Search PubMed⌕ Search

Biomedical subjects

H Mizoguchi

Publications and source records attributed to H Mizoguchi.

At least 19 recordsLinked to original sources
PubMed1992

Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice.

Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8+ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-alpha and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3 gamma and completely lacked CD3 zeta, which was replaced by the Fc epsilon gamma-chain. Expression of the tyrosine kinases p56lck and p59fyn was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.

Animals↗
PubMed1992

Detection of novel germ-line p53 mutations in diverse-cancer-prone families identified by selecting patients with childhood adrenocortical carcinoma.

BACKGROUND: Germ-line p53 mutations appear to be inherited among the members of families diagnosed with Li-Fraumeni syndrome (LFS). The mutations detected in those families to date have been clustered in exon 7 of the p53 gene and, typically, have been single-base substitutions resulting in amino acid changes. PURPOSE: Our aim was to define the spectrum of p53 mutations associated with LFS. METHODS: From seven cancer-prone families identified by selecting members with childhood adrenocortical carcinoma as probands, we chose two families, each of which had two members from whom specimens could be obtained for genetic analysis. To detect germ-line p53 gene mutations in these individuals, we performed polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis with Taq polymerase and oligonucleotide primers specific for p53 gene sequences. Genomic DNA extracted from fresh tissue samples and paraffin-embedded tumor samples was amplified, denatured, and electrophoresed on neutral polyacrylamide gels. PCR amplification was also carried out using total RNA from adrenocortical carcinoma samples of the proband in family 1. PCR products were purified, subcloned, and sequenced. RESULTS: We detected novel germ-line p53 mutations in affected members of both cancer-prone families. In the proband of family 1, a single-base deletion was detected at the first nucleotide of codon 307 in exon 8 of the p53 gene, resulting in a premature stop codon in exon 10. In family 2, we detected an A to C transversion at the second nucleotide of codon 286 in exon 8, both in DNA isolated from the adrenocortical tumor of the proband and in DNA isolated from the astrocytoma of the proband's father. This single-base substitution resulted in an amino acid substitution of alanine for glutamic acid. Both of these mutations are located outside the highly conserved region of the p53 gene where mutations in patients with LFS have been reported previously. CONCLUSION: Our results indicate that a wide range of germ-line p53 mutations is inherited in members of diverse-cancer-prone families.

Adrenal Cortex Neoplasms↗
PubMed1992

Interleukin-11 enhances human megakaryocytopoiesis in vitro.

We investigated the effect of recombinant human interleukin-11 (rhIL-11) on human megakaryocytopoiesis. Nonadherent and T-cell-depleted human bone marrow (BM) mononuclear cells were cultured in a serum-free agar culture system. rhIL-11 alone did not stimulate the growth of human megakaryocyte colonies. However, when rhIL-11 was combined with optimal or suboptimal doses of rhIL-3, the number and size of the megakaryocyte colonies increased. The same results were obtained when highly purified BM CD34-positive cells were used as target cells. Next, we investigated the effect of rhIL-11 on the ploidy of megakaryocytes. The ploidy distribution of individual cells in megakaryocyte colonies obtained by rhIL-11 in combination with rhIL-3 was significantly shifted towards higher values. Furthermore, when highly purified CD41-positive BM cells were cultured in the presence of rhIL-11, the ploidy distribution was shifted towards higher values. This effect was not suppressed by anti-IL-6 antibody. These results suggest that rhIL-11 acts directly as a megakaryocyte potentiator and may play a role in regulating human megakaryocytopoiesis.

Antigens, CD↗
PubMed1992

Granular lymphocyte leukemia with pure red cell aplasia: usefulness of gene analysis in assessing therapeutic effect.

