Continuous drop type of orthostatic hypotension.
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Humans↗
Biomedical subjects
T Yokota
Publications and source records attributed to T Yokota.
Vocal cord abductor paralysis in spinocerebellar ataxia type 1.
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Adult↗
Inhibition of human immunodeficiency virus replication by RD6-Y664, a novel benzylhydroxylamine derivative.
We have examined novel benzylhydroxylamine derivatives for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in cell cultures. Among the series, O-(2-chloro-6-fluorobenzyl)hydroxylamine (RD6-Y664) was found to be the most potent inhibitor of HIV-1. The EC50 for HIV-1 strain IIIB was 1.6 micrograms/ml with a selectivity index greater than 38 in MT-4 cells. It also inhibited the replication of other HIV strains including a non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutant, a nucleoside RT inhibitor-resistant mutant and HIV-2, in acutely infected cells. However, the compound did not affect HIV-1 production in chronically infected cells. A time-of-addition experiment and detection of proviral DNA synthesis suggested that RD6-Y664 targeted an early step of the viral replication cycle, presumably a process prior to reverse transcription. In fact, an assay for HIV-1 RT revealed that the compound did not suppress enzyme activity. Furthermore, RD6-Y664 did not show any inhibition of gp120-CD4 interaction, or binding of anti-CXCR4 antibody to CXCR4.
Anti-HIV Agents↗
Mouse model of respiratory syncytial virus infection to evaluate antiviral activity in vivo.
In this study, we have developed a practical mouse model for evaluating in vivo the antiviral activity of compounds against respiratory syncytial virus (RSV) infection. BALB/c mice are not particularly susceptible to RSV infection; however, infection rates were improved by pretreatment with the immunosuppressive agent cyclophosphamide (CYP). When mice were inoculated intranasally with RSV A2 strain, the pulmonary RSV titres of CYP-pretreated 10-week-old mice were higher than those of untreated 10-week-old and 28-week-old mice, peaking on days 4 and 5 post-infection. Sections of lung from RSV-infected mice pretreated with CYP, taken on day 4 post-inoculation, showed widespread evidence of interstitial pneumonia and other significant pathological changes. We also confirmed that ribavirin, a representative antiviral agent, significantly reduced the pulmonary RSV titres of mice pretreated with CYP when administered intraperitoneally.
Animals↗
Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217.
The non-nucleoside reverse transcriptase (RT) inhibitor RD4-2217 is a thiadiazole derivative that has proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. In this study we examined genotypic and phenotypic characteristics of RD4-2217-resistant mutants that have been obtained by serial passage of HIV-1 in MT-4 cells in the presence of increasing concentrations (0.05, 0.25, 1 and 10 microM) of the compound. The strains obtained, III(B/2217RE/0.05) and III(B/2217RE/0.25,) were two- and 15-fold resistant to RD4-2217, respectively, whereas III(B/2217RE/1) and III(B/2217RE/10) displayed 161- and >238-fold resistance, respectively. Both III(B/2217RE/1) and III(B/2217RE/10) had two amino acid substitutions, V1891 and T2401, in the RT. Furthermore, RD4-2217 did not inhibit the replication of an HIV-1 molecular clone, which had the same mutation, at concentrations up to 10 microM, indicating that the V1891 plus T2401 mutation confers high-level resistance to RD4-2217. Interestingly, the replicability of III(B2217RE/1) and III(B/2217RE/10) appeared to be lower than that of wildtype III(B) in MT-4 cells, suggesting that the V1891 plus T2401 mutation may impair the enzymatic activity of HIV-1 RT.
Anti-HIV Agents↗
Emergency abdominal surgery for small bowel perforation secondary to metastatic lung cancer.
Emergency surgery for bowel perforation caused by metastases from lung cancer is rare. Two cases of small bowel perforation due to metastasizing lung cancer are reported. Both patients were admitted as a surgical emergency case. One of the two patients presented herein survived and was discharged from the hospital. Perforated small bowel due to metastatic lung cancer is a highly fatal event that occurs in the late phases of the disease. Despite the poor prognosis, early and appropriate therapy will occasionally yield successful surgical palliation. Patients with known lung cancer who develop abdominal complaints should be examined thoroughly and treated quickly.
