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Biomedical subjects

S Okamura

Publications and source records attributed to S Okamura.

At least 109 records · Page 6Linked to original sources
PubMed1996

Generation of human natural killer cells from peripheral blood CD34+ cells mobilized by granulocyte colony-stimulating factor.

We studied the generation of human natural killer (NK) cells from CD34+ cells that were isolated from peripheral blood stem cells (PBSC) mobilized by granulocyte colony-stimulating factor (g-CSF). The isolated CD34+ cells were cultured in the presence of a combination of interleukin-1 (IL-1alpha), IL-2, and stem cell factor for 5 weeks without marrow stroma. We found that the CD34+ cells isolated from G-CSF-mobilized PBSC (G-CSF/PBSC) could differentiate into a population of NK cells which were CD56+(bright)/CD3- and showed morphologic characteristics of large granular lymphocytes. Immunophenotypic analysis of the NK cells thus generated showed that a small proportion of them expressed CD2, CD8 and CD16 surface markers and approximately half of them coexpressed CD7. This NK population exhibited cytotoxic activity against a NK-sensitive cell line, K562. These observations suggest that CD34+ cells from G-CSF/PBSC contain precursors of NK cells that can differentiate into functional NK cells.

Adult↗
PubMed1996

Immunophenotyping of peripheral blood mononuclear cells collected by cytotoxic and cytotoxic/G-CSF mobilization.

We investigated surface immunophenotypes of peripheral blood mononuclear cells (PBMC) collected by cytotoxic and cytotoxic/G-CSF mobilization of peripheral blood stem cells (PBSC) from 38 patients with haematological malignancies in complete remission who underwent consolidation chemotherapy. PBMC were collected by leucapheresis during the haematopoietic recovery phase after intensive chemotherapy. G-CSF was used for mobilization of PBSC in 19 cases. Surface immunophenotyping of frozen-thawed PBMC was performed by flow cytometry. Our findings showed that monocytes and T cells were the two major cell components of PBMC. There were very few B cells in PBMC. Expression of CD45RO and HLA-DR was elevated in lymphocytes, suggesting that T cells in PBMC were activated. The percentage of CD34 positive cells were significantly increased in PBMC collected by cytotoxic/G-CSF mobilization (group 1) compared with PBMC collected by cytotoxic mobilization (group 2). There were significantly higher percentages of CD14 and CD33 positive cells in group 1 than in group 2. The percentage of CD4 positive lymphocytes positive for HLA-DR was significantly higher in group 1 compared with group 2. These observations indicated that PBMC contained a large number of monocytes and activated T cells, especially in cytotoxic/G-CSF mobilization.

Adolescent↗
PubMed1996

Reversible primary hypothyroidism with blocking or stimulating type TSH binding inhibitor immunoglobulin following recombinant interferon-alpha therapy in patients with pre-existing thyroid disorders.

OBJECTIVE: Treatment with recombinant interferon-alpha (rIFN-alpha) may induce autoimmunity. We have evaluated the effect of rIFN-alpha on pre-existing thyroid disease with special reference to changes in TSH receptor antibody. DESIGN AND PATIENTS: Five patients, who had a history of autoimmune thyroid disease diagnosed between 2 and 16 years earlier (three patients had Graves' disease while two had Hashimoto's thyroiditis), were treated with rIFN-alpha for chronic hepatitis C. Before, during and after rIFN-alpha therapy, we determined thyroid function, antithyroid antibody, thyroid echogenicity and the surface phenotype of the peripheral and intrathyroidal lymphocytes. RESULTS: Four of the patients developed overt hypothyroidism after 4-7 months of rIFN-alpha therapy, and two of them had a preceding history of low-uptake thyrotoxicosis. Recovery of thyroid function was observed in all four patients. Strongly positive blocking type TSH receptor antibody was detected and an increase in the percentage of CD19 positive cells in the intrathyroidal lymphocytes was also observed in three of the patients even though the goitre size increased in two of them. One of the patients became thyrotoxic later when stimulating type TSH receptor antibody became positive. Another patient suffered from reversible hypothyroidism although stimulating type TSH receptor antibody remained strongly positive throughout the clinical course. CONCLUSIONS: Our data thus indicated a high incidence of an unusual type of reversible hypothyroidism with TSH receptor antibodies in patients with chronic hepatitis C and pre-existing autoimmune thyroid disease after recombinant interferon-alpha therapy through a mechanism involving both the humoral and cellular immune systems.

Adult↗
PubMed1996

Rotenone, a mitochondrial NADH dehydrogenase inhibitor, induces cell surface expression of CD13 and CD38 and apoptosis in HL-60 cells.

