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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 19 recordsLinked to original sources
PubMed1997

Tetrahydronaphthalene lignan compounds as potent anti-HIV type 1 agents.

Anti-HIV-1 activity of tetrahydronaphthalene (THN) derivatives of lignan compounds was studied. THN derivatives prevented cell death caused by HIV-1 infection in MT-4 cells. They also inhibited giant cell formation by HIV-1 in Sup-T1 cells, and p24 production in HIV-1-infected H9 cells. The 50% effective concentration (ED50) of the most active compound, 1737 [5,6,7-trimethoxy-4-(3,4,5-trimethoxyphenyl)-1,3,3a,4,9,9a-hexahydron aphtho[2,3-c]thiophene], for inhibition of the cytopathic effects of HIV-1 infection ranged from 0.15 to 0.8 microM. The 50% cytotoxic concentration (CC50) of compound 1737 measured by the viability of MT-4 cells was 58 microM, indicating a selective index (CC50/ED50) of 70-400. Substitution of the phenyl ring with other structures markedly decreased cytotoxicity but did not affect the antiviral activity of the compounds. This resulted in compounds with a high selective index. One such compound was 1738 [7-methoxy5,6-methylenedioxy-4-(4-benzyloxy-3-methoxyphenyl)1,3,3a ,4,9,9a-hexahydronaphtho[2,3-c]thiophene], with a selective index higher than 770. The time-of-addition experiment indicated that these compounds acted at or near the reverse transcription step of the HIV-1 life cycle. THN derivatives inhibited HIV-1 reverse transcriptase (RT) in vitro at a concentration of 1 microM. Resistant viruses selected in the presence of THN derivatives showed some degree of cross-resistance to other nonnucleoside RT inhibitors, but not to the nucleoside RT inhibitor, AZT. THN derivatives failed to inhibit replication of pyridinone- and nevirapine-resistant HIV strains. However, compound 1737 inhibited replication of a TIBO-resistant strain more effectively than the wild-type HIV-1. Consistent with this result, compound 1737 also inhibited TIBO-resistant RT more effectively than the wild-type RT in vitro. These results suggested that THN derivatives interact with RT in a manner similar to but slightly different from that of other nonnucleoside HIV-1 RT inhibitors.

Anti-HIV Agents↗
PubMed1997

Elevated concentrations of the small stress protein HSP27 in rat renal tumors.

The expression of two small stress proteins, alpha B crystallin and the 27-kDa heat shock protein (HSP27), was studied quantitatively and immunohistochemically in normal kidney and renal tumors in rats. Levels of alpha B crystallin in renal cell tumors tended to be higher than in normal kidney (P = 0.07), but with a wide range of values, whereas they were significantly lower in mesenchymal tumors (P < 0.0001). In contrast, HSP27 concentrations in both renal cell (mean +/- SD: 1790 +/- 940 ng/mg protein, n = 15) and mesenchymal (1260 +/- 1080 ng/mg protein, n = 10) tumors were significantly higher than the normal kidney value (142 +/- 30 ng/mg protein, n = 10, P < 0.0001). A positive correlation was found between alpha B crystallin and HSP27 levels limited to the renal cell tumor case (Pearson's correlation coefficient, r = 0.68, P < 0.01). Immunohistochemistry revealed the loops of Henle to be positive for alpha B crystallin, whereas HSP27 staining was positive in glomerular and interstitial vascular walls and epithelial cells of proximal and distal tubules. Positive immunostaining for alpha B crystallin was demonstrated in six of nine renal cell tumors (67%) studied and for HSP27 in all of the nine cases (100%).

Animals↗
PubMed1997

A bag carrier for continuous intravenous hyperalimentation.

We designed a new bag-carrier device system for continuous intravenous hyperalimentation. The patient carries it on his shoulder and can both walk up and down stairs and go out. The use of this device is simple and easy, and was found to increase the patient's opportunity to engage in physical activity.

Equipment Design↗
PubMed1997

Hypothalamic neuronal histamine: implications of its homeostatic control of energy metabolism.

