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Biomedical subjects

T Hiramoto

Publications and source records attributed to T Hiramoto.

At least 19 recordsLinked to original sources
PubMed1992

Abnormalities of pulmonary function in patients with non-insulin-dependent diabetes mellitus.

To examine the possible association between the vascular complications of diabetes and changes in pulmonary function, we performed pulmonary function tests including assessment of the diffusing capacity (%DLco) in 80 patients with non-insulin-dependent diabetes mellitus (45 males and 35 females) without overt lung or heart disease. The mean age of the subjects was 57.9 years and the mean duration of diabetes was 10.8 years. The %DLco decreased significantly as the duration of diabetes increased (r = -0.38, p less than 0.01), and the same relationship was also observed in non-smoking subjects (N = 37). The reduction in %DLco was greater in patients with diabetic microangiopathy (especially nephropathy) and in those treated with insulin. Other pulmonary function tests (%VC, FEV1.0, PaO2 and PaCO2) showed no relationship to the duration of diabetes, the degree of microangiopathy or the type of treatment. These results suggest that diabetic microangiopathy may play an important role in the decrease of %DLco.

Aged↗
PubMed1991

Influence of reduced presynaptic myocardial norepinephrine stores on left ventricular contractility.

Many investigators have reported that myocardial norepinephrine content is decreased in congestive heart failure. However there have been no studies of how decrease in myocardial norepinephrine might influence myocardial contraction. To clarify whether decreased myocardial norepinephrine per se affects myocardial contraction, we observed the change in left ventricular contractility during 30 min of left stellate ganglion stimulation in control and acutely reserpinized dogs. We obtained left ventricular max dp/dt and left ventricular end-systolic pressure-segment length relationships as indicators of left ventricular contractility. Both parameters decreased after left stellate ganglion stimulation in reserpinized dogs (left ventricular max dp/dt: 2064 +/- 200 to 1608 +/- 168 mmHg/s, left ventricular end-systolic pressure-segment length slope 117 +/- 22 to 79 +/- 14 mmHg/mm, n = 8, P less than 0.05), while they did not change in controls. In reserpinized dogs, left ventricular norepinephrine content decreased to one-third that of controls before the stimulation, and further decreased after stimulation. These data indicate that lowered myocardial norepinephrine itself may be responsible for the negative effect on left ventricular contractility in congestive heart failure.

Animals↗
PubMed1991

Responses of atrium and ventricle to sustained sympathetic nerve stimulation.

To determine whether chronotropic and atrial inotropic responses to sympathetic nerve stimulation are maintained longer than ventricular inotropic response, the present study was performed with control and acute reserpinized dogs. We stimulated the right stellate ganglion of both groups supramaximally for 60 min and compared right atrial responses (chronotropism and inotropism) with left ventricular (LV) dP/dtmax. In the control group, heart rate (HR) immediately increased and was only slightly attenuated with 60 min of stimulation, and right atrial (RA) inotropic response was less attenuated than was LV response (7% in HR, 33% in RA dP/dtmax, 50% in LV dP/dtmax, P less than 0.01, from the peak value of each response). RA and LV norepinephrine (NE) content was decreased by the stimulation but remained higher than the LV control value. In the reserpinized group, NE content in the RA was low before the stimulation and was further decreased by the stimulation. In this group, HR response was attenuated (27% in HR, P less than 0.01) as was LV dP/dtmax, and the difference in contractile responsiveness between atrium and ventricle disappeared (58% in RA dP/dtmax vs. 61% in LV dP/dtmax, NS). The results indicate that the chronotropic response was only slightly attenuated and that the atrial contractile response was attenuated less than the ventricular response, with sustained sympathetic nerve stimulation in the normal heart. This can be ascribed to the much higher NE content in the RA than that in the LV.

Animals↗
PubMed1991

Myocardial alpha 1-adrenoceptors mediate positive inotropic effect and changes in phosphatidylinositol metabolism. Species differences in receptor distribution and the intracellular coupling process in mammalian ventricular myocardium.

