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Biomedical subjects

S Kubota

Publications and source records attributed to S Kubota.

At least 163 records · Page 9Linked to original sources

Binding of human prothymosin alpha to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev.

Rex of human T-cell leukemia virus type I (HTLV-I) and Rev of human immunodeficiency virus 1 (HIV-1) are post-transcriptional regulators of viral gene expression. By means of affinity chromatography, we purified an 18-kDa cellular protein that bound to the conserved leucine-motif/activation domain of HTLV-I Rex or HIV-1 Rev. The protein that was purified through a Rev-affinity column was found to bind to Rex immunoprecipitated with anti-Rex IgG from an HTLV-I-producing cell line. We analyzed the purified approximately 18-kDa protein biochemically and identified it as prothymosin alpha. The binding activity of prothymosin alpha to Rev or Rex was completely abolished when the epsilon-amino groups of its lysine residues were chemically modified by N-succinimidyl-3-(4-hydroxy-3,5-diodo- phenyl)propionate. The functional relationship between the nuclear protein prothymosin alpha and Rex-Rev is discussed.

Amino Acid Sequence↗

A pilot study of combination therapy of radiation and local administration of OK-432 for esophageal cancer. Five-year survival and local control rate.

BACKGROUND: Combination therapy consisting of radiation and local administration of OK-432 was administered to 73 patients with esophageal cancer without distant metastases. Seventy patients were examined. The average age was 71 years. There were 60 males and 10 females. The mean tumor length was 7.0 cm. METHODS: One mg of OK-432 was administered endoscopically to and around the cancerous lesion at the beginning of radiotherapy and a second dose of 0.5 mg of OK-432 was given in the same manner 2 weeks later. X-ray irradiation was given at a daily dose of 1.6-1.8 Gy, five fractions a week. The average total dose was 61.1 Gy. RESULTS: Complete responses were obtained in 49 of the 70 patients (70.0%), and partial responses (PR) in the remaining 21. The 5-year cause-specific survival rate of the 70 patients was 33.1%. The 5-year survival rate of the 49 patients with CR was 44.9%, and there were no patients with PR who survived more than 2 years. The 5-year survival rate of the 13 patients with T1 (UICC, 1987) was 79.6%, of the 24 patients with T2/3 41.1%, and of the 33 patients with T4 11.6%. The 5-year survival rates of the 18 patients with tumors less than 5 cm in length and the 40 patients with tumors 5 to 10 cm were 59.9 and 37.9%, respectively. In the patients with tumors more than 10 cm in length, the 4-year survival rate was 14.6%. Sixty-nine of the 70 patients were discharged in good condition and were able to take food orally. CONCLUSIONS: This combination therapy may contribute not only to the survival rate, but also to patients' quality of life.

Aged↗

Ornithine decarboxylase is directly involved in mouse mammary carcinoma cell invasion in vitro.

To elucidate the role of ornithine decarboxylase (ODC) in cancer cell invasion, we have compared the invasiveness of mouse mammary carcinoma, FM3A and its variant cell line, EXOD, which overproduces ODC. We have found that EXOD cells showed about 5.6-fold more invasiveness through a reconstituted basement membrane (Matrigel) compared to FM3A cells. To elucidate the underlying mechanism of increased invasiveness of EXOD cells, we analyzed gelatinase activity in conditioned media derived from FM3A and EXOD cells. EXOD cells secreted approximately 3-fold 72kDa gelatinase compared to FM3A cells. Cell attachment ability to Matrigel was also studied. Although FM3a and EXOD cells showed increased attachment to Matrigel in a dose-dependent manner, EXOD cells showed higher cell attachment ability compared to FM3A cells. Anti-72kDa gelatinase neutralizing antibody suppressed EXOD cell invasion through Matrigel. Further, antisense oligonucleotides of ODC suppressed EXOD cell invasion through Matrigel. Although the causal relationship among ODC expression, gelatinase secretion and cell attachment ability remains to be elucidated, the results suggest that both overproduction of ODC and 72kDa gelatinase secretion are directly involved in increased invasiveness of EXOD cells.

Animals↗

[A study on the usefulness of stress assessment based on the THP health measurement--comparison with the general health questionnaire].

