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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 955 records · Page 53Linked to original sources

[Left ventricular diastolic reserve during acute pressure loading in hypertrophic cardiomyopathy and dilated cardiomyopathy].

To evaluate left ventricular diastolic reserve during acute pressure loading, changes in mitral flow velocity patterns before and after the elevation of blood pressure were analyzed by pulsed Doppler echocardiography in 11 cases of hypertrophic cardiomyopathy (HCM), nine cases of dilated cardiomyopathy (DCM), and 11 control subjects. Systolic blood pressure was elevated 25% above basal values by methoxamine infusion (0.01 mg/kg/min). Before and after methoxamine, left ventricular dimension and mitral flow velocity pattern were obtained by M-mode and pulsed Doppler echocardiography, respectively. The peak velocity in the rapid filling and atrial contraction phases and time-velocity integrals were measured from the flow pattern. After methoxamine, left ventricular diastolic dimension was significantly increased in all groups, from 43.8 +/- 4.7 mm to 47.4 +/- 4.9 mm in the control subjects, from 43.7 +/- 6.3 mm to 47.2 +/- 6.0 mm in HCM, and from 57.9 +/- 6.4 mm to 60.6 +/- 5.9 mm in DCM. Left ventricular systolic dimension was significantly increased from 48.6 +/- 8.4 mm to 52.8 +/- 8.3 mm in DCM, but not in the control subjects or HCM. The peak velocity in the rapid filling phase was significantly increased from 60 +/- 16 cm/sec to 69 +/- 14 cm/sec in the control subjects and tended to be increased from 44 +/- 13 cm/sec to 52 +/- 12 cm/sec in HCM. The extent of this increase tended to be less in HCM. However, the peak velocity in the rapid filling phase tended to decrease in DCM. There were no consistent trends of changes in the peak velocity in the atrial contraction phase in any groups. The mitral velocity integral increased from 502 Hz-sec to 621 Hz-sec in the controls and from 525 Hz-sec to 613 Hz-sec in HCM, but it did not increase in DCM. These findings suggest that there is impaired diastolic reserve during acute pressure loading in HCM and DCM and that the diastolic disturbance might be reflected in the early diastolic phase, rather than in the late diastolic phase.

Adult↗

Pharmacokinetics of an active cadralazine metabolite in plasma and blood vessels of spontaneously hypertensive rats.

The plasma and blood vessel (aorta and mesenteric artery) levels of (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-hydrazinopyridazine (ISF-2405), an active metabolite of cadralazine, were determined and compared with the changes in blood pressure in spontaneously hypertensive rats after single oral administration of cadralazine. The mean plasma level of ISF-2405 reached a maximum at 0.5 h after oral administration of 3 mg/kg of cadralazine, followed by a rapid elimination with a half-life of 1.0 h, whereas the mean aorta level of ISF-2405 reached a maximum at 4 h after dosing, followed by a slow elimination with a half-life of 6.5 h. The mean mesenteric artery levels of ISF-2405 were almost the same as the mean aorta levels over the time investigated. Both patterns of aorta and mesenteric artery levels of ISF-2405 were in good agreement with those of the hypotensive effects. These findings substantiate the assumption that the slow onset and long duration of the pharmacological effect of cadralazine is closely related to the distribution pattern of the active metabolite ISF-2405 in blood vessels, a target tissue of antihypertensive vasodilator drugs.

Animals↗

[Barbiturate therapy in 16 cases with intracranial lesion with special reference to the indication and limitation].

The effects and indications of barbiturate therapy for brain protection, and prevention and reduction of the intracranial hypertension were investigated using an ultrashort acting barbiturate, thiamylal, in sixteen cases with intracranial lesions. Final outcome of the treatment revealed 8 good recoveries which were actively administered thiamylal during operation or immediately after. On the other hand, four cases, whose intracranial pressures (ICPS) of over 40 mmHg could not be controlled suffered brain death. Barbiturate therapy was not effective for brain protection of primary damaged lesions. It is concluded that barbiturate therapy may provide a satisfactory reduction of the intracranial hypertension in cases during the early postoperative stage or of under 40 mmHg initial ICP.

Adolescent↗

Enzymatic hydrolysis of haloperidol decanoate and its inhibition by proteins.

When [14C]haloperidol decanoate, a long-acting neuroleptic and an ester of haloperidol and decanoic acid, was incubated in human whole blood and plasma and in rat plasma and homogenates of rat brain, lung, liver, kidney, pancreas and muscle, no hydrolysis of the ester was seen. Although the decanoate was hydrolyzed by partially purified carboxylesterase, addition of rat plasma or liver homogenate to the enzymic reaction mixture resulted in marked inhibition of hydrolysis, whereas addition of the defatted residues of plasma or liver produced only partial inhibition. The enzymic hydrolysis was inhibited also by beta-lipoprotein and albumin, depending on their concentrations. The assumption that interaction between haloperidol decanoate and protein resulted in inhibition of the hydrolytic reaction mediated by the enzyme was validated by kinetic models and experimental data. The kinetics were apparently competitive. Based on the kinetic analysis, the interaction between the decanoate and albumin or beta-lipoprotein was investigated by measuring their equilibrium constants and extent of protein binding. Haloperidol decanoate appeared to interact with several proteins; this was exemplified by other measures of protein binding, an increasing effect of proteins on the solubility, and the partition ratio of the ester. The interaction between haloperidol decanoate and proteins caused marked stabilization of this ester against enzymatic hydrolysis and, thereby, influenced its metabolism.

