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Biomedical subjects

S Okamura

Publications and source records attributed to S Okamura.

At least 19 recordsLinked to original sources

Granulocyte colony-stimulating factor receptors on human acute leukemia: biphenotypic leukemic cells possess granulocyte colony-stimulating factor receptors.

Granulocyte colony-stimulating factor (G-CSF) receptors on the gated leukemic blast cells from newly diagnosed patients with acute leukemia or crisis of chronic myelogenous leukemia were investigated using flow cytometric detection. Surface marker analysis and cytochemical studies were conducted simultaneously to characterize the blast cells. Among 24 leukemia cases examined, G-CSF receptor-positive blast cells were detected in all 11 cases of acute myeloblastic leukemia even though the percentage range of positive cells was widely variable. On the other hand, they were not detected on the blast cells from patients with peroxidase-negative acute lymphoblastic leukemia with no myeloid surface antigens. However, G-CSF receptors were demonstrated in significant amounts on blast cells from 5 of 8 cases of peroxidase-negative acute leukemia expressing both myeloid and lymphoid surface antigens (biphenotypic leukemia). The percentage of blast cells positive for G-CSF receptors was significantly smaller in biphenotypic cases [33 +/- 14% (SD)] than in acute myeloblastic leukemia cases [65 +/- 22%] (P less than 0.01). The percentage expression of CD13 antigen by blast cells was significantly related to their percentage positivity for G-CSF receptors (rs = 0.50, P less than 0.05). These findings indicate that the distribution of flow cytometrically detectable G-CSF receptors on leukemic cells possessing myeloid characteristics may be related to the maturation process.

Antigens, CD

Chemosensitivity and DNA ploidy in head and neck squamous cell carcinomas.

The succinate dehydrogenase activity and cellular DNA content of human head and neck squamous cell carcinomas were examined, and the chemosensitivity and ploidy status were compared with histologic differentiation. The average decrease of enzyme activity in the poorly differentiated squamous cell carcinomas was significantly greater than that of well- and moderately differentiated squamous cell carcinomas. Statistically significant differences were also noted with relation to the original site of the primary tumor. The chemosensitivity of a tumor with DNA aneuploidy tended to be lower among the well- and moderately differentiated squamous cell carcinomas and higher among the poorly differentiated type. We conclude from this study that simultaneous analysis of the chemosensitivity and DNA ploidy will aid not only in selecting effective antitumor drugs but also in predicting changes in cellular characteristics during the course of disease.

Antineoplastic Agents

Influence of preoperative treatment and surgical operation on immune function of patients with esophageal carcinoma.

Multiple immunological parameters, including total lymphocyte count, lymphocyte subpopulations (CD2+, CD19+, CD3+, CD4+ and CD8+), phytohemagglutinin (PHA) response, and natural killer (NK) activity, were measured in 66 patients with previously untreated esophageal carcinoma. The influence of preoperative treatment and/or surgical operation on the immune function were evaluated in 40 patients. The PHA response and NK activity of the patients with esophageal carcinoma were 229 +/- 103 S.I.% and 18.5 +/- 11.9% lysis, respectively, and were significantly depressed as compared with the control. The CD4+/CD8+ ratio, PHA response, and NK activity in stage IV were also significantly depressed compared to that in stages I-III. Preoperative treatment induced significant reductions in the total lymphocyte count (1,994 +/- 644 to 670 +/- 274/mm3), PHA response (219 +/- 77 to 159 +/- 59 S.I.%), and NK activity (19.7 +/- 13.2 to 11.1 +/- 10.3% lysis) as well as a significant gradual decrease in the CD4+/CD8+ ratio (2.09 +/- 1.42 to 0.69 +/- 0.48), while the surgical operation significantly influenced only the total lymphocyte count. This study demonstrates that preoperative treatment induces a more pronounced influence on the immune function than surgical operation alone, in patients with esophageal carcinoma in which the immune function is disturbed prior to these treatments.

Adult

Long-term survival of human myeloid progenitor cells induced by a mouse bone marrow stromal cell line.

Mouse endothelial-adipocyte cell line (14F1.1), which induces proliferation of mouse stem cells in culture, is also capable of supporting long-term survival in culture of human myeloid progenitor cells; colony forming unit-granulocyte/macrophage (CFU-GM) was recovered from cultures incubated with the 14F1.1 cell line after over a month of incubation. The CFU-GM population increased beyond the input number, whereas, in control cultures initiated without stromal cells, the number of progenitors gradually declined. Addition of a relatively low concentration of human colony-stimulating factors (CSFs) into the cultures promoted the formation of "cobblestone areas," where mouse stroma and human hemopoietic cells closely interacted. 14F1.1 supernatant alone did not support the survival of human CFU-GM but synergized with the function of human granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate adherent macrophage proliferation.