We previously demonstrated that the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene was overexpressed in human acute myelogenous leukemia (AML) cells. Since this finding suggested that ND2 gene expression was related to myeloid differentiation, we here investigated the effects of rotenone, a specific NADH dehydrogenase inhibitor, on HL-60 cell growth, differentiation and death. Fifty nM rotenone inhibited the growth of HL-60 cells and caused an increase in the cell population in the G(2) +M phase. In the quantitative comparison of myeloid antigen, the expression of CD13 and CD38 were relatively increased in the rotenone-treated cells. These findings suggest that the inhibition of NADH dehydrogenase changes the cell cycle and induces some specific surface antigens of HL-60 cells. On the other hand, the expression of ND2 gene remained unchanged after the rotenone treatment, suggesting the rotenone-mediated mitochondrial inhibition did not affect the mitochondrial gene expression. Five mu M rotenone strongly inhibited the cellular proliferation. Electron microscopy and an electrophoretic analysis of DNA showed that the majority of the HL-60 cells were induced into typical apoptosis within 24-48 hours. On the basis of this and other studies, we believe that mitochondrial function is directly involved in both cellular differentiation and apoptotic cell death.

ADP-ribosyl Cyclase↗
PubMed1996

[Clinical value of carbohydrate antigens, sialyl Lewis-x and sialyl Lewis-a in gastrointestinal cancer].

To evaluate clinical importance of the expression of sialyl Lewis-X (sLe(x)) and sialyl Lewis-a antigen (sLe(a)) in gastrointestinal cancers, we examined immunohistochemically expression of the two antigens in esophageal, gastric, colorectal, and pancreatic cancer. Expression of sLe(x) and sLe(a) were associated with several clinicopathologic features which reflect tumor aggressiveness in esophageal, gastric and colorectal cancer, but not in pancreatic cancer. In esophageal and colorectal cancer, survival rate of the patients with sLe(x) positive tumors was significantly poorer than that of the patients with sLe(x) negative tumors, while in gastric cancer that with sLe(a) positive tumors was significantly poorer than that with sLe(a) negative. Cox's multivariate analysis revealed that sLe(x) expression status was one of the significant discriminants of prognosis in colorectal cancer patients and sLe(a) status in gastric cancer patients. These results suggest that sLe(x) and sLe(a) expression could be involved in aggressiveness of gastrointestinal cancer and might prove to be a potent marker for prognosis in patients with gastric cancer and colorectal cancer.

Adult↗
PubMed1995

Association of an activator with an RNA polymerase II holoenzyme.

RNA polymerase II holoenzymes have been described that consist of RNA polymerase II, a subset of general transcription factors, and four SRB proteins. The SRB proteins, which were identified through a selection for genes involved in transcription initiation by RNA polymerase II in vivo, are a hallmark of the holoenzyme. We report here the isolation and characterization of additional SRB genes. We show that the products of all nine SRB genes identified thus far are components of the RNA polymerase II holoenzyme and are associated with a holoenzyme subcomplex termed the mediator of activation. The holoenzyme is capable of responding to a transcriptional activator, suggesting a model in which activators function, in part, through direct interactions with the holoenzyme. Immunoprecipitation experiments with anti-SRB5 antibodies demonstrate that the acidic activating domain of VP16 specifically binds to the holoenzyme. Furthermore, the holoenzyme and the mediator subcomplex bind to a VP16 affinity column. These results provide a more complete description of the RNA polymerase II holoenzyme and suggest that this form of the transcription apparatus can be recruited to promoters via direct interactions with activators.

Amino Acid Sequence↗
PubMed1995

Small ileal neurofibroma causing intussusception in a non-neurofibromatosis patient.

Neurofibromas in the small intestine are usually accompanied by von Recklinghausen's disease (neurofibromatosis), and usually originate in the intramuscular plexus of Auerbach. We present here a solitary neurofibroma, which caused an ileocolic intussusception, originating in the submucosal plexus of Meissner in a non-neurofibromatosis patient. To our knowledge, there is no previous report of a neurofibroma originating in the plexus of Meissner. This condition was clearly confirmed by macroscopic and microscopic evaluation.

Adult↗
PubMed1995

Efficacy of ipriflavone and 1 alpha vitamin D therapy for the cessation of vertebral bone loss.

