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Biomedical subjects

A Kubota

Publications and source records attributed to A Kubota.

At least 145 records · Page 8Linked to original sources

The c-kit molecule and the surface immunophenotype of human acute leukemia.

The proto-oncogene c-kit encodes the receptor for a stem cell factor (c-kit molecule). Expression of the c-kit molecule on the gated leukemic blast cells from newly diagnosed patients with leukemia was analysed by flow cytometry using the monoclonal antibody (17F11). Among 35 myeloid leukemia cases examined, significant c-kit-positive blast cells were detected in 24 cases (69%), even though the percentage of positive cells was widely variable. The correlation between the percentage of cells positive for the c-kit molecule and the percentage of cells positive for CD34 was found to be statistically significant (rs = 0.36, p < 0.05). Fifteen cases of myeloid leukemia were positive for lymphoid markers. The mean percentage of the cells expressing c-kit molecule among the lymphoid marker-positive cases was significantly larger than that among the lymphoid marker-negative cases (p < 0.05). All 19 lymphoid leukemia cases were c-kit-negative, including 8 cases which were positive for some myeloid markers. Stem cell factor enhanced the colony growth in five out of six acute myeloblastic leukemia cases expressing the c-kit molecule. On the other hand, SCF did not stimulate colony growth in any of the four cases which were not positive for the c-kit molecule. These findings indicated that the distribution of flow cytometrically detectable c-kit molecules on leukemic cells is related to the morphologic and immunologic classification of these leukemic cells and to the expression of the CD34 cell surface molecule on some myeloid leukemic cells. On such cells, expression of the c-kit molecule may have a functional role and be related to the maturation process.

Adult↗

[Analysis of DNA ploidy using fresh frozen tissues from head and neck squamous cell carcinomas].

The DNA ploidy of fresh frozen tissues from head and neck squamous cell carcinomas was determined by flow cytometry, with the aim of investigating whether DNA ploidy correlates with various clinical and pathological parameters. The subjects were 51 patients who had undergone radical surgery in our department. The DNA ploidy pattern was classified into three types, diploid, single aneuploid and multiploid, according to the DNA index and the DNA histogram. This is our original classification. No particular correlation could be detected between the DNA ploidy pattern and sex, age, primary tumor site or disease stage. The degree of tissue differentiation tended to be poorer in aneuploid than in diploid tissues. The efficacy of chemotherapy was higher in aneuploid than in diploid cases. The recurrence rate was significantly lower in diploid than in multiploid cases. When disease stage, degree of histological differentiation, the efficacy of chemotherapy and the DNA ploidy pattern were subjected to multivariate analysis for correlation with prognosis, the DNA ploidy pattern showed the highest correlation. Our results suggest that the DNA ploidy, as analyzed by flow cytometry, can serve as useful prognostic factor.

Adult↗

[A case of sudden death of a patient with hypopituitarism].

We report a 29-year-old woman who died due to pituitary insufficiency. After a normal delivery 2 years previously, she had suffered from amenorrhea and displayed decreased libido. She was discovered in convulsions by her husband when he returned home, and was admitted to an emergency hospital. Despite various treatments, she died. Her blood glucose level on admission was low, 32 mg/dl. Autopsy findings showed thin public hair and almost no axillary hair. The right and left adrenal glands weighed 1.7 g and 1.2 g, respectively. Histologically, the anterior pituitary gland showed severe bleeding and necrosis, and the middle lobe showed lymphocytic infiltration; the posterior lobe was almost normal. The adrenal glands showed marked atrophy of the cortex and deposition of calcium in the medulla. The thyroid gland, which weighted 15 g, showed diffuse interstitial lymphocytic infiltration, indicative of chronic lymphocytic thyroiditis. Atrophy of the ovaries and uterine endometrium was also observed. These findings indicated that death had been due to pituitary insufficiency. The histopathology of the pituitary, which showed lymphoid hypophysitis, and its association with lymphoid thyroiditis suggested that the pituitary insufficiency was not due to ischemic injury after delivery, a condition which can result from massive hemorrhage, but rather had arisen as a result of an autoimmune process.

Death, Sudden↗

[The detection of GLUT2 gene mutation by polymerase-chain reaction single stranded conformation polymorphism (PCR-SSCP) method].

The polymerase chain reaction-single stranded conformation Polymorphism (PCR-SSCP) procedure was applied to examine whether the mutation in the liver/islet glucose transporter (GLUT2) gene could be associated with non-insulin-dependent diabetes mellitus (NIDDM) in Japanese. Samples were processed through 30-40 cycles of 1 min denaturation at 94 degrees C, 1 min annealing at 55-68 degrees C for 1-2 min, extention at 72 degrees C for 1 min, and denaturation at 94 degrees C for 1 min. We identified a silent mutation in codon 479 for PheTTT/TTC.

