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T Shishido

Publications and source records attributed to T Shishido.

At least 91 records · Page 5Linked to original sources
PubMed1998

The brain is a possible target for an angiotensin-converting enzyme inhibitor in the treatment of chronic heart failure.

BACKGROUND: Although many lines of evidence have shown beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on patients with chronic heart failure (CHF) after myocardial infarction (MI), the target of ACE inhibitors still remains unclear. The objectives of the present study were to evaluate the dipsogenic response to centrally administered angiotensin and to examine the effect of central administration of an ACE inhibitor on cardiac remodeling in rats with CHF after large MI. METHODS AND RESULTS: The drinking responses to intracerebroventricular (i.c.v.) injections of saline and angiotensin I (100 ng) were measured in 22 male Sprague-Dawley rats with or without CHF at 2-5 weeks after the ligation of the left coronary artery. The dipsogenic responses to i.c.v. angiotensin I were significantly larger in rats with CHF and large MI (infarct size > 30%) than in sham-operated rats. Pretreatment with losartan abolished the significant difference between the two groups. Left ventricular (LV) weights of 32 surviving rats with CHF were measured after the 3-week subcutaneous infusions of vehicle (s.c.-VEH) and captopril (1 mg x kg(-1) x h(-1), s.c.-CAP) or the 3-week i.c.v. infusions of vehicle (i.c.v.-VEH) and captopril (50 microg x kg(-1) x h(-1), i.c.v.-CAP). The LV weights normalized by body weights of s.c.-CAP rats were significantly smaller than those of s.c.-VEH rats (1.73 +/- 0.04 vs 2.08 +/- 0.09 g x kg(-1); P < .01); those of i.c.v.-CAP rats were also significantly smaller than those of i.c.v.-VEH rats (1.84 +/- 0.08 vs 2.1 +/- 0.10 g x kg(-1); P < .05). CONCLUSIONS: These results suggest that the brain is a possible target for ACE inhibitors in the treatment of CHF after MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Inhibition of liver metastasis of human pancreatic carcinoma by angiogenesis inhibitor TNP-470 in combination with cisplatin.

The anti-tumor and anti-metastatic effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and cisplatin (CDDP), an anti-neoplastic agent, were investigated using our established liver-metastasizing pancreatic carcinoma line, HPC-3H4. HPC-3H4 was injected into the spleens of nude mice. Mice were randomly divided into 5 groups; a control group given saline solution, a group receiving 45 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP, and a group receiving 0.25 mg/kg CDDP. In the control group, liver metastasis developed in 14 of 15 mice (93.3%). Liver metastasis developed in 9 of 11 mice (81.8%) receiving 0.25 mg/kg CDDP. It developed in 11 of 15 mice (73.3%) receiving 45 mg/kg TNP-470, in 17 of 18 mice (94.4%) receiving 90 mg/kg TNP-470, and in 4 of 10 mice (40%) receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP. TNP-470 in combination with CDDP displayed a significant inhibitory effect on liver metastasis compared to the control. Although TNP-470 alone and CDDP alone had no effect on the tumor growth in vivo, 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP had a significant effect. In vitro examinations demonstrated that the growth of HPC-3H4 cells was only mildly inhibited by TNP-470, but the production of vascular endothelial growth factor (VEGF) by HPC-3H4 was clearly inhibited by TNP-470. The inhibitory effect on the production of VEGF was not strong with CDDP treatment. These results indicate that the angiogenesis inhibitor TNP-470 in combination with low-dose CDDP has inhibitory activity against liver metastasis of human pancreatic carcinoma.

Animals↗
PubMed1998

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve.

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01-5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was > 0.8 in the frequency range of 0.01-4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.

Afferent Pathways↗
PubMed1998

A new method to measure regional myocardial time-varying elastance using minute vibration.