Although the "Total Health Promotion Plan (THP)" drawn up by the Labor Ministry includes a self-administered stress checklist (THP-SC) as a health measurement, THP-SC has not been utilized in the way that it had been planned. Hence, we studied the usefulness of this list by comparing it with the General Health Questionnaire (GHQ). We made a questionnaire that included both THP-SC and the 60-item GHQ, and collected answers from 261 white-collar workers (male, average age 43.7). The GHQ was evaluated using the Goldberg's method. When analyzing THP-SC, the number of answers indicating stress was counted, and the respondents were divided into two groups based on the cut-off points of 75 percentile or 90 percentile. In the 60-item GHQ, 48 respondents out of 243 with valid answers had a higher score than the cut-off point, and in the 12-item GHQ, 77 out of 256 had a higher score. The average number of THP-SC was 5.67 +/- 3.19. Concerning the relationship with GHQ, many items of the 'A' section of THP-SC were significant. The comparison also suggested that four or more items checked in 'A' section or seven or more items checked in the whole list would mean that a respondent may be under stress.

Adult↗

Chromosome elimination in three Baltic, south Pacific and north-east Pacific hagfish species.

We have confirmed that chromosome elimination occurs in the cells of Myxine glutinosa, collected from the Baltic Sea off Sweden, Eptatretus cirrhatus from the south Pacific Ocean off the east coast of New Zealand, and E. stoutii from the north-east Pacific Ocean off Canada, similar to cells of four Japanese hagfish species. In M. Glutinosa, E. cirrhatus type A, E. cirrhatus type B and E. stoutii, the differences in chromosome number between spermatogonia (44, 72, 80 and 48) and somatic cells (28, 34, 34 and 34) were 16, 38, 46 and 14 respectively. The amount of DNA eliminated from presumptive somatic cells averaged 43.5%, 48.7%, 54.6% and 52.8% respectively. Euchromatic chromosomes and/or parts of chromosomes in addition to heterochromatic chromosomes were clearly eliminated in E. cirrhatus and E. stoutii. Adding our previous observations of four Japanese hagfish species, chromosome elimination occurs in all seven of the hagfish species. These results suggest that this phenomenon, chromosome elimination, generally occurs in the order Myxinida. In addition, B-chromosomes were observed in the germ cells of E. cirrhatus and E. stoutii, similar to the cells of E. okinoseanus, E. burgeri and Paramyxine atami (E. atami). This fact suggests that B-chromosomes might exist generally in the family Eptatretidae.

Animals↗

Antigenic alteration in major piroplasm surface proteins of Theileria sergenti during infection.

Theileria sergenti piroplasms were purified from different parasitemia peaks of cattle infected with parasitized erythrocytes or sporozoites during persistent infection. Their reactivities with monoclonal antibodies 13F5 and C9, which recognize 23 kDa and 32 kDa piroplasm surface proteins, respectively, were analyzed. Antigenic differences were observed among parasites from different parasitemia peaks during persistent infection when cattle were infected with sporozoites. Results of two-dimensional polyacrylamide gel electrophoresis showed that the 23 and 32 kDa proteins were expressed in all samples tested, regardless of their reactivities with the monoclonal antibodies. In contrast, parasites obtained from cattle inoculated with parasitized erythrocytes showed no antigenic alteration over a 2 month observation period. The results suggest that antigenic alteration of T. sergenti during persistent infection is related to whether the parasites proliferate through extraerythrocytic schizont stage in cattle or sporozoite and other sexual stages in tick vector.

Animals↗

Use of a human immunodeficiency virus type 1 Rev mutant without nucleolar dysfunction as a candidate for potential AIDS therapy.

Applications of transdominant mutants of human immunodeficiency virus type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been attempted for gene therapy against AIDS, because the Rev protein is essential for viral replication. We have previously reported that a mutant Rev protein (dRev) lacking its nucleolar targeting signal remained out of nuclei in expressed cells and strongly inhibited the function of Rev. To investigate the effects of dRev on HIV-1 replication, we established several dRev-expressing human cell lines with two different vector systems and examined virus production in these cells. An HIV-1-derived vector containing drev cDNA was constructed and introduced into CD4-positive HeLa cells and cells of the human T-cell line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication, syncytium formation, and cell death caused by HIV-1 infection were remarkably suppressed, and the same vector also conferred a resistant phenotype on CEM cells. The production was also suppressed in CEM cells containing the drev gene driven by a cytomegalovirus promoter. In addition, we found that dRev did not cause nucleolar dysfunction in a transient assay, in contrast to other transdominant mutants and wild-type Rev. Since dRev cannot migrate into the nuclei, it is expected not to interfere with nuclear/nucleolar functions of the host cell. We conclude that dRev is one promising candidate as an antiviral molecule for gene therapy against AIDS.

