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Biomedical subjects

M Kamakura

Publications and source records attributed to M Kamakura.

At least 37 records · Page 2Linked to original sources

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Acute Disease↗

Fight against infectious diseases.

During early Meiji era in Japan, there were frequent epidemics of fatal acute communicable diseases such as cholera, dysentery and smallpox, and preventive measures and preparations for acute infectious diseases were urgently needed. Together with improvement of scientific preparations, the Communicable Disease Prevention Law was promulgated in 1897. Then gradually until 1940's, the focus of preventive measures have been shifted from acute infectious diseases to chronic ones, particularly tuberculosis. After the World War II, except the short period of social confusion, major legally-defined communicable diseases had been decreasing rapidly mainly due to the use of antibiotics and improvement of environmental sanitation. At the same time, the introduction of preventive vaccination marked a new era for the prevention of infectious diseases and was largely responsible for the remarkable decrease of infant mortality in Japan. Recently the concept of defense by vaccination against infectious diseases has evolved from group-oriented to individual-oriented, so that the Preventive Vaccination Law was drastically revised in 1994. Currently, effective counter-measures against newly emerged infectious diseases, as viral hepatitis, institution-acquired infection, viral hemorrhagic fever etc., have been implemented. For the future, improvement of infections disease surveillance, vaccine development and expansion of vaccination coverage along with monitoring side-effects, preventive health education on AIDS/STDs, addressing the special needs of foreigners living in Japan and international collaboration for disease control abroad are all vital to the success of protection of the public's health from infectious diseases in Japan.

Communicable Disease Control↗

[Experience in administration low dose all-trans retinoic acid for a child with acute promyelocytic leukemia].

Ten year old boy with acute promyelocytic leukemia (APL) was treated with all-trans retinoic acid (ATRA). Immediately after the oral administration of ATRA (nine mg/m2 three times a day), DIC was controlled, and complete remission was achieved at day 39. The patient received ATRA therapy for 47 days, and then followed by conventional chemotherapy. Plasma ATRA level after 90 minutes of drug administration was 84.6 ng/ml. The superoxide generating activity of neutrophils in the bone marrow and peripheral blood was measured by chemiluminescence. The phagocytic function of neutrophils was markedly reduced in the ATRA-induced remission period, and was normal in the chemotherapy-induced remission. APL could be induced complete remission by three divided small doses of ATRA, and the ATRA-induced differentiated neutrophils might have lower phagocytic function.

Child↗

[Clinical study on a concomitant therapy with fluconazole and human recombinant granulocyte colony stimulating factor in the treatment of systemic fungal infections with hematological disorders].

The clinical efficacy and the safety of concomitant therapy with fluconazole and recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared with fluconazole monotherapy in neutropenic patients with hematological disorders. The clinical efficacy rate was 73.5% (25/34) in the combination therapy and 48.1% (37/77) in monotherapy. The difference between the two is statistically significant. Side effects were not observed in the combination group, but laboratory abnormalities were found in 6 patients with an incident rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected as empiric therapy for systemic fungal infection associated with hematological disorders, since this combination therapy showed high efficacy and low incident of side effects. Some patients, however, did not show increased neutrophil counts in spite of rhG-CSF administration.

Adolescent↗

Oxidative stress response in yeast: glutathione peroxidase of Hansenula mrakii is bound to the membrane of both mitochondria and cytoplasm.

The yeast Hansenula mrakii IFO 0895 induces glutathione peroxidase (GPx) when the cells are exposed to the oxidative stress such as lipid hydroperoxide, superoxide- and hydroxy radical-generating conditions. To clarify the localization of GPx in H. mrakii cell, distribution of the enzyme was investigated. After centrifugation of the yeast protoplast homogenates at 2500 x g for 10 min, 67% of total GPx activity was recovered from the supernatant (Sup. 1) and 33% was from the pellet (Pellet 1). When the Sup. 1 was fractionated by sucrose density gradient ultracentrifugation, GPx activity was essentially recovered from the mitochondria fraction. Submitochondrial localization of the enzyme showed that 95% and 2.5% of the enzyme was recovered from the inner and outer membrane, respectively. No GPx activity was detected neither in intermembrane space nor in matrix of mitochondria. On the other hand, at least 12% of total GPx activity was recovered from the purified plasma membrane which was obtained from the Pellet 1 by successive sucrose density gradient centrifugation. Thus, the GPx of H. mrakii is present in the inner and outer membrane of mitochondria as well as the plasma membrane.

Cell Membrane↗

[Efficacy of combination chemotherapy with miconazole and G-CSF in deep mycosis accompanying hematological diseases].