A patient with granular lymphocyte leukemia (GLL) of the CD3+, CD4-, CD8+ phenotype accompanied by pure red cell aplasia (PRCA) is described. Surface marker analysis, nonmajor histocompatibility complex (MHC)-restricted cytotoxicity assay, gene analysis, and in vitro colony assay were performed on the granular lymphocytes before and after treatment. Cyclophosphamide therapy was highly effective, and after remission clonal granular lymphocytes were no longer identified by T-cell antigen receptor (TCR) gene analysis or surface marker analysis. Lymphocytes obtained after remission did not exhibit elevated levels of non-MHC-restricted cytotoxicity, nor did they demonstrate a suppressive effect on erythroid colony formation. TCR gene analysis proved to be a sensitive parameter for evaluating the residual malignant granular lymphocytes. Gene analysis will be useful both for timing the discontinuation of treatment and for the early detection of relapse. Various factors possibly related to the development of PRCA in this patient were investigated and their significance is discussed.

Bone Marrow↗
PubMed1992

Differential expression of non-major histocompatibility complex-restricted cytotoxicity in patients with granular lymphocyte-proliferative disorders associated with or unassociated with severe anemia.

Of 27 patients with granular lymphocyte-proliferative disorders (GLPD), 18 patients had CD3+ T-cell-lineage GLPD (T-GLPD), and 9 patients had CD3-CD16+ natural killer (NK) cell-lineage GLPD (NK-GLPD). In 9 of the 18 patients with T-GLPD, severe anemia of less than or equal to 7.5 g/dl hemoglobin (mean 5.4 g/dl) and erythroid hypoplasia in the bone marrow developed, while the remaining 9 patients with T-GLPD and 9 patients with NK-GLPD exhibited hemoglobin levels of greater than or equal to 10.0 g/dl, and erythroid hypoplasia was not found. The number of leukocytes, neutrophils, lymphocytes or granular lymphocytes in the peripheral blood, or the percentage of lymphocytes in the bone marrow did not differ significantly between the patients with T-GLPD associated with severe anemia and those with T-GLPD not associated with severe anemia, and the immunophenotypes of peripheral blood mononuclear cells (PBMC) were not significantly different either. However, when non-major histocompatibility complex (MHC)-restricted cytotoxicity was assayed with PBMC, T-GLPD patients with severe anemia and NK-GLPD patients exhibited significantly higher levels of non-MHC-restricted cytotoxicity than T-GLPD patients without severe anemia. Because PBMC obtained from T-GLPD patients with severe anemia were shown not to lyse erythroblasts directly, the possibility that patient PBMC lyse erythroblasts in the bone marrow and thus cause anemia seems unlikely. The pathogenesis of anemia in GLPD was discussed.

Anemia↗
PubMed1992

Stimulatory effect of tumor necrosis factor-alpha on the growth of CMK, a human megakaryoblastic leukemia cell line.

Recombinant human tumor necrosis factor-alpha (TNF-alpha) was found to stimulate the growth of CMK, a human megakaryoblastic leukemia cell line. This stimulatory effect of TNF-alpha was blocked by anti-TNF-alpha antibody, but antibodies to recombinant human interleukin 3, granulocyte-macrophage colony-stimulating factor and interleukin 6 (all growth factors for CMK cells) did not reduce the stimulatory effect of TNF-alpha. Scatchard analysis showed that CMK cells expressed TNF-alpha receptors on the cell surface. The growth of CMK cells was also stimulated by lymphotoxin, which shares the same receptor as TNF-alpha. These results suggest that TNF-alpha stimulated the growth of CMK cells directly via its specific receptor.

Antibodies↗
PubMed1992

A bispecific antibody detects cytotoxic T lymphocytes of unknown antigen specificity in patients with granular lymphocyte-proliferative disorders.

A simple and sensitive method for the detection of cytotoxic T lymphocytes (CTL) of unknown antigen specificity was investigated. Using anti-CD3 Fab' x anti-CD10 Fab' bispecific antibody or intact anti-CD3 monoclonal antibody, we induced cytotoxicity for CD10+, Fc gamma receptor-positive Daudi target cells in peripheral blood mononuclear cells (PBMC) obtained from patients with granular lymphocyte-proliferative disorders (GLPD). The results indicated that the bispecific antibody was much more efficient than the intact anti-CD3 monoclonal antibody in inducing cytotoxicity. Since CD3+CD4-CD8+ granular lymphocytes in patients with GLPD are considered to be in vivo-primed CTL of unknown antigen specificity, this bispecific antibody method may be useful for detecting in vivo-primed CTL within PBMC. By using this bispecific antibody, it will be possible to detect circulating in vivo-primed CTL in other clinical conditions.

