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Biomedical subjects

H Mizoguchi

Publications and source records attributed to H Mizoguchi.

At least 271 records · Page 15Linked to original sources

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↗

[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↗

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↗

[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↗

[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↗

[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↗

[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↗

[Aplastic anemia].

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Anemia, Aplastic↗

[Mutations of the p53 gene in hematologic neoplasms].

The p53 gene encodes a nuclear phosphoprotein and is now considered as a tumor suppressor gene. Mutations of the p53 gene have frequently been observed in several types of solid tumors and are believed to be implicated in the development of these tumors. Recent studies have shown that the p53 gene is altered in chronic myelogenous leukemia (CML) in blast crisis. In CML, alterations of the p53 gene may play an important role in the development of blast crisis. More recently, p53 mutations have been reported in other types of hematologic neoplasms, such as acute leukemia, adult T-cell leukemia, and malignant lymphoma. These observations suggest that inactivation of the p53 gene is involved in the tumorigenesis of various types of hematologic neoplasms.

Blast Crisis↗

[Multicenter clinical evaluation of red cell concentrates stored up to 6 weeks in MAP, a new additive solution].

The clinical safety and efficacy of transfusion of red cell concentrates stored in MAP solution (MAP-CRC) containing mannitol, adenine, glucose, phosphate and citrate, into 39 anemic patients were evaluated. In 23 patients, infusion of MAP-CRC was alternated with infusion of ordinary CRC as a control. The MAP-CRC and CRC used in this study were stored at 4 degrees C for an average of 38.2 +/- 2.6 days (n = 52) and 18.1 +/- 2.2 days (n = 26), respectively. Red cell recovery was 77.5% for MAP-CRC and 82.5% for CRC, based on calculation of the increase in hemoglobin level one day after transfusion. There were no differences between patients transfused with MAP-CRC and those transfused with CRC in clinical findings or biochemical data. No major side-effects other than pyrexia associated with the underlying infections were seen in patients transfused with MAP-CRC. MAP-CRC stored up to 42 days is apparently as safe and effective as stored CRC. This new additive solution may therefore be useful for the future expansion of the indications for autologous blood transfusion by facilitating the collection and storage of more blood in the liquid state for a longer period, and may also be useful in obtaining more plasma from whole blood as source plasma.

Adenine↗

Activation via the CD3 and CD16 pathway mediates interleukin-2-dependent autocrine proliferation of granular lymphocytes in patients with granular lymphocyte proliferative disorders.

Granular lymphocytes (GLs) in patients with GL-proliferative disorders (GLPDs) are known to express the interleukin-2 receptor (IL-2R) beta chain (p70-75) constitutively and to proliferate in response to stimulation with IL-2 via the beta chain. In this report, we found that the anti-CD3 monoclonal antibody (MoAb) OKT3 could induce the proliferation of GLs from patients with T-cell lineage GLPDs (T-cell receptor-alpha beta+/CD3+16+), but not that of natural killer (NK) cell lineage GLs (T-cell receptor-alpha beta-/CD3-16+). In contrast, the anti-CD16 MoAb 3G8 that reacts with NK-lineage GLs could induce the proliferation of these GLs but not that of GLs with a T-cell phenotype. Furthermore, the anti-CD16 MoAbs CLB FcR gran1 (VD2) and OK-NK, which react with both T- and NK-lineage GLs, induced the proliferation of GLs with both T- and and NK-cell phenotypes. The proliferative response induced via the CD3 or IgG Fc receptor III (Fc gamma RIII: CD16) pathway was shown to be associated with the IL-2-dependent autocrine pathway by various findings, including the induction of endogenous IL-2 production, the coexpression of the IL-2R alpha chain (p55) and the IL-2R beta chain, and the inhibition of GL proliferation by anti-IL-2 or anti-IL-2R MoAb. These results suggest that GL proliferation is mediated at least partly through the IL-2-dependent autocrine pathway, and that the TCR/CD3 complex in T-cell phenotype GLs and the Fc gamma RIII in both T- and NK-cell phenotype GLs play a role in their activation in GLPDs.

Antibodies, Monoclonal↗

The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors.

Three cancer cell lines, IMC-2, IMC-3 and IMC-4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC-2 in nude mice was markedly faster than that of the IMC-3 and IMC-4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC-2 cells in response to EGF, but no change for IMC-3 and IMC-4 cells. We examined response to EGF of IMC-2 cells with regard to expression of a growth-related oncogene (c-fos), proteinases and their inhibitors. Expression of c-fos was transiently increased in IMC-2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase-type plasminogen activator and 72-kDa type-IV collagenase in IMC-2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor-I (PAI-I) and tissue inhibitor of metalloproteinases-I (TIMP-I) in IMC-2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF.

