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Biomedical subjects

T Shimamoto

Publications and source records attributed to T Shimamoto.

At least 19 recordsLinked to original sources

The expression pattern of erythrocyte/megakaryocyte-related transcription factors GATA-1 and the stem cell leukemia gene correlates with hematopoietic differentiation and is associated with outcome of acute myeloid leukemia.

To understand the clinical implications of transcription factors and their biologic roles during cellular differentiation in the hematopoietic system, we examined the expression of GATA-1, GATA-2, and stem cell leukemia (SCL) gene in human leukemia cell lines and various leukemia patients using the reverse transcriptase-polymerase chain reaction. Cell lines exhibiting megakaryocytic or erythrocytic phenotypes had GATA-1, GATA-2, and SCL gene transcripts, while monocytic cell lines had no detectable GATA-1, GATA-2, or SCL gene mRNA. In some myeloid cell lines, GATA-1 expression, but not SCL gene expression, was detected; GATA-1 expression in HL-60 cells was downregulated during the process of monocytic differentiation. We next examined GATA-1, GATA-2, and SCL gene expression in 110 leukemia samples obtained from 76 patients with acute myeloid leukemia (AML), 19 with acute lymphoblastic leukemia (ALL), and 15 with chronic myeloid leukemia in blast crisis (CML-BC). SCL gene expression was usually accompanied by GATA-1 expression and was preferentially detected in patients with leukemia exhibiting megakaryocytic or erythrocytic phenotypes, while patients with monocytic leukemia were clustered in the group with no detectable GATA-1 expression. None of the patients with ALL or CML-lymphoid-BC expressed SCL. De novo AML patients with SCL gene expression had a lower complete remission (CR) rate and had a significantly poorer prognosis. Among the patients with AML not expressing SCL, a high percentage of patients with CD7+ AML and CD19+ AML had detectable GATA-1, while patients with GATA-1-negative AML had the best CR rate (87.5%). Our results suggest that the expression pattern of transcription factors reflects the lineage potential of leukemia cells, and GATA-1 and SCL gene expression may have prognostic value for the outcome of patients with AML.

Acute Disease

The nuclear pore-targeting complex binds to nuclear pores after association with a karyophile.

We recently showed that a karyophilic protein forms a stable complex, termed nuclear pore-targeting complex (PTAC), with cytoplasmic components prior to nuclear pore-binding. In this study, we cloned a cDNA encoding a 97 kDa of PTAC (PTAC97). Recombinant PTAC97 completely reconstitutes the nuclear binding-step in conjunction with a 58 kDa component of PTAC (PTAC58) in the semi-intact cell-free transport assay. Biochemical analysis reveals that PTAC58 binds to a karyophilic protein, and PTAC97 is associated with PTAC58 in a 1:1 molar ratio. A complex of PTAC97 and PTAC58 targets nuclear pores, depending on the presence of a karyophile. These in vitro results suggest that the first step in nuclear import occurs through the targeting-complex formation of a karyophile with PTAC58 bound to PTAC97.

Amino Acid Sequence

The formation of the 2',5'-phosphodiester linkage in the cDNA priming reaction by bacterial reverse transcriptase in a cell-free system.

Bacterial reverse transcriptase (RT) is responsible for synthesis of multicopy single-stranded DNA (msDNA) consisting of single-stranded DNA linked to an internal guanosine residue of RNA by an unusual 2',5'-phosphodiester linkage. Here we purified a bacterial RT to homogeneity from Escherichia coli harboring the RT gene from retron-Ec73. The purified RT-Ec73 was able to synthesize msDNA in a cell-free system using an RNA template produced in vitro by T7 RNA polymerase. The in vitro synthesized msDNA was released from the template RNA only when treated with yeast debranching enzyme DBR1, a specific nuclease for a 2',5'-phosphodiester linkage. The position of the branching G residue in the template RNA and the DNA sequence of the cell-free product were identical to those of msDNA-Ec73 synthesized in vivo. These results clearly demonstrate that the formation of the 2',5'-phosphodiester linkage in msDNA synthesis is carried out by RT itself.

