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Biomedical subjects

A Horiuchi

Publications and source records attributed to A Horiuchi.

At least 19 recordsLinked to original sources

Species and sex differences of aflatoxin B1-induced glutathione S-transferase placental form in single hepatocytes.

Species and sex differences of aflatoxin B1 (AFB1)-induced glutathione S-transferase placental form (GST-P) positive single hepatocytes have been investigated 48 h after an intraperitoneal injection of AFB1 to young male and female Fischer rats (2 mg AFB1/kg body wt) and male Syrian golden hamsters (6 mg AFB1/kg body wt). The presence of GST-P positive hepatocytes was examined by the immunohistochemical method. Male rats formed three times as many AFB1-induced GST-P positive hepatocytes as females. Pretreatment of both male and female rats with an inhibitor of GSH synthesis, buthionine sulfoximine (BSO) (4 mmol/kg body wt), 2 h and 4 h before AFB1 injection increased AFB1-induced GST-P positive hepatocytes by about 120% above the controls. Male hamsters formed several-fold less AFB1-induced GST-P positive hepatocytes than male rats. Pretreatment with BSO did not increase AFB1-induced GST-P positive hepatocytes in hamsters even though it produced an increase in hepatic necrosis. It appears that GSH and GSH S-transferases play an important role in modulating hepatic AFB1-DNA binding and AFB1-induced GST-P positive hepatocytes in rats and hamsters.

Aflatoxin B1

Correlation between killing activity towards the murine L929 cell line and expression of membrane-associated lymphotoxin-related molecule of human lymphokine-activated killer cells.

Human lymphokine-activated killer (LAK) cells expressed a membrane-associated lymphotoxin-related molecule (mLT) which was detected by flow cytometric analysis with anti-lymphotoxin antibody. Upon removal of exogenous interleukin-2 from LAK cell culture medium and another 24 h cultivation, the expression of mLT was decreased. Corresponding to the decrease of mLT expression, the killing activity of LAK cells towards L929 cells was remarkably reduced and killing of MIA PaCa-2 and U937 cells was moderately reduced, whereas killing of Daudi and K562 cells was fully restored. The supernatant of mLT-expressing LAK cells had no cytotoxic activity towards L929 cells in the absence of actinomycin D. Moreover, not only the killing of L929 cells but also that of human tumor cell lines (MIA PaCa-2, U937) by mLT-expressing LAK cells was partially inhibited in the presence of anti-lymphotoxin antibody. These results suggest an involvement of mLT in the killing of some tumor target cells by LAK cells.

Animals

Changes in the productivity of cytokines and active-oxygen in peripheral blood cells following surgery.

An investigation was carried out on the productivity of cytokines and active-oxygen by peripheral blood cells during the pre- and post-operative periods. While the preoperative production of tumor necrosis factor (TNF) and interleukin-1 alpha (IL-1 alpha) was elevated, that of lymphotoxin (LT) and interferon-gamma (IFN-gamma) were slightly suppressed. In the postoperative period the peak TNF and IL-1 alpha and active-oxygen productivity was elevated, while LT and IFN-gamma productivity was suppressed in patients with an intraoperative bleeding volume of more than 1,000 ml compared to those with that of less than 1,000 ml. Thus, stress stimulates the TNF and IL-1 alpha and active-oxygen producing system, that is, the macrophage-neutrophil system, and suppresses the LT and IFN-gamma system, being, the inflammatory helper T cell system, in the early postoperative period.

Adult

Effects of gamma-interferon and FK506 on resting B cell proliferation of New Zealand black/white F1 mice.

We examined the effects of gamma-interferon (gamma-IFN) and the new immunosuppressant FK506 on resting B cell proliferation of New Zealand black/white F1 hybrid (B/W F1) mice, an animal model of human systemic lupus erythematosus (SLE). gamma-IFN and FK506 inhibited in a dose-dependent manner both B cell proliferation and autoantibody production of resting B cells respectively. There was a synergistic interaction between gamma-IFN and FK506 in their inhibition and they did not exhibit cell cytotoxicity. This in vitro synergism of gamma-IFN and FK506 may have clinical application in that low doses of gamma-IFN and FK506 combinations may be effective to correct polyclonal B cell activation of patients with SLE.

