Decreased serum ubiquinol-10 levels in healthy subjects during exercise at maximal oxygen uptake.
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Adult↗
Biomedical subjects
T Okamoto
Publications and source records attributed to T Okamoto.
Management of hyperthyroidism due to Graves' and nodular diseases.
Endocrine surgeons have had an important role in the management of hyperthyroidism due to either Graves' disease or toxic nodule(s). Since alternative treatments such as antithyroid drugs or radioiodine are also available, the decision-making for management should be based on clear assessment of advantages and limitations of each of the treatment options. Surgery provides rapid resolution of these conditions, and cure rates are high, although it may be associated with perioperative complications and postoperative thyroid dysfunction. The authors' experience in the surgical treatment of hyperthyroidism and a review of the recent literature are outlined in this report.
Graves Disease↗
Prevention of renal cell carcinoma by active vitamin D3.
We studied the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D (Vit D)] in patients with renal cell carcinoma (RCC) and the influence of 1,25(OH)2D3 (Vit D3) on gap junctional intercellular communication (GJIC) during carcinogenesis. The serum Vit D levels were measured by a competitive protein-binding assay using the chromatographic method. Using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, noncytotoxic concentrations of Vit D3 and the tumor promoters N-nitrosodimethylamine (NDMA) and N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested against cultured human renal proximal tubular cells (HRPTCs). GJIC function was assayed by the scrape-loading dye transfer technique. Cx43 mRNA expression was also examined by the reverse transcriptase-polymerase chain reaction (RT-PCR). Serum Vit D levels in patients with RCC were lower than those in controls (p< 0.001). Patients with T3 to T4 (rapid-growth) tumors had lower levels of Vit D than did patients with T1 to T2 (slow-growth) tumors (p < 0.001). Vit D3 enhanced the GJIC function of HRPTCs (p < 0.05), whereas NDMA and EHEN suppressed it (p < 0.05). When the cells were treated with tumor promoters and Vit D3 simultaneously, the GJIC functions remained at pretreatment levels. We also demonstrated Cx43 mRNA expression in RPTECs treated with EHEN and VitD3 simultaneously. These data suggest that a decrease in the serum Vit D level is one of the risk factors for development and progression of RCC, and Vit D3 may prevent RCC by preserving GJIC during carcinogenesis.
Adult↗
Early detection of relapse and evaluation of treatment for mixed chimerism using fluorescence in situ hybridization following allogeneic hematopoietic cell transplant for hematological malignancies.
In order to detect chimerism, fluorescence in situ hybridization (FISH) and cytogenetic analyses were performed on bone marrow cells from 47 patients with hematological malignancies following allogeneic hematopoietic cell transplant (HCT). The dual-color XY, major Bcr-Abl (M-Bcr-Abl), and specific alpha-satellite probes were used for sex-mismatched HCT, chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) cases with karyotypic abnormalities before HCT, respectively. Donor cells were found using FISH analysis in all 32 cases examined within 2 months following HCT, confirming engraftment. In six cases, however, cytogenetic analysis failed to detect donor cells due to lack of metaphases. Relapse occurred in four of the six cases in which mixed chimerism was detected using FISH analysis after 6 months of HCT. In contrast, after 12 months of HCT, no relapse was found in 24 patients without host cells. For two patients with mixed chimerism, gradual reduction of immunosuppressants or donor lymphocyte infusion resulted in the disappearance of host cells as analyzed using FISH analysis. In three extramedullary relapse cases, however, cytogenetic relapse preceded morphological and FISH relapse. These findings suggest that FISH analysis is more useful for detecting residual host cells after HCT, and the combination of FISH and cytogenetic analyses provide a more detailed evaluation for HCT patients. The results also indicate that monitoring of mixed chimerism using FISH analysis after 6 months of HCT is important for allowing the early detection of hematological relapse.
Female↗
Efficiency of adenovirus-mediated gene transfer into hepatocytes by liver asanguineous perfusion method.