Animals

CD7-positive acute myeloid leukemia: further evidence of cellular immaturity.

Among 63 cases of acute myeloid leukemia (AML), 14 were found to express the CD7 antigen, a cell surface marker usually found at an early stage during T lineage differentiation. The CD7-positive AML cases consisted of 5 cases of M1, 3 cases of M2, 3 cases of M4, 1 case of M5, 1 case of M6 and 1 case of M7. Among these 63 cases, the proportion of blast cells expressing the CD34 antigen was examined. The proportion of CD34-stained cells among the CD7-positive AML cases, although varying, was significantly larger than that among the CD7-negative AML cases (P less than 0.05). As the CD34 antigen was expressed on hematopoietic progenitor cells and was considered to reflect an early hematopoietic stage, the high proportion of cells expressing CD34 among the CD7-positive AML cases may support the notion that CD7-positive AML cells are immature.

Adolescent

Circulating CD34+ hematopoietic progenitors in the harvesting peripheral blood stem cells; enhancement by recombinant human granulocyte colony-stimulating factor.

The number of circulating progenitor cells increases during the period of hematopoietic recovery following myeloablative therapy. These progenitor cells were used for autologous transplantation in order to reconstitute hematopoiesis. As an indicator of the circulating progenitor cells, the number of granulocyte-macrophage colony forming units (CFU-GM), which is measured by means of a long-term cell culture, has been widely used. Recently, a cell surface marker, CD34, which can easily be measured by means of flowcytometry, was found to represent immature hematopoietic progenitor cells, which are very close to stem cells. Therefore, the relationship between the number of CD34 positive cells (CD34+ cells) and the number of CFU-GM in the peripheral blood following chemotherapy was studied in 9 patients selected to undergo autotransplantation. The number of peripheral blood CD34+ cells was found to be significantly correlated with that of CFU-GM (r = 0.81). When four out of 9 patients received recombinant human granulocyte-colony stimulating factor (rG-CSF) administration, a significant increase in the release of peripheral blood CD34+ cells as well as peripheral blood CFU-GM was observed (P less than 0.01). Thus, the measurement of CD34+ cells is useful for predicting the number of circulating CFU-GM.

Adolescent

Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions.

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4-5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.

Adult

Detection of the granulocyte colony-stimulating factor receptor using biotinylated granulocyte colony-stimulating factor: presence of granulocyte colony-stimulating factor receptor on CD34-positive hematopoietic progenitor cells.

Granulocyte colony-stimulating factor (G-CSF) was linked to NHS-biotin to yield biotinylated G-CSF (b-G-CSF), which retained the ability to stimulate colony formation by normal bone marrow (BM) cells in methylcellulose. The use of streptavidin-phycoerythrin conjugate in conjunction with flow cytometry demonstrated that the binding of biotinylated G-CSF to its receptor is saturable, competitive, and specific. A 100-fold molar excess of unlabeled G-CSF almost completely inhibited the binding of the biotinylated G-CSF to the human leukemia cell line U937, which is known to possess the G-CSF receptor. G-CSF receptors were clearly detected by flow cytometry on adult human peripheral granulocytes and monocytes, but not on lymphocytes. Using this method, the expression of G-CSF receptors on hematopoietic progenitor cells in bone marrow and umbilical cord blood, detected as CD34-positive (CD34+) cells, were examined. A small but significant number of CD34+ cells were detected among the bone marrow mononuclear cells and umbilical-cord-blood mononuclear cells (4.28% +/- 0.31%, 1.09% +/- 0.20%, respectively). The percentage of CD34+ BM mononuclear cells was significantly higher than for cord blood mononuclear cells (P less than 0.01). These CD34+ cells were then analyzed by biotinylated G-CSF binding. CD34+ cells from bone marrow contained 25.8% +/- 7.9% G-CSF receptor positive cells and those from cord blood possessed 29.2% +/- 7.0% of G-CSF receptor-positive cells. The difference was not statistically significant.

Antigens, CD

Serum granulocyte colony-stimulating factor levels in umbilical cord blood of normal full-term neonates.

We measured granulocyte colony-stimulating factor (G-CSF) levels in cord blood of 59 normal full-term neonates immediately after birth and the subsequent changes in G-CSF levels of 16 cases by our modified enzyme-linked immunosorbent assay (ELISA) for G-CSF. Ten out of 59 cases examined (17%) showed G-CSF levels in cord blood after delivery between 20 and 57 pg/ml, although in the remaining cases, the G-CSF levels were below 20 pg/ml, which was our minimal detection level. A direct relationship between G-CSF levels and white blood cell count, absolute granulocyte numbers in cord blood, gestation age or weight was not observed. Although G-CSF levels in cord blood after delivery remained below 20 pg/ml in 5 cases out of 16 tested, those in the remaining 11 cases (69%) subsequently became elevated after delivery. The peak G-CSF level in cord blood after delivery ranged from 26-364 pg/ml, and the time of it was between 4.5 and 18 h. As G-CSF level per wet weight of placenta was high (124 x 29 pg/ml), these subsequent elevations of G-CSF in cord blood after delivery may result from a gradual influx from the placenta.