We developed a new technique to evaluate regional myocardial elastance using minute vibration. In 13 isolated cross-circulated canine hearts, we applied small sinusoidal vibrations of displacement to the left ventricular surface at various frequencies (50-100 Hz). Using the measured displacement and force between the vibrator head and myocardium, we derived myocardial elastance on the basis of the equation of motion for a given moment of the cardiac cycle. Simultaneous solution of the equations of motion at different frequencies yielded a unique value of elastance. Time-varying myocardial elastance increased from diastole (0.028 +/- 0.211 x 10(6) dyn/cm) to systole (0.833 +/- 0.391 x 10(6) dyn/cm). The end-systolic elastance (ees) linearly correlated with end-systolic left ventricular elastance (r = 0.717, P < 0.001) and also with the end-systolic Young's modulus (r = 0.874, P < 0.0001). We also measured ees at both ischemic and nonischemic regions during coronary occlusion. Young's modulus, estimated by normalizing ees by the wall thickness and by the estimated mass, did not change significantly at the nonischemic regions, whereas it decreased significantly from 2.303 +/- 0.556 to 1.173 +/- 0.370 x 10(6) dyn/cm2 at the ischemic region after coronary occlusion (P < 0.005). We conclude that this technique is useful for the quantitative assessment of regional myocardial elastance.

Animals↗
PubMed1998

ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.

We developed a miniaturized conductance catheter for in situ rat left ventricular (LV) volumetry. After the validation study of the conductance volumetry in 11 rats, we characterized the end-systolic pressure-volume relationship (ESPVR) in 24 sinoaortic-denervated, vagotomized and urethan-anesthetized rats. Stroke volume (SV) measured with the conductance catheter correlated closely with that measured by electromagnetic flowmetry (r > 0.95). No significant difference was found between the in situ LV end-diastolic volumes measured by conductance volumetry and postmortem morphometry; a linear regression analysis indicated that the correlation coefficient was 0.934, that the slope was not significantly different from 1, and that the intercept was not significantly different from 0. During cardiac sympathotonic conditions, the ESPVR was curvilinear. The estimated slope of ESPVR (end-systolic elastance, Ees) by quadratic curve fitting at end-systolic pressure of 100 mmHg was 2,647 +/- 846 mmHg/ml. Bilateral cervical and stellate ganglionectomy depressed contractility and made the ESPVR linear; a quadratic equation did not improve the fit. Ees was 946 +/- 55 mmHg/ml with the volume-axis (V0) intercept of 0.076 +/- 0.007 ml. Administration of propranolol (1 mg/kg) further reduced Ees (573 +/- 61 mmHg/ml, P < 0.001) and increased V0 slightly (0.091 +/- 0.011 ml). We conclude that the conductance catheter method is useful for the assessment of the ESPVR of the in situ rat left ventricle and that the ESPVR displays contractility-dependent curvilinearity.

Animals↗
PubMed1998

Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.

We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 +/- 1.4 vs. 0.7 +/- 0.6 beats . min-1 . Hz-1, P < 0.01). In contrast, the Ees responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 +/- 0.34 vs. 0.76 +/- 0. 42 mmHg . ml-1 . Hz-1). Fixed-rate pacing significantly decreased the Ees response to right sympathetic stimulation (0.53 +/- 0.43 mmHg . ml-1 . Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 +/- 0.32 mmHg . ml-1 . Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of Ees to dynamic sympathetic stimulation.

Animals↗
PubMed1998

Accumulation of cAMP augments dynamic vagal control of heart rate.

Recent investigations in our laboratory using a Gaussian white noise perturbation technique have shown that simultaneous sympathetic stimulation augmented the gain of the transfer function from vagal stimulation frequency to heart rate response. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined in anesthetized rabbits how three pharmacological interventions known to cause intracellular accumulation of cAMP affected the transfer function. Isoproterenol (0.3 microg . kg-1 . min-1 iv) increased the dynamic gain of transfer function from 7.12 +/- 0.67 to 12.4 +/- 1.21 beats . min-1 . Hz-1 (P < 0.05) without changing the corner frequency or the lag time. Similar augmentations were observed when forskolin (5 microg . kg-1 . min-1 iv) or theophylline (20 mg/kg iv) was administered under conditions of beta-adrenergic blockade. These results suggest that the accumulation of cAMP at postjunctional effector sites contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

Animals↗
PubMed1998

Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate.