In order to examine the efficacy of the combination chemotherapy with miconazole and G-CSF, patients with deep mycosis and suspected deep mycosis were divided into 3 groups. Group I: miconazole and G-CSF were administered simultaneously. Group II: miconazole was administered later during G-CSF administration. Group III: only miconazole was administered. Of a total of 117 cases 105 cases were analyzed including group I 37 cases, group II 39 cases and group III 29 cases, excluding 12 dropout and inadequate cases. Of the 105 cases, deep mycosis were 31 and suspected deep mycosis were 74, and underlying diseases were hematological malignancies such as leukemias. Efficacy judged mainly by the change of fever was 62.2% (23/37) in group I, 43.6% (17/39) in group II, and 41.4% (12/29) in group III, respectively. Efficacy was better in the patients whose neutrophil counts increased from less than 500/microliters to more than 500/microliters (group I 75.0%, group II 72.7%) than in the patients whose neutrophil counts were less than 500/microliters throughout the time of miconazole administration (group I 33.3%, group II 33.3%). Adverse effects were minimal in 3 groups (group I 15.4%, group II 17.4%, group III 15.6%). It is concluded that the combination with miconazole and G-CSF is effective in the treatment of deep fungal infections.

Adult↗

Studies on rat hepatic hydroxysteroid sulfotransferase--immunochemistry, development and pI variants.

Rat hepatic hydroxysteroid sulfotransferase with sulfoconjugates androsterone (androsterone-sulfating sulfotransferase) is an oligomer consisting of several subunits with distinct pI values but with the same molecular mass (pI variants). N-terminal amino acid sequences of the pI variants are all identical. The enzyme is exclusively present in the liver, in which its lobular localization is sex-dependent. The localization of the enzyme is markedly different from that of an isoenzyme of phenol sulfotransferase. In weanling and adult female rats, the relative abundance of the pI variants is different. During development from weanling stage to adulthood, the amounts of acidic variants increase, whereas the relative levels of alkaline variants remain constant.

Aging↗

Immunochemical characterization of developmental changes in rat hepatic hydroxysteroid sulfotransferase.

A major isoenzyme of hepatic androsterone-sulfating sulfotransferase (AD-ST) was purified from adult female rats. The activity was purified 122-fold over that found in the cytosol and showed a single protein band with a subunit molecular mass of 30 kDa after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified enzyme exhibited four isoelectric variants of subunits on denaturing isoelectrofocusing gels (pI = 5.8, 6.1, 6.7 and 7.2). Rabbit antiserum raised against the enzyme specifically detected AD-ST polypeptide in rat liver cytosol. Immunoblot analysis of liver cytosol from female and male rats at various ages showed good correlation between the levels of AD-ST activity and AD-ST polypeptide. Significant levels of AD-ST activity and polypeptide were detected in senescent male rats, though normal adult male rats have very low levels of AD-ST activity and protein. The relative content of the isoelectric variants of AD-ST were different in liver cytosol of weanling and adult females, indicating that age- and gender-related alterations of hepatic AD-ST activity are primarily determined by the levels of AD-ST polypeptide and the relative amounts of the four isoelectric variants of the enzyme.

Aging↗

Purification of a rat liver phenol sulphotransferase (P-STG) with the aid of guanidine hydrochloride treatment.

An isoenzyme of phenol sulphotransferase, designated P-STG, was purified 157-fold from male rat liver cytosol by diethylaminoethyl-cellulose (DEAE-cellulose) and agarose-hexane-adenosine-3',5'-bisphosphate affinity chromatography. The P-STG fraction obtained after DEAE-cellulose chromatography rapidly lost its activity during storage at 4 degrees C, however, the activity was recovered by the addition of 1.6 M guanidine hydrochloride (Gndn HCl) followed by dialysis. Gndn HCl also substantially improved the yield of P-STG in a subsequent purification step using affinity chromatography, while the specific activity of the purified P-STG was not changed by Gndn HCl treatment. It is possible that the Gndn HCl treatment caused P-STG recovery from an inactivated to an active form rather than reactivating it for increased activity. Purified P-STG is a homodimer with a native molecular mass of 67 kDa; the subunit molecular mass is 35 kDa. Immunoblot analysis carried out with antibodies raised against the purified enzyme indicated that male rat liver contains a higher level of the enzyme than female rat liver. This enzyme is also expressed in the kidney and the stomach. P-STG reaches maximum activity when 1-naphthol, 2-naphthol and 4-nitrophenol are used as substrates at pH 5.5. Using dopamine as a substrate the pH optimum is about 9.0. P-STG activity is markedly inhibited by the addition of sodium chloride to the reaction mixture.

Animals↗

[Treatment of paroxysmal nocturnal hemoglobinuria with danazol].

Glucocorticoid and androgen therapy have been used with moderate success in paroxysmal nocturnal hemoglobinuria (PNH). However, both are poorly tolerated, especially in women, although the side effects of glucocorticoid can be diminished by alternate day therapy. We have treated two patients with PNH with danazol. One of patient is man, 64 years old age with stomach cancer, and the other patient is 34-year-old man. Their disease has existed for 6-14 years. They required many blood transfusions, their hemoglobins ranging between 7.1 and 9.9 grams per deciliter. When treated with danazol by mouth, the hemoglobin level increased approximately 2 to 5 grams in each patient within 3 week, and clinical hemoglobinuria improved. None of the patients has had any side effects.