Base Sequence

The role of ribonuclease H in multicopy single-stranded DNA synthesis in retron-Ec73 and retron-Ec107 of Escherichia coli.

Bacterial reverse transcriptase is responsible for the synthesis of multicopy single-stranded DNA (msDNA). Reverse transcriptases from retron-Ec73 and retron-Ec107 do not contain an RNase H domain. Cellular RNase H is therefore considered to be required to make the mature form of msDNA. We found that RNase HI, but not RNase HII, is required for the production of the mature form of both msDNAs.

Base Sequence

Clinical and biologic characteristics of CD7+ acute myeloid leukemia. Our experience and literature review.

Six patients with acute myeloid leukemia (AML) expressing CD7 antigen (CD7+ AML) were studied. They consisted of five patients with M1 and one with an M2 morphology. Two cases expressed other lymphoid-associated antigens, in addition to CD7. The complete remission rate was 50%. One patient had central nervous system recurrence. Cytogenetic analysis demonstrated normal karyotypes in all the cases. All but one had germline configurations of the T-cell receptor (TCR) genes and immunoglobulin heavy chain gene. However, all did not have detectable recombinase activating gene-1 activity by the RT-PCR technique. We performed colony formation assay in two patients, and no enhancement of colony formation by granulocyte colony-stimulating factor was noted. The results presented here, together with those reported previously, suggest that CD7+ AML may demonstrate lineage infidelity.

Adult

Flow cytometric DNA analysis of gastric smooth muscle tumors.

BACKGROUND: To better understand the malignant grade of gastric smooth muscle tumors, the DNA content of these tumors was studied. METHODS: In 43 patients with gastric smooth muscle tumors, the cellular DNA content was determined by flow cytometry and compared with the histologic classification and the prognosis. RESULTS: Flow cytometry indicated that all 21 leiomyomas and 9 of the 10 low-grade leiomyosarcomas were diploid; 10 of the 12 high-grade leiomyosarcomas were aneuploid. All patients with leiomyomas and 8 of the 11 patients with diploid leiomyosarcomas had neither local recurrence nor metastasis. By contrast, 8 of the 10 patients with aneuploid leiomyosarcomas died of their disease (mean survival, 41 months; range, 18-78 months). CONCLUSIONS: These results indicate that the DNA ploidy pattern shown by flow cytometry is related closely to the histologic classification and prognosis of gastric smooth muscle tumors.

Adult

Cloning and nucleotide sequence of the gene (citC) encoding a citrate carrier from several Salmonella serovars.

The nucleotide sequence of the citC coding for the citrate carrier in several Salmonella serovars has been determined, and the amino acid sequence of the carrier protein was deduced. The predicted citrate carrier from Salmonella pullorum and Salmonella enteritidis consists of 446 amino acids with a molecular weight of 47,621, whereas that from Salmonella dublin is the same 446 amino acids with the slightly different molecular weight of 47,591, because 1 amino acid residue was substituted. The predicted proteins are highly hydrophobic (69% nonpolar amino acids). The hydropathy profile suggests that the proteins are composed of 11-12 hydrophobic membrane-spanning segments with two hydrophilic cores in the middle of the protein sequence. No homology in the nucleotide and amino acid sequences was found in the molecular structures of citA, citP, and tctI genes. The citC-coding citrate transport activity is Na(+)-dependent and specific for citrate only. The transcript from the citC gene was not detected in the total RNA from several Salmonella serovars except S. dublin in Northern blot analysis, although the promoter of the citC genes appeared to be functional in Escherichia coli and Salmonella typhimurium strains using the lacZ fusion assay. These results suggested that the citC gene-coding citrate carrier is probably a TctIII system such as that identified previously in S. typhimurium.

Amino Acid Sequence

Alcohol drinking and high blood pressure: data from a 1980 national cardiovascular survey of Japan.