Base Sequence↗

Morphological studies on the placenta.

Morphological studies were done on 109 placentae of 6 to 43 gestational weeks. Soft x-ray figures are useful for detecting the development of the placenta, which is closely correlated to enlargement of cotyledon and vascular growth in the chorionic villi. At histological figures, chorionic villi, corresponding to intermediate mature villi at the early gestational weeks, reveal large size with edematous stroma and prominent interstitial cells. Their size becomes smaller with aging, with decreased interstitial cells and stroma. At the early gestational period until 23 weeks, chorionic villi are lined by two cell layers of S-(syncytial) and C-(cytotrophoblastic) cells. After 24 gestational weeks C-inner lining decreases in number. Syncytial knots become marked after 32 weeks. As aging, the intervillous space becomes narrow and is occupied by the small sized terminal and mature chorionic villi with congestive capillaries. Syncytial knots and fibrin deposit around chorionic villi are increased with placental aging. By the immunohistoenzymatical examination, S-lining is positive by hCG (human Chorionic Gonadotropin) at the early gestation, but is markedly positive by hPL(human Placental Lactogen) and SP-1 (Specific Protein 1) lately.

Chorionic Villi↗

Pathological studies on the placenta from pre-term and term maternal toxicosis.

Fifty one placentae with maternal pre-term and term toxicosis were studied pathologically. In the severe pre-term maternal toxicosis, the placenta reveals hyperplasia of syncytial cytotrophoblasts(S-cells) with knots, fibrin deposit at their surface, fibrinoid degeneration of the stroma, in addition to marked interstitial fibrosis of chorionic villi. The basement membrane is thick and cytotrophoblasts(C-cells) are scattered beneath it. Decidual arteries are hyalinized, but a few decidual arteries are thick and almost obstructed in their lumina. On the other hand, the placenta of maternal term toxicosis show chorionic villi with few C-cells under the thin S-cell lining. Their basement membrane is thin with well developed vasculosyncytial membrane. Decidual arteries are more hyalinized and widened. These pathological changes seen in term maternal toxicosis are the severer than those of placental aging.

Eclampsia↗

The anti-tumor arotinoid Ro 40-8757 protects bone marrow from the toxic effects of cyclophosphamide.

The arotinoid Ro 40-8757 is a novel compound that has significant therapeutic activity against chemically induced breast tumors in rats. The results of combination therapy with cyclophosphamide, plus the arotinoid showed that the anti-tumor effects were additive. However, all of the rats given CPA alone died between week 6 and week 10 of treatment. None of the animals in the group treated with the combination died. Administration of a single dose of Ro 40-8757 to non-tumor bearing mice resulted in a transient increase in bone-marrow-progenitor cells after 2 days and a decrease in splenic progenitors at day 4. Treatment of mice with the combination demonstrated that the marrow progenitors were protected from the toxic effects of CPA by the arotinoid. Direct addition of Ro 40-8757 to mouse bone-marrow cells in clonogenic assay cultures containing WEHI-3-conditioned medium plus erythropoietin showed no significant enhancement by the arotinoid. The results suggest that this compound may exert its protective effect through the hemopoietic micro-environment.

9,10-Dimethyl-1,2-benzanthracene↗

Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype.

Somatostatin exerts diverse effects in various tissues upon binding its specific membrane receptors. Recently, we have cloned three different somatostatin receptor subtypes. Here we report the sequence and functional expression of a fourth and a fifth human somatostatin receptor subtype, termed hSSTR4 and hSSTR5, respectively. The hSSTR4 encodes a protein of 388 amino acids and the hSSTR5 is a protein of 364 amino acids. There is 42-60% identity among the amino acid sequences of the five human somatostatin receptor subtypes identified to date. RNA blotting studies reveal that the hSSTR4 is expressed as a single transcript of 4.8 kb in MIA PaCa-2 cells, a cell line derived from human pancreatic cancer while the hSSTR5 is undetectable in the tissues examined. The hSSTR4 and hSSTR5 transiently expressed in COS1 cells exhibit specific binding to somatostatin-14 with IC50 values of 1.6 and 0.16 nM, respectively. We also have characterized the binding affinity of various somatostatin analogues to the hSSTR4 and hSSTR5. The rank of the potency of the analogues are: somatostatin-14 = somatostatin-28 >> RC-160 >> SMS201-995 for the hSSTR4 and somatostatin-28 > somatostatin-14 >> RC-160 > SMS201-995 for the hSSTR5. These results suggest that diverse actions of somatostatin are mediated by at least five somatostatin receptor subtypes with potentially different function.