Recent investigations in our laboratory using a Gaussian white noise technique showed that the transfer function representing the dynamic properties of transduction from vagus nerve activity to heart rate had characteristics of a first-order low-pass filter. However, the physiological determinants of those characteristics remain to be elucidated. In this study, we stimulated the vagus nerve according to a Gaussian white noise pattern to estimate the transfer function from vagal stimulation to the heart rate response in anesthetized rabbits and examined how changes in acetylcholine kinetics affected the transfer function. We found that although increases in the mean frequency of vagal stimulation from 5 to 10 Hz did not change the characteristics of the transfer function, administration of neostigmine (30 microg . kg-1 . h-1 iv), a cholinesterase inhibitor, increased the dynamic gain from 8.19 +/- 3.66 to 11.7 +/- 4.88 beats . min-1 . Hz-1 (P < 0.05), decreased the corner frequency from 0.12 +/- 0.05 to 0.04 +/- 0.01 Hz (P < 0.01), and increased the lag time from 0.17 +/- 0.12 to 0.27 +/- 0.08 s (P < 0.05). These results suggest that the rate of acetylcholine degradation at the neuroeffector junction, rather than the amount of available acetylcholine, plays a key role in determining the dynamic properties of transduction from vagus nerve activity to heart rate.

Acetylcholine↗
PubMed1998

[Successful management for chemorefractory testicular cancer with brain and lung metastases. A case report].

This is a report of successful management for a far advanced, chemorefractory testicular cancer patient. A 29-year-old male was referred to our hospital for the treatment of progressive lung metastases with elevated hCG level, which had recurred after complete remission following 3 courses of BEP chemotherapy and progressed after transient partial regression following 2 courses of intensified EP chemotherapy. In addition, a 3 cm in diameter, solitary brain metastasis was detected on CT. First, we performed wedge resection of bilateral pulmonary lower lobe for chemorefractory pulmonary metastases. Histological examination revealed viable embryonal carcinoma identical to the primary one. Thereafter, whole brain irradiation in combination with VIP chemotherapy (etoposide 100 mg/m2, cisplatin 20 mg/m2 and ifosfamide 1200 mg/m2 daily for 5 consecutive days) was carried out to treat brain metastasis. By 2 cycles of VIP therapy and irradiation (36 Gy), partial tumor regression and normalization of hCG level were achieved, leading to salvage surgery of the brain metastasis which histologically proved to be necrosis. Following an additional cycle of VIP therapy, the patient has been free of recurrence 24 months after completion of the treatment.

Adult↗
PubMed1998

[High-dose biweekly CHOP chemotherapy with granulocyte colony-stimulating factor support for patients with aggressive non-Hodgkin lymphoma].

A pilot study of high-dose biweekly cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with granulocyte colony-stimulating factor support was carried out at 11 centers. Twenty-five patients with aggressive non-Hodgkin lymphoma under the age of 65 years old were registered. Lowest values of leukocytes and neutrophils scored grade 3 and 4 levels of Eastern Co-operative Oncology Group Toxicity Criteria in over 50% of the courses. Very rapid recovery of leukocytes and neutrophils was observed, and the duration of leukocytes under 1,000/microliter was less than 3 days in 72.2% of the courses. Leukocyte counts exceeded 2,000/microliter within 3 days in 69.1% of the courses. In most patients the hemoglobin and platelet count remained at grade 1 or 2 levels. Fever was seen in 15 out of 110 courses. In two-thirds of the 15 courses, fever disappeared within 3 days. Thus, administration of the CHOP protocol at biweekly intervals was feasible in 76.5% of the courses. Of 22 evaluable patients, there were 11 complete (CR) and 9 partial (PR) responses with an overall response rate of 90.9%. Among 13 high risk patients excluding 9 low and low-intermediate groups by International Prognostic Index, 7 CRs (53.8%) and 5 PRs (38.5%) were observed. This protocol is promising for aggressive chemotherapy of non-Hodgkin lymphoma.

Adult↗
PubMed1997

Acute methamphetamine administration increases tyrosine hydroxylase mRNA levels in the rat locus coeruleus.

Tyrosine hydroxylase (TH) mRNA levels in the rat substantia nigra (SN), ventral tegmental area (VTA) and locus coeruleus (LC) were measured by in situ hybridization histochemistry 1, 4, 6 and 24 h after a single injection of methamphetamine (MAP, 4 mg/kg, i.p.) or an equivalent volume of saline. TH mRNA levels in LC were transiently increased (130% of control saline group, P < 0.05) at 1 h after MAP injection, and returned to basal levels within 4 h. In contrast, acute MAP administration did not significantly affect TH mRNA levels in SN and VTA. These findings are the first to demonstrate TH mRNA expression in the different responses of catecholaminergic neurons to acute MAP administration.