Many epidemiological cross-sectional studies have confirmed that alcohol drinking is related to high blood pressure. However, the impact of alcohol drinking on high blood pressure in the general population including older people has only been reported on in a few studies. The association between alcohol drinking and blood pressure or the prevalence of hypertension was examined using cross-sectional data of 4795 men and 6102 women aged 30-94, randomly selected from the Japanese population in 1980. The response rates were 74 and 84% for men and women, respectively. The prevalence of hypertension adjusted for body mass index (BMI, kg/m2) was significantly higher in everyday male drinkers than in male non-drinkers from the youngest age group (30-39 years) to oldest age group (70 years and over). A relationship between alcohol and blood pressure was found only in the youngest age group (30-39 years) of female drinkers. In each 10-year age-group of men, the BMI-adjusted systolic and diastolic blood pressures in everyday drinkers were 7-10 and 4-6 mmHg higher than those in non-drinkers. The relationship between alcohol and blood pressure in men was confirmed by multiple regression analysis adjusting for age and BMI in both younger (30-59 years) and older (60-94 years) people. The impact of alcohol drinking on blood pressure in men should be taken into account in the primary prevention of blood pressure related diseases and in the treatment of hypertension in both younger and older people.

Adult

Heterotopic pancreas diagnosed by endoscopic ultrasonography and endoscopic injection of ethanol to make a histologic diagnosis.

A gastric submucosal tumor in a 56-year-old man was presumed to be heterotopic pancreas on the basis of endoscopy and endoscopic ultrasonography. To obtain a histologic diagnosis we injected ethanol at the tumor site to create an artificial ulcer. This facilitated the removal of endoscopic biopsy specimens from the submucosal layer so that histologic examination could confirm the presence of heterotopic pancreatic tissue.

Choristoma

The role of the seminal vesicles and coagulating glands in fertilization in the rat.

To investigate the role of the seminal vesicles (SV) and coagulating glands (CG) in fertilization in the rat, partial resections of the SV (25%--group B), 50%--group C, and 75%--group D) or bilateral resection of the SV alone (100%--group E), or together with the CG (group F) were undertaken. In other groups, bilateral resection of the CG only (group G), or bilateral resection of the CG with ipsilateral SV resection (group H) were performed. A group of sham-operated rats served as controls (group A). There were no significant differences among groups A, B, C and D in the number of fertile rats post-operatively but significant differences were evident in groups E, F, G, H when compared with the control group (P less than 0.01 for all groups). Only the fertile rats were able to form copulatory plugs (CP) post-operatively. Bilateral ligation of the SV ducts was performed in ten fertile rats. Post-operatively, the proportion of fertile rats was decreased significantly (P less than 0.01). Removal of the ligatures resulted in a significant increase (P less than 0.01) in fertility. It was also demonstrated that the addition of rat seminal vesicular secretions (SVS) to epididymal sperm suspensions resulted in a significant decrease (P less than 0.001) in sperm motility. These results suggest that the SV and CG are necessary for fertility in rats, and that one role of SVS is the formation of a CP and not the maintenance of sperm motility.

Animals

A study on the placental transport mechanism of vitamin K2 (MK-4).

The present study was primarily concerned with in vitro investigation of vitamin K2 (MK-4) transport using human placental villous tissues, with the objective of elucidating the placental transport mechanism of vitamin K2. 1. When vitamin K2 (MK-4) was not administered to gravidae, the observed concentrations of vitamin K2 were 0.32 +/- 0.07 ng/ml in the maternal venous blood, undetectable in umbilical venous blood, and 1.01 +/- 0.37 ng/g wet tissue in the placental villous tissue. 2. When vitamin K2 was administered to gravidae, (20 mg/day x 7 days per os), the corresponding concentrations were 0.89 +/- 0.21 ng/ml in the maternal venous blood, 0.18 +/- 0.06 ng/ml in umbilical venous blood, and 5.38 +/- 1.05 ng/g wet tissue in the placental villous tissue. 3. In vitro studies using placental villous tissue indicated that vitamin K2 transport into villous tissue is not active, but suggested the existence of a highly vitamin K2 specific transport system in the human placenta. On the other hand, the results of comparison studies of transport of vitamin K2 and vitamin K1 into villous tissue indicated that transport activity with respect to the former vitamin was higher. Moreover, comparison of vitamin K2 transport into villous tissue at the end of the first trimester and at full term revealed that transport was somewhat higher during the final stage. In summary, the above results indicated that whereas transport of vitamin K1 into the fetus is not especially pronounced, transport into the placental villous tissue is comparatively good.