Species-dependent variations of myocardial alpha 1-adrenoceptor-mediated positive inotropic effects of epinephrine were assessed in relation to characteristics of alpha 1-receptor bindings and acceleration of phosphatidylinositol metabolism in the isolated rat, rabbit, and dog ventricular myocardium. Epinephrine in the presence of the beta-adrenoceptor antagonist bupranolol (10(-6) M) elicited a positive inotropic effect through activation of alpha 1-adrenoceptors in rat and rabbit, whereas in dog ventricular myocardium, bupranolol abolished the positive inotropic effect of epinephrine. [3H]Prazosin bound to membrane fractions derived from rat, rabbit, and dog ventricular muscle with high affinities in a saturable and reversible manner. In dog, Bmax and Kd values of alpha 1-adrenoceptor binding sites were identical to those in rabbit ventricular muscle. The Bmax value of alpha 1-adrenoceptors in rat ventricle was the highest, amounting to two to four times those in rabbit and dog. Epinephrine displacement curves for the specific binding of [3H]prazosin in the membrane fraction of these species showed high and low affinity sites with slope factors significantly less than unity, which were shifted to single low affinity sites with slope factors close to unity by addition of 5'-guanylylimidodiphosphate. Accumulation of [3H]inositol 1-phosphate [( 3H]IP1) in ventricular slices prelabeled with [3H]myo-inositol was increased by epinephrine in a time- and concentration-dependent manner in rat ventricular slices. [3H]IP1 accumulation likewise was facilitated by alpha 1-adrenoceptor stimulation in rabbit ventricular slices, whereas the extent of [3H]IP1 accumulation was much less than that in rat. In dog ventricular slices, [3H]IP1 was not accumulated by epinephrine. In rabbit papillary muscle, the time course of increase in contractile force induced by alpha-adrenoceptors coincided with the prolongation of the action potential duration with a similar time course, which is in strong contrast to previous findings in rat that the contractile response was dissociated from the electrophysiological response to alpha-adrenoceptor stimulation. The present results indicate that a wide range of variation of alpha 1-adrenoceptor-mediated regulation of myocardial contractility may be ascribed to different contributions of facilitatory as well as inhibitory regulatory processes that lead to intracellular Ca2+ mobilization subsequent to myocardial alpha 1-adrenoceptor activation among mammalian species.

Action Potentials↗
PubMed1990

The preferential inhibition of alpha 1- over beta-adrenoceptor-mediated positive inotropic effect by organic calcium antagonists in the rabbit papillary muscle.

Experiments were carried out to elucidate the mechanism that the positive inotropic effect mediated by alpha 1-adrenoceptors is more susceptible to organic calcium antagonists than the beta-adrenoceptor-mediated effect. Verapamil and diltiazem displaced the specific binding of [3H]prazosin to the membrane fraction derived from the rabbit ventricular myocardium, verapamil being about 70 times more potent than diltiazem. Nifedipine did not displace the binding. While these compounds suppressed the positive inotropic effect mediated via alpha 1-adrenoceptors in a concentration-dependent manner, there was no correlation between the potency of the compounds to displace the [3H]prazosin binding and to inhibit the alpha-mediated positive inotropic effect. The relative potency of three calcium antagonists to decrease the basal force of contraction and the alpha 1-mediated effect (of the same extent as compared to basal force of contraction) was consistent to each other. The positive inotropic effect mediated by beta-adrenoceptors was inhibited much less, and was enhanced by low concentrations of organic calcium antagonists. The differential action of calcium antagonists on the alpha- and beta-mediated positive inotropic effect was mimicked by lowering the extracellular calcium concentration to 1/2, 1/4 and 1/8 of that in normal Krebs-Henseleit solution (2.5 mmol/l). These results indicate that the alpha 1-adrenoceptor blocking activity does not play an essential role for the preferential inhibition of alpha-mediated positive inotropic effect by organic calcium antagonists. Difference in the subcellular mechanism involved in mobilization of intracellular Ca2+ subsequent to alpha 1- and beta-adrenoceptor activation may be responsible for the differential inhibitory action of calcium antagonists in the rabbit heart.

Animals↗
PubMed1989

Preponderance of beta- over alpha-adrenoceptors in mediating the positive inotropic effect of phenylephrine in the ferret ventricular myocardium.

[3H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (Kd = 0.25 nmol/l and Bmax = 27 fmol/mg protein in the right ventricle). [3H]CGP-12177, a beta-adrenoceptor ligand, bound to the membrane fraction with a Kd value of 0.29 nmol/l and a Bmax of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37 degrees C, phenylephrine elicited a concentration-dependent positive inotropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 mumol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 mumol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both alpha- and beta-adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, beta-adrenoceptors predominate over alpha-adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of beta-adrenoceptors is not especially high when compared with other species.

Adrenergic beta-Antagonists↗
PubMed1989

Repair of 254 nm ultraviolet-induced (6-4) photoproducts: monoclonal antibody recognition and differential defects in xeroderma pigmentosum complementation groups A, D, and variant.