In a series of studies on histaminergic functions in the hypothalamus, probes to manipulate activities of histaminergic neuron systems were applied to assess its physiologic and pathophysiologic implications using non-obese normal and Zucker obese rats, an animal model of genetic obesity. Food intake is suppressed by either activation of H1-receptor or inhibition of the H3-receptor in the ventromedial hypothalamus (VMH) or the paraventricular nucleus, each of which is involved in satiety regulation. Histamine neurons in the mesencephalic trigeminal sensory nucleus modulate masticatory functions, particularly eating speed through the mesencephalic trigeminal motor nucleus, and activation of the histamine neurons in the VMH suppress intake volume of feeding at meals. Energy deficiency in the brain, i.e., intraneuronal glucoprivation, activates neuronal histamine in the hypothalamus. Such low energy intake in turn accelerates glycogenolysis in the astrocytes to prevent the brain from energy deficit. Thus, both mastication and low energy intake act as afferent signals for activation of histaminergic nerve systems in the hypothalamus and result in enhancement of satiation. There is a rationale for efficacy of a very-low-calorie conventional Japanese diet as a therapeutic tool for weight reduction. Feeding circadian rhythm is modulated by manipulation of hypothalamic histamine neurons. Hypothalamic histamine neurons are activated by an increase in ambient temperature. Hypothalamic neuronal histamine controls adaptive behavior including a decrease in food intake and ambulation, and an increase in water intake to maintain body temperature to be normally constant. In addition, interleukin-1 beta, an endogenous pyrogen, enhanced turnover of neuronal histamine through prostaglandin E2 in the brain. Taken together, the histamine neuron system in the hypothalamus is essential for maintenance of thermoregulation through the direct and indirect control of adaptive behavior. Behavioral and metabolic abnormalities of obese Zucker rats including hyperphagia, disruption of feeding circadian rhythm, hyperlipidemia, hyperinsulinemia, and disturbance of thermoregulation are essentially derived from a defect in hypothalamic neuronal histamine. Abnormalities produced by depletion of neuronal histamine from the hypothalamus in normal rats mimic those of obese Zuckers. Grafting the lean Zucker fetal hypothalamus into the obese Zucker pups attenuates those abnormalities. These findings indicate that histamine nerve systems in the brain play a crucial role in maintaining homeostatic energy balance.

Adaptation, Physiological↗
PubMed1997

Angiotensin-converting enzyme inhibitor up-regulates cardiac beta-receptors in cultured neonatal rat myocytes.

In patients with congestive heart failure (CHF), beta-receptor up-regulation is regarded as one of the mechanisms leading to improved function and prognosis. To clarify whether beta-receptor up-regulation is involved in the mechanisms underlying the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors, we investigated the actions of ACE inhibitors and an angiotensin II type 1 receptor (AT1) antagonist on beta-receptors of neonatal rat cultured cardiac myocytes. Angiotensin II (A-II) increased the spontaneous beating frequency of the cells, and the effect was completely antagonized by the AT1 antagonist CV-11974. Under control conditions, beta-receptor density (Bmax) and affinity (Kd) were measured by radiobinding assay with the hydrophilic ligand [3H]CGP-12177, and were 103 +/- 11 fmol/mg protein and 3.4 +/- 0.4 nmol/L, respectively. Captopril increased the beta-receptor density of myocytes and augmented the response to isoproterenol. Bmax was increased by 34% after 24 h treatment with 10(-6) mol/L captopril. CV-3480, and ACE inhibitor that contains no sulfhydryl group, but neither A-II nor the AT1 antagonist, also up-regulated beta-receptors. The results suggest that beta-receptor up-regulation contributes at least partly to the beneficial cardiac effects of ACE inhibitors in patients with CHF. ACE inhibitors and AT1 antagonists seem to play different roles in clinical practice.

Angiotensin II↗
PubMed1997

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction].

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.

Brain Diseases↗
PubMed1996

Ornithine decarboxylase activity in rat intestinal mucosa and liver is stimulated by central administration of 2-deoxy-D-glucose but not of 2,5-anhydro-D-mannitol.