Animals↗

A possible mechanism of increased sodium influx in red cells with abnormal membrane lipid levels induced by phospholipase A2.

Membrane transport--sodium (Na+) influx and calcium (Ca2+) uptake--was examined in human mature red cells treated with phospholipase A2 (PLase A2) from snake venom. PLase A2-induced conversion of phosphatidyl choline (PC) to lysophosphatidyl choline (L-PC) was associated with a marked increase in Na+ influx and Ca2+ uptake. After L-PC was removed from the cell membrane of the PLase A2-treated red cells in the presence of albumin, an additional increase in Ca2+ transport was observed. These results indicate that membrane lipid abnormalities, such as increased L-PC and/or a loss of total lipids, appear to induce increased membrane transport.

Adenosine Triphosphate↗

The cytological features and DNA content of cervical adenocarcinoma.

The relationship among cytological features, DNA content, and degree of histological differentiation of cervical adenocarcinoma was investigated in an attempt to discover a more accurate means of screening for this cancer. In highly differentiated adenocarcinoma (so-called adenoma malignum), the nuclei were only somewhat more irregular in size and shape than those of normal columnar epithelial cells. The cells were arranged in slightly multilayered clusters. The cells of well-differentiated adenocarcinoma were usually columnar in shape, and they exfoliated side by side in clusters. In moderately differentiated adenocarcinoma, solitary cells with markedly atypical nuclei were combined with multilayered cell clusters. The cells from poorly differentiated adenocarcinoma were roundish, occurred as solitary cells or irregularly overlapping cell clusters, and showed markedly atypical nuclei. As the degree of histological differentiation decreased, as determined by measurement of the DNA content of the cells, the DNA distribution covered a wider range in terms of ploidy, and the number of cells exceeding tetraploid DNA content increased.

Adenocarcinoma↗

Prophylactic treatment for superficial bladder cancer following transurethral resection.

A total of 130 primary cases with superficial bladder cancer were entered in the prospective randomized group study. The prophylactic treatments compared consisted in intravesical instillation of adriamycin (20 mg/-40 ml or 30 mg/30 ml), mitomycin C (20 mg/40 ml) or thio-TEPA (30 mg/30 ml), and noninstillation treatments with etretinate or tegafur; control patients were also studied. All agents were administered for 2 years. Recurrences were significantly suppressed in the instillation groups compared with control and non-instillation groups. Significant suppression of recurrence was observed in stage 1 or grade 2 disease treated with prophylactic instillation administered over the first 24 months of a 48-month observation period. These results may indicate the clinical usefulness of prophylactic instillation, but the long-term effect of intravesical instillation is still uncertain. A long-term follow-up study is therefore necessary.

Administration, Intravesical↗

Effects of hypoglycaemia on early embryogenesis in rat embryo organ culture.

As congenital malformations may be caused by perturbations of glycolytic flux on early embryogenesis [16], effects of hypoglycaemia were investigated by using rat embryo organ culture. Nine and one-half day old rat embryos were grown in vitro for 48 h (day 9 1/2 to 11 1/2) in the presence of hypoglycaemic serum for different hours during the culture period. Hypoglycaemic serum was obtained from rats given insulin intraperitoneally. On exposure to hypoglycaemic serum during the first 24 h of culture (day 9 1/2 to 10 1/2), embryos showed marked growth retardation and had increased frequencies of neural lesions (42.7% versus 0%, p less than 0.01), in contrast to hypoglycaemic exposure during the second 24 h of culture (day 10 1/2 to 11 1/2), where only minor growth retardation and low frequencies of neural lesions (2.4% versus 0%, NS) were seen. Even exposure to hypoglycaemic serum for a relatively short period (8 h) during the first 24 h of culture resulted in neural lesions at the frequency of 9.3-13.3%. The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the principal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.

Animals↗

Sympathetic control of blood flow to AVAs and capillaries in nasal and facial tissues supplied by the internal maxillary artery in dogs.