OBJECTIVE: This study investigated whether a combined regimen of ipriflavone and 1 alpha vitamin D is effective in stopping postmenopausal bone loss. METHODS: Ninety-eight postmenopausal women were recruited and randomly assigned to one of four groups: group 1, ipriflavone alone; group 2, 1 alpha vitamin D alone; group 3, combined regimen of ipriflavone and 1 alpha vitamin D; group 4, no treatment. Vertebral bone mineral density, measured by dual energy X-ray absorptiometry, serum alkaline phosphatase, calcitonin, parathyroid hormone, osteocalcin, urinary calcium and hydroxyproline were measured before and at the 6th, 12th and 18th month of the study. All comparisons were made using Student's t-test of means. RESULT: There was a significant reduction in vertebral bone loss in the patients receiving the combined therapy (mean loss after 18 months 0.33% in the combination group vs. 2.37%, 1.15% and 3.70% in the ipriflavone alone, 1 alpha vitamin D alone, and control groups, respectively; P < 0.001). CONCLUSION: These findings suggest that the combined regimen could prevent postmenopausal bone loss.

Drug Therapy, Combination↗
PubMed1995

Analysis of c-kit expression of human erythroleukemia cell line, HEL: clonal variation and relationship with erythroid and megakaryocytic phenotype.

The proto-oncogene c-kit encodes the receptor for a stem cell factor. We examined HEL, a human erythroleukemia cell line, in order to clarify the correlation between the c-kit receptor (KR) expression and lineage-specific phenotype. Although HEL cells are known to express KR, we found two relatively distinct HEL cell populations in terms of KR expression. We then subcloned HEL cell lines with clone sorting on the basis of KR expression and compared their various characteristics. The highly KR-expressing subline, HEL-P1, expressed a high level of glycophorin A (GPA), a known erythroid lineage marker. HEL-N1, in which most of the cells were KR-negative, showed a higher megakaryocytic lineage marker CD41b expression than HEL-P1. However, the expression of granulomonocytic lineage markers were not significantly different between the two subclones. Cell growth rate and cell cycle analysis also did not detect significant differences between the sublines. HEL-P1 cells gradually lost their KR expression in serum-containing culture, while the percentage of KR-positive HEL-N1 cells increased in serum-free culture. These observations indicate that KR expression was associated with the synchronous expression of GPA and inversely correlated with CD41b, and reversible transitions between KR-positive cells and KR-negative cells exist. We suggest that KR plays an important part in commitment of erythroid and megakaryocytic precursor cells.

Antigens, CD↗
PubMed1995

Endoscopic assessment of invasion of colorectal tumors with a new high-frequency ultrasound probe.

The present study was carried out to clarify the usefulness of and problems associated with a new ultrasound probe in the assessment of invasion of colorectal tumors. Normal colorectal wall of 23 resected specimens from colorectal cancer cases was examined in vitro with the probe. Fifty-one patients with colorectal carcinoma and 16 patients with rectal carcinoid tumor were presurgically examined using the probe via the biopsy channel of a conventional colonoscope. After endoscopic and ultrasonographic examination, 27 patients underwent endoscopic resection and 40 underwent surgical resection. The ultrasonographic findings were compared with histologic findings in all cases. Carcinomas and carcinoid tumors were visualized as an echo-poor region with the probe. The overall accuracy rate for depth of invasion was 76% (39/51) for colorectal cancer. The accuracy rates for tumors limited to the mucosa and tumors invading the submucosa were 83% and 90%, respectively; these rates were higher than those for tumors invading the muscularis propria (50%) and beyond the muscularis propria (73%). In all 16 cases of carcinoid tumor, the depth of invasion was accurately shown to be limited to the submucosa. This probe is useful to assess invasion of colorectal tumors, especially small and flat lesions limited to the mucosa or submucosa.

Adult↗
PubMed1995

Jejunal pouch reconstruction after total gastrectomy for cancer. A randomized controlled trial.

OBJECTIVE: The authors determined the optimum reconstruction procedure after total gastrectomy in terms of the quality of life of the patients. SUMMARY BACKGROUND DATA: Gastric replacement with various enteric reservoirs has been used to improve the postprandial symptoms and nutrition of patients after total gastrectomy. However, the effect of each is uncertain because no prospective randomized studies have been conducted. METHODS: A randomized controlled trial was conducted to compare the usefulness of the three reconstruction procedures of simple Roux-en-Y (RY; N = 10), pouch and Roux-en-Y (PR; N = 10), and pouch and interposition (PI; N = 10). In each subject, the postprandial symptoms, food intake in a single meal, body weight, serum nutritional parameters, and emptying time of the gastric substitute were evaluated. RESULTS: The PR group showed significantly greater food intake in a single meal than the RY and PI groups, and greater weight recovery than the PI group. A gastric emptying test also revealed satisfactory retention capacity and emptying time of the gastric substitute in the PR group. CONCLUSIONS: Pouch and Roux-en-Y reconstruction is the most useful of the three procedures for improving the postoperative quality of life. In patients with pouch and interposition reconstruction, the clinical assessment was quite poor, even though it is a physiologic route.