Animals↗
PubMed1997

Synthesis and evaluation of novel rhodacyanine dyes that exhibit antitumor activity.

Rhodacyanine dyes and several analogous delocalized lipophilic cations (DLCs) were synthesized and evaluated as novel antitumor agents. Rhodacyanine dye consists of two heteroaromatic rings such as thiazoles at both termini of the conjugate systems and 4-oxothiazolidine (rhodanine) in the middle of it. Compounds with such a unique double-conjugate structure were found to inhibit the growth of several tumor cell lines, such as colon carcinoma CX-1, and to exhibit relatively low toxicity against normal kidney cell line CV-1 (e.g., IC50(CX-1) = 50 nM, IC50(CV-1) = 17.3 microM; selectivity index = 346 for compound 5). These compounds were also found to be efficacious in the tumor-bearing nude mice model (e.g., against human melanoma LOX; T/C (%) = 168 for compound 5). Structural modifications on rhodacyanine, including deletion of a heteroaromatic ring involved in the merocyanine conjugate system and replacement of rhodanine with a structurally related moiety such as 4-oxoimidazolidine or 4-oxo-1,3-dithiolane, resulted in a loss of the selectivity and/or the activity. Our current structure-activity studies imply that the double-conjugate system with a rhodanine moiety is essential for the selective activity of rhodacyanine dyes, and we find this class of compounds as unique antitumor agents candidates.

Animals↗
PubMed1997

Effects of repeated methamphetamine administration on dopamine D1 receptor, D2 receptor and adenylate cyclase type V mRNA levels in the rat striatum.

Dopamine D1 receptor (D1R), D2 receptor (D2R) and adenylate cyclase type V (AC5) mRNAs in the rat dorsal striatum (CPu) and ventral striatum (Acb) were measured by in situ hybridization histochemistry (ISHH) after repeated methamphetamine (MAP) administration. MAP (4 mg/kg) or an equivalent volume of saline was administered intraperitoneally once daily for 10 days to male Wistar rats. After 7 days of abstinence, behavioral experiment with MAP-challenge revealed that a significant behavioral sensitization was achieved in MAP-treated animals. The animals were sacrificed 7 days after the last injection and brain sections were analyzed by ISHH using 35S-labeled antisense oligonucleotide probes. We found that D1R mRNA levels in the CPu were significantly increased (124% of control, P < 0.01). In contrast, repeated MAP-treatment did not significantly affect the expression of D1R mRNA in Acb or mRNA for D2R or AC5. It was concluded that MAP-induced behavioral sensitization is accompanied by increased D1R mRNA levels in CPu.

Adenylyl Cyclases↗
PubMed1997

Close correlation between increased sialyl-Lewisx expression and metastasis in human gastric carcinoma.

Expression of sialyl-Lewisx (sLex) antigen was studied immunohistochemically in 110 resected human gastric carcinomas using an anti-sLex monoclonal antibody. Lymph node, liver, and peritoneal metastases were clearly more prevalent in tumors expressing high levels of sLex than in those with no or low-level sLex expression. No correlation was found between sLex expression and histologic grade or histologic type of the Lauren classification. Among the tumors with lymph node metastasis, 44% expressed high levels of sLex in both the primary tumor and involved lymph nodes, and 14% of the metastatic lesions demonstrated increased sLex expression. The 5-year survival rate of the patients undergoing complete (R0) gastric resections was 60% in the sLex high-expression group, which was significantly lower than that of the sLex low-expression group (81%) and of the no-expression group (87%) (p < 0.05). These results suggest that high-level sLex expression is related to both an increased risk of metastasis and poor prognosis in gastric cancer patients.

Adult↗
PubMed1997

Changes in cellular composition induced by neocarzinostatin pretreatment in Meth A-bearing mice and the responsible antitumor effector cells.

