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Biomedical subjects

M Kambe

Publications and source records attributed to M Kambe.

At least 73 records · Page 4Linked to original sources

Enhancement of chemotherapeutic effects with focused shock waves: extracorporeal shock wave chemotherapy (ESWC).

The effects of shock waves in combination with various anti-cancer agents i.e. Bleomycin(BLM), Cis-platinum (CDDP) and 5-fluorouracil(5-FU) on various human cancer cells were examined. It was only with BLM that enhancement was evident in all cell lines. The degree of chemotherapeutic enhancement was proportional to the amount of shock wave energy applied. Ladder formation of DNA in GCIY, a gastric cell line, was observed only when treated with both BLM and shock waves in combination. When SW 480, a colon cancer cell line, transplanted into the back of nude mice were treated with a combination of i.v. injected BLM and regional exposure to shock waves, a significant enhancement of chemotherapeutic effects was observed in terms of the tumor growth curve. When cancer cells exposed to shock waves and observed under scanning and transmission electron microscopes, microvilli on the cell surface disappeared and numerous dimples(diameters distributed from 0.05 to 0.5 microns) became apparent. These dimples were concluded to be pores penetrating through the cell membrane, because reagents such as propidium iodide or 5(6)-carboxyfluorescein could enter cells treated shock waves.

Animals↗

[The present and future of clinical physiologic tests].

The symposium on clinical physiologic tests was designed in the 44th congress of all central laboratory divisions of national university hospitals at 28, 29 May in 1997. The title of symposium was "the present and future of clinical physiologic tests" which was named by professor M. Itoh. Four symposists were nominated among the specialists on clinical physiologic tests of members of above congress. Professor M. Itoh and Professor H. Kawaguchi spoke about Erectric Cardio Graphy (ECG) and main heart function tests and Professor M. Kambe spoke about pulmonary function tests and Professor M. Okada spoke about the using methods of clinical physiologic test data in remote and distant medicine. The special feature of clinical laboratory division in Japanese large hospitals is that has clinical physiologic tests part and the clinical laboratory division of hospitals in foreign countries has no clinical physiologic tests part. So, we expect more development of clinical physiologic tests part in nearly future.

Asthma↗

Potentiation of the intracellular Ca2+ response to arginine vasopressin by increased cytosolic-free Mg2+ in rat vascular smooth muscle cells.

Although the inhibitory effects of extracellular Mg2+ on Ca2+ influx are well established, little is known about the effects of intracellular Mg2+ on Ca2+ handling. In the present study, the effects of cytosolic-free Mg2+ concentration in the physiological (submillimolar) range on Ca2+ handling were investigated after stimulation of rat vascular smooth muscle cells with arginine vasopressin. Cytosolic Mg2+ was manipulated by culturing cells in medium containing different Mg2+ concentrations. Peak cytosolic-free Ca2+ concentration responses to arginine vasopressin (1 mumol/1) were measured in the presence and absence of external Ca2+. The results suggest that an increase in cytosolic-free Mg2+ concentration increases both Ca2+ discharge from intracellular stores and Ca2+ influx, whereas a decrease in intracellular Mg2+ attenuates Ca2+ influx.

Animals↗

Angiotensin I-converting enzyme gene polymorphism and salt sensitivity in essential hypertension.

We undertook the present study in 66 Japanese patients with essential hypertension to identify genetic factors associated with salt sensitivity. Patients were classified into salt-sensitive or salt-resistant groups on the basis of changes in their mean blood pressures from a week of a low salt diet (50 mmol/d) to a week of a high salt diet (340 mmol/d). Salt sensitivity and resistance were studied in relation to a 287-bp insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme gene detected by a polymerase chain reaction method and the haptoglobin phenotype determined by polyacrylamide gel electrophoresis. Patients with the angiotensin I-converting enzyme gene genotype II were more apt to be salt sensitive than patients with the ID and DD genotypes, although plasma renin activity was similar in each group. The frequency of the I allele in the salt-sensitive group was significantly higher than that in the salt-resistant group (chi2 = 7.4, odds ratio = 2.78). However, there was no significant relationship between haptoglobin phenotype and salt sensitivity. These data suggest that an I/D polymorphism of the angiotensin I-converting enzyme gene is a genetic factor associated with salt sensitivity of blood pressure independently of plasma renin activity in Japanese patients with essential hypertension.

Adult↗

Platelet Ca2+ is not increased in stroke-prone spontaneously hypertensive rats: comparative study with spontaneously hypertensive rats.