Animals

[A case of Vibrio cholerae non-O1 septicemia with liver cirrhosis].

A case of Vibrio cholerae non-O1 septicemia is described in this paper. A 45-year-old male with a three year history of liver cirrhosis, was admitted to our division with hematemesis, abdominal pain, high fever and a loss of consciousness. Three days before onset of symptoms, he traveled to Ishigaki Island and ate a raw lobster. Two days after, his temperature rose to 39.7 degrees C and the blood pressure dropped to 36/- mmHg. By endoscopic examination, an ulcer was found in the stomach, and the bleeding was stopped by electrical coagulation. Blood culture showed growth of V. cholerae non-O1. The organism was found to be sensitive to OFLX, CZX, MINO, LMOX and CP. Although DIC, infections of fungus and MRSA occurred as complications, he recovered by adequate procedures. Subsequently, he left this division after eight weeks. There are various reports related to V. cholerae non-O1 septicemia in foreign countries, but few cases have been reported in Japan. And these cases had severe underlying diseases such as leukemia and liver cirrhosis.

Bacteremia

Renal dopamine receptors and pre- and post-cAMP-mediated Na+ transport defect in spontaneously hypertensive rats.

We have reported defective coupling of the renal tubular DA1 dopamine receptor to adenylyl cyclase in both the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive rat. Since Na+, 5'-guanyl imidodiphosphate [Gpp(NH)p], and N-ethylmaleimide (NEM) reduce agonist affinity for brain D1 dopamine receptors, we compared the effects of these agents on agonist affinity in proximal tubules from SHR and its normotensive control, the Wistar-Kyoto rat (WKY), to delineate further the site of the DA1-adenylyl cyclase coupling defect. In WKY, the D1/DA1 agonist, fenoldopam, competed for 125I-Sch 23982 at a high-affinity site (KiH = 1.8 +/- 0.8 x 10(-8) M) and a low-affinity site (KiL = 7.6 +/- 1.1 x 10(-5) M, n = 6). Na+ (150 mM) or Gpp(NH)p (10(-4) M) converted KiH to KiL. NEM, which alkylates sulfhydryl groups, also converted all the binding to KiL; this effect could be prevented by prior treatment with 10(-4) M fenoldopam. In contrast, in SHR, fenoldopam detected only a KiL (7.8 +/- 1.4 x 10(-5) M, n = 6). Neither Na+, Gpp(NH)p, nor NEM had any effect on KiL. To study a functional expression of these binding sites, the effect of 5 x 10(-5) M fenoldopam or 8-(chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (8-CPT-cAMP) on Na+/H+ exchange activity in proximal tubular brush-border membrane vesicles was tested. In WKY, the inhibitory effects of these agents on the exchanger increased with the age of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

[Overt leukemia from MDS associated with marked basophilia].

A 52-year-old woman was admitted to our hospital because of leukocytosis. She had been diagnosed with RAEB in another hospital in past time. At the admission, the white cell count was 30,900/microliter with blasts (14.0%) and marked basophilia (49.0%). Bone marrow aspiration revealed with 30.2% blasts and 21.1% basophils. Having obtained those results, diagnosis of RAEB in transformation was made. After admission, number of basophils in peripheral blood increased gradually, and level of histamine in serum was elevated significantly. Multiple peptic ulcers in stomach and bowel and high fever were induced due to histaminemia. Despite several therapy she died because of respiratory failure and septisemia. Although the mechanism of basophilia in this patient could not be clarified, there was a possibility that basophilia in this patient might be differentiated from leukemic clone because almost basophils in peripheral blood were mature and those had many granules including metachromasia by stained with toluidine blue.

Basophils

[Studies on pseudo-Chediak-Higashi granules formation in acute promyelocytic leukemia].