Acquired Immunodeficiency Syndrome↗

A genetic analysis of mixed population in Theileria sergenti stocks and isolates using allele-specific polymerase chain reaction.

In order to differentiate parasite populations bearing two allelic forms of p33/32, an immunodominant piroplasm surface protein of Theileria sergenti, two sets of oligonucleotide primers were designed to amplify either of the two allele by the polymerase chain reaction (PCR). Each set of the primers differentially amplified either of Ikeda- or Chitose-type p33/32 genes. By using this allele-specific PCR and restriction enzyme digestion of amplified products, parasite populations within field isolates collected from different geographical regions in Japan were analyzed. Both of the allelic forms were detected in 13 samples out of 20 isolates and stocks by PCR. Either of Ikeda or Chitose type of p33/32 allele was detected in the other 7 samples. These results indicated that the majority of T. sergenti-infected calves (11/15) in Japan harbored mixed parasite populations bearing at least two different alleles of p33/32.

Alleles↗

Hereditary hemorrhagic telangiectasia showing severe anemia which was successfully treated with estrogen.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) is a bleeding disorder attributed to a vascular developmental abnormality. It is transmitted as an autosomal dominant trait. A 63-year-old female was admitted because of repeated episodes of severe anemia which resulted from bleeding of telangiectases in the gastric mucosa. Conventional therapies including endoscopical microwave coagulation and ethanol injection were not effective. The persistent anemia necessitated frequent blood transfusion. Estrogen was orally administrated and blood transfusion became unnecessary. Thus, estrogen therapy should be considered as one of the effective treatments for recurrent severe anemia due to hereditary hemorrhagic telangiectasia.

Administration, Oral↗

[A single session of transurethral balloon laser thermotherapy for benign prostatic hyperplasia].

BACKGROUND: The objective of this study is to evaluate the efficiency of a new method of transurethral balloon laser thermotherapy (TUBAL-T) using prostalase in patients with benign prostatic hyperplasia. METHODS: From September 1993 to March 1994, 21 men were treated with a single session of TUBAL-T for the relief of bladder outlet obstruction secondary to benign prostatic hyperplasia. Thirteen of them had hormonal therapy before TUBAL-T and have no mediation after treatment (group A). Eight men had no hormonal therapy before and after TUBAL-T (group B). The clinical efficacy of this modality was evaluated by analysing the subjective and objective responses following the treatment. The laser balloon, equipped with a cooling system for preservation of urethral mucosa, delivers a Nd:YAG laser into the prostate. Treatment was performed by using a laser powder of 30 to 50 watts for 40 minutes. At 3 months after treatment, the clinical efficacy was evaluated by subjective symptom score, and residual urine volume, uroflowmetry and prostatic volume by transrectal ultrasound as objective data. RESULTS: In group A, subjective symptom scores decreased by an average of 72.8%, the average uroflow rates and the peak uroflow rates increased by an average of 44% and 45.9%, the post-void residual urine volume rates decreased by an average of 58.4% and ultrasonography showed that the prostatic volume decreased in 8 men but increased in 5 men. In group B, symptom score decreased by an average of 85.1%, the average uroflow rates and the peak uroflow rates increased by an average of 46.2%, the post-void residual urine volume rates decreased by average of 83.4% and ultrasonography showed that the prostatic volume decreased by an average of 35.6%. CONCLUSION: During the treatment and follow-up period, no adverse effect was detected. These results suggest that TUBAL-T for the relief of bladder outlet obstruction secondary to BPH is a useful therapy.

Aged↗

[A case of gas-producing brain abscess with subdural empyema: timing of the operation for brain abscess].

A case of gas-producing brain abscess with subdural abscess was reported. An 18-year-old boy was admitted with a five-day history of vomiting and high grade pyrexia. Plain skull roentgenograms demonstrated left frontal multiple gas bubbles. CT scan and MRI showed that both brain and subdural abscesses contained gas in the left frontal area. Antibiotics and glyceol were intravenously administrated. In serial CT scans, subdural abscess was not recognized, while brain abscess was enhanced in a ring. Seven days after admission, milky white pus with a fecal odor was aspirated using CT guided stereotactic apparatus, and the catheter was left in the abscess cavity. Culture of the pus grew peptostreptococcus. On the 22nd hospital day, repeated aspiration and drainage were performed for the residual brain abscess. The patient gradually improved after the aspiration with continuous administration of antibiotics, and he was discharged on the 59th hospital day with no neurological deficits. Based on our experience and a review of the literature, the treatment of choice is aspiration in the late cerebritis stage of brain abscess.