We previously reported that tumor eradication was induced by a single injection of neocarzinostatin (NCS) between 1 day and 4 weeks before Meth A transplantation in Balb/c mice via augmenting host-mediated antitumor activity. In order to elucidate the mechanism of this tumor eradication, the cellular components of spleen and regional lymph nodes, tumor infiltrating cells and antitumor effector cells were investigated. Pretreatment with NCS on day -3 caused an increase in the percentage of T-cell subsets, a decrease in the percentage of B-cells, Mac-1+ cells and asialo GM1+ cells and a decrease of the total cell number in the spleen. These changes were observed before but not during the period of tumor regression and were also observed in non-transplanted mice with NCS treatment. In the lymph nodes, while B-cells increased on Meth A transplantation, this was suppressed by NCS pretreatment. Although histological examination of tumor nodules showed the presence of only a few host immune cells in the tumor tissue, the area of necrosis was already extensive on day 7 and expanded thereafter. In vivo depletion of whole T-cells, T-cell subsets or asialo GM1+ cells by antibody treatment suggests that the antitumor effector cells in tumor eradication were Thy1,2+/Lyt2+, and at least some of which also express asialo GM1 antigen and that L3T4+ T-cells were also involved in tumor eradication.

Animals↗
PubMed1997

Changes of behavior and monoamine metabolites in the rat brain after repeated methamphetamine administration: effects of duration of repeated administration.

1. The authors studied the mechanism of the reverse-tolerance phenomenon caused by long-term administration of central stimulant drugs. Methamphetamine(MAP) was chronically administered to rats, and the reverse-tolerance phenomenon was studied in terms of behavioral changes and changes in monoamine metabolites, the latter being examined by in vivo microdialysis of the extracellular compartment of the corpus-striatum. The authors also studied [3H]SCH23390 and [3H]spiperone binding to striatal membranes after chronic MAP administration. 2. MAP(4 mg/kg) or saline was administered intraperitoneally once daily to male rats. In Groups 1 and 2, 10 and 30 injections of MAP were given, respectively. In Groups 3 and 4, animals received 10 and 30 injections of saline as controls. One week after the final injection, all rats were challenged with 4 mg/kg MAP. 3. Groups 1 and 2 displayed more intense stereotypy than Groups 3 and 4, indicating that behavioral sensitization had been achieved in the former. Dopamine(DA) levels increased rapidly in response to MAP challenge in all groups, with the increases in Groups 1 and 2 being more marked than that in Groups 3 and 4. Group 1 showed greater persistence and a higher rate of DA increase than Group 2. 4. The number of D1 and D2 dopamine receptors did not change after the repeated MAP administration. 5. The rate of increase in DA release induced by MAP was dependent on the duration of repeated administration, and there was no correlation between the intensity of stereotypy and the rate of increase in DA release induced by MAP. These findings suggest that enhancement in DA release is unlikely to be the sole cause of behavioral sensitization.

Animals↗
PubMed1997

Extension of hemorrhage after reperfusion of occluded coronary artery: contrast echocardiographic assessment in dogs.

OBJECTIVES: The aim of this study was to elucidate the progression of intramural hemorrhage complicated by reperfusion with the use of myocardial contrast echocardiography. BACKGROUND: Although hemorrhagic infarction is known to occur in ischemia followed by reperfusion, its onset and sequence have not been well characterized. METHODS: In 20 anesthetized dogs, 3-h occlusion of the left circumflex-coronary artery was followed by reperfusion. The area at risk during coronary occlusion was approximately 25%. Myocardial contrast echocardiogram was examined, and the time-intensity curves for both ischemic and nonischemic areas were obtained at baseline, at 3 min after reperfusion and then at 15-min intervals until 90 min after reperfusion. The wall thickness of both areas was also measured. RESULTS: Gross hemorrhage in the reperfused areas was observed in five dogs (Group H) but not in seven dogs (Group NH). All wall segments were opacified at 3 min after reperfusion in both groups. However, the contrast defect spread significantly with time after reperfusion in Group H but not in Group NH (18.7 +/- 3.4% and 3.3 +/- 1.8%, respectively, at 90 min after reperfusion p < 0.005). The wall of the risk area at 90 min after reperfusion had thickened to 1.3 times baseline thickness in Group H but was unchanged in Group NH. The other eight dogs were excluded from study because of fatal arrhythmias or the existence of collateral circulation during coronary occlusion. CONCLUSIONS: Both progression of the contrast defect area on myocardial contrast echocardiography and a gradual thickening of the wall with reperfusion are characteristic of hemorrhagic infarction.

Animals↗