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Biomedical subjects

K Mabuchi

Publications and source records attributed to K Mabuchi.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Risk factors for primary breast cancer in Japan: 8-year follow-up of atomic bomb survivors.

BACKGROUND: Findings from the Life Span Study (LSS) of the health effects of exposure to atomic bomb radiation have documented a strong dose-response relation between radiation exposure and breast cancer incidence. PURPOSE: We analyzed data from the LSS cohort to identify nonradiation risk factors for breast cancer and to determine whether these factors were independent of the effects of radiation on breast cancer occurrence. METHODS: Breast cancer incidence was ascertained among a cohort of 22,200 residents of Hiroshima and Nagasaki, Japan, who had completed a mail survey between 1979 and 1981 to study nonradiation risk factors for disease. During the subsequent follow-up period (average 8.31 years), 161 cases of primary breast cancer were identified through population-based tumor registries in the two cities. RESULTS: The risk of breast cancer was inversely related to age at menarche and weakly positive in relation to age at menopause and years of menstruation. A significant negative association of full-term pregnancy against breast cancer was observed, although the number of pregnancies beyond the first was not related to the rate of breast cancer in the cohort. Women having their first full-term pregnancy before age 30 were at decreased risk of breast cancer relative to older women, but there was no trend. A nonsignificant, positive trend in risk was associated with increasing weight and body mass (kg/m2). The risk of breast cancer among women with a history of estrogen use was 1.64 (95% confidence interval 1.02-2.64) and with diabetes 2.06 (95% confidence interval 1.27-3.34). It was not possible to distinguish among additive and multiplicative models of the joint association of radiation dose and various non-radiation-related exposures (age at menarche, full-term pregnancy, female hormone preparations) identified in this analysis. CONCLUSIONS: Nonradiation risk factors for breast cancer among Japanese atomic bomb survivors were consistent with those identified among other populations of women, although the prevalence of common risk factors was low. Reproductive factors and hormone use appear to act independently of radiation exposure on the risk of breast cancer among this population.

Aged↗
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p53 mutations in lung cancers from non-smoking atomic-bomb survivors.

Tobacco smoke contains many carcinogens and has been linked with the development of lung cancer. We sequenced the conserved regions of the p53 tumour suppressor gene in lung cancers from 17 non-smokers from Hiroshima, Japan; 9 were atomic-bomb survivors. The mutations were predominantly transitions (all G:C to A:T); there were no G:C to T:A transversions. By contrast, lung cancers from 77 Japanese smokers have a predominance of G:C to T:A transversions in which the guanine residues occur on the non-transcribed DNA strand. These findings further implicate tobacco smoke carcinogens in the molecular pathogenesis of lung cancer.

Adult↗
PubMedDate not supplied

Lung cancer among pesticide workers exposed to inorganic arsenicals.

Cancer mortality was studied in 1,393 persons exposed to high air concentrations of inorganic arsenicals for varying lengths of time during the manufacture and packaging of pesticides at a plant in Baltimore, Maryland. Employees consisting of 1,050 males and 343 females were traced for the period 1946 to 1977, and vital status was determined for 86.9% of males and 66.8% of females. The observed number of deaths from all and selected causes was compared with the number expected from the Baltimore City mortality experience in terms of the Standardized Mortality Ratio (SMR). A significantly increased SMR was found for lung cancer and anemias in males. The SMR for lung cancer was especially high in males with presumed high exposure to arsenicals. A dose-response relationship was suggested by the SMR for lung cancer which increased with increasing duration of exposure to arsenicals, but no such relationship was evident for nonarsenicals. Although smoking habits could not be examined in the study subjects, the authors believe that the findings provide additional epidemiologic evidence on the respiratory carcinogenicity of occupational exposure to airborne inorganic arsenicals.

Arsenicals↗
PubMedDate not supplied

In vitro and in vivo evaluation of a jellyfish valve for practical use.

A practical model (Model-1) of a jellyfish valve was developed, which was composed of a valve seat and a flexible membrane. The valve seat has 12 spokes to hold the membrane, and is made of solution-cast polyurethane coated with segmented polyurethane or Cardiothane. The flexible membrane is 200 microns thick, and made of segmented polyurethane or Cardiothane by a casting method. The valves were built into a sac type blood pump. In mock circulation tests, this jellyfish valve revealed performance superior to Bjork-Shiley (B-S) valves. No stagnation point was observed in the flow visualization study, and durability testing is ongoing beyond 7.5 months. The valves were used in animal artificial heart experiments for up to 112 days with good performance. No thrombi were formed on the valve membrane or around the spokes. Although a ring thrombus was observed behind the valve, it would be prevented by perfect adhesion of the valve seat to the blood pump. The plasma free hemoglobin level was less than 2 mg/dl during these experiments. These results suggest that a jellyfish valve (Model-1) is useful in ventricular assist devices, and in short-term bridge use of a total artificial heart.