Efficient targeted gene delivery is essential for successful gene therapy. In this study, we examined the liver asanguineous perfusion method (LAP) for adenovirus-mediated gene transfer to the liver from the standpoints of efficiency, tissue-specificity and safety. The adenoviral vector containing the E. coli LacZ gene driven by the CAG promoter was delivered to the livers of rats by LAP. This method involves selective in situ perfusion, with the liver isolated by clamping of the afferent and efferent blood vessels to prevent adenoviral vector dissemination and genetic modification of nonhepatic organs. We demonstrated that gene transfer to the liver by LAP was not uniform, but more efficient than by intravenous (i.v.) or intraportal (i.p.) infusion, and caused no obvious liver damage or high mortality. As determined by specific histochemical staining and polymerase chain reaction, the amount of vector DNA transferred to the nonhepatic organs by LAP was significantly less than that transferred by the other two methods. Our data suggest that LAP is clearly superior to i.v. or i.p. infusion in terms of efficiency, specificity and safety of gene delivery to the liver. Further reduction in surgical risk is needed for the clinical application of gene therapy.
Adenoviridae↗
Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease.
Elemental diet (ED) therapy has been established as primary therapy for Crohn's disease, and home enteral nutrition (HEN) has been reported to control relapse at a dose of more than 30kcal/kg of ideal body weight. However, a decrease in ED compliance with long-term use is becoming problem. We developed an n-3 fatty acid-rich diet and carried out nutritional education specifically for Crohn's disease patients using HEN to facilitate compliance and to improve their nutritional status. After the introduction of this n-3 rich diet, disease activity was not altered, and nutritional status, especially serum n-3 fatty acid levels, improved. The remission periods in patients with poor compliance seemed to be prolonged by the nutritional education. Thus, a n-3 rich diet in combination with nutritional education specific for Crohn's disease patients is very important for the in maintenance of high compliance and for maintaining nutritional balance.
Adolescent↗
Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats.
Butyrate enemas have been reported to be effective in ulcerative colitis. However, long-term use is difficult because of the troublesome procedure and the unpleasant smell. We therefore investigated the effects of the oral administration of Clostridium butyricum M588 (CBM588), an enterobacterium producing butyrate, in dextran sodium sulfate (DSS)-induced colitis in rats. First, we confirmed the effects of pre-treatment with a butyrate enema on DSS colitis. We then studied the efficacy of oral administration of CBM588 which was started 1 week prior to the induction of DSS colitis. In the CBM588 group, the ulcer index and myeloperoxidase (MPO) activity in the distal colon were significantly lower than in the control group. Proliferating cell nuclear antigen (PCNA) immuno-positive cells were increased around the ulcer in the CBM588 group. In regard to the contents of the cecum and colon, the proportions of Lactobacillus and Eubacterium were increased in the cecum in the CBM588 group. Further, there were significant increases of n-butyrate, propionate, and acetate concentrations in the cecum in the CBM588 group. These results indicated that the oral administration of CBM588 alleviated DSS-induced colitis, and may be useful instead of butyrate enema.
Acetates↗
Generalized peritonitis due to spontaneously perforated pyometra presenting as pneumoperitoneum: report of a case.
We report a rare case of generalized peritonitis due to a ruptured pyometra in an 86-year-old woman, and also conduct a review of the previous Japanese literature. The patient presented with muscle guarding and rebound tenderness. Computed tomography (CT) disclosed a cystic mass in the peritoneal cavity, in which an air-fluid level was noted. Pneumoperitoneum around the uterus due to gas production of anaerobic bacteria was noted on a CT. At laparotomy, the uterus was markedly enlarged with a necrotic area on the uterine fundus, which was found to be perforated. A supravaginal hysterectomy and drainage were performed. We found only eight cases of a ruptured pyometra presenting as pneumoperitoneum in the Japanese literature between 1977 and 1999. The most common cause of pneumoperitoneum is a perforation of the gastrointestinal tract. However, other possible causes, as seen in our patient, should also be taken into consideration. Although it is rare, a perforated pyometra should therefore also be considered when elderly women present with acute abdominal pain.
Aged↗
Rib metastasis appearing 8 years after surgery for lung cancer: report of a case.
A 39-year-old man underwent a right upper lobectomy and lymph node dissection for right lung adenocarcinoma on March 7, 1988. He was referred for an evaluation of a systemic bone scintillation scan on October 29, 1996. A hot spot at the right fourth rib was recognized. After performing needle aspiration cytology, a diagnosis of adenocarcinoma was made. This case was considered to be rib metastasis occurring 8 years after surgery for lung cancer. In general, regular follow-up examinations are performed for at least 5 years after surgery; however, surgeons should also keep such late metastatic cases in mind.
