. After this, the end-to-side anastomosis between the efferent part and the bottom of proximal horizontal portion of the graft was performed by CDH (Ethicon, Somerville, NJ, USA) or Olsen's one layer method. These three patients received this operation and were relieved from persistent dysphagia. This method is a safe and easy procedure for relief from dysphagia and for recovery of quality of life for patients with this complication. However, it is of utmost importance to perform a reconstruction followed by profluent passage at the first operation.

Aged↗
PubMed2003

Safety and growth suppressive effect of intra-hepatic arterial injection of AdCMV-p53 combined with CDDP to rat liver metastatic tumors.

Surgical resection is thought to be the best treatment for liver carcinoma, including hepatocellular carcinoma and metastatic liver carcinoma if there are a small number of tumors. Liver carcinoma is one of the main causes of death from cancer worldwide. The prognosis of liver carcinoma is still poor. Mutation of p53, which is well known as a tumor suppressor gene, is observed in many cases of advanced liver carcinoma. Cancer gene therapy using p53, which transduces the wild-type p53 gene in the tumor, is a promising new strategy for treating liver carcinoma. Selective and less invasive gene delivery to the liver tumor is necessary for clinical liver tumor gene therapy. The first purpose of the current study was to determine the best way to deliver the gene of interest to the liver tumor selectively. The second purpose was to study the tumor suppressive effect of intrahepatic arterial injection of an adenovirus vector with the p53 gene (AdCMV-p53), followed by administration of CDDP and noting its side effects. We injected AdCMV-LacZ via hepatic arteries of rats bearing RCN-9 colon cancer metastasis in the liver. Injection via the hepatic artery resulted in more successful gene transduction to the liver tumor in a tumor-selective manner than did injection via the portal vein. At 48 hrs after arterial injection of AdCMV-p53, CDDP (3 mg/kg) was administered in the peritoneal cavity of each rat. The use of CDDP with arterial injection of AdCMV-p53 resulted in more extensive apoptosis in the rat liver tumors without any deterioration in liver function. In conclusion, hepatic arterial injection of an adenovirus vector is better than portal vein injection for gene transduction efficiency, and causes no liver function disorder even when the injection is combined with CDDP.

Adenoviridae↗
PubMed2002

Adult case of squamous cell carcinoma arising on congenital esophageal stenosis due to fibromuscular hypertrophy.

This study relates to an adult case of squamous cell carcinoma arising on congenital esophageal stenosis. The patient was a 65-year-old man who had suffered from dysphagia and vomiting since birth and was diagnosed as having congenital esophageal stenosis. The patient had not received any treatment because his symptoms were mild. The patients suffered from severe dysphagia since he was 20 years old and had received balloon therapies several times; however, the effects were transient. After admission to our hospital, he underwent a transhiatal esophagectomy without thoracotomy. Histopathological examination of the resected specimen revealed a thick muscular mucosae associated with hypertrophic fibromuscular components and poorly to moderately differentiated squamous cell carcinoma in the region of stenosis. This case report is the first of a patient with squamous cell carcinoma arising on congenital esophageal stenosis.

Aged↗
PubMed2001

Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation.

Hypoxic induction of the early growth response-1 (Egr-1) transcription factor initiates proinflammatory and procoagulant gene expression. Orthotopic/isogeneic rat lung transplantation triggers Egr-1 expression and nuclear DNA binding activity corresponding to Egr-1, which leads to increased expression of downstream target genes such as interleukin-1b, tissue factor, and plasminogen activator inhibitor-1. The devastating functional consequences of Egr-1 up-regulation in this setting are prevented by treating donor lungs with a phosphorothioate antisense oligodeoxyribonucleotide directed against the Egr-1 translation initiation site, which blocks expression of Egr-1 and its gene targets. Post-transplant graft leukostasis, inflammation, and thrombosis are consequently diminished, with marked improvement in graft function and recipient survival. Blocking expression of a proximal transcription factor, which activates deleterious inflammatory and coagulant effector mechanisms, is an effective molecular strategy to improve organ preservation.

Animals↗
PubMed2001

Interleukin-2 receptor beta subunit-dependent and -independent regulation of intestinal epithelial tight junctions.

Interleukin (IL)-15 is able to regulate tight junction formation in intestinal epithelial cells. However, the mechanisms that regulate the intestinal barrier function in response to IL-15 and the involved subunits of the IL-15 ligand-receptor system are unknown. We determined the IL-2Rbeta subunit and IL-15-dependent regulation of tight junction-associated proteins in the human intestinal epithelial cell line T-84. The IL-2Rbeta subunit was expressed and induced signal transduction in caveolin enriched rafts in intestinal epithelial cells. IL-15-mediated tightening of intestinal epithelial monolayers correlated with the enhanced recruitment of tight junction proteins into Triton X-100-insoluble protein fractions. IL-15-mediated up-regulation of ZO-1 and ZO-2 expression was independent of the IL-2Rbeta subunit, whereas the phosphorylation of occludin and enhanced membrane association of claudin-1 and claudin-2 by IL-15 required the presence of the IL-2Rbeta subunit. Recruitment of claudins and hyperphosphorylated occludin into tight junctions resulted in a more marked induction of tight junction formation in intestinal epithelial cells than the up-regulation of ZO-1 and ZO-2 by itself. The regulation of the intestinal epithelial barrier function by IL-15 involves IL-2Rbeta-dependent and -independent signaling pathways leading to the recruitment of claudins, hyperphosphorylated occludin, ZO-1, and ZO-2 into the tight junctional protein complex.