Biological Transport

Surgical repair versus medical treatment of varicocele in the rat: pharmacological manipulation of the varicocelized testicle.

Human chorionic gonadotropin, kallikrein, indomethacin, and hydralazine were administered to different groups of varicocelized rats, while surgical repair of the varicocele was performed in another group of rats. The effects of conservative and surgical treatment on epididymal sperm content and motility, the weights of the testes, epididymis, and male accessory genital glands, and fertility were compared between each group and a sham-treated group of rats. Surgical repair significantly improved all the evaluated parameters and all the conservative regimens, except hydralazine, resulted in a significant improvement in most parameters. Our results indicate that stimulation of the Leydig or/and Sertoli cells of a varicocelized testicle can counteract some of the detrimental consequences of the varicocele itself.

Animals

Leukemic phase of intermediate non-Hodgkin's lymphoma with cells showing different matured stages in invaded various organs.

A 56-year-old male was admitted to our hospital with lymphocytosis (16.4 x 10(9)/l; 79% lymphocytes including 50% small lymphocytes), generalized lymphadenopathy, massive splenomegaly, and heavily infiltrated bone marrow. Immunophenotype analysis of the neoplastic cells in the bone marrow revealed that they were B cells (CD20 + CD19 + Ia1 + sIgM+) positive for CD10. By contrast, the cells in the lymph node were CD20 + CD19 + Ia1 + sIgM+ but negative for CD10. The patient was tentatively diagnosed as having lymphosarcoma cell lymphoma, however, the final diagnosis was leukemic phase of intermediate lymphocytic lymphoma. We concluded that CD10+ neoplastic cells in the bone marrow and peripheral blood had differentiated to CD10- cells.

Antigens, Differentiation

Helicobacter pylori infection and gastroduodenal disease: a comparison of endoscopic findings, histology, and urease test data.

To determine the prevalence and significance of Helicobacter pylori (H. pylori) infection, biopsies of the antral mucosa were obtained from 139 patients and 43 asymptomatic volunteers. The specimens were examined by hematoxylin-eosin staining and the ureas test. The detection rate of H. pylori by histologic examination was 91.3% in patients with duodenal ulcer, 75.0% in those with combined duodenal and gastric ulcer, 63.6% in those with gastric ulcer, 22.9% in those with gastric carcinoma, 36.4% in those with gastric adenoma, 14.3% in those with gastric hyperplastic polyp, and 51.7% in those with gastritis, and the respective percentages detected by the urease test were 91.3%, 75.0%, 54.5%, 28.6%, 27.3%, 14.3%, and 44.8%. H. pylori was also detected in 10/43 (23.3%) asymptomatic healthy volunteers by histology and the urease test. The prevalence of H. pylori was significantly higher in the patients than in the asymptomatic healthy volunteers (p < 0.05). H. pylori was detected in 62.9% of patients with endoscopic erosive gastritis and in 97.9% of those with histologically proven chronic active gastritis. The urease test was positive in 77/82 patients who were histologically positive for the organism (sensitivity: 93.9%), and it was negative in 98/100 patients who were negative by histology (specificity: 98.0%). Thus, there was over 90% agreement between the urease test and histology. Our investigations showed that H. pylori was closely related to peptic ulcers and antral gastritis, and that the urease test provides a simple, rapid and accurate diagnosis of H. pylori infection.