Adenocarcinoma↗
A case of chronic hepatitis C developing insulin-dependent diabetes mellitus associated with various autoantibodies during interferon therapy.
We report a case of chronic hepatitis C presenting insulin-dependent diabetes mellitus (IDDM) associated with various autoantibodies including possible anti-insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis received IFN therapy. The thyroid function was well-controlled by administration of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks after starting IFN (reaching 530 million units of total dose), marked thirst happened, with increased fasting plasma glucose level (488 mg/dl) and decreased daily urinary C peptide immunoreactivity level (less than 4.2 microg/day). IDDM occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA, and thyroid autoantibodies titers increased, but without pancreatic islet cell antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was stopped and insulin treatment was started, but plasma glucose level was not controlled well. AIRA became negative 2 months later, however, insulin antibody (IA) was positive when tested after 18 months. Serum HCV RNA has been negative, and a normal level of serum transaminase has been observed since IFN therapy. It is likely that IFN therapy induced the immunological disturbance and resulted in occurrence of various autoantibodies and IDDM in the patient.
Antibodies, Antinuclear↗
Transient treatments with L-glutamate and threo-beta-hydroxyaspartate induce swelling of rat cultured astrocytes.
We characterized swelling of rat cultured astrocytes induced by L-glutamate and its analogues. Among L-glutamate receptor agonists, L-glutamate, L-aspartate, L-cysteic acid, DL-homocysteic acid, quisqualate and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) increased astrocytic intracellular volume (3H-OMG space), while kainate, and N-methyl-D-aspartate did not. Threo-beta-hydroxyaspartate (TBHA), D-aspartate and L-trans-pyrrolidine-2,4-dicarboxylic acid, high-affinity substrates for Na+-dependent L-glutamate transporters, increased astrocytic 3H-OMG space. L-Glutamate (0.5 mM) increased astrocytic 3H-OMG space to 300% of control in 40-60 min. The increase in 3H-OMG space by 1 mM TBHA was comparable to the L-glutamate-induced one. After a 10 min-exposure to 0.5 mM L-glutamate, astrocytic 3H-OMG space was further increased to 200% even in the absence of L-glutamate. Astrocytes transiently exposed to L-glutamate did not increase their cell volume in K+-free medium and in the presence of 1 mM ouabain, a Na+-K+ ATPase inhibitor. The increase after a transient exposure was also observed by a treatment of 1 mM TBHA, but not by 0.5 mM quisqualate. These results suggest that the volume increases after a transient treatment are mediated by activation of Na+-dependent L-glutamate transporter.
3-O-Methylglucose↗
Genetic instability in intestinal metaplasia is a frequent event leading to well-differentiated early adenocarcinoma of the stomach.
To understand the development of well-differentiated adenocarcinoma in the stomach, we examined genetic instability in 31 patients with stage Ia gastric cancer. Triplets of tissue specimens (normal/metaplasia/tumour) from 33 lesions were examined for microsatellite instability (MSI) and loss of heterozygosity (LOH), using nine microsatellite loci. Frameshift mutations in the transforming growth factor beta receptor type II (TGF-betaRII) (A)(10), Bcl-2-associated X protein (BAX) (G)(8), hMSH3 (A)(8) and hMSH6 (C)(8) genes were also studied. In this study, a high incidence of MSI (MSI-H) was defined as samples containing 30% or more MSI positive loci, and a low incidence of MSI (MSI-L) as samples which had less than 30% MSI. MSI-L was observed in 19 cancerous lesions (58%), and MSI-H in three (9%). Eleven intestinal metaplasia lesions (33%) showed MSI-L, but no metaplasia lesions exhibited MSI-H. Frameshift mutation was observed in only one cancerous lesion (3%) at the (A)(10) tract of TGF-betaRII. In contrast, LOH was observed in 24 cancerous lesions (73%), and in 15 (45%) of intestinal metaplasia lesions. Intriguingly, these alterations tend to be coincident between metaplasia and cancerous lesions in the same sets of specimens, and there was no case that showed alterations in metaplasia, but not in cancerous lesions. These findings suggest that metaplasia and well-differentiated adenocarcinoma in the stomach may have the same molecular backgrounds, and that these two lesions may be chronologically connected.