Adult↗
PubMed1995

High serum levels of granulocyte-macrophage colony-stimulating factor in patients with liver cirrhosis and granulocytopenia.

Leucopenia is often observed in patients with liver cirrhosis. We measured levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with liver cirrhosis by a sensitive enzyme linked immunosorbent assay. Eight out of 22 patients with liver cirrhosis had detectable serum GM-CSF (range, 55 to 245 pg/ml:mean, 135 pg/ml). Serum GM-CSF was detected in all patients with a granulocyte count below 2.0 x 10(9)/l, but in only one patient with a granulocyte count above 2.0 x 10(9)/l. Haemoglobin concentration, platelet count, serum albumin, total bilirubin and aminotransferase levels did not correlate with serum GM-CSF levels. These findings may reflect a feedback mechanism between the number of circulating granulocytes and serum GM-CSF levels in patients with cirrhosis.

Adult↗
PubMed1995

Magnetic resonance angiography in prostatodynia.

Three-dimensional magnetic resonance venography (3D MRV) of the prostate and the pelvic cavity was demonstrated in 8 normal subjects and 12 patients with prostatodynia. In all normal subjects and patients, 3D MRV images were successfully obtained. The deep dorsal vein of the penis sends major branches into the anterior and lateral capsular veins as well as into the internal pudendal vein. In patients with prostatodynia, the anterior and lateral capsular veins were much thicker in diameter than those in normal subjects, suggesting venous congestion. This congestion was also remarkable in the venous plexuses behind the bladder or along the lateral side of the pelvis in patients with prostatodynia. Another characteristic sign of the disease was a narrowing or an interruption of the internal pudendal vein. Prostatodynia is postulated to be caused by intrapelvic venous congestion.

Adult↗
PubMed1995

In vitro study of deoxymethylspergualin on functions of lymphocytes and bone marrow cells from healthy volunteers.

15-Deoxy-11-O-methylspergualin (MeDSG) is an analogue of 15-deoxyspergualin, which has potent immunosuppressive activity. The present study was designed to evaluate the in vitro effects of MeDSG on the functions of peripheral blood mononuclear cells (PBMC) and bone marrow cells derived from healthy volunteers. MeDSG failed to suppress the proliferation of PBMC stimulated with mitogens. In the allogeneic mixed lymphocyte reaction, MeDSG strongly suppressed both the proliferation of lymphocytes and the generation of alloreactive cytotoxic T lymphocytes, but did not affect the cytolytic activity of the established cytotoxic T lymphocytes. MeDSG had no effect on the cytolytic activity of natural killer cells. Concerning positive hematopoietic regulators, MeDSG had a slight enhancing effect on the release of granulocyte-macrophage colony-stimulating factor and a slight inhibitory effect on the release of interleukin-6 and granulocyte-colony-stimulating factor from PBMC stimulated with mitogens. Significantly, MeDSG completely suppressed the colony formation of bone marrow cells in the presence of granulocyte colony-stimulating factor.

Bone Marrow↗
PubMed1995

High-frequency granuloid colony-forming ability of G-CSF receptor possessing CD34 antigen positive human umbilical cord blood hematopoietic progenitors.

The presence of granulocyte colony-stimulating factor receptor (G-CSFR) in CD34+ hematopoietic progenitors is demonstrated by flow cytometry. Cord blood mononuclear cells (MNCs) contain about 1.09 +/- 0.2% CD34+ cells, 0.32 +/- 0.1% CD34+/G-CSFR+ (G-CSFR+) cells, and 0.77 +/- 0.1% CD34+/G-CSFR- (G-CSFR-) cells. The colony-forming ability of G-CSFR+ cells in the presence of G-CSF, granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), and erythropoietin (Epo) was higher than that of G-CSFR- cells (29.5 vs. 9.8%; p < 0.01). In the fraction of G-CSFR+ cells, the most frequently formed colony type was CFU-G/GM, while burst-forming unit-erythroid (BFU-E) or colony-forming unit-macrophage (CFU-M) were rare. On the other hand, the incidence of BFU-E and CFU-G/GM was similar in the fraction of G-CSFR- cells. This indicates that most granuloid colonies of CD34+ cells were derived from G-CSFR+ cells. These results suggest a lineage commitment for the vast majority of G-CSFR+ hematopoietic progenitors.

Antigens, CD↗