Antibodies↗
PubMed1992

Langerhans-cell histiocytosis in an adult patient with multiple myeloma.

A 44-year-old man who had suffered for 6 years from multiple myeloma developed multiple papules on the face and chest. Histological examination of these papules revealed the infiltration of predominantly histiocytic cells into the dermis and into parts of the epidermis. These cells were seen on electron-microscopic study to have Langerhans granules in the cytoplasm, which led to a diagnosis of Langerhans-cell histiocytosis concomitant with multiple myeloma. Possible explanations for this unusual association are discussed.

Adult↗
PubMed1992

[Plasma beta-glucan levels in deep fungal infections accompanying hematological diseases and clinical efficacy of miconazole--a multi-institutional study].

Miconazole (400-1200 mg/day) was administered to patients with deep mycosis and suspected deep mycosis, and the efficacy evaluated. beta-Glucan was determined as the early diagnostic parameter of deep mycosis, and the relationships between the clinical efficacy of miconazole and the titers of beta-glucan were also evaluated. Forty-nine cases were evaluated, including 2 cases of deep mycosis and 47 cases of suspected deep mycosis. Most of the patients had hematological malignancies. The rate of efficacy was 100% (2/2) in deep mycosis, 66.0% (31/47) in suspected deep mycosis, and 67.3% (33/49) in total. beta-Glucan was determined in 39 cases before the administration of miconazole. The rate of beta-glucan positivity was 100% (1/1) in deep mycosis and 44.7% (17/38) in suspected deep mycosis. beta-Glucan was also determined before and after the administration of miconazole in 11 cases. The titers of beta-glucan became negative in 6 cases, decreased in 2 cases and increased in 3 cases. Thus, the beta-glucan titers became negative or decreased in 72.7% (8/11) of the cases. Efficacy of miconazole was 83.3% (5/6) in the cases in which beta-glucan became negative, 50.0% (1/2) in the cases in which the titers of beta-glucan decreased, and 33.3% (1/3) in the cases in which the titers of beta-glucan increased. Miconazole was effective in the treatment of deep mycosis, and the titers of beta-glucan correlated well with the clinical efficacy of miconazole. The determination of beta-glucan appears to be useful for the diagnosis of deep mycosis.

Adolescent↗
PubMed1992

Heterogeneity in epidermal growth factor responsiveness and tumor growth of human maxillary cancer cell lines.

We have established three cell lines (IMC-2, IMC-3, and IMC-4) from a human maxillary tumor, which exhibited different sensitivities to epidermal growth factor (EGF). It was inhibitory to colony-forming abilities of IMC-3 and IMC-4 cells in culture, while it affected that of IMC-2 cells slightly if at all. The differential sensitivities to EGF among the three cell lines were reproducibly observed when several cell sublines were further established from tumors appearing in nude mice. Saturation-binding kinetics with 125I-EGF showed similar levels of EGF-binding activities among the three cell lines. However, IMC-2, IMC-3, and IMC-4 showed almost similar sensitivities to cisplatin. Autophosphorylation of EGF receptor in the presence of EGF proceeded at similar levels among the three cell lines. Tumor growth was followed in nude mice when IMC-2, IMC-3, and IMC-4 at 1 x 10(7) cells were inoculated. The IMC-2 tumors enlarged at much faster rates than the other two cell lines. The IMC-4 tumors showed very slow growth rates, and IMC-3 tumors enlarged at an intermediate rate. These data suggest that the maxillary tumor used comprised cell populations that differed in their growth behaviors in response to EGF.

Carcinoma, Squamous Cell↗
PubMed1992

Decreased level of transforming growth factor-beta in blood lymphocytes of patients with aplastic anemia.

