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Biomedical subjects

M Kusaka

Publications and source records attributed to M Kusaka.

At least 91 records · Page 5Linked to original sources
PubMed1992

[Hypothyroidism followed by interferon-alpha as adjuvant therapy of renal cell carcinoma: a case report].

A 58-year-old male patient was admitted to the hospital complaining of weight loss. Abdominal computerized tomographic (CT) scan disclosed a mass shadow in the left kidney. From the results of further examination, including drip infusion pyelography (DIP) and angiography, he was preoperatively diagnosed as having a left renal tumor. Left radical nephrectomy was performed on March 15, 1990. The lesion was histologically diagnosed as renal cell carcinoma (clear cell subtype, grade 2) confined by the renal capsule (stage I). No distant metastases were detected. Interferon-alpha was administered every other day as adjuvant chemotherapy. After the patient experienced muscle pain in his thighs and shoulders after exercise on February 11, 1991, the serum creatine phosphokinase (CPK) level progressively increased up to 2,329 U/l. On the basis of the results of various examinations reflecting thyroid gland function, he was diagnosed as having primary hypothyroidism due to Hashimoto's disease. Thyroid function improved after administration of triiodothyronine and thyroxine. Interferon has been reported to influence thyroid function, and, in this case, interferon-alpha therapy may have induced the primary hypothyroidism associated with Hashimoto's disease.

Chemotherapy, Adjuvant↗
PubMed1991

Mutant protein of recombinant human granulocyte colony-stimulating factor for receptor binding assay.

A new mutant protein of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was produced for the studies on receptors for human G-CSF. The mutant protein [(Tyr1, Tyr3]rhG-CSF), the biological activity of which was almost equal to that of rhG-CSF, was prepared by the replacement of threonine-1 and leucine-3 of rhG-CSF with tyrosine. The radioiodinated preparation of the mutant protein showed high specific radioactivity and retained full biological activity for at least 3 weeks. The binding capacity of the radioiodinated ligand was compared with that of [35S]rhG-CSF. Both radiolabeled ligands showed specific binding to murine bone marrow cells. Unlabeled rhG-CSF and human G-CSF purified from the culture supernatant of the human bladder carcinoma cell line 5637 equally competed for the binding of labeled rhG-CSFs in a dose-dependent manner, demonstrating that the sugar moiety of human G-CSF made no contribution to the binding of human G-CSF to target cells. In contrast, all other colony-stimulating factors and lymphokines examined did not affect the binding. Scatchard analysis of the specific binding of both labeled ligands revealed a single class of binding site with an apparent dissociation constant (Kd) of 20-30 pM and 100-200 maximal binding sites per cell. These data indicate that the radioiodinated preparation of the mutant protein binds the same specific receptor with the same affinity as [35S]rhG-CSF. The labeled mutant protein also showed specific binding to human circulating neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Potent anti-angiogenic action of AGM-1470: comparison to the fumagillin parent.

The anti-angiogenic activity of AGM-1470, a new synthetic analog of fumagillin isolated from Aspergillus fumigatus, was extensively examined both in vitro and in vivo using four different types of assay and compared to that of the fumagillin parent. Locally administered AGM-1470 inhibited the angiogenesis in the chick embryo chorioallantoic membrane assay and the rat corneal assay. In the rat sponge implantation assay, systemically administered AGM-1470 inhibited angiogenesis induced by basic fibroblast growth factor. Furthermore, in the rat blood vessel organ culture assay, AGM-1470 (1-1,000 ng/ml) was found to selectively inhibit the capillary-like tube formation of endothelial cells with a minimal effect on the non-endothelial cell growth. AGM-1470 showed more potent anti-angiogenic activity and less toxicity than the fumagillin parent. Therefore, AGM-1470 is much better than the fumagillin parent as anti-angiogenic compound.

Animals↗
PubMed1991

Intracranial pressure monitoring using a programmable pressure valve and a telemetric intracranial pressure sensor in a case of slit ventricle syndrome after multiple shunt revisions.