Repair kinetics of ultraviolet (UV) light-induced (6-4) photoproducts in xeroderma pigmentosum complementation group A, D, and variant cells were studied by the enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody raised against (6-4) photoproducts, together with unscheduled DNA synthesis (UDS) and loss of T4 endonuclease V-susceptible sites (ESS). Group AXP35KO cells completely failed to repair both ESS (cyclobutane pyrimidine dimers) and antibody-recognizing (6-4) photoproducts until tested 24 h after irradiation, and had 2% early-time UDS. Group DXP43KO cells showed about 10% removal of both (6-4) photoproducts and ESS in 24 h, despite showing a residually higher level of 40% early-time and cumulative UDS. Thus, the results substantiated the extreme UV hypersensitivity of XP group A and D cells. However, XP52KO variant cells exhibited the normal level of UDS and ESS loss, but a slightly reduced repair of antibody-recognizing (6-4) photoproducts at 6 and 12 h after irradiation, which may account for a small UV hypersensitivity of the XP variant cells.

Antibodies, Monoclonal↗
PubMed1989

Clinical and photobiological characteristics of xeroderma pigmentosum complementation group F: a review of cases from Japan.

A 61-year-old female patient with xeroderma pigmentosum (XP), registered as XP46KO, was assigned to complementation group F by the cell fusion-complementation method. The XP46KO fibroblasts in culture exhibited a defective DNA repair capacity of 10-15% unscheduled DNA synthesis and a 3-fold sensitivity to the lethal effect of 254 nm ultraviolet light compared with normal cells. The patient had mild clinical symptoms consisting of numerous pigmented freckles and a small number of seborrheic keratosis-like papules. She had no skin cancers in the sun-exposed areas of the skin and so far no neurological abnormalities. A review of 11 Japanese group F patients revealed very mild skin symptoms with no ocular or neuro-psychiatric abnormalities. Single skin cancers occurred in only 3 of the 11 patients with an average age of 52 years for their first skin malignancy.

DNA↗
PubMed1989

Pulmonary lymphangiomyomatosis in childhood? Marked smooth muscle cell proliferation of the lung in a preadolescent girl with repeated pneumothorax and progressive dyspnea.

A 13-year-old girl with repeated spontaneous pneumothorax and progressive dyspnea is described. The biopsy specimen of the lung showed marked proliferation of smooth muscle cells in the thickened bullous wall and alveolar septa, which was similar to the findings of the pulmonary lymphangiomyomatosis. Pulmonary lymphangiomyomatosis is one of the diseases which should be considered when children have progressive dyspnea, chylous effusions and repeated spontaneous pneumothorax.

Adolescent↗
PubMed1988

Further characterization of the myocardial alpha-adrenoceptors mediating positive inotropic effects in the rabbit myocardium.

[3H]Prazosin bound with high affinity to the membrane fraction derived from the rabbit ventricular myocardium. Oxymetazoline displaced [3H]prazosin from its binding site, did not elicit a positive inotropic effect but antagonized the positive inotropic effect of phenylephrine mediated by alpha-adrenoceptors in the presence of a beta-antagonist. Naphazoline was more potent in displacing [3H]prazosin and behaved as a weak partial agonist. YM-12617 (5-[2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide HCl), a potent selective alpha 1-antagonist, displaced [3H]prazosin and antagonized the alpha-mediated positive inotropic effect with equal potency. Thus, a good correlation was found between the potency of alpha-antagonists to displace [3H]prazosin and their ability to antagonize the alpha-mediated positive inotropic effect. On the other hand, there was no significant correlation between the Ki and the pD2 value of the alpha-agonists (norepinephrine, epinephrine, phenylephrine and naphazoline), indicating that there is a non-linear relationship between agonist binding to myocardial alpha 1-adrenoceptors and subsequent functional changes. Myocardial alpha 1-adrenoceptors showed some pharmacological characteristics which appear to be different from those in smooth muscle tissues.

Adrenergic alpha-Agonists↗
PubMed1988

Phorbol ester does not mimic, but antagonizes the alpha-adrenoceptor-mediated positive inotropic effect in the rabbit papillary muscle.

The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) was used to examine the hypothesis that phosphoinositide turnover is involved in the regulation of myocardial contractility mediated by stimulation of alpha-adrenoceptors in the mammalian cardiac muscle. Exposure of the isolated rabbit papillary muscle electrically driven at a rate of 1 Hz at a temperature of 37 degrees C to TPA in concentrations of 10-1000 nmol/l for 30 min did not affect the basal force of contraction. The concentration-response curve for the positive inotropic effect of (-)-phenylephrine mediated by stimulation of alpha-adrenoceptors in the presence of (+/-)-bupranolol (100 nmol/l) was shifted to the right and downward by TPA in concentrations of 30-1000 nmol/l, while the effect of (-)-phenylephrine mediated by stimulation of beta-adrenoceptors in the presence of prazosin (100 nmol/l) was not decreased, but slightly enhanced by exposure of the muscle to relatively low concentrations of TPA (10-100 nmol/l). Incubation of the membrane fraction isolated from the rabbit ventricular muscle with TPA in vitro under the same condition as employed in the physiological experiments decreased the specific binding of [3H]prazosin but not that of [3H]CGP-12177, while the non-tumor promoting phorbol ester, alpha PDD, was ineffective. These results indicate that activation of protein kinase C by TPA does not mimic the positive inotropic effect of catecholamines mediated by activation of myocardial alpha-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Almitrine enhances in low dose the reactivity of pulmonary vessels to hypoxia.