Total blood flow and perfusion pressure (PP) of the internal maxillary artery (IMA) were recorded bilaterally during electrical stimulation (8 V, 2ms) of the right cervical sympathetic nerve at frequencies (f) of 0.3, 0.5, 1.0 and 3.0 Hz in anesthetized, paralyzed and artificially ventilated dogs. Distribution of IMA-FLOW to precapillaries (CAP-FLOW) and arteriovenous anastomoses (AVA-FLOW) was determined by the tracer microspheres technique. During electrical stimulation (ES) IMA-FLOW was affected only unilaterally and decreased in a hyperbola-like fashion with the increase of f, while contralateral IMA-FLOW remained unchanged. Systemic blood pressure as well as PP of both IMA remained unchanged while heart rate was only increased during ES at maximal f. The reduction of IMA-FLOW was mainly due to marked vasoconstrictor responses of the AVAs, which were already attained at low f while significant vasoconstrictor responses of precapillaries occurred at higher f and were less pronounced. The early response of AVAs to increasing sympathetic activation enables IMA-FLOW to be adjusted in a physiological range of sympathetic activities, before CAP-FLOW is substantially reduced. The predominance of AVA-FLOW in blood flow control of the IMA was also supported by the conformity in their hyperbolic relationship with maxillary resistance at rest and during enhanced levels of sympathetic vasoconstrictor activity.

Animals↗

Color analysis method for estimating the oxygen saturation of hemoglobin using an image-input and processing system.

A color analysis method which enables both qualitative and quantitative analyses of an object's color was developed. The method uses a color image-input and processing system composed of a 3-tube video camera and a digital image analyzer, which quantizes a color image into values of red, green, and blue brightness, then processes these values. We introduced a spectrophotometric principle by the Beer-Lambert law, and were able to establish a color model to analyze an object's color. In the coordinate space based on our color model, the hue of the object's color is represented by the direction from the origin, and the density by the distance from the origin. This new method was used to analyze the colors of hemoglobin solutions at various oxygen saturations and concentrations. The results agreed with the known conditions, indicating the validity of the model and its usefulness for quantitative as well as qualitative analyses of color.

Algorithms↗

Individual differences in psychophysiological responses after alcohol ingestion.

We have conducted a study on the individual differences in psychophysiological responses to alcohol. The subjects were 12 flushers and 12 non-flushers. In the flushers, significant increases in the blood acetaldehyde (AcH) level, skin temperature and pulse rate were found. In the non-flushers, on the contrary, no significant increase was observed. There was no difference between the flushers and the non-flushers concerning the change in the blood ethanol (EtOH) level nor the change of P1 and P2 latencies in photopalpebral reflex (PPR). Also, no difference was found in the change of the state anxiety level. From these results, we concluded that there exists an obvious discrepancy between the central inhibitory response (elicited by EtOH) and the autonomic response (elicited by AcH) of the human subjects to a small amount of alcohol.

Acetaldehyde↗

Threshold dissociation of thermoregulatory effector responses in febrile rabbits.

When the core temperature stabilizes at a hyperthermic level after iv injection of lipopolysaccharide (LPS), the threshold core temperature for cutaneous vasoconstriction (Thcv) is significantly increased in hot and neutral environments, while the threshold core temperature for shivering (Thsh) is not significantly altered in hot or cold environments but is significantly reduced at thermoneutrality. This type of dissociated threshold alterations of thermoregulatory effector responses seems to be typical for the febrile response of rabbits to LPS. Because the same threshold dissociation can be demonstrated after icv injection of LPS, the systemic and the central effects of LPS in the generation of fever seem to be mediated by identical mechanisms. Prostaglandins of the E series (PGE), one of the mediators considered as important in fever generation, cause parallel increases in Thcv and Thsh when injected icv. This indicates that the mode of action of PGE on the central targets producing hyperthermia differs from that of the ensemble of mediators involved in the generation of LPS fever in rabbits. In rabbits pretreated with aspirin, the threshold dissociation after iv LPS injection still occurs. This indicates that factors other than PGE play an important role in the generation of the threshold dissociation of thermoregulatory effector responses, which is typical for LPS fever. These data indicate also that the states of activity of the thermoregulatory effectors involved in the febrile responses can be altered individually and that the activities of these effectors during LPS fever are quite different from their activities in the control state.

Animals↗

Determination of ISF-2405, an active metabolite of cadralazine, in plasma and tissues by radioimmunoassay.

A radioimmunoassay has been developed which makes possible sensitive and specific determination of an active metabolite of cadralazine, (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-hydrazinopyridazine (ISF-2405), in plasma and tissues. On account of its lability in a sample solution, ISF-2405 in biological samples was selectively derivatized to a stable form, (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-(3,5-dimethyl-1-pyrazolyl) pyridazine (ISF-3349), by treatment with acetylacetone. The concentration of ISF-2405 was determined by the assay of the resultant ISF-3349. Antiserum against ISF-3349 was elicited in guinea pigs immunized with the ISF-3349 derivative coupled with bovine serum albumin. The obtained antiserum was highly specific for ISF-3349, and did not cross-react with either cadralazine or its metabolites. [Pyrazole-4-3H]labeled ISF-3349 with a specific activity of 13.9 Ci/mmol was used as the radioligand. Assays of ISF-2405 in plasma and tissues were possible over the concentration range from 0.4 to 6.4 ng/ml with 1 ml of plasma, and from 2 to 64 ng/g with 100 mg of tissue. Plasma and blood vessel levels of ISF-2405 in rats after single oral administration of cadralazine have also been determined by the present method.

Animals↗