It has been shown that 2-deoxy-D-glucose (2-DG) inhibits glucose utilization and elicits feeding through the lateral hypothalamus. In contrast, 2,5-anhydro-D-mannitol (2,5-AM), blocking glycogenolysis and/or gluconeogenesis, elicits feeding through the ventromedial hypothalamus. The aim of the present study was to determine whether ornithine decarboxylase (ODC) activity in the rat small intestine is stimulated by infusion into the third ventricle of 2-DG or of 2,5-AM. Under anesthesia, a cannula was implanted into the third ventricle one week before the experiment. Each rat was infused with 6, 12, and 24 mumol 2-DG or 2,5-AM into the third ventricle without disturbing the behavior. Ingestive behavior was observed for one h after the infusion. ODC activity in the intestinal mucosa and the liver was measured 2 h after the infusion. Additionally, ODC activity was measured in vagotomized rats. Both test solutions elicit feeding at 24 mumol/rat. Infusion of 2-DG into the cerebroventricle significantly increased ODC activity in the duodenal and jejunal mucosa and the liver. In contrast to 2-DG, infusion of 2,5-AM did not increase ODC activity in the intestinal mucosa or liver. Truncal vagotomy attenuated the increase of ODC activity in the intestinal mucosa and liver induced by 2-DG. The present study showed that 2-DG, but not 2,5-AM, increased ODC activity in the peripheral organs, indicating that glucose-metabolism at specific sites of the central nervous system, including the lateral hypothalamus, is important for stimulatory signals to ODC activity. It is also indicated that the stimulatory signals from the central nervous system are mediated, at least in part, via the efferent vagal nerve.

Animals↗
PubMed1996

Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state.

The activated protein C (APC)-resistance test is a simple and reliable method for detecting reduced sensitivity to the anticoagulant action of this protein. We investigated the sensitivity to APC in 180 Japanese controls and in 96 Japanese patients with venous and arterial thrombosis (28 with deep vein thrombosis; 13 with pulmonary thromboembolism; 41 with cerebral infarction; and 14 with coronary artery disease). All of the patient groups showed significantly reduced sensitivity to APC, reflected by the lower normalized APC-sensitivity ratio (n-APC-SR), as compared with healthy control. The APC-sensitivity ratio was negatively correlated with plasma activated factor VII levels. These results suggest that the low n-APC-SR is related to venous or arterial thrombotic disease. The APC resistance may serve as a potential marker for assessing the hypercoagulable state.

Adult↗
PubMed1996

Elevated concentrations of gamma-enolase in renal cell tumors in rats: similarity to renal cell carcinoma in man.

Concentrations of enolase isozymes in normal kidney and renal cell tumors in rats were determined using a highly sensitive enzyme immunoassay, and the isozymes were immunohistochemically localized in tissue sections. Levels of alpha-enolase in renal cell tumors were significantly lower than in normal kidney, whereas those of gamma-enolase were significantly elevated (mean +/- SD: 211 +/- 129 ng/mg protein, n = 15, as compared to 27.1 +/- 2.9 ng/mg protein, n = 7). The proportion of gamma-enolase in the total enolases in the tumor tissues (1.6 +/- 0.5%) was significantly higher than in normal kidney (0.15 +/- 0.05%). Immunohistochemistry revealed epithelial cells of all nephron segments to be positive for the alpha-isozyme, whereas gamma-enolase staining was strongly positive only in the loops of Henle, being faint in the distal tubules and absent in the proximal tubules. Both alpha- and gamma-enolases demonstrated positive immunostaining in all of the seven renal cell tumors studied. These findings indicate that an isozyme switch from alpha- to gamma-enolase occurs during rat kidney carcinogenesis, taking into account the derivation from proximal tubules, consistent with the findings for renal cell carcinomas in man.

Animals↗
PubMed1996

Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study.

The interaction between clearance of phenytoin, valproic acid, phenobarbital and carbamazepine, and changes in body weight was determined in a 19-year-old obese woman with epilepsy (body weight 93 kg, BMI 36.3 kg/m2). The patient, who was given daily oral doses of 100 mg phenobarbital, 350 mg phenytoin, 800 mg valproic acid and 800 mg carbamazepine over 5 months was hospitalized for obesity treatment. The daily dosage of each drug was held constant during treatment of the obesity. Blood samples were taken five times. Weight reduction was 7 kg (7.5%) over 46 days. Estimation of the pharmacokinetic parameters in each drug was performed by Higuchi's Bayesian program, PEDA Pearson's correlation coefficient (r) between clearance and body weight was calculated for each drug. High positive correlations were found between clearance and body weight for phenytoin (r = 0.800) and valproic acid (r = 0.785), but not for phenobarbital (r = -0.227) and carbamazepine (r = 0.152). Clearance of phenytoin and valproic acid may be potentially affected by small changes in body weight.