Adult↗

[A study of the differentiation inducibility of cultured cells by environmental chemical substances].

The author conducted an experimental study of the cell differentiation inducibility of some environmental chemical substances which currently draw attention because of their influences on the human body, using an azaguanine-resistant PCC4 cell line, a clone derived from mouse teratocarcinoma OTT 6050. Cells in monolayer culture or suspension culture were exposed to the test substances and the survival and morphological changes of the cells were determined. It was extremely rare that embryonal carcinoma cells exposed and cultured in a monolayer showed differentiation in the control group, with the rate of both epithelial cell-like and fibroblast-like morphological changes being less than 1%. Cells cultured in normal medium following exposure and incubation in suspension culture showed various patterns of differentiation according to the type and concentration of the test substance. In the cell groups exposed to mono, di-methylformamide, fibroblast-like differentiation was observed most frequently, while little or no epithelial differentiation was seen. These findings were in contrast to those observed in the cell groups exposed to mono, di-methylacetamide. For dimethyl sulfoxide it is considered that there is a relatively limited range of optimal concentration for differentiation induction within the concentration range which is free from cell toxicity. Polybrene and diethylene glycol were proven to have low differentiation inducibility. As to the differentiation induction potency of extracts (tar) of granules in exhausts from light-duty (4 cylinder) and heavy-duty (6 cylinder) diesel engines, no concentration-response relation was seen for the differentiation inducibility of light-duty tar and no constant tendency was observed for heavy-duty tar.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗

[Essential thrombocythemia with Philadelphia chromosome].

Essential thrombocythemia is a myeloproliferative disorder not known to have consistent cytogenetic abnormalities. A 38-year-old woman with essential thrombocythemia having Philadelphia chromosome (Ph1) is reported. The patient first presented with gastrointestinal bleeding, accompanied by thrombocytosis. Treatment of the gastrointestinal bleeding did not influence the elevation of platelet counts. The patient's clinical and hematological manifestations were consistent with essential thrombocythemia, but not with any other myeloproliferative diseases. Ph1 chromosome was constantly proved in bone marrow preparations from this patient over two years and four months and gave us a certain impression that Ph1 chromosome might have had some relation to development of essential thrombocythemia to chronic myelogenous leukemia in this patient.

Adult↗

Lymphocytapheresis in a patient with severe aplastic anemia.

A 17-year-old Japanese boy with severe aplastic anemia was treated with oxymetholone and prednisolone for 9 weeks without improvement. He then received 2 courses of bolus methylprednisone therapy without improvement and developed a severe liver dysfunction due to this bolus therapy. He had no HLA-compatible sibling for a bone marrow transplantation, and antithymus globulin was not available. A total of 7 lymphocytapheresis treatments were performed, using an IBM 2997 cell separator, over a period of 9 weeks. Hematological and clinical improvement were noted and felt to be related with these lymphocytapheresis treatments, and further therapy was not required. Three years have past since the patient has undergone lymphocytapheresis, and he remains in good health. Thus, lymphocytapheresis may be an alternative therapy for cases of severe aplastic anemia for those patients who have no compatible donor for bone marrow transplantation and when antithymus globulin is not available.

Adolescent↗

Rings and double minutes in a case with blastic phase of chronic myelocytic leukemia.

The patient studied was a 33-year-old female in the blastic phase of chronic myelocytic leukemia resistant to busulfan. The results of cytogenetic studies of bone marrow cells were as follows: The abnormal chromosomes were double Ph1, +19, +6, +B, ring D, double ring D, double minutes (DM) of various sizes, etc. The mean number of DM per cell was increased in 4-day culture compared with that in 1-day culture.

Adult↗

Effects of diltiazem hydrochloride on the reduction of blood pressure, and cardiac and renal functions in essential hypertensive patients with renal dysfunction.

Diltiazem hydrochloride was administered at a dose of 180 mg/day for 12 weeks to 10 essential hypertensive patients with slightly or moderately decreased renal plasma flow (RPF) in order to study its antihypertensive effect as well as the effects on cardiac and renal functions. The administration of diltiazem hydrochloride produced significant decreases in systolic pressure, diastolic pressure, and mean blood pressure. Right and left ventricular ejection fractions, max. dv/dt, and min. dv/dt assessed by cardiac pool scintigraphy were slightly increased, but these changes were not statistically significant. The glomerular filtration rate (GFR) and RPF were slightly increased, while renovascular resistance (RVR) was significantly reduced. No consistent tendency was observed in changes in plasma renin activity (PRA) and plasma aldosterone level. From these results, it was suggested that diltiazem hydrochloride is a potent antihypertensive drug which has no adverse effects on cardiac and renal functions in the treatment of essential hypertensive patients with slightly or moderately decreased RPF.

Adult↗