A case of hydrocephalus showing slit ventricle syndrome after multiple shunt revisions was treated with a programmable pressure valve, and intracranial pressure was monitored with a telemetric sensor. High pressure setting produced positive and normal values of intracranial pressure in this patient. We report our experiences.

Cerebrospinal Fluid Shunts↗
PubMed1991

Anemia in new congenital adult type polycystic kidney mice.

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.

Anemia↗
PubMed1991

Plasma renin activity and norepinephrine as predictors for antihypertensive effects of nifedipine and captopril.

To examine predictors for the efficacy of antihypertensive agents, we investigated the effects of nifedipine and captopril on blood pressure (BP) and humoral factors in patients with essential hypertension. Eleven essential hypertensive patients (mean age: 54) were treated with long acting nifedipine at 20 to 40 mg/day for 8 weeks and 25 essential hypertensives (mean age: 51) were treated with captopril at 37.5 to 75 mg/day. Blood pressure was measured every 2 weeks. Plasma renin activity (PRA), and plasma concentrations of aldosterone, epinephrine and norepinephrine were determined before and at the end of treatment. Both nifedipine and captopril decreased BP (nifedipine: mean BP 119 +/- 3 to 101 +/- 2 mm Hg, captopril: 124 +/- 2 to 100 +/- 2, P less than .01 for each), whereas neither of them affected heart rate. The 8-week treatment of nifedipine showed no significant effect on humoral factors. Captopril increased PRA by 63% (P less than .05) and decreased plasma epinephrine by 42% (P less than .01) and norepinephrine by 35% (P less than .01). The change in mean BP was positively correlated with pretreatment PRA (r = 0.68, P less than .01) in nifedipine-treated patients and inversely with pretreatment norepinephrine (r = -0.53, P less than .01) in captopril treatment. The results suggest that both nifedipine and captopril were effective antihypertensive agents and that the long term treatment of nifedipine is more effective in essential hypertensives with lower PRA, while captopril is more effective in those with higher plasma norepinephrine concentration.

Aged↗
PubMed1991

Significance of intracellular free calcium and magnesium and calcium-regulating hormones with sodium chloride loading in patients with essential hypertension.

This study was designed: (1) to test the hypothesis that the pressor response to sodium chloride loading in patients with essential hypertension is associated with disorder of divalent cations (calcium and magnesium); and (2) to clarify the relationship between intracellular free calcium concentration and serum levels of calcium-regulating factors and intracellular magnesium concentration. With sodium chloride loading, mean blood pressure, urinary calcium and magnesium excretions and platelet calcium concentration were increased, and serum total and ionized calcium, magnesium concentrations and erythrocyte magnesium concentration were decreased. Change in mean blood pressure was correlated with changes in parathyroid hormone (r = 0.49, P less than 0.05), serum total and ionized calcium (r = -0.50, P less than 0.05) and erythrocyte magnesium (r = -0.56, P less than 0.05) and platelet calcium concentrations (r = 0.46, P less than 0.05). In addition, change in platelet calcium concentration was related to changes in parathyroid hormone (r = 0.44, P = 0.05), serum total and ionized calcium (r = -0.66, P less than 0.01) and erythrocyte magnesium concentration (r = -0.49, P less than 0.05). It is concluded that the pressor effect of excessive sodium chloride intake on blood pressure in patients with essential hypertension is associated with a disorder of divalent cations and that alteration of the intracellular free calcium concentration with sodium chloride loading may occur through handling of serum total and ionized calcium, parathyroid hormone and/or intracellular magnesium concentration.

Adult↗
PubMed1991

Metoprolol oxidation polymorphism in a Korean population: comparison with native Japanese and Chinese populations.