Levels of transforming growth factor-beta (TGF-beta) activity in the conditioned medium of blood lymphocytes of twelve patients with aplastic anemia (AA), nine patients with myelodysplastic syndromes (MDS) and five normal volunteers were investigated. We were able to observe growth inhibitory activity on porcine endothelial cells only after acidification of the materials. The growth inhibitory activity is neutralized by anti-TGF-beta antibody. It indicates that TGF-beta exists as a latent form in the conditioned medium. On the basis of growth inhibition assay, the mean level of TGF-beta production of MDS patients was estimated to be 188 +/- 199 pg/1 x 10(7) cells and that of normal volunteers was 668 +/- 314 pg/1 x 10(7) cells. In contrast, the lymphocytes of almost all of the AA patients failed to produce detectable amounts of TGF-beta. No correlation between TGF-beta levels and peripheral blood parameters could be detected. Stimulation of lymphocytes by phytohemagglutinin is known to increase the production of TGF-beta. Induction of TGF-beta production was also observed in AA (45% of normal controls). Possible roles of the decreased production of TGF-beta in the pathogenesis of AA were discussed.

Adult↗
PubMed1992

[Clinical study of total parathyroidectomy and autotransplantation for secondary hyperparathyroidism].

From April 1983 to September 1991 total parathyroidectomy (PTX) and parathyroid autotransplantation were carried out in 27 patients for secondary hyperparathyroidism. Of these patients, 13 were males and 14 were females. Their average age was 43 years old and their mean duration of dialysis was 126.4 months. As preoperative clinical symptoms, bone pain was observed in 19 cases, joint pain in 18, decrease of height in 7, pruritus in 3, muscle pain in 2, red eyes in 2 and others in 2. As roentgenographic findings, subperiosteal bone resorption and skull-salt and pepper were demonstrated in 26 cases, rugger jersey spine in 15, soft tissue calcification in 11, and pathological fractures in 4. Four parathyroid glands were removed in 23 cases, three glands in 4. Serum calcium level decreased remarkably within 24 hours after parathyroidectomy in all cases. The average total weight of parathyroid glands was 4.48 g. The preoperative diagnostic accuracy of echogram was 94% and that of CT scan was 90%. The clinical improvement after PTX was excellent in 12 cases and good in 11. The roentgenographic improvement of skull and/or finger bone more than one year after PTX was excellent in 11 cases and good in 11. Judging from histopathological findings of the bone, the clinical and roentgenographic improvement was observed better in the osteitis fibrosa group than in mild group. A significant correlation was found between the level of preoperative c-PTH and the weight of resected parathyroid glands. The level of preoperative ALP correlated with intact-PTH and was higher in the osteitis fibrosa group than in the mild group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma.

To clarify the incidence, timing and pathogenetic significance of p53 gene alterations in the progression of small-cell lung carcinoma (SCLC), 17 primary tumors, 13 metastases and nine cell lines from 27 patients were analysed by a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Allelic losses and mutations of the p53 gene were detected in 24 out of 25 informative cases (96%) and 23 out of 27 cases (85%) respectively. Simultaneous losses and mutations were detected in all 16 stage III-IV tumors, while these alterations were detected only in 3 of 6 stage I-II tumors. When allelic losses and/or mutations were detected in the primary tumors, the same alterations were always maintained in the process of metastasis. In three cases, identical p53 alterations were detected among different organ metastases. The mutations detected in five cell lines were also detected in the corresponding original tumors. These results suggest that the alterations of the p53 gene are common and early events, but probably not the first events, in the development of SCLC, and that these alterations are essential for the maintenance of malignant phenotypes in the progression of SCLC.

Base Sequence↗
PubMed1992

[Effects of dietary proteins on analgesic activity of tolerance and physical dependence on morphine in rats].

Effects of dietary proteins such as casein and egg albumin on analgesic activity of, tolerance to and physical dependence on morphine in rats were examined. There was no difference in analgesic activity after acute administration of morphine 10 mg/kg, s.c. between rats treated with casein food or egg albumin food and normal food for 5 or 21 days. The development of tolerance to morphine analgesia in rats treated with albumin food but not with casein food was suppressed during daily morphine 10 mg/kg, s.c. on 5 consecutive days. Rats were treated with casein or albumin food mixed with morphine (0.5 mg/g of food) for 5 days. Morphine intake in rats treated with albumin food was significantly decreased as compared to that with morphine admixed casein or normal food. Body weight loss by naloxone in morphine-dependent rats was significantly less in both casein food and albumin food groups than in the normal food group. These results suggest that chronic dietary treatment with albumin may produce a partial inhibition of development of tolerance to morphine analgesia and that with casein may attenuate morphine withdrawal manifestation in rats.