Amino Acid Sequence↗

Chemotherapy for recurrent adeno- and adenoidcystic carcinomas in the head and neck.

We have investigated the effectiveness of chemotherapy for patients with recurrent adeno- and adenoidcystic carcinomas in the head and neck. Fourteen cases received a monthly combination chemotherapy regimen of cyclophosphamide, pirarubicin and cisplatin (CAP therapy). A response rate of 36% (5/14) was achieved. There was one complete response and four partial responses. The median duration of response was 37 months in the complete response case and 16 months (range, 6 to 20) in the partial response cases. The toxicity of this chemotherapy was acceptable. The result demonstrates that CAP therapy is an effective regimen for adeno- and adenoidcystic carcinomas. It may also be available as induction or adjuvant chemotherapy for patients with advanced tumors of these cancers.

Adenocarcinoma↗

Clinical application of recombinant human erythropoietin for treatments in patients with head and neck cancer.

The therapeutic effects of intravenous recombinant human erythropoietin (r-hEPO) administration on anemia induced by radiation therapy (3 cases), chemotherapy (18 cases) and combined therapies (5 cases) in patients with head and neck malignancies were examined. The effectiveness was evaluated by the changes in the hemoglobin concentration examined before and after the r-hEPO administration. The r-hEPO administration combined with anticancer therapies improved anemia induced by all three treatments. The therapeutic effectiveness of r-hEPO injection was also noted on anemia induced by all of four different chemotherapeutic regimens that have been ordinarily used for head and neck malignancies. Furthermore, the efficacy of the different dose schedules, 3000 IU (12 cases) or 6000 IU (14 cases), three times a week, was compared. Both of the r-hEPO dose schedules were effective for anemia, but the efficacy of 6000 IU was superior to that of 3000 IU. No significant changes were observed in the number of white blood cells and platelets and the results of biochemical examinations after the r-hEPO injection. There were no objective side-effects related to the r-hEPO administration. These results suggest that anemia induced by chemotherapy and/or radiotherapy could be prevented by r-hEPO administration. The addition of r-hEPO to anticancer therapies would make it possible to pursue the planned therapeutic schedules, prevent the decrease of immunity after allogeneic blood transfusion and bring about an-improvement in the prognosis of patients with malignancies.

Adult↗

Autologous tumor cell killing activity of tumor-associated lymphocytes in patients with head and neck carcinomas.

In order to select the most cytotoxic effector cells for adoptive immunotherapy, lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TILs) and autologous mixed lymphocyte tumor cell culture (MLTC) cells derived from peripheral blood mononuclear cells (PBMC) in the same subject with head and neck carcinomas were prepared. The autologous tumor cell killing activity and cell surface phenotypes of each of the three effector cells were studied. MLTC cells cultured with interleukin-2 (IL-2) showed the strongest cytotoxic activity among these three different effector cells. Although TILs had suppressed killing activity immediately after isolation, after successive cultivations with IL-2, a cytotoxic activity against autologous tumor cells stronger than that of LAK cells appeared. Both IL-2 stimulated MLTC cells and TILs showed an enrichment of CD8 positive and CD11 negative cells in a CD3 positive subpopulation.

Antigens, Surface↗

The sensitivity of head and neck squamous cell carcinomas to tumor necrosis factor-alpha.

Sensitivities to recombinant human tumor necrosis factor-alpha (TNF-alpha) and chemotherapeutic agents (cisplatin, peplomycin, methotrexate) were evaluated in 20 tumor cells of head and neck squamous cell carcinomas, using a dye uptake method. Also, numbers of TNF receptors of these tumor cells were measured by Scatchard plot analysis. There was no relationship between the number of TNF-alpha receptors and the sensitivity to TNF-alpha. Furthermore, there was no correlation between the sensitivity to TNF-alpha and that to chemotherapeutic drugs, nor between the sensitivity to TNF-alpha and the clinical response to chemotherapy including of cisplatin and peplomycin. The sensitivity to TNF-alpha was higher in poorly differentiated carcinomas than in well differentiated ones.

Antineoplastic Agents↗

Restriction fragment length polymorphisms of the CYP11B1 gene in the Japanese population.

Restriction fragment length polymorphisms (RFLPs) of the CYP11B1 gene were studied in Japanese using cDNA clone P450c11 as a probe. Genomic DNAs from 60 unrelated Japanese individuals were digested with 8 different restriction enzymes and analyzed by Southern blot hybridization. Two RFLPs were detected in MspI digests of the DNA. One (A) was characterized by polymorphic bands at 3.4 and 2.5 kilobase-pairs (kb) and the other (B) by polymorphic bands at 1.7 and 1.2 kb. The third RFLP was observed in PvuII-digested samples and was polymorphic at 5.8 and 4.0 kb bands. Two of the three RFLPs found, RFLP (A) and (C), have not been described in the only previous report which was based on Caucasian samples. We also examined the RFLPs of a 3 generation family of 11 beta-hydroxylase deficiency caused by an abnormality of the CYP11B1 gene. All the family members were homozygous in all three RFLPs and was thus not informative.