Almitrine bismesylate (Alm) has been shown to increase arterial oxygen tension in patients with chronic obstructive pulmonary disease. This effect is though to be attributable to the enhancement of hypoxic pulmonary vasoconstriction (HPV). We evaluated the effect of various doses of Alm on HPV in terms of blood flow diversion associated with anoxic challenge to the left lower lobe (LLL) in dogs with the LLL and the rest of the lung separately ventilated. The stimulus-response curve shifted to the right with increasing rate of Alm infusion, suggesting that Alm enhances the reactivity of the pulmonary vessels to hypoxia. Low doses of Alm enhanced HPV, while higher doses attenuated it. This suggests that the degree of vasoconstriction in hypoxic and non-hypoxic regions depends on the dose of Alm. The same effects of Alm were also observed in peripheral chemoreceptor denervated dogs. It is supposed that the vasoconstriction induced by Alm may be attributable to a direct effect on pulmonary vessels rather than to a nervous reflex effect.

Almitrine↗
PubMed1988

The effect of sustained stellate ganglion stimulation on left ventricular contractility in the dog.

Although a progressive reduction in left ventricular contractility during sustained left stellate ganglion stimulation has been well documented, there have been no reports on the contractile state after nerve stimulation. Left ventricular contractility after cessation of 60 min of electrical (10 V. 10 Hz. 1 msec) left stellate ganglion stimulation has been assessed in open chest dogs. Before and 15 min after stimulation, left ventricular contractility was evaluated by the end-systolic pressure-segment length relationship using ultrasonic crystals during a stepwise aortic constriction to increase left ventricular afterload. Restimulation of the left stellate ganglion was also performed 15 min after cessation of the first stimulation. After sustained left stellate ganglion stimulation, the end-systolic points shifted to the right from the control and the slope of multiple pressure-segment length coordinates significantly decreased (102.5 +/- 16.1 to 76.5 +/- 10.2 mmHg/mm, mean +/- S.E., p less than 0.05, n = 5), indicating a depression of left ventricular contractility. Increased left ventricular dP/dt max and norepinephrine level in the coronary sinus gradually returned to near base line during 60 min of stimulation. These reduced responses lasted for at least 15 min after cessation of stimulation. The myocardial norepinephrine content was reduced to 0.59 +/- 0.08 (mean +/- S.E.) ng/mg wet tissue from 0.90 +/- 0.15 of the control level (p less than 0.05). These data suggested that left ventricular contractility decreased after sustained cardiac sympathetic nerve stimulation, probably due to norepinephrine reduction in the myocardium.

Animals↗
PubMed1988

No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D.

A 31-year-old female patient with xeroderma pigmentosum (XP) XP43KO was assigned to complementation group D by the cell-fusion complementation methods. Cultured XP43KO cells from our patient had the defective DNA repair phenotype showing a residual level of ultraviolet (UV)-induced unscheduled DNA synthesis (45% of normal) and an eightfold higher sensitivity to 254-nm UV killing, compared with normal cells. The phototest on the patient revealed the delayed maximum reaction to UV-B-induced erythema and lower minimal erythema doses at 290- and 300-nm monochromatic wavelengths. However, the XP43KO patient showed no apparent neurologic abnormalities and rather mild or moderate skin lesions at the age of 31 years, although DNA repair deficiency in XP43KO cells from our patient fell into the range of group D cells.

Adult↗
PubMed1987

[A case of malignant histiocytosis with paraplegia].

A 66-year-old man was admitted for shortness of breath and showed fever, abdominal fullness and paraplegia. Monocytosis amounting to 25% and an elevation of serum LDH (4,281 mIu), were remarkable in the laboratory findings. He died of pulmonary insufficiency about a month after admission. On autopsy hepatomegaly (1950 g), splenomegaly (780 g), but no lymphadenopathy and small infarction in the thoracic spinal cord causing paraplegia was noted. Histopathologically, the invasion of the tumor cells into the liver, spleen, lymph nodes, bone marrow and other organs was observed. Malignant histiocytosis was diagnosed by histologic and immunohistochemical studies (lysozyme positive, S-100 protein negative).

Aged↗