Animals↗

Fluorescent probes for retinoic acid receptors: molecular measures for the ligand binding pocket.

Two fluorescent probes for nuclear retinoic acid receptors (RARs) have been developed, both containing a biologically active retinoid moiety and a fluorescent dansyl moiety, but differing in the length of the spacer arm connecting the two moieties. Both probes bind RARs at their retinoid-binding sites, revealing the usefulness of the compounds as fluorescent RAR probes. By measuring the specific increase of the probes' fluorescence intensity caused by the binding to RARs, the linearized length of the RAR's retinoid-binding pocket could be estimated.

Binding, Competitive↗

Fluorescent and photoaffinity labeling probes for retinoic acid receptors.

A fluorescent probe for retinoid receptors (RARs) was designed and prepared. The probe consists of a retinoid moiety and a dansyl moiety, i.e., 2-[3-(5-dimethylaminonaphthalene-1-sulfonyl)- aminopropyl-1-oxy]-4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carboxamido]benzoic acid: DAM-3. DAM-3 specifically bound RARs. Additionally, a photoreactive RAR fluorescent probe was designed and prepared, i.e., 2-[3-(5-azidonaphthalene- 1-sulfonyl)aminopropyl-1-oxy]-4-[(5,6,7,8-tetrahydro-5,5,8,8- tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (ADAM-3). ADAM-3 irreversibly and specifically bound RARs using ultraviolet irradiation.

Affinity Labels↗

Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody.

An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr-labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.

Antigens, CD↗

Counteraction of estradiol-induced activation of tissue-type plasminogen activator in a human breast cancer cell line by an anti-estrogen, LY117018.

LY117018 is a non-steroid anti-estrogen which exhibits about 100 times higher affinity for estrogen receptor than tamoxifen, another anti-estrogen. The cell line ES-1, which was isolated from human breast cancer MCF-7 cells, was highly sensitive to the cytocidal action of estradiol. Growth of ES-1 cells was inhibited by 10(-8)M 17 beta-estradiol, a concentration that stimulated the growth of parental MCF-7 cells. The estradiol-induced growth inhibition of ES-1 cells was almost completely reversed by treatment with LY117018, but not by treatment with tamoxifen. The relative binding affinity of LY117018 for estradiol receptor was equal to that of estradiol in both MCF-7 and ES-1 cells. Treatment of ES-1 cells with estradiol specifically induced tissue-type plasminogen activator (t-PA), whereas such estradiol-induced activation was not observed in parental MCF-7 cells. Quantitative immunoreactive assays and Northern blot analysis showed that estradiol-induced expression of t-PA was blocked by LY117018 in ES-1 cells. The inhibitory effect of tamoxifen was about 100 times lower than that of LY117018. The inhibition of t-PA gene expression by LY117018 might be due to competitive inhibition with estradiol in estradiol receptor binding.

Breast Neoplasms↗

Correlation between the proliferative response to granulocyte colony-stimulating factor and the positivity of transferrin receptor in acute myeloblastic leukemia cells.

The use of granulocyte colony-stimulating factor (G-CSF) after chemotherapy for acute myeloblastic leukemia (AML) has been reported. However, there is a drawback in that G-CSF may stimulate the proliferation of AML progenitors. To determine the parameter(s) indicative of responsiveness of AML blasts to G-CSF, various surface phenotypes of blasts were examined in relation to the blast colony formation stimulated by G-CSF in 39 AML patients. A correlation was found only with transferrin receptor positivity among the various phenotypes studied. The population mean of percentages of transferrin receptor-positive blasts in the group responding to G-CSF in vitro was significantly higher than that of blasts in the group not responding to G-CSF. A further correlation was found between transferrin receptor positivity and the number of G-CSF receptors on the blasts; that is, blasts expressing more G-CSF receptors have greater transferrin receptor positivity. In our previous study, we observed that blasts with a large number of G-CSF receptors produce more colonies in response to G-CSF. These results indicated that blasts expressing more transferrin receptors have a larger number of G-CSF receptors and may show more active proliferation in response to G-CSF. Therefore, the proliferative response of blasts to G-CSF can be predicted by examining transferrin receptor positivity. The clinical use of G-CSF in AML patients may be recommended when the patient's blasts have a low level of transferrin receptor expression. The measurement of transferrin receptors on blasts, instead of the rather complicated G-CSF receptor determination, would be a useful indicator for the safer application of G-CSF in AML patients.

Antigens, CD↗