Adrenal Hyperplasia, Congenital↗

A case of Goldenhar syndrome associated with growth hormone deficiency.

We have experienced the case of a 10-year-old boy who had Goldenhar syndrome accompanied by growth hormone (GH) deficiency. His height increased after treatment with growth hormone was administered. We found no untoward effects of the hormone and we consider that treatment with GH is useful for patients who present with Goldenhar syndrome associated with growth hormone deficiency.

Child↗

Anterior sagittal anorectoplasty as a redo operation for imperforate anus.

Based on the idea of transsphincteric approach by Peña, we applied anterior sagittal anorectoplasty (ASARP) as a redo operation in 10 patients, who present moderate to severe fecal incontinence postoperatively. Those patients exhibited anal opening located anteriorly to the center of contraction of external sphincter muscles. Operation is begun with making a circumferential skin incision in the mucocutaneous junction around the anal opening, extending posteriorly along the median line to the center of the external sphincter muscles. Upon confirming the vertical muscle and the external sphincter muscles, the rectal tube, being dissected free, is mobilized backward to be placed at the center of the vertical muscles and enclosed by the muscle. After the operation, an improvement was noted in either clinical symptoms or scores, being particularly marked for incontinence and staining scores. Anorectal manometry and barium enema studies also showed a significant improvement. These results provide ample justification of ASARP as a redo operation for imperforate anus being worthwhile trying in properly selected patients with poor anorectal function following the primary operation.

Anus, Imperforate↗

Levels of serum granulocyte colony-stimulating factor in patients with cerebrovascular diseases.

The role of leukocytes in the pathogenesis of cerebrovascular disease, in particular, cerebral ischemic disease has recently become a focus of research. Several studies have reported that a positive correlation between increased functional activities of neutrophils and the risk of cerebral ischemic disease. Granulocyte colony-stimulating factor (G-CSF) is known to be not only a granulocyte proliferating factor but also a potent activator of mature neutrophils. In this study, we measured the serum G-CSF levels in 143 patients with cerebrovascular diseases and in 100 patients with other diseases, using our established enzyme-linked immunosorbent assay (ELISA) for G-CSF The minimal detection level was 20 pg/ml G-CSF. In patients with cerebral infarction, G-CSF could be detected in 18.3% and in patients with cerebral hemorrhage, it could be detected in 9.8% of analyzed samples. On the other hand, 6% of the patients with other diseases had measurable levels of G-CSF. The differences among these three groups were statistically significant according to the chi 2 test (p < 0.01). Our findings that there was a significantly high frequency of elevated levels of G-CSF among patients with cerebrovascular diseases, may indicate that the action of G-CSF as a potent activator of neutrophils plays some role in the occurrence of cerebrovascular disease, in particular, cerebral infarction.

Adult↗

Augmented production of interleukin 6 by co-culture of human bone marrow adherent cells and human leukemic cells.

Human Dexter-type culture of bone marrow (BM) cells maintains long-term hematopoiesis in the presence of an adherent stromal layer. These BM adherent cells produce hematopoietic growth factors constitutively or inducively and support developing hematopoietic cells. To elucidate the ability of cytokine production by BM adherent cells, the cytokine levels of the culture supernatant of BM adherent cells were measured by enzyme-linked immunosorbent assays. Constitutive production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL-6) by the unstimulated BM adherent cells was demonstrated. Levels of granulocyte colony-stimulating factor (G-CSF) were below detectable levels (< 10 pg/ml). The IL-6 level was significantly increased in the co-culture supernatant with KG1 cells or U937 cells (P < 0.01: P < 0.05, respectively). Even when the adherent cells and cell line cells were separated by a membrane filter, the IL-6 level was significantly higher than the control culture (P < 0.01). Co-culture with these cell lines was supposed to induce the increased production of IL-6, which was mediated by some soluble cytokines. The GM-CSF level was not increased in the supernatant co-cultured with any of the cell lines, except with K562 cells. However, K562 cells alone secreted a detectable level of GM-CSF and the increased level of GM-CSF was considered to be due to the production of GM-CSF by K562 cells. G-CSF was not detectable in the supernatant co-cultured with any cell line cells. This result indicates that the cytokine production was regulated by the interaction of BM adherent cells and some leukemic cells.

Bone Marrow↗