Enzyme-Linked Immunosorbent Assay

Aplastic anemia in a male with loss of the Y chromosome.

We carried out chromosomal analysis of a 33-year-old male who was diagnosed as having aplastic anemia. The patient showed severe pancytopenia, a normal NAP score, hypoplastic marrow and no myelodysplastic changes. 45,XO was found in all bone marrow cells examined, and in 10% of peripheral blood cells examined. To our knowledge, this is the first reported case of male aplastic anemia to show loss of the Y chromosome in all bone marrow cells examined, and this case may suggest a possible mechanism of juvenile onset of aplastic anemia.

Adult

[Irritable bowel syndrome--criteria, sub-classification, etiology].

The irritable bowel syndrome (IBS) is a very common condition in gastroenterology clinics, but yet it is one of the pooly understood. A international working team in Rome, 1988, proposed that IBS is a functional intestinal disorder with chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. IBS was sub-classified into 3 groups; abdominal pain as the prominent feature with diarrhea, with constipation, with both while painless diarrhea and simple constipation without pain were excluded from IBS. There is a lot of data suggesting that IBS has a gut dysmotility, which is influenced by many stimuli (food, hormone, drug, menses, mechanical dilatation), including psychological stress. Moreover, currently available evidences implicate that IBS is a more generalized disorder of smooth muscle function not only in the intestine but also outside of the intestine.

Colonic Diseases, Functional

Hypoinsulinemia in a patient with isolated ACTH deficiency.

We report on a patient with isolated ACTH deficiency accompanying deficient insulin response to glucose. The subject is a 59 year-old male. He was admitted to our hospital because of a hypoglycemic attack. Urinary excretion of 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) was low. Plasma ACTH levels decreased and serum cortisol levels were undetectable. ACTH did not respond to CRF stimulation for three consecutive days. Antibodies to At-T 20 cells (anterior pituitary cell-derived cell line) were positive in the serum of this patient. Serum immunoreactive insulin (IRI) levels were not detected throughout the day. The urinary excretion of C-peptide decreased to 9.8 micrograms/day. IRI responses on 75 g oral glucose tolerance test (OGTT) were examined at one and two months after the start of cortisol supplementation. No remarkable IRI response was observed, although blood glucose levels were maintained within the normal range. Eight months after the start of cortisol supplementation, the insulin response to 75 g OGTT appeared. The present study suggests that the recovery from hypo-insulinemia may be delayed even after normalization of serum cortisol levels in ACTH deficiency. This may be possibly due to the salutary effects of cortisol in maintaining plasma insulin levels. The time lag may be due to other factors also.

Adrenocorticotropic Hormone

[Diagnosis and classification of leukemia].

Modern diagnosis and classification of leukemia are reviewed. The FAB (French, American, British) classification, introduced in the late 1970s has been the basis for most studies to date. During the 15 years since then, new categories such as M7 and M0 were added to the classification. The MIC proposal (morphology, immunology, cytogenetics) has been an important development which emerged from the knowledge about chromosomal changes and immunophenotyping. Improvement in diagnosis and classification will emerge from studies employing all the above techniques, including DNA analysis, in the 1990s.

Humans

[Pharmacokinetics and toxicological study on the intraperitoneal administration of cisplatin and etoposide in gynecological malignancies].

We administered cisplatin and etoposide into the peritoneal cavity of 13 postoperative patients with gynecological malignancies, and studied the pharmacokinetics and toxicity in the combination of both drugs. Cisplatin 100 mg/body and etoposide 200 mg-400 mg/body were mixed together in 500 ml or 1,500 ml of normal saline and administered intraperitoneally on the day of operation and two or three weeks later. The peritoneal peak level of free cisplatin, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. However, there was no difference in the peritoneal and plasma AUC. The peritoneal level and AUC of etoposide, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. Among the groups of 1,500 ml, peritoneal and plasma levels and AUC were almost proportional to the doses. Nausea and vomiting were experienced in all patients. With the increase of etoposide, more marrow suppression was observed. However, we encountered no other significant side effects. In conclusion, intraperitoneal administration of cisplatin and etoposide in this setting can be used safely with minimum side effects, and the dilution of 1,500 ml seems to be better.

Adult