Adolescent↗

[An immunohistochemical study of the relationship between p53 expression and the DNA ploidy pattern using image cytometry in colorectal carcinoma].

We studied p53 expression in 46 colorectal carcinomas by immunohistochemistry. We examined the relationship between p53 expression and the pathological findings, the prognosis and tumor proliferative activity by Ki-67 staining or DNA ploidy pattern using an image cytometer. Expression of p53 was observed in 41.3% of carcinomas. No correlation was found between p53 expression and the depth of invasion, lymph node metastasis or Dukes' stage. No difference in survival was found between p53 positive and negative patients after curative surgery. We also studied the DNA ploidy pattern using an image cytometer in 28 carcinomas. Aneuploidy was found more frequently in the p53 positive areas than in the negative ones, but there was no significant difference. The DNA index showed no difference between the p53 positive and negative areas. We examined proliferating activity using Ki-67. There was no difference in the Ki-67 labeling index between p53 positive and negative areas. In the present study, there was no correlation between p53 expression and pathological findings, prognosis, tumor proliferative activity using Ki-67 staining or DNA ploidy pattern. Thus, p53 expression was suggested to have little relationship to grade of malignancy.

Cell Division↗

[Mechanism of overshoot elevation of left ventricular ejection fraction during recovery after exercise in normal subjects and patients with coronary artery disease, assessed by 99mTc exercise radionuclide ventriculography].

An "overshoot" (OS) elevation of ejection fraction above resting levels has been demonstrated during recovery after exercise. To characterize the hemodynamic changes during recovery after bicycle exercise, we used radionuclide ventriculography under the Swan-Ganz catheter insertion in 16 normal subjects and 15 patients with coronary artery disease (CAD) at rest, during bicycle exercise and after exercise periods. In normal subjects, the ejection fraction increased from resting value during peak exercise, and showed overshoot elevation in the early recovery period. In patients with CAD, the ejection fraction decreased from resting value during peak exercise, then showed overshoot elevation in the early recovery period. In normal subjects, the end-diastolic volume (EDV) and the end-systolic volume (ESV) decreased from resting value during OS. In patients with CAD, the EDV at OS was not different from that at rest, the ESV decreased from resting value during OS. The systemic vascular resistance increased from resting value during OS. The systolic blood pressure/ESV, index for ventricular contractility, increased from resting value during OS in both groups. Thus, the decreased systemic vascular resistance does not playing a major role during recovery after exercise, whereas enhanced contractility is evident in both normal subjects and patients with CAD.

Coronary Disease↗

[Prognostic significance of 123I-metaiodobenzylguanidine scintigraphy in dilated cardiomyopathy].

The prognostic factor was identified by performing 123I-Metaiodobenzylguanidine (MIBG) myocardial scintigraphy on 17 patients with dilated cardiomyopathy (DCM). During 5 years period, 9 patients had cardiac events, four of whom died, six were admitted due to heart failure and five had ventricular tachycardiac events. At the starting point, we collected rest early and 3-hr-delayed MIBG SPECT along with rest 201T1 (T1) SPECT. In the SPECT, regional tracer uptake was scored using 4-grades defect score (0 = normal to 3 = uptake-defect), and summed up to total defect score (TDS). At the same time, we estimated left ventricular end-diastolic dimension/body surface area (LVDd/BSA), end-systolic dimension/body surface area (LVDs/BSA) and left ventricular ejection fraction (LVEF) by echo-cardiography, pulmonary arterial wedge pressure (PAWP) and New York Heart Association (NYHA) symptom class. We compared the clinical and hemodynamic parameters between the patients with cardiac events (group A) and the other patients (group B). TDS of delayed MIBG SPECT (p < 0.001), TDS of early MIBG SPECT (p < 0.05), TDS of T1 SPECT (p < 0.01), LVDd/BSA (p < 0.01), LVDs/BSA (p < 0.001) and NYHA class (p < 0.05) of group A were significantly larger than those of group B. But, LVEF of group A was significantly less than that of group B (p < 0.01). On multivariate analysis, the following parameters were independent predictors of cardiac events: TDS of delayed MIBG SPECT (p < 0.001), PAWP (p = 0.0124) and LVDd/BSA (p = 0.0026). These data suggest that delayed MIBG scintigraphy is thought to be important to predict cardiac events in patients with DCM.

3-Iodobenzylguanidine↗