We have reported that cytosolic Ca2+ concentration ([Ca2+]i) is increased in platelets from spontaneously hypertensive rats (SHR) in both basal and thrombin-stimulated conditions. To determine whether the correlation between blood pressure and cellular Ca2+ metabolism exists in stroke-prone SHR (SHRSP), we investigated Ca2+ handling using fura 2 and aggregation response in platelets of 12- to 13-week-old male SHRSP, SHR, and Wistar-Kyoto rats (WKY). Systolic pressure was highest in SHRSP and lowest in WKY (213 +/- 8, 172 +/- 7, and 135 +/- 5 mm Hg, respectively). Basal [Ca2+]i was significantly higher in SHR than WKY (45.9 +/- 4.5 versus 41.2 +/- 4.8 nmol/L, P<.05), and that in SHRSP (40.2 +/- 2.8 nmol/L) was similar to that in WKY. Thrombin (0.1 IU/mL)-stimulated [Ca2+]i rise was greater in SHR and smaller in SHRSP than in WKY in the presence of extracellular Ca2+ (530 +/- 50 and 408 +/- 52 versus 475 +/- 50 nmol/L, respectively; P<.05). The recovery rate from the peak [Ca2+]i response to thrombin was greatest in SHRSP and least in WKY. Ionomycin (5 micromol/L)-stimulated [Ca2+]i rise was similar in WKY, SHR, and SHRSP (731 +/- 97, 743 +/- 88, and 683 +/- 70 nmol/L, respectively). Thrombin-induced maximum platelet aggregation response was higher in SHR and lower in SHRSP than WKY (82 +/- 4 percent and 61 +/- 15 percent versus 73 +/- 6 percent, respectively; P<.05). In contrast to SHR, basal [Ca2+]i in SHRSP was similar to that in WKY, and thrombin-stimulated [Ca2+]i was attenuated. These result suggest that platelet Ca2+ handling differs between SHR substrains and that an increased [Ca2+]i is not obligatory in genetically hypertensive rats.

Animals↗

Effects of insulin on calcium metabolism and platelet aggregation.

The influence of insulin on platelets in vitro has not been exhaustively investigated. To clarify whether insulin affects Ca2+ metabolism in platelets directly or through alteration of other systems regulating intracellular Ca2+ homeostasis, we examined the effect of insulin both alone and in combination with prostaglandin E1 on platelet aggregation and Ca2+ metabolism. Incubation of rat platelets with insulin reduced thrombin-induced Ca2+ influx but did not change thrombin-evoked release of Ca2+ from internal stores or the size of internal Ca2+ stores. The interactive effects of insulin with prostaglandin E1 were only additive, and insulin did not augment the effects of prostaglandin E1 on platelet Ca2+ metabolism. In contrast, insulin did not inhibit thrombin-induced platelet aggregation but did augment inhibition of platelet aggregation by prostaglandin E1. Our results suggest that insulin inhibits platelet function by both prostaglandin E1-dependent and -independent mechanisms.

Animals↗

Modulation of target tissue response to angiotensin II and sodium sensitivity in Japanese patients with essential hypertension.

"Non-modulators" are essential hypertensive patients who fail to modulate an adrenal response, renovascular response, or both, to angiotensin II (Ang II). The aim of the present study was to characterize "non-modulators" among Japanese patients with normal-renin essential hypertension and to determine whether non-modulation is related to sodium sensitivity of blood pressure. The increase in plasma aldosterone concentration (PAC response) and the decrease in renal plasma flow (RPF response) in response to Ang II infusion (3 ng/kg/min) were assessed in 15 Japanese patients with essential hypertension who received a high sodium diet (250 mEq/d) followed by a low sodium diet (10 mEq/d). The subjects were divided into two groups (6 modulators and 9 non-modulators) based on their ability to modulate the PAC response during sodium restriction. There was no significant difference between modulators and non-modulators in electrolyte balance or in plasma Ang II levels on either diet. Changes in the PAC response during sodium restriction were significantly correlated with the change in mean blood pressure during sodium restriction (r = -0.67, p < 0.01), while changes in the RPF response were not. RPF responses in both groups decreased during sodium restriction, although an effect on the RPF response in non-modulators was unexpected. These results suggest that non-modulators do exist among Japanese patients, but that this defect does not involve both the adrenal gland and the kidney. Apparently, only non-modulation of the adrenal response is involved in the mechanism of sodium sensitivity.

Adult↗

Enhancing the effect of anticancer drugs against the colorectal cancer cell line with electroporation.