Adenocarcinoma↗
Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection.
AIDS and the bare lymphocyte syndrome (BLS) are severe combined immunodeficiencies. BLS results from mutations in genes that regulate the expression of class II major histocompatibility (MHC II) determinants. One of these is the class II transactivator (CIITA). HIV and its transcriptional transactivator (Tat) also block the expression of MHC II genes. By binding to the same surface in the cyclin T1, which together with CDK9 forms the positive transcription elongation factor b (P-TEFb) complex, Tat inhibits CIITA. CIITA can also activate transcription when tethered artificially to RNA. Moreover, a dominant-negative CDK9 protein inhibits the activity of MHC II promoters. Thus, CIITA is a novel cellular coactivator that binds to P-TEFb for the expression of its target genes.
Animals↗
Total and prolonged filling of the lungs with Ringer's solution under extracorporeal lung assist (ECLA) in dogs.
BACKGROUND: Massive alveolar lavage has been used clinically to remove materials accumulated in the alveoli. Recently, filling the lungs with oxygenated perfluorochemical (total liquid ventilation) has been investigated. However, effects of complete and prolonged filling of bilateral lungs with aqueous fluid, such as saline or Ringer's solution, has not been evaluated, although it is possible to sustain gas exchange without the natural lung by using extracorporeal circulation and an artificial lung (extracorporeal lung assist: ECLA). It is also not known whether the lung can recover gas exchange ability after prolonged fluid filling. METHODS: Normal mongrel dogs were endotracheally intubated under general anesthesia and mechanically ventilated. After initiation of venoarterial ECLA, warmed lactated Ringer's solution was instilled into the lungs through the endotracheal tube, and the lungs were completely filled at a hydrostatic pressure of 15 cmH2O (fluid-filled group: group F). After the lungs were filled for 4 h, the fluid was drained and ventilation was re-instituted. ECLA, then mechanical ventilation was gradually weaned within 24 h after fluid drainage. In control group (group C), dogs were kept apneic for 4 h with their lungs inflated at an airway pressure of 15 cmH2O with air. RESULTS: Transient hypoxemia occurred during fluid filling but every dog could be weaned from ECLA and mechanical ventilation to spontaneous respiration. The average rate of fluid absorption from the lung during fluid filling was 4.2+/-1.8 ml kg(-1) h(-1). After fluid drainage and restart of mechanical ventilation, bilateral lungs were expanded and well aerated. Total static respiratory system compliance (static compliance) remained unchanged even after fluid filling, and the weight of the lung water did not increase significantly compared to that in group C. Total urine volume was significantly increased in group E Histologically, alveolar structures were preserved and no interstitial edema or bleeding was seen in either group. CONCLUSION: Complete filling of the bilateral lungs for 4 h with lactated Ringer's solution under ECLA causes no deterioration in gas exchange or static compliance in normal dogs, although transient hypoxemia occurs during fluid filling.
Animals↗
Microarray fabrication with covalent attachment of DNA using bubble jet technology.
We have developed a method for fabricating DNA microarrays that uses a Bubble Jet ink jet device to eject 5'-terminal-thiolated oligonucleotides to a glass surface. The oligonucleotides are covalently attached to the glass surface by heterobifunctional crosslinkers that react with the amino group on the substrate and a thiol group on the oligonucleotide probe. Using this method, we fabricated DNA microarrays that carried 64 groups of 18-mer oligonucleotides encoding all possible three-base mutations in the mutational "hot spot" of the p53 tumor-suppressor gene. These were screened with a fluorescently labeled synthetic 18-mer oligonucleotide derived from the p53 gene, or segments of the p53 gene that had been PCR amplified from genomic DNA of two cell lines of human oral squamous cell carcinoma (SCC). This allowed us to discriminate between matched hybrids and 1 bp-mismatched hybrids.
Base Sequence↗
The expression and localization of neutral endopeptidase 24.11/CD10 in human gestational trophoblastic diseases.
Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptidase that hydrolyzes various bioactive peptides. NEP is distributed in both normal and neoplastic cells and plays a functional role by modulating cellular responses to peptide substrates. Recently, NEP has been shown to be expressed in normal placental trophoblasts, suggesting its physiological role during pregnancy. In the present study, we investigated the expression of NEP in hyperplastic and anaplastic trophoblasts in gestational trophoblastic diseases (GTDs). Flow cytometric analysis demonstrated that NEP was expressed in all choriocarcinoma cell lines examined. The NEP enzyme activity in these cell lines correlated with cell-surface protein levels and was abolished by the NEP inhibitor phosphoramidon. On immunoblot analysis, NEP protein was detected in both hydatidiform mole and choriocarcinoma tissues as a double band of 95 and 100 kDa similar to that of the normal placental tissues. Immunohistochemical analysis revealed that NEP was present on syncytiotrophoblasts, while no or very faint NEP immunoreactivity was observed on cytotrophoblasts in the normal placenta. Similarly, NEP in hydatidiform mole and invasive mole was localized on the membrane of syncytiotrophoblasts, but not on hyperplastic cytotrophoblasts. In contrast, in choriocarcinoma, NEP was highly expressed not only on syncytiotrophoblastic cells but also on invading anaplastic cytotrophoblasts. In addition, NEP was also expressed on intermediate trophoblasts in placental site trophoblastic tumors. In summary, this is the first study demonstrating the expression of NEP/CD10 in GTDs. The differential localization of NEP among various trophoblastic tumors suggests that NEP may play a functional role in the regulation of trophoblast transformation and human chorionic gonadotropin secretion.
Blotting, Western↗
Association of cytomegalovirus interstitial pneumonitis with HLA-type following allogeneic bone marrow transplantation.
Certain human leukocyte antigens may increase the risk of cytomegalovirus interstitial pneumonitis, an important complication of bone marrow transplantation. The prevalence of this pneumonitis was compared between patients possessing either HLA-B51 or HLA-B52 and patients without either antigen. The role of tumor necrosis factor-alpha in cytomegalovirus interstitial pneumonitis was also studied. Among 72 patients undergoing allogeneic bone marrow transplantation at our institution during the past 5 years, HLA-B51 or -B52 was detected in 29. Among these 29 patients, 13 (45%) developed cytomegalovirus interstitial pneumonitis, a significantly higher rate (P < 0.001) than among patients without these HLA types (4/43, 9%). In the pre-conditioning and stable phases, tumor necrosis factor-alpha levels were higher in patients with HLA-B51 or HLA-B52 than in patients without (P < 0.05; t-test). Throughout the period from pre-conditioning to around day 40, except on day 0, tumor necrosis factor-alpha levels were also significantly higher (P < 0.05 to P < 0.001) in patients developing cytomegalovirus infection than in those without it. These results suggest that HLA-B51 and HLA-B52 may be risk factors for cytomegalovirus interstitial pneumonitis after bone marrow transplantation, with an increase of tumor necrosis factor-alpha also being involved.
Adolescent↗
Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage fluids as early detection of acute GVHD following BMT: evidence of a significant relationship.
We evaluated the relationship between CMV and human herpes virus-6 (HHV-6) reactivation and the incidence of grades 2 to 4 acute GVHD post BMT. Bronchoalveolar lavage fluid (BALF) samples extracted from 54 BMT recipients on post-BMT day 35 were analyzed by PCR for detection of CMV DNA, HHV-6 DNA and CMV plus HHV-6 DNA. CMV DNA was detected in 26 patients and 13 (50%) developed grades 2 to 4 acute GVHD. Of the 28 who were CMV negative, only six (21.4%) developed grades 2 to 4 acute GVHD. HHV-6 was detected in 18 patients, and 11 (61.1%) developed grades 2 to 4 acute GVHD. Of the 36 who were HHV-6 negative, only eight (22.2%) developed grades 2 to 4 acute GVHD. CMV and HHV-6 were detected in 13 patients, and eight (61.5%) developed grades 2 to 4 acute GVHD. Of the 23 who were negative for both CMV and HHV-6, only three (13%) developed grades 2 to 4 acute GVHD. In all experiments, the difference between the groups was significant (P<0.05, P<0.05 and P<0.01, respectively). We conclude that herpes virus infection, in particular CMV concurrent with HHV-6 reactivation, is predictive of moderate to severe acute GVHD.
Adolescent↗