Adenocarcinoma↗
Poorly differentiated, solid-type adenocarcinoma of the stomach.
Data of 58 cases of poorly differentiated, solid-type adenocarcinoma of the stomach treated at our hospital between 1985 and 1995 were reviewed and compared to data of 146 cases of non-solid-type carcinoma in order to determine whether there are distinguishable clinicopathological features between these two types of carcinoma. Significant differences were observed with respect to tumor size, stage, macroscopic appearance, depth of invasion, histologic growth pattern, lymph node metastasis, microscopical lymphatic invasion and vascular permeation. Patients in the solid-type cancer group tended to have smaller tumors; the disease was in the early stage in 48% of the patients, and total gastrectomy was performed in only 20 of the 58 patients. Nodal involvement, lymphatic invasion and vascular permeation were also less common in patients with solid-type cancer. The overall survival rate of patients with solid-type carcinoma was higher than that of patients with non-solid-type carcinoma, though no significant differences were observed when corrected for stage. Our results suggest that poorly differentiated solid-type carcinoma of the stomach should be regarded as a distinct type of adenocarcinoma that has a good prognosis. The significant prognostic factors for this type of gastric cancer are lymphatic invasion and tumor location.
Adenocarcinoma↗
Clinicopathologic prognostic features in patients with gastric cancer associated with esophageal or duodenal invasion.
BACKGROUND: We evaluated the influence of several clinicopathologic variables on 5-year survival of patients with gastric cancer associated with esophageal or duodenal invasion, and determined the significance of resection line involvement. PATIENTS AND METHODS: A review of the database for gastric adenocarcinoma at Sendai National Hospital between January 1985 and December 1995 identified 923 patients who underwent gastric cancer resection. Of these patients, 37 were reported to have tumour infiltration of the esophagus or duodenum on histological examination of the resected specimens. Univariate and multivariate analyses of patients with esophageal or duodenal invasion were performed to evaluate the prognostic significance of clinicopathologic features. Then the patients were divided into two groups based on the results of microscopic examination: a tumour wedge-positive group for resection margins of less than 5 mm in width and a tumour wedge-negative group for resection margins of more than 5 mm in width. There were 8 patients in the narrow (margin-positive) group and 29 patients in the wide margin (margin-negative) group, respectively. RESULTS: Univariate analysis revealed that the significant prognostic factors were nodal involvement (p=0.0004) and gross type (p=0.0031). Multivariate analysis of the esophagus or duodenum-invaded cancer cases, however, revealed that only nodal involvement was a significant prognostic factor. There were statistical correlations between these groups (margin-positive and margin-negative groups) and the Borrmann type of tumour and tumour size. The survival rate was worse in patients with tumour line involvement. CONCLUSIONS: Multivariate analysis revealed that the prognosis of patients with esophageal or duodenal invasion was affected only by nodal involvement independently. The risk of surgical margin involvement was high in cases of a large Borrmann type-4 tumour and infiltrative carcinoma.
Adult↗
Malignant fibrous histiocytoma: a method to control intraoperative hemorrhage by clamping the feeding arteries.
Malignant fibrous histiocytoma (MFH), also referred to in the past as malignant fibrous xanthoma and fibroxanthosarcoma, is a tumor of mesenchymal tissue origin. A case of retroperitoneal MFH was reported. In this paper, we describe a method of hemostasis and intraoperative control of hemorrhage during resection of retroperitoneal MFH by snaring the feeding arteries. The patient was successfully operated on using this technique.
Arteries↗
[Ataxia with isolated vitamin E deficiency].
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Ataxia↗
[Surgical treatment of N2 involved non-small cell lung cancer--the systematic extended lymph node dissection based on the regional lymphatic drainage].