Electroporation was applied in vitro and in vivo in the treatment of human colorectal cancer cell lines to study whether it can enhance the effect of bleomycin (BLM), 5-fluorouracil (5-FU) and cis-platinum (CDDP). We used LS174T and Colo320 cells derived from human colon cancer as target cells in this study. When the LS174T cells were used as target cells, the IC50 of BLM decreased to 10(-3) times, while that of 5-FU decreased to only about one fifth with the application of electric current. In the case of the Colo320 cells, the IC50 of BLM and 5-FU were about one hundredth and a half, respectively. The effect of CDDP was not enhanced with electric current. In vivo experiments were also performed using LS174T cells transplanted subcutaneously (s.c.) into nude mice. By treatment with intravenously (i.v.) administered BLM and simultaneous application of the electric current, tumors were markedly decreased in size after three weeks.

Animals↗

Comparison of hypocholesterolemic effects induced by dietary linoleic acid and oleic acid in hamsters.

We investigated the differences between the hypocholesterolemic effects induced by dietary linoleic acid and those induced by oleic acid in hamsters. Addition of 5% linoleic acid or oleic acid to a 0.1% cholesterol-supplemented diet diminished the increases in plasma total and low density lipoprotein (LDL) cholesterol induced by cholesterol alone. Linoleic acid decreased high density lipoprotein (HDL) cholesterol in comparison with cholesterol alone, whereas oleic acid did not. As compared with a standard diet or a cholesterol-supplemented diet, linoleic acid and oleic acid each prevented hepatic LDL receptor suppression, although linoleic acid was more effective. Oleic acid prevented the increase in plasma cholesteryl ester transfer protein (CETP) activity induced by dietary cholesterol, whereas linoleic acid did not. Neither linoleic acid nor oleic acid altered hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity. Only oleic acid increased hepatic cholesterol 7 alpha-hydroxylase activity. These results suggest that dietary linoleic and oleic acids diminish the cholesterol-induced increases in plasma total and LDL-cholesterol by preventing hepatic LDL receptor suppression, and in the case of oleic acid by also preventing the increase in the plasma CETP activity. These effects on cholesterol 7 alpha-hydroxylase activity may influence bile lipid metabolism.

Animals↗

Non-invasive evaluation of abdominal aortic properties: lumped circuit model and estimation of its parameters.

To non-invasively determine abdominal aortic properties, a five-element lumped circuit model was adopted. The model consists of resistance due to blood viscosity (R1), inertia of blood flow, compliances of the vessel (C1, C2), resistance of the peripheral arteries (R2) and the impedance of the of the femoral arteries (termination). Patterns of the central velocity of the upper abdominal aorta and the femoral artery are measured by pulsed Doppler echocardiography, and contours of flow volume rates are calculated. The pressure pattern of the lower limb is recorded by a pulse wave transducer and corrected according to sphygmomanometer values. Contours are transformed into respective Fourier transform components. The current transfer function is described theoretically and calculated from the acquired Fourier components. Values of every element are evaluated by the nonlinear least squares method. In 94 subjects (17-92 years), the values of each element are estimated. R2 values are greater in the elderly group than in the young group and r1 (R1/cm) increased with age. This model demonstrates that vessel compliance (C1 + C2 (C1 + C2/cm)) decreases with age, and it is suggested that this may be a useful marker of arteriosclerosis.

Adolescent↗

Effect of the transmembrane gradient of magnesium and sodium on the regulation of cytosolic free magnesium concentration in human platelets.

1. To clarify the mechanism by which cytosolic free Mg2+ concentrations ([Mg2+]i) are regulated in human platelets, we investigated platelet membrane permeability to Mg2+ by altering extracellular Mg2+ concentrations, and tested the existence of a Na(+)-Mg2+ exchanger by manipulating the transmembrane Na+ gradient. 2. Platelet [Mg2+]i was 421 +/- 52 mumol/l in healthy men. [Mg2+]i remained constant during a 120 min exposure to nominally zero (low) or 5 mmol/l (high) external Mg2+ concentrations. 3. Preincubation of platelets with 10(-4) mol/l ouabain effectively decreased the transmembrane Na+ gradient. The ouabain-induced increase in [Mg2+]i was statistically significant after 30 min of exposure (14.6 +/- 2.0%) and reached 24.6 +/- 4.5% after 60 min. Similarly, the replacement of extracellular Na+ with N-methyl-D-glucamine significantly increased [Mg2+]i by 48.5 +/- 3.9% and 78.8 +/- 12.5%, respectively. 4. These results suggest that [Mg2+]i is well controlled in the presence of large transmembrane Mg2+ concentration gradients, and a Na(+)-Mg2+ exchanger may be involved in the regulation of [Mg2+]i in human platelets.

Blood Platelets↗

Intravenous administration of L-arginine inhibits angiotensin-converting enzyme in humans.