Leukemic cells from acute promyelocytic leukemia containing pseudo-Chediak-Higashi (P-CH) granules in a 38-year-woman were studied with ultrastructural and cytochemical techniques to evaluate the origin and nature of the granules. Wright-Giemsa stain revealed giant granules to be azurophilic. Cytochemical stain revealed p-CH granules ot the basic of their peroxidase and glycoprotein content. Electron microscopy revealed numerous giant granules formed by fusion of azurophilic granules these morphological, different type granules were classified into four types, 1) circular granule with homogeneous matrix, 2) circular granule with heterogeneous change by autolysis, 3) Auer body-like granule with crystalline arrangement, 4) vacuolar formation. The results demonstrate that the Auer body-like granule of P-CH granules in leukemic cells is a morphologically variant type of the classical Auer body observed in common acute myeloid leukemia.

Adult

[Clinical effects of cefodizime in severe infections complicated with hematological diseases. Hanshin Infection Study Group].

One hundred thirty-eight patients with severe infections accompanying hematological diseases were treated with cefodizime (CDZM). CDZM was administered by intravenous injection at daily doses ranging from 2 g to 8 g for about 3 to 18 days. Clinical efficacies of CDZM were excellent in 30 cases, good in 37 cases, fair in 1 case and poor in 53 cases. The efficacy rate was 55.4%. The efficacy rate was 56.4% in patients from whom causative organisms were not identified. The efficacy rate against Gram-negative bacteria (66.7%) was higher than that against Gram-positive bacteria (28.6%). No significant differences in the efficacy rates were found among groups of patients with different initial neutrophil counts (less than 100, 100-499, and over 500/microliters). Skin eruption caused by CDZM was observed in 2 patients (1.5%). Hepatic disorders, renal dysfunction and urinary test abnormality (protein and urobilinogen) were observed in 7 (5.0%), 1 (0.7%) and 1 (0.7%), respectively. Therefore, CDZM was considered to be a clinically useful antibiotic for severe infections complicated with hematological diseases.

Adolescent

[Therapeutic effects of cefuzonam against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.

Adolescent

[Therapeutic effects of meropenem against severe infections in patients with hematopoietic disorders. Hanshin Study Group of Hematopoietic Disorders and Infection].

The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.

Adolescent

[Late phase II study of MST-16 (sobuzoxane) efficacy for malignant lymphoma].

A late phase II study with MST-16 for malignant lymphoma was performed with the collaboration of 11 institutions belonging to the Hanshin Hematological Disease Treatment Research Group. Out of a total 40 patients entered into the study, 37 cases (33 of NHL and 4 HD) were evaluated for efficacy and 27 cases for side effects. The response rate was 29.7% (2 cases of CR and 9 PR). The factors affecting response rate were histological classification, phenotype of tumor cell surface and stage of disease. Bone marrow suppression and G-I disorders were the main toxicities observed, but they disappeared by the cessation of MST-16 treatment.

Adult

Studies of membrane-associated and soluble (secreted) lymphotoxin in human lymphokine-activated T-killer cells in vitro.

The expression, release, and cytolytic activity of membrane-associated lymphotoxin was examined in cultures of phytohemagglutinin-P (PHA-P) and interleukin 2 (IL-2)-stimulated human T-lymphokine-activated killer (T-LAK) cells in vitro. Lymphotoxin (LT/TNF-beta) was identified on the membrane of T-LAK cells using flow cytometry. The membrane form of LT (mLT) is detected not only on T-LAK cells but also on LT-secreting human B-cell lymphoid cell lines, RPMI 1788 and Raji, but not on U937 or K562 cells. Maximum expression of mLT on T-LAK cells and the secretion of LT into the supernatant depended on the concentration of IL-2. Expression of mLT on T-LAK cells was reduced by stimulation with PHA-P; however, supernatant LT levels greatly increased. Both expression of mLT and release of soluble LT was reduced after incubation of T-LAK cells with actinomycin D (ActD) or cycloheximide (CHx). Paraformaldehyde-fixed T-LAK cells caused cytolysis of WEHI 164 cells in vitro, which was blocked by anti-LT but not anti-TNF antibody. These data support the concept that mLT may be an intermediate form to secreted LT, and that the mLT form is cytolytically active.

Cell Line

[Hematologic abnormalities associated with rheumatoid arthritis].