From the study on regional lymphtic drainage, we have decided the extent of lymphadenectomy as follows; a) For the left lung cancer and the right upper lobe primary, systematic bilateral mediastinal dissection (R3 alpha) through a median sternotomy, b) For the cases with the highest mediastinal node involvement, lower half of radical neck dissection (R3 gamma) through a cervical collar incision in addition to a). The cN diagnosis by CT interpretation and pN diagnosis were compared. The under estimated rates of N were 32% of 137 patients with the left lung primary. 46 patients with pN2(+) included 14 patients (31%) with pN3 disease. As for the right upper lobe primary, 17 patients with pN2(+) included 13 patients (76%) with pN3 disease. Postoperative survival rates calculated with Kaplan-Meiermethod; 1) The five-year survival rates were 43% of 46 patients with pT1-3 N2-3 of the left lung primary. 2) As for the right upper lobe primary, the two-year survival rates were 51% of 17 patients with pT1-4 N2-3. 3) The three-year survival rates of 26 patients with pN3 gamma diagnosed as cN0-3 alpha preoperatively were 41%. These systematic extended dissection (R3 alpha, R3 gamma) would bring better prognosis in the patients with pN2-3 disease.
Carcinoma, Non-Small-Cell Lung↗
[Phylogeny of nociceptors].
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Animal Population Groups↗
Borrmann's type IV gastric cancer: clinicopathologic analysis.
OBJECTIVE: To determine whether there is a specific pattern of clinicopathological features that could distinguish Borrmann's type IV gastric cancer from other types of gastric cancer. DESIGN: A retrospective study of patients with advanced gastric cancer treated between 1985 and 1995. SETTING: The Department of Surgery, Sendai National Hospital, a 716-bed teaching hospital. PATIENTS: The clinicopathologic features of 88 patients with Borrmann's type IV carcinoma of the stomach were reviewed from the database of gastric cancer. The results were compared with those of 309 patients with other types of gastric carcinoma. MAIN OUTCOME MEASURES: Gender, age, tumour size, depth of invasion, histologic type, cancer-stromal relationship, histologic growth pattern, nodal involvement, lymphatic and vascular invasion, type of operation, cause of death and 5-year survival. RESULTS: Women were afflicted as commonly as men in the Borrmann's type IV group. These patients tended to be younger and to have larger tumours involving the entire stomach than patients with other types of cancer. Histologic type was commonly diffuse and scirrhous, and serosal invasion was prominent with infiltrative growth. Nodal involvement and lymphatic invasion were more common in patients with Borrmann's type IV than in those with other types of gastric cancer. The disease was advanced in most instances and a total gastrectomy was performed in 55% of the patients. The survival rate of patients with Borrmann's type IV tumour was lower than for patients with other types of gastric cancer (p < 0.005, log-rank test). CONCLUSIONS: In Borrmann's type IV gastric cancer, early detection and curative resection are crucial to extend the patient's survival. Aggressive postoperative chemotherapy is recommended when a noncurative resection is performed.
Adenocarcinoma↗
Localization of alpha-tocopherol transfer protein in rat brain.
Vitamin E (alpha-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. Alpha-tocopherol transfer protein (alpha-TTP), which was identified as a product of the causative gene for familial isolated vitamin E (FIVE) deficiency, is a cytosolic liver protein which plays an important role in the efficient circulation of plasma vitamin E in the body. In the present study, we detected the message for alpha-TTP at low levels in some rat tissues including brain, spleen, lung and kidney. In the brain, the alpha-TTP transcript was detected predominantly in the cerebellar cortex, as revealed by in situ hybridization histochemistry. In the cerebellar cortex, clusters of the hybridization signal were aligned with the Purkinje cell layer, although the signal was not detected in the Purkinje cells, but in the small cells around the Purkinje cells. This distribution pattern strongly suggests that the message for alpha-TTP is expressed in the Bergmann glial cells. Combined with the previous observation that there was severe Purkinje cell loss in patients with FIVE deficiency, the present data suggest that vitamin E is supplied to the Purkinje cells from the surrounding Bergmann glial cells with the help of alpha-TTP.
Animals↗
An alternative form of poly(ADP-ribose) polymerase in Drosophila melanogaster and its ectopic expression in rat-1 cells.
We here report an alternatively spliced form of PARP lacking exon 5 of the Drosophila PARP gene encoding the auto-modification domain. The alternative form of PARP (PARP II) consists 804 amino acids with a molecular weight of 92.3 kDa. The deduced amino acid sequence of PARP II was completely matched to that of PARP I encoded by a full-length Drosophila PARP cDNA, except it lacks the region corresponding to the auto-modification domain. To examine the function of PARP II, stable transformants of Rat-1 cells in which PARP II was ectopically expressed by MMTV-LTR were isolated and characterized. After induction with dexamethasone, PARP II transformants showed slower growth and showed morphological changes with loss of spindled shape compared to cells transformed with the vector or PARP I. The PARP II-transformed cells incorporated propidium iodide after induction; however, Annexin V and TUNEL analysis indicated these changes were not due to apoptosis.