The iv administration of L-arginine, a precursor of endothelium-derived relaxing factor/nitric oxide, is known to decrease blood pressure in humans by its direct vasodilatory effects. The purpose of the present study was to determine whether L-arginine infusion modifies the renin-angiotensin (Ang)-aldosterone system as well as blood pressure and renal hemodynamics. L-Arginine and saline vehicle were iv administered to 10 healthy male subjects in random order on different days. L-Arginine infusion (500 mg/kg over 30 min) decreased mean blood pressure (from 81.2 +/- 2.7 to 74.0 +/- 2.5 mm Hg; P < 0.001) and renal vascular resistance (from 0.085 +/- 0.007 to 0.074 +/- 0.006 mm Hg/mL.min; P < 0.01) and increased heart rate (from 60.3 +/- 2.7 to 69.7 +/- 2.1 beats/min; P < 0.001) and renal plasma flow (from 616.6 +/- 37.8 to 701.0 +/- 49.2 mL/min; P < 0.05). L-Arginine reduced serum Ang-converting enzyme activity (from 10.4 +/- 0.6 to 8.9 +/- 0.5 nmol/mL.min; P < 0.05) and plasma Ang-II (from 19.3 +/- 3.3 to 12.7 +/- 2.8 pg/mL; P < 0.001), but had no effect on PRA or the glomerular filtration rate. The saline vehicle did not alter any of these parameters. The iv administration of L-arginine (endothelium-derived relaxing factor/nitric oxide) may reduce the plasma Ang-II concentration by inhibiting Ang-converting enzyme. The mechanism by which L-arginine infusion decreases blood pressure can be at least in part explained by inhibition of the renin-Ang system.

Adult↗

Differences in immune responses to tumor induced in syngeneic hosts by injection of hybrid and parental tumor cells.

Immunization of C3H/He mice with L-FM3A#2 hybrid cells, made by fusion of ascitic mammary carcinoma FM3A#2 cells with 8-azaguanine resistant LAG cells, both of C3H/He mouse origin, resulted in spleen T cell-dependent resistance to the parental FM3A/R cells. These spleen T cells, purified by passing through a nylon fiber column, could be demonstrated to have Thy-1.2 and Lyt-2.1 antigens, and not L3/T4 antigens. After immunizing with irradiated FM3A/R cells, cytotoxic cells other than cytotoxic T lymphocytes (CTL) appeared, these presumably being nonphagocytic macrophages or polymorphonuclear cells. In this case, anti MM antiserum was generated at an earlier stage than when mice were immunized with the L-FM3A#2 cells. The cytotoxic mechanism is discussed as to the significance of the surface antigen.

Animals↗

Unrestricted T cell-mediated cytotoxicity to major histocompatibility antigen generated with tumor hybrid cells.

Splenic T cells from C3H/He mice injected with the LFM3A#2 hybrid cells intraperitoneally (i.p.) showed cytotoxic activity against the parental FM3A/R tumor cells. We studied the target antigens recognized by cytotoxic T cells (CTL) and the following results were obtained. 1) CTL specifically recognized the MM antigens on the surface of target cells in effector phase. 2) The H-2K or H-2D antigens were not involved in T cell effector function.

Animals↗

[The uses of computer systems in daily medical care].

This paper describes the use of computer systems for daily primary medical care. They are two computer systems for selection of the sets of suitable clinical laboratory tests to diagnose the diseases. One of them is a system which has an electronic medical textbook and another is a system using an IC card. This paper also describes a plan for the use of clinical laboratory tests to diagnose the respiratory diseases. Several problems are suggested for management of the clinical laboratory data of respiratory diseases by computer.

Clinical Laboratory Information Systems↗

[Volume pulse wave and respiratory diseases].

We always record the volume pulse wave and oxygen saturation by using a pulse oximeter. The volume pulse wave fluctuation was induced by respiration; we have used this phenomenon to diagnose or assess respiratory diseases. First, differential diagnosis of sleep disorders, that is, central apnea, obstructive apnea, and respiration in upper airway resistance, by using only a pulse oximeter. Second, we used this phenomenon to evaluate dyspnea. When a big volume pulse wave fluctuation exists, most patients feel dyspnea, if they are awake and alert. Then, we monitored coughs by recording the volume pulse wave. Due to the pleural pressure change induced by the cough, the volume pulse wave reveals a characteristic form. This form changes with the intensity of the cough. Then we can evaluate the frequency and intensity of the cough. For recording the volume pulse wave, the pulse oximeter will be widely applicable in respiratory diseases.

Asthma↗