Adult↗
PubMed1996

Transplantation of lean fetal hypothalamus restores hypothalamic function in Zucker obese rats.

Rats with lesions to the ventromedial hypothalamus (VMH) manifest obesity, hyperphagia, and hyperinsulinemia, and fetal VMH transplantation into the third cerebroventricle of VMH-lesioned rats reduces the development of obesity caused by the lesion. The aim of this study was to determine whether the hyperphagia, hyperlipidemia, and hyperinsulinemia of obsese Zucker rats could be corrected by the transplantation of lean fetal Zucker hypothalamic tissue into the third cerebral ventricle of Zucker obese rats. After the fetal hypothalamic transplant (obese-HY), the rate of weight gain was significantly diminished compared with the unoperated Zucker obese rats and the obese rats that received the transplantation of a similar amount of frontal cortical tissue from the same fetus (obese-FC). Food intake was significantly lower, and plasma triacylglycerol and insulin concentrations were also significantly reduced in the obese-HY rats compared with the obese and obese-FC rats. The weight of the adrenal glands, the plasma adrenocorticotropic hormone concentration, the liver weight, and the liver lipid content in obese-HY were significantly less than those observed in the obese and obese-FC animals. There were no significant differences between the obese and the obese-FC animals or between unoperated Zucker lean rats and lean rats transplanted with lean fetal hypothalamus in all the parameters we determined in this study. Neovascularization and normal cellular morphology of the transplanted fetal hypothalamic tissue suggest that the transplanted neural and glial cells were viable and physiologically functional. In conclusion, this study offers evidence suggesting that the hypothalamic-pituitary-adrenal function is defective in Zucker obese rats, resulting in excessive weight gain, hyperphagia, hyperlipidemia, and hyperinsulinemia. The hypothalamic dysfunction in the Zucker obese rats is corrected by the transplantation of lean fetal hypothalamus.

Adrenal Glands↗
PubMed1996

Factor VII hyperactivity and endothelial cell damage are found in elderly hypertensives only when concomitant with microalbuminuria.

We studied the relationship among albuminuria, factor VII (FVII) hyperactivity, and endothelial cell damage in 6 elderly hypertensive subjects. The plasma levels of activated FVII (FVIIa), FVII coagulant activity, FVII antigen (FVIIag), von Willebrand factor (vWF), and thrombomodulin were measured to assess FVII hyperactivity and endothelial cell damage, and urinary albumin excretion rate (UAE) was calculated using 12-hour nighttime (7 pm to 7 am) urine collection (mean for 2 consecutive nights). We performed 24-hour ambulatory blood pressure monitoring in all 61 hypertensive patients and classified them into a white-coat hypertension group (n=12) and a sustained hypertension group (n=49). For the levels of FVII, vWF, and thrombomodulin, there were no differences between the white-coat hypertension group and normotensive control subjects (n=25). In the sustained hypertensive group, only the microalbuminuric subgroup (UAE, 15 to 300 microgram/min: n=30) showed significant elevation compared with the normotensive group for the level of FVIIa (mean [95% confidence interval]: 4.0 [3.6 to 4.4] versus 3.0 [2.6 to 3.3] ng/mL, P<.001), the FVIIa/FVIIag ratio (an indicator of activation of FVII zymogen to FVIIa) (1.33 [1.19 to 1.50] versus 1.04 [0.92 to 1.19], P<.01), the level of vWF (188 [165 to 214] % versus 144 [129 to 160] %, P<.01), and thrombomodulin (11.7 [10.3 to 13.3] versus 9.3 [8.5 to 10.3] ng/mL, P<.01). In contrast, none of these levels in the normoalbuminuric hypertensive group (UAE <15 microgram/min, n=19) differed from that in the normotensive control group. These results suggest that among elderly hypertensives, only those with microalbuminuria show enhancement of FVII activation and endothelial cell damage, while patients with white-coat hypertension and normoalbuminuric hypertensives do not show these accompanying abnormalities. Thus, increased levels of FVII activity and markers of endothelial cell damage might account for the higher risk of cardiovascular events in essential hypertension with microalbuminuria.