Anemia is frequently found in patients with rheumatoid arthritis (RA) and is the most common extra-articular manifestation RA. The majority of patients with RA have a mild normocytic hypochromic anemia which correlates with the erythrocyte sedimentation rate and with activity of the disease. White blood cell counts are usually in the normal range or only slightly elevated. The differential white blood cell count is usually within normal limits. Eosinophilia and thrombocytosis are often associated with RA. Hematologic abnormalities of RA is correlated to the activity of the disease, and therefore the most important aspect of treatment lies in the general control of the chronic inflammation.

Anemia

[Efficacy of leukocyte-depleted platelet concentrates for prevention of HLA-alloimmunization in patients with frequent platelet transfusions: a prospective multi-institutional study using a polyester platelet filter].

A prospective multi-institutional study was conducted to assess the efficacy of leukocyte-depleted platelet concentrates, prepared by a method using a newly developed polyester filter, in the prevention of HLA-alloimmunization in patients with hematological disorders. Patients who were expected frequent platelet transfusions, were assigned into two groups, receiving either standard platelet concentrates (control group) or leukocyte-depleted platelet concentrates prepared through a polyester platelet filter, Sepacell-PL (filtered group). All patients received leukocyte-depleted red cell products. Of III patients enrolled, 72 were evaluable, 23 in the control and 49 in the filtered group. Both groups were comparable according to age, sex ratio, underlying disorders, previous exposure to alloantigens by transfusion and/or pregnancy. There was no statistically significant difference in the number and duration of transfusion in the two groups. There were significant differences in HLA-alloimmunization rate (9 cases out of 23, 39% in the control group versus 4 cases out of 49, 8% in the filtered group; p less than 0.01) and refractoriness to platelet transfusion from random donors (6 cases out of 23, 26% in the control group versus 2 cases out of 49, 4% in the filtered group; p less than 0.05). These results indicated that leukocyte-depleted platelet concentrates prepared through the polyester platelet filter are beneficial to reduce HLA-alloimmunization in patients with frequent platelet transfusions.

Adolescent

[A study of combination chemotherapy (BHAC-ACVP) for adult acute lymphocytic leukemia. Hanshin Co-operative Study Group of Hematological Malignancies].

Twenty-nine adult patients with acute lymphocytic leukemia (ALL) were treated with combination chemotherapy consisting of behenoyl-ara-C, adriamycin, cyclophosphamide, vindesine and prednisolone (BHAC-ACVP regimen). Complete remission (CR) was obtained in 7 of 13 (54%) of the previously untreated, and 4 of 16 (25%) of the previously treated patients. Six of 10 (60%) L1 and 5 of 17 (29%) L2 patients achieved CR. Side effects such as nausea, GPT elevation and fever were observed, but these were not severe in most cases. The result indicates that BH-AC is useful for the treatment of adult patients with ALL.

Antineoplastic Combined Chemotherapy Protocols

Effects of the cyclic nucleotide phosphodiesterase inhibitors, rolipram, 3-isobutyl-1-methylxanthine, amrinone and zaprinast, on pancreatic exocrine secretion in dogs.

The effects of the cyclic phosphodiesterase (PDE) inhibitors, rolipram, 3-isobutyl-1-methylxanthine (IBMX), amrinone and zaprinast on pancreatic exocrine secretion were investigated in anesthetized dogs. Rolipram (1-30 nmol), IBMX (44-440 nmol) or zaprinast (1-10 mumol) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but amrinone (up to 53 mumol) did not. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by rolipram and IBMX, but neither was affected by zaprinast. Rolipram elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with rolipram were additive. Rolipram and IBMX, but not zaprinast, increased cyclic AMP concentration but did not affect cyclic GMP concentration. These results suggest that rolipram, IBMX and zaprinast have direct secretory properties on pancreatic exocrine glands of the dog, which may be mediated through the increase of intracellular cyclic AMP concentration, by inhibiting PDE activity. Furthermore, the pancreatic PDE enzyme in the dog pancreas may be mainly a type IV.

1-Methyl-3-isobutylxanthine