Animals↗
PubMedDate not supplied

Use of a total right heart bypass model for analyses of abnormal hemodynamics in total artificial heart animals, and the function and regulatory mechanisms of a natural heart.

By fixing the function of one ventricle, a total right heart bypass model can clarify the function and regulatory mechanism of the natural heart, and the etiology of abnormal hemodynamics in TAH animals such as increased CVP blood pressure and hepatic congestion. The pulmonary artery of a right heart bypass in a goat was clamped proximally; the pulmonary circulation was thus supplied entirely by the artificial heart and the systemic circulation by the natural heart. This model enabled studies of long-term effects of an artificial right heart on systemic circulation at a right heart output of 80-100 ml/kg/min; the response of the natural left heart to changes in output of the right heart; and the response of the natural left heart and artificial right heart to treadmill exercise. It was found that only slight increase in CVP or no increase in blood pressure was observed during the experiment (112 days); a rapid increase in output of the RAH resulted in an increase in left atrial pressure, stroke volume and output of the left ventricle, and a decrease in its heart rate at rest; and significant increase in both artificial right heart and natural left heart output and heart rates were observed during treadmill exercise, despite the marked decrease in left atrial pressure. The above results suggest that the increase in CVP and blood pressure in total artificial heart animals are not due to factors involving the artificial right heart, and that although left ventricular function acts in accordance with Starling's law at rest, this is no longer true during treadmill exercise.

Animals↗
PubMedDate not supplied

Development of a new circulatory assist method with the combined effects of intra-aortic balloon pumping and counter pulsation. First report.

Current circulatory assist methods, such as intra-aortic balloon pumping (IABP), are not always adequate to save acute circulatory failure patients. Therefore, a stronger, percutaneously accessible method is required. We found that the combination of IABP and CP generated a profound circulatory assist effect, and we have consequently developed a new assist system in this study. A sac type blood pump with a volume of 20 ml and a single port without a valve, was developed for CP. In the mock circulatory test, a 20 ml stroke volume was obtained using a cannula with a 5 mm diameter under the following driving conditions: air pressure = 200/-100 mmHg; S/D = 50%; pulse rate = 100 bpm. In vivo experiments were performed using four mongrel dogs with body weights of 12-20 kg. A cannula for CP was inserted via the brachial artery or subclavian artery into the aortic root. The pump flow (PF), coronary artery flow (CF), renal arterial flow (RF), and aortic pressure (AP) were measured, and the combined effects of IABP and CP were compared with their individual effects. In the most effective case, a marked increase in diastolic AP (60%), cardiac output (40%), and CF (100%) was obtained by the combination of IABP and CP, which produced a remarkable effect compared with the single use of IABP and CP. There was no negative effect on RF by this assist method. As this new circulatory support system has many circulatory assist effects, and is percutaneously accessible, it will be available for clinical use.

Animals↗
PubMedDate not supplied

Fabrication of a jellyfish valve for use in an artificial heart.

For a valve to be fabricated seamlessly into an artificial heart (AH) blood pump, a jellyfish valve has been developed, in which a thin membrane is fixed at the center of a valve seat having several spokes to protect against prolapse of the membrane. The valve is superior in performances to a Björk-Shiley valve, and reveals good blood compatibility. The valve would be very useful not only for AH animal study, but for future clinical use in infants to adults. Several institutions are already trying the valve. In this paper, the fabrication of the jellyfish valve is introduced, and in vitro and in vivo results summarized. A computer aided design (CAD) system was developed to cut a male wax mold of the valve seat. The input parameters to the CAD are diameter, height, thickness of rim, number of spokes, width and thickness of spokes, etc. Jellyfish valves with diameters of 4 to 27 mm have already been fabricated for many types of AHs and assist pumps.

Animals↗
PubMedDate not supplied

Changes with respect to time in the in vivo adsorption of plasma proteins onto artificial heart blood pumps.

The distribution of adsorbed plasma proteins (albumin, IgG, and fibrinogen) on 10 artificial heart blood pumps coated with 2 segmented polyurethanes was evaluated quantitatively after long-term in vivo experiments with goats to determine how the adsorption of plasma proteins on the pumps was affected by the kinds of biomaterials used, and by the pumping duration. The adsorbed plasma proteins on the materials were determined quantitatively using the iodine-125 conjugated antibody method. Microscopically, the adsorbed plasma proteins were marked by the gold colloid conjugated antibody method, and analyzed using a field emission scanning electron microscope. The macroscopic results showed that: 1) the adsorbed plasma proteins on KP-13 were more evenly and finely distributed than those on Cardiothane; 2) with KP-13, the adsorption of IgG and albumin at the center of the pumps was significantly less than in the peripheral areas, and the adsorbed IgG and albumin decreased significantly as the pumping duration increased; 3) in contrast, the adsorbed fibrinogen increased significantly with time; and 4) with Cardiothane, the tendencies for adsorbed IgG and albumin to decrease, and for adsorbed fibrinogen to increase, were less significant than with KP-13. Microscopically, the gold colloids marking plasma proteins were found to not cover the whole of the surface, but were found scattered randomly or in clusters, with no relationship observed between the distributions of the three plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMedDate not supplied

The second and third model of the flow transformed pulsatile total artificial heart.