Adult

Therapeutic effects of oral rebamipide and in combination with cimetidine on experimental gastritis in rats.

The present study evaluated the therapeutic effects of rebamipide alone and in combination with cimetidine on experimental gastritis established by the administration of 5 mM sodium taurocholate (TCA) for 6 months in rats. Morphological and biochemical analyses were performed to determine the effects of rebamipide, administered alone or in combination with cimetidine, on chronic, atrophic and erosive gastritis. Rebamipide and cimetidine were administered to rats as a dietary admixture for 4 weeks after withdrawal of TCA. Rebamipide dose-dependently reduced the total length of the erosion, normalized the mucosal thickness and increased the number of parietal and total cells, and tended to reduce interstitial infiltration of inflammatory cells and proliferation of collagenous fibers. Moreover, histochemical and biochemical studies also showed rebamipide to be effective. Rebamipide increased the PAS-positive mucus and normalized the reduced gastric mucosal SOD activity. The therapeutic effect of rebamipide on the experimental gastritis was enhanced by the combined use of cimetidine. These results suggest that rebamipide has a therapeutic effect on chronic atrophic erosive gastritis induced by TCA, and that the mechanism of the therapeutic effect is partially due to the increase in PAS-positive mucus and gastric mucosal SOD activity. Furthermore, the enhanced effect of the combination therapy of rebamipide with cimetidine was considered to be due to the actions of both cimetidine and rebamipide.

Administration, Oral

[A nested case-control study of risk factors for intracerebral hemorrhage and cerebral infarction classified by computed tomographic findings].

Risk factors for intracerebral hemorrhage (ICH) and cerebral infarction (CI), were studied by a prospective study of 7,390 men and women aged 40-69 without a history of stroke living in three rural populations in Japan. Baseline examinations were done for populations in Akita-Ikawa and Akita-Ishizawa in 1975-1979, and for Ibaraki-Kyowa in 1981-1987, and followed until 1989 for Akita-Ikawa and Ibaraki-Kyowa and 1987 Akita-Ishizawa. There were 246 stroke cases diagnosed by clinical criteria during the follow-up period in which 74 percent (n = 181) had data from computed tomography (CT) performed within three weeks of the onset. According to these CT-findings, 181 stroke were classified as 48 with ICH, 50 with CI in penetrating artery regions (penetrating artery infarction), 33 with CI in cortical artery regions (cortical artery infarction), and 31 with subarachnoid hemorrhage while there were 19 with stroke without any evident CT abnormality. Cortical artery infarction was further classified as embolic type (n = 17) and thrombotic type (n = 9) according to clinical findings of the onset and presence of possible embolic sources such as atrial fibrillation, congenital heart disease, myocardial infarction and heart valve diseases. Using a nested case-control design, risk variables at baseline examination were compared between 131 stroke cases, 48 ICH and 83 CI, with 655 controls matched for sex, age (+/- 3), and the follow-up year. Univariate analysis showed that high blood pressure was associated with all types of stroke. From conditional logistic regression analysis significant risk variables were found to be high blood pressure for ICH and penetrating artery infarction, while atrial fibrillation and ST-T abnormality in electrocardiogram (ECG) were risk variables for cortical artery infarction. Associations with hypertensive or arteriosclerotic changes in ocular fundus were stronger for penetrating artery infarction than ICH and cortical artery infarction. ST-T abnormality in ECG was associated with embolic type cortical artery infarction and high blood pressure was associated with the thrombotic type, although the number of cases were small. Compared to controls, cortical artery infarction showed a higher mean value of serum total cholesterol for thrombotic type cortical infarction, and lower mean values for embolic type and ICH, but none of them reached statistical significance. The present study also suggests that duration of hypertension varied with type of stroke. ICH may develop due to acute effects of hypertension, while penetrating artery infarction and cortical artery infarction develop by chronic effects of hypertension.

Adult