We examined metoprolol oxidation capacity in 218 unrelated, healthy Korean subjects using the 8 h urinary metabolic ratio (MR) of metoprolol to alpha-hydroxymetoprolol after an oral dose of 100 mg metoprolol tartrate. The results were compared with those from 295 Japanese and 107 mainland Chinese whose metoprolol oxidation capacities were assessed in a similar manner. The frequency of occurrence of poor metabolisers (PMs) was 0.5% (1/218) in the Korean, 0.7% (2/295) in the Japanese and 0% in the Chinese population. However, the respective mean (+/- s.d.) MRs (0.84 +/- 1.14 and 0.87 +/- 0.90) in the Korean and Japanese extensive metabolisers (EMs) were significantly (P less than 0.001) less than that in the Chinese EMs (2.81 +/- 2.35), and the mode of the distribution histogram and the probit plot of data for Chinese EMs were shifted to the right compared with those for Korean and Japanese EMs. The results indicate that Koreans, like Japanese and mainland Chinese, have a much lower frequency of the PM phenotype of debrisoquine/sparteine-type oxidation compared with that reported for Caucasian populations. Chinese EMs appear to have a lower capacity to metabolise metoprolol to alpha-hydroxymetoprolol compared with Korean or Japanese EMs.

Adolescent↗
PubMed1991

Granulocyte colony-stimulating factor (G-CSF) receptors on acute myeloblastic leukaemia cells and their relationship with the proliferative response to G-CSF in clonogenic assay.

The number and the affinity of granulocyte colony-stimulating factor (G-CSF) receptors expressed by blast cells in acute myeloblastic leukaemia (AML) were determined using radiolabelled recombinant human G-CSF (rhG-CSF). Eighteen of 20 patients demonstrated specific binding, and Scatchard analysis revealed a single class of high affinity (Kd 15-130 pM) G-CSF receptors on the AML blasts. The number of G-CSF receptors varied from 55 to 1,200 per cell (mean 278). In the remaining two patients, specific binding was not observed. The number of G-CSF receptors did not differ significantly between various AML subtypes, but the mean receptor number was the highest on type M2 blasts. A chemical cross-linking study revealed that the G-CSF receptor has an approximate molecular weight of 140,000. Autoradiography showed heterogeneity of the distribution of G-CSF receptors on the AML blasts obtained from a single patient. The number of colonies stimulated by the addition of rhG-CSF varied from 0 to 566 per dish, and blast colony formation was observed in eight of 20 patients. The population mean of G-CSF receptor number expressed by blasts that formed colonies on stimulation with rhG-CSF was significantly higher than that on blasts which did not form colonies. These results suggest that a proliferative response of AML blasts to G-CSF may be predicted when the blasts express a large number of G-CSF receptors. Accordingly, it may be safer to restrict the clinical use of G-CSF to AML patients who have blasts with a low G-CSF receptor expression and no response to G-CSF in blast colony assay.

Granulocyte Colony-Stimulating Factor↗
PubMed1991

Significance of intracellular cations and calcium-regulating hormones on salt sensitivity in patients with essential hypertension.

Although the existence of salt sensitivity in essential hypertensives has been well known, the precise mechanism(s) has not yet been elucidated. The aim of this study was to clarify the relation between the responses in blood pressure, extra- and intracellular cations and calcium-regulating hormones to oral NaCl loading in essential hypertensives. After oral NaCl loading, mean blood pressure, urinary excretions of calcium and magnesium, and PLT[Ca2+]i were significantly increased. [Ca2+]o and E[Mg]i were decreased. The changes (delta) in mean blood pressure by NaCl loading positively correlated with delta PLT[Ca2+]i and delta PTH, and negatively with delta[Ca2+]o and delta E[Mg]i. Delta PLT[Ca2+]i positively correlated with delta PTH and negatively with delta[Ca2+]o and delta E[Mg]i. From these results, the blood pressure response to oral NaCl loading is associated with the alternation of [Ca2+]i metabolism in which the changes in magnesium metabolism and calcium-regulating hormones may be involved.