Base Sequence↗
PubMed2001

NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model.

Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-kappaB), plays a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-kappaB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-kappaB decoy, we tested whether the activated NF-kappaB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections of NF-kappaB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-kappaB, is involved in the pathogenesis of neuropathic pain.

Animals↗
PubMed2001

Ultrasound activates the auditory cortex of profoundly deaf subjects.

Using three-dimensional PET, the cortical areas activated by bone-conducted ultrasound were measured from five profoundly deaf subjects and compared with the cortical areas of normal-hearing subjects activated by stimuli through bone-conducted ultrasonic, air-conducted, bone-conducted, and vibro-tactile hearing aids. All of the hearing aids, including the ultrasonic hearing aid, consistently activated the medial portion of the primary auditory cortex of the normal volunteers. The same cortical area was also significantly activated in the profoundly deaf subjects although the percentage increase in regional cerebral blood flow (rCBF) was smaller than in normal subjects. These results suggest that extra-cochlear routes convey information to the primary auditory cortex and can therefore produce detectable sound sensation even in the profoundly deaf subjects, who reported a sensation themselves.

Adult↗
PubMed2001

Emergence of anti-inflammatory monocytes in long-term surviving hosts of IL-10-transduced liver allografts.

We previously reported that transduction of IL-10 to rat liver allografts facilitates survival prolongation after orthotopic liver transplantation (OLT). In the current study, we examined Lewis hosts of IL-10-transduced allografts that had survived longer than 50 days in order to characterize peripheral blood mononuclear cells (PBMC). Phenotype analysis of the PBMC demonstrated an 18-fold increase in monocytes (CD11b/c(+)) with a massive increase in the monocyte/lymphocyte ratio. The monocytes expressed downregulated MHC class II (RT1B) but upregulated Fcgamma receptors in comparison with monocytes from the control hosts. The capacity of enriched monocytes to secrete TNF-alpha in response to LPS stimulation was downregulated in the survivors, while production of IL-10 was comparable. The monocytes from long-term survivors significantly inhibited the donor antigen stimulated secretion of IFN-gamma and IL-2. Monocytosis characterized by a shift to anti-inflammatory monocytes is associated with survival prolongation in the hosts of IL-10 transduced liver allografts.

Animals↗
PubMed2001

Attenuation of a field Sendai virus isolate through egg-passages is associated with an impediment of viral genome replication in mouse respiratory cells.

We investigated the mechanisms responsible for attenuation of mouse pathogenicity of Sendai virus (SeV) through passages in eggs. A highly virulent clone, E0, derived from the field SeV Hamamatsu strain, was successively passaged in hen's eggs. Analysis of the mouse lethal dose 50% (MLD50) of virus clones obtained from the viruses at egg-passages 1, 15, 30 and 50 demonstrated that attenuation of E0 by egg-passage occurred due to the gradual appearance of and replacement by virus variants possessing higher MLD50. Comparison of viral replication in the mouse lung and mouse pathogenicity with the representative SeV clones, E0, E15c12, E30c12 and E50c19, obtained from the respective egg-passages revealed that the low pathogenicity of the egg-passaged clones was due to poor multi-cycle viral replication in the lung. Furthermore, MLD50s of the SeV clones were found to be negatively correlated with the replication capability in primary mouse pulmonary epithelial (MPE) cells; the egg-passaged clones with more attenuated phenotypes showed lower replication capability in MPE cells. In the MPE cells infected with the SeV clones at m.o.i. 10, however, viral protein and mRNA syntheses of the egg-passaged clones were enhanced or comparable to those of the parental E0 clone at 1 day and 2 days post infection (p.i.) but decreased more rapidly thereafter. In contrast, viral genome synthesis of the egg-passaged clones in the cells at 2 days p.i. was several times lower than that of E0. These results strongly suggest that attenuation of a virulent field SeV strain by egg-passage occurs due to the appearance and selection of virus variants possessing poor propagation capacity in mouse respiratory epithelial cells, which is caused primarily by an impediment of viral genome replication.

Animals↗
PubMed2001

A novel strategy of decoy transfection against nuclear factor-kappaB in myocardial preservation.

BACKGROUND: Nuclear factor-kappaB (NFkappaB) is critical for the transcription of multiple genes involved in myocardial ischemia-reperfusion injury. Therefore, we hypothesized that blocking NFkappaB would attenuate ischemia-reperfusion injury after prolonged myocardial preservation, resulting in an improvement in cardiac function. METHODS: Double-stranded oligodeoxynucleotides with a specific affinity for NFkappaB (NFkappaB decoy group) or a scrambled decoy group were transfected into rat hearts using a hemagglutinating virus of Japan-liposome method. After 16 hours of preservation in Euro-Collins solution at 4 degrees C, the cardiac grafts were heterotopically transplanted into recipient rats of the same strain. RESULTS: Fluorescein isothiocyanate staining showed introduction of double-stranded oligonucleotides into the nuclei of endothelial cells and cardiomyocytes. After 1 hour of reperfusion the NFkappaB decoy group showed significantly higher degrees of recovery of left ventricular function as well as significantly lower levels of serum creatine phosphokinase, myocardial water content, tissue IL-8, and neutrophil infiltration than did the scrambled decoy group (p < 0.05). CONCLUSIONS: Gene transfection of the NFkappaB decoy attenuates ischemia-reperfusion injury after prolonged heart preservation. As a result, this method appears to be a novel strategy for enhanced myocardial preservation.

Animals↗