For the purpose of future total implantation, a new pulsatile total artificial heart, a flow transformed pulsatile total artificial heart (FTPTAH), in which the continuous flow from a single centrifugal pump (CFP) was converted to pulsatile flow by switching two three-way valves that could alternately perfuse the systemic and pulmonary circulation, was proposed, and the data from the prototype model were reported. As the next step, the second model, in which a CFP and a spool valve (SV) driven with a solenoid were fabricated in one piece, was made and tested in a mock circulatory system. The system could send 4.7 L/min of pulsatile output alternately to the pulmonary artery and aorta, with 30 and 100 mmHg afterload, respectively, at 3000 rpm CFP. However, three problems were encountered: the output was not enough, mixture or inversion of venous and arterial blood in the CFP would occur, and heat generation at the solenoid was very severe. To solve these problems, a third model was designed in the current study. To increase pump output, hydrodynamic analysis was performed. The SV was divided into inlet and outlet to control the blood mixture or inversion. To suppress heat generation, each SV was driven back and forth by two solenoids, one on each side of the SV. The model revealed satisfactory results in a mock circulatory system.

Biomedical Engineering↗
PubMedDate not supplied

A new apparatus for chronic observation of the microcirculation in situ to evaluate artificial organ performance.

Chronic study of the peripheral circulation and metabolism is very important in evaluation of artificial organ performance. However, there has been no way to observe the microcirculation in situ, chronically and continuously, without restriction. In this study, the authors developed a new apparatus that could be implanted and connected to an artificial organ that would allow continuous observation of the microcirculation while the subject is awake. The apparatus uses a charge coupled device (CCD) under a new principle: thin living tissue, such as mesentery, is put directly on a highly integrated CCD and transilluminated with a light emitting diode (LED). The vascular nets in the tissue are projected onto the CCD like a contact photograph, which is sent to a television screen and can be analyzed for motion and function. A 0.5 inch CCD with 25K pixels was used in this study. The cover glass of the CCD was removed so the tissue would be able to directly contact the CCD surface. The CCD, as well as LED, were molded with hard polyurethane as electrical insulation. The apparatus is 35 mm in diameter and 10 mm high with a micro stand for lighting with the LED, which is easy to implant in a goat or calf. The resolution of this apparatus was tested by putting a micro scale on the CCD surface. Several tenths of micrometers could be seen. In an animal experiment with a rabbit, configurations of arterioles and venules and their motions could be observed continuously for a night until the electrical insulation was broken. This method might be a strong weapon in artificial organs research.

Animals↗
PubMedDate not supplied

Results of animal experiments using an undulation pump total artificial heart: analysis of 10 day and 19 day survival.

An undulation pump is a special rotary blood pump in which rotation of a brushless DC motor is transformed to an undulating motion by a disc in the pump housing attached by means of a special link mechanism. In the blood pump, a closed line between the disc and housing moves from the inlet to the outlet by this undulating disc motion, which sucks and pushes the blood from the inlet to the outlet. Because the same phenomena occurs at both sides of the disc, a continuous flow is obtained when the motor rotational speed is constant. The pump flow pattern can be easily changed from continuous flow to pulsatile flow by controlling the motor drive current pattern. A seal membrane made of segmented polyurethane protects the blood from invading the link mechanism as well as the motor. UPTAH is fabricated with two undulation pumps and two brushless DC motors. Its size is 75 mm in diameter and 80 mm long, and it has one of the great advantage of no compliance chamber required in the system. UPTAHs were implanted under cardiopulmonary bypass (CPB) into the chest cavities of 16 goats, each weighing between 41 and 72 kg. No anticoagulant and antiplatelet agent was used after the surgery. The left atrial pressure was automatically controlled to prevent its elevation and sucking of the atrial wall into the atrial cuff. The following results were obtained: (1) UPTAHs fit well into all the goats; (2) the longest survival was 19.8 days, the cause of death was bleeding from the aortic anastomosis; (3) No thrombus was observed in the blood pump despite no anticoagulant use. Hemolysis depended upon the length of CPB during surgery. When CPB time was within 2 hours, hemolysis level returned to baseline within a few days of the surgery. UPTAH is a promising implantable TAH, because of its small size and easy controllability.

Animals↗
PubMedDate not supplied

Synthesis and action of PAF in human eosinophils.