Aged↗
PubMed1996

Assessment of atrioventricular nodal electrophysiological characteristics after radiofrequency catheter ablation of the slow pathway in atrioventricular nodal reentrant tachycardia--3-month follow up.

Radiofrequency catheter ablation of the slow pathway is commonly used to treat atrioventricular (AV) nodal reentrant tachycardia. However, there has been little study of the follow-up assessment of AV nodal physiology. We compared AV nodal electrophysiological characteristics before, immediately after, and again 3 months after successful catheter ablation in 17 patients (mean age 50 +/- 16 years). Sinus cycle length, Wenckebach cycle length, A-H interval at a paced cycle length of 600 ms, effective refractory period and functional refractory period of the fast pathway were significantly changed immediately after catheter ablation, but had recovered 3 months after the procedure. There were no significant differences between the electrophysiological parameters immediately after catheter ablation and those 3 months after the procedure under the intravenous injection of atropine sulfate. We conclude that, due to changes in autonomic nervous tone, AV nodal electrophysiological characteristics are influenced immediately after catheter ablation of the slow pathway in AV nodal reentrant tachycardia.

Adult↗
PubMed1996

Effect of radiofrequency catheter ablation of the slow pathway on the atrioventricular node.

Although the effective refractory period (ERP) of the fast pathway is reported to be shortened after radiofrequency catheter ablation of the slow pathway in atrioventricular nodal reentrant tachycardia (AVNRT), whether the atrioventricular (AV) nodal physiology maintains the same condition over the long term is controversial. To assess the AV nodal physiology after catheter ablation of the slow pathway in AVNRT, the A-H interval and ERP of the fast pathway were measured before, immediately after and 3 months after catheter ablation in 12 patients. We compared these factors in 12 patients with left concealed accessory bypass tract to clarify the mechanism of the electrophysiological change in the AV node. Both the A-H interval and ERP of the fast pathway were significantly shortened from 111 +/- 18 to 96 +/- 17 ms and 365 +/- 68 to 261 +/- 52 ms immediately after catheter ablation (p < 0.01), and recovered to 128 +/- 44 and 372 +/- 80 ms 3 months after catheter ablation. There were no significant differences in the A-H interval of the fast pathway between the period immediately after and 3 months after catheter ablation following administration of atropine sulfate (99 +/- 52). There were no significant differences in the ERP of the fast pathway between the period immediately after and 3 months after catheter ablation following administration of atropine sulfate (248 +/- 33 ms). On the contrary, there were no significant changes in the A-H interval and ERP of the AV node at these two times in patients with Wolff-Parkinson-White (WPW) syndrome. The change in characteristics of AV nodal physiology was observed only immediately after catheter ablation in AVNRT, but not in WPW syndrome. The change in electrophysiology immediately after catheter ablation was similar to that following administration of atropine sulfate in AVNRT 3 months after catheter ablation. These findings suggest that catheter ablation does not cause a permanent change in AV nodal physiology and that the location of the ablated site plays an important role in AV nodal physiology.

Adult↗
PubMed1996

Rapid coronary vasodilation by nitroglycerin tapes.

We analyzed the acute, direct effects of nitroglycerin (NTG) tape on the coronary arteries and hemodynamics in 38 patients who underwent coronary angiography. The diameters of the 3 main coronary arteries were compared among the angiograms obtained at baseline, 15 minutes following transdermal administration of 10 mg (8 patients) or 25 mg (30 patients) of NTG (Millisrol tape), and after intracoronary injection of 2.5 mg isosorbide dinitrate (ISDN). Only the left main trunk and proximal portion of the left anterior descending artery dilated after 10 mg of transdermal NTG administration (p < 0.05). However, every measured coronary segment (segments 1-8, 11, and 13) dilated (p < 0.05) after 25 mg of NTG. Systemic blood pressure decreased slightly but significantly from 150 +/- 22 to 147 +/- 21 mmHg during the study, with no change in heart rate. Left ventricular end-diastolic pressure decreased significantly from 16 +/- 7 to 14 +/- 5 mmHg. We conclude that 25 mg of transdermal NTG tape dilates coronary arteries and is applicable for acute coronary syndrome, with few complications.

Administration, Cutaneous↗