Analgesics, Opioid↗
PubMed1992

[Treatment of elderly patients with hematological malignancies].

Treatment of elderly patients with hematological malignancies is difficult and a matter of controversy. Low responsiveness to therapy and high risk of mortality have been reported. The risk of chemotherapeutic death increases after age 60, and an age-adjusted chemotherapy schedule is needed. In stage III and IV Hodgkin's disease, for example, an age-adjusted COPP regimen may be adopted. Many non-Hodgkin lymphomas (NHL) of elderly patients have a slow course. However, for intermediate to high grade aggressive NHL, dose-reduced CHOP regimen, or non- or low-dose methotrexate-containing programs like BECALM, CNOP, and low dose-ACOP-B are acceptable. MACOP-B regimen with G-CSF may be used for patients under age 65. For the treatment of elderly patients with AML, it is reported that a reduced-dose DAT regimen is better than the standard dose for inducing CR in patients older than 60. In elderly AML patients over 60, the dose-adjustment reported by Mori, or low-dose cytarabine with G-CSF, is recommended. Information about elderly patients with acute lymphoblastic leukemia is scarce. Aggressive treatments like L-17 M regimen are not tolerable by elderly patients, and a combination chemotherapy consisting of vincristine and prednisolone is recommended.

Aged↗
PubMed1992

[Acid-base disturbances in hematologic diseases].

In this article, the acid-base disturbances encountered in hematologic diseases are discussed. Occurrence of lactic acidosis (LA) without obvious clinical tissue hypoxia has been reported in patients with leukemia and lymphoma. Most of the patients with LA had liver involvement and clinical evidence of impaired hepatic function, suggesting that both increased production and decreased lactate metabolism are necessary for the development of LA in leukemia and lymphoma. Acute tumor lysis syndrome consists of hyperuricemia, hyperpotassemia, and hyperphosphatemia with hypocalcemia following neoplastic cell lysis, particularly in lymphoproliferative disorders. In patients with multiple myeloma (MM), proximal renal tubular acidosis (Fanconi syndrome) associated with Bence Jones proteinuria has been reported. In addition, MM is one of the first conditions recognized to be associated with lower anion gap.

Acidosis, Lactic↗
PubMed1992

[Use of diltiazem in the anesthetic management of epinephrine predominant pheochromocytoma].

This report describes a case of epinephrine predominant pheochromocytoma successfully managed intraoperatively with an infusion of diltiazem. A 50-yr-old woman with a 10-yr history of diabetes mellitus was admitted to the hospital because of thirst and general fatigue. A cystic left adrenal tumor was found on computed tomographic scan. Although resting plasma catecholamine levels were normal, plasma norepinephrine and epinephrine levels obtained from the left adrenal vein were 1.6 ng.ml-1 (normal, 0.04-0.35) and 6.2 ng.ml-1 (normal, less than 0.12), respectively. Diltiazem was administered i. v. at a rate of 3 micrograms.kg-1.min-1 before induction of anesthesia. Anesthesia was induced with enflurane 2-3% and nitrous oxide in oxygen, followed by tracheal intubation facilitated with vecuronium. Anesthesia was maintained with enflurane 1-3% and nitrous oxide in oxygen. Paralysis was maintained with vecuronium. Hypertension during the manipulation of the tumor was controlled by increasing the inspired concentration of enflurane or by increasing the infusion rate of diltiazem to 5 micrograms.kg-1.min-1. There was no tachyarrhythmia. The infusion of diltiazem was continued until the draining vein from the tumor had been ligated. Hypotension, after removal of the tumor, was treated by the rapid infusion of fluid. Plasma norepinephrine and epinephrine levels during tumor manipulation were 1.18 ng.ml-1 and 6.57 ng.ml-1, respectively.

Adrenal Gland Neoplasms↗