We compared the level of PAF precursor as well as the synthesis and the catabolism of PAF in eosinophils with those in neutrophils. The modes of action of PAf on these two types of cells were also compared.

Cells, Cultured↗
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Modulation by l-leucovorin of 1-hexylcarbamoyl-5-fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice.

Experimental biochemical modulation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) with l-leucovorin (LV) was carried out using human gastric (H-111) and colon (Co-4) carcinoma xenografts serially transplanted into nude mice. Thirty-five or 70 mg/kg HCFU dissolved in 0.2 ml of 1% hydroxymethyl cellulose was administered po daily for 3 weeks except Sundays, and 50, 100, 200 or 300 mg/kg LV dissolved in 0.2 ml physiological saline was administered po 30 min before administration of HCFU. The biochemically modulated antitumor activity was evaluated in terms of actual tumor weight, the relative mean tumor weight and the degree of inhibition of thymidylate synthetase (TS) in the tumors at the end of the experiments, assayed according to the method of Spears et al. Although 35 mg/kg HCFU was ineffective against gastric carcinoma H-111, combination with 200 or 300 mg/kg LV resulted in a positive antitumor effect of HCFU on this strain without any increase of side effects in terms of body weight loss and mouse mortality. The colon carcinoma strain Co-4 showed marginal sensitivity to HCFU (35 mg/kg) alone, but 50 or 100 mg/kg LV modulated the antitumor activity of HCFU on Co-4 to produce a significant positive effect without any increase in toxicity, and HCFU administered with 100 mg/kg LV was more effective than the maximum tolerated dose of HCFU (70 mg/kg) alone. The TS inhibition rate was closely related to the biochemical modulation of HCFU antitumor activity by LV, suggesting that the modulation involves an increase of the ternary complex of TS, 5,10-methylene tetrahydrofolate from LV and 5-fluorodeoxyuridine 5'-monophosphate (FdUMP). Combination of HCFU and LV is therefore thought to be useful in increasing the antitumor activity of HCFU on gastrointestinal carcinomas without enhancing its toxicity.

Animals↗
PubMedDate not supplied

Suppression of the natriuretic effects of exogenous atrial natriuretic peptide in animals with total artificial hearts.

Atrial natriuretic peptide (ANP) was administered intravenously to three goats at a dose of 0.1 micrograms/kg/min for 40 min both before total artificial heart (TAH) placement and at 1, 7, and 14 postoperative weeks to determine whether exogenous ANP exhibits the same effect on animals with TAHs as it does on normal animals. No significant changes in the increases in plasma levels of ANP and cyclic guanosine monophosphate (c-GMP) were observed during ANP administration after TAH insertion. In preoperative animals, urine volume and urinary sodium excretion increased greatly during ANP administration, but this natriuretic effect was strongly suppressed in TAH animals. The changes in the decreases in arterial pressure and in central venous pressure (CVP) or right atrial pressure that occurred during the administration of ANP were not significant either pre- or post-operatively. Thus, only the natriuretic effect of ANP on the kidney was significantly suppressed in TAH animals, which might be due to some down-regulation of ANP receptors in the kidney, the production of some antagonists of ANP, sympathetic hypertonicity, or the elevation of CVP.

Animals↗
PubMedDate not supplied

Blood compatibility of the jellyfish valve without anticoagulant.

The blood compatibility of the jellyfish valve was studied. Artificial heart (AH) blood pumps incorporating jellyfish valves were connected to 18 goats as total artificial hearts (TAHs) and pumped for 1 to 125 days without anticoagulant or antiplatelet drugs. No thrombus was formed on the valve membrane or around the valve seat. Scanning electron microscopy showed almost no platelet deposition or microfibrin clot formation on the valve membrane, including its central region; the spokes of the valve seat were also free from platelet and microfibrin clots. No calcification was observed during these tests, and plasma free hemoglobin was between 2 and 7 mg/dl. The jellyfish valve revealed good blood compatibility, even without anticoagulant use.

Animals↗
PubMedDate not supplied

A new pulsatile total artificial heart using a single centrifugal pump.

A new pulsatile total artificial heart (TAH) system, combining a single centrifugal pump (CFP) with two three-way valves, was developed. One port of each three-way valve was connected to the inlet and outlet of a CFP, respectively. The other two ports of each valve ware connected to the right and left atrium, pulmonary artery, and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow. A prototype system composed of a Sarns' CFP and solenoid valves was connected to a mock circulatory system resulting in 1) a pulsatile TAH that could be produced with a single CFP, 2) 5 L/min of pulsatile output with a normal flow wave form that can be obtained alternately on the right and left side by switching the solenoid valves, and 3) flow balance between the left and the right that could be controlled easily by the length of switching duration. This new system could be miniaturized and is feasible for a totally implantable TAH.

Blood Flow Velocity↗