Adult↗
PubMed1990

Effect of recombinant human granulocyte colony-stimulating factor on human neutrophil adherence in vitro.

We measured the effects of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the adherence of human neutrophils by using a dacron fiber system to assay the adhesive ability of neutrophils. rhG-CSF enhanced neutrophil adherence to dacron fibers. N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced neutrophil-neutrophil interaction (neutrophil aggregation) in addition to neutrophil-dacron interaction, whereas rhG-CSF did not cause neutrophil aggregation. These results indicated that rhG-CSF increases the adhesive ability of neutrophils without neutrophil-neutrophil interaction, and the action of rhG-CSF in neutrophil activation is different from the neutrophil activation caused by fMLP.

Cell Adhesion↗
PubMed1990

Neutrophil kinetics of recombinant human granulocyte colony-stimulating factor-induced neutropenia in rats.

Single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) immediately induced a decrease in the number of circulating neutrophils in rats. This neutropenia occurred 10 minutes after the injection but disappeared 40 minutes after injection. This transient neutropenia was dose-dependently induced by rhG-CSF and also induced by repeated injections. We studied the kinetics of circulating neutrophils in transient neutropenia. rhG-CSF markedly decreased the number of 3H-diisopropylfluorophosphate (3H-DFP) labeled neutrophils in the circulation 10 minutes after injection but the labeled neutrophils recovered to near the control level 40 minutes after the injection. These results indicate that the neutrophil margination accounts for the neutropenia and the marginated neutrophils return to the circulation.

Animals↗
PubMed1990

Effect of recombinant human erythropoietin on new anaemic model rats induced by gentamicin.

The effects of recombinant human erythropoietin (r-HuEPO) on haematological parameters were studied in rats in which uraemia and anaemia had been induced by gentamicin, an aminoglycoside antibiotic and a nephrotoxic agent. After the occurrence of slight polycythaemia, the red blood cell count, haematocrit and haemoglobin concentration decreased by 20-30% compared with those of the control (saline-injected) rats. At the end of gentamicin treatment, the endogenous serum EPO level had decreased to about 40% compared with that of control rats. Gentamicin-treated rats showed marked elevation of blood urea nitrogen, extensive tubular necrosis in the kidney and haemosiderin deposition in the spleen. In the osmotic fragility test, the fragility of erythrocytes significantly increased compared with that of control rats. These findings indicate that the anaemia induced by gentamicin is due not only to a deficiency of EPO but also to an enhancement of fragility of erythrocytes in an azotaemic environment. The administration of r-HuEPO during anaemia markedly increased red blood cell count, haematocrit and haemoglobin concentration. It is suggested that a gentamicin-treated rat is a useful and convenient anaemic model and r-HuEPO is useful for treatment of anaemia in acute renal failure.

Anemia↗
PubMed1989

Effects of treatment with captopril on exercise tolerance and plasma catecholamines in elderly hypertensives.

We examined the effects of antihypertensive therapy with captopril, an angiotensin converting enzyme inhibitor, on exercise tolerance and humoral factors in 19 elderly patients (greater than 60 years old) with essential hypertension. Captopril (37.5-75 mg/day) was administered for 8 weeks. Fourteen of the 19 patients in whom captopril was effective took a treadmill exercise test according to Kattus' protocol. Exercise tolerance was increased in all patients (from 13.1 +/- 1.3 to 16.5 +/- 1.0 min, P less than 0.01). Captopril attenuated the rise in blood pressure during the exercise test but did not affect the heart rate. Resting values of plasma adrenaline decreased by 47% and noradrenaline by 17%, with no significant changes in plasma renin activity (PRA) or aldosterone. The change in mean blood pressure showed an inverse relationship to pretreatment plasma noradrenaline (r = -0.73, P less than 0.01). The results show that captopril is effective in the treatment of hypertensive elderly patients, and suggest that the sympathetic nervous system is involved in the mechanism of the antihypertensive response to captopril therapy.

Aged↗