Amino Acid Sequence↗
Novel anti-respiratory syncytial(RS) viral compounds: benzodithiin derivatives.
Benzodithiin derivatives are highly potent and specific inhibitors of respiratory syncytial virus (RSV) replication in vitro. The most potent and selective congener of a benzodithiin derivative is 1,4-dihydro-2,3-benzodithiin(RD3-0028). According to the modified 3-(4,5-dimethylthiazole-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) assay developed in our laboratories, this compound has a 50% effective concentration of 4.5 microM and a 50% cytotoxic concentration of 271.0 microM, which is superior to that of ribavirin. This compound also inhibits RSV strain subgroups A and B and clinical isolates. RD3-0028, however, does not inhibit the replication of influenza A virus, measles virus, herpes simplex virus types 1 and 2, or human cytomegalovirus. Two other benzodithiin derivatives [1,4-dihydro-6-methyl-2,3-benzodithiin (RD3-0270) and 1,4-dihydro-5-methyl-1-2,3-benzodithiin (RD3-0284)] also inhibit RSV replication at a selectivity index greater a factor of 20. These results suggest that the benzodithiin skeleton is an important structure for inhibitory activity against RSV replication.
Antiviral Agents↗
Inhibition of influenza virus RNA polymerase by 5'-capped short RNA fragments.
We have demonstrated that 5'-capped short RNA fragments inhibit the expression of chloramphenicol acetyltransferase (CAT) in the murine 76 cell line, derived which expresses the genes for the RNA polymerases (PB1, PB2, and PA) and the nucleoprotein (NP) of influenza virus in response to treatment with dexamethasone. We have synthesized 5'-capped short RNA fragments (8-13 ntds long) with a 5'-capped structure (m7GpppGm) using T7 RNA polymerase. The 5'-capped short RNA fragments (8-13 ntds long) were encapsulated in liposomes and were tested for their inhibitory effect by a CAT-ELISA assay using the clone 76 cells. The RNA fragments that were 9-12 ntds long showed inhibitory effects. In particular, the 9 ntds long RNA fragment, was highly inhibitory. On the other hand, the inhibitory effect of the 13 ntds long RNA fragment was considerably decreased in comparison with the other short RNA fragments. The minimal RNA chain length required for priming activity was found to be 12 ntds long. Furthermore, the 5'-capped RNA fragments exhibited higher inhibitory activities than the antisense phosphorothioate oligonucleotide (PB2-AUG-as, 20 ntds long) complementary to the site of the PB2-AUG initiation codon. Liposome encapsulation protected the RNA fragments in serum-containing medium and substantially improved their cellular accumulation.
DNA-Directed RNA Polymerases↗
A selective switch-on system for self-renewal of embryonic stem cells using chimeric cytokine receptors.
Propagation of embryonic stem (ES) cells with an undifferentiated pluripotential phenotype depends on leukemia inhibitory factor (LIF). The LIF receptor complex is composed of a heterodimer of LIF receptor alpha (LIFR alpha) and gp130. To activate LIFR signaling pathways independently from endogenous ones, we constructed chimeric receptors by linking the extracellular domain of human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha or beta (hGMR alpha or beta) to the transmembrane and cytoplasmic regions of either mouse LIFR alpha or gp130. hGMR alpha-mLIFR/hGMR beta-mgp130 or hGMR alpha-mgp130/hGMR beta-mgp130, but not hGMR alpha-mLIFR/hGMR beta-mLIFR, preserved the self-renewal activity in A3 ES cells. All of these chimeric receptors were phosphorylated after hGM-CSF stimulation without phosphorylation of endogenous gp130. Phosphorylation of the signal transducer and activator of transcription 3 through chimeric receptors correlated with the undifferentiated phenotype. Therefore, these chimeric receptors prove useful to analyze mechanisms of the self-renewal of ES cells.
Animals↗