Biomedical subjects

I Ninomiya

Publications and source records attributed to I Ninomiya.

At least 55 records · Page 3Linked to original sources

PubMed1997

Effects of acute arterial bleeding on renal sympathetic nerve activity in young and old anesthetized rats.

We compared the change in renal sympathetic nerve activity (RNA) during hemorrhage in young and old rats. Young (10 weeks) and old (80 weeks) male Wistar rats were anesthetized, and RNA together with arterial pressure (AP) and heart rate (HR) were measured under spontaneous respiration. Acute arterial bleeding, 1ml/100g body weight, was carried out to induce hypotension and hypovolemia. With bleeding, mean AP (MAP) decreased from 110 +/- 12 to 23 +/- 11mmHg (mean +/- SEM) and from 93 +/- 15 to 15 +/- 6mmHg in young and old rats, respectively. The difference in the change of MAP between the young and old rats was not significant. With bleeding, mean RNA increased by 46 +/- 21% and 20 +/- 16% in young and old rats, respectively. The increase in mean RNA of the old rats was significantly lower than that of the young rats. We estimated the gain of the baroceptor-renal sympathetic nervous system by using the formula delta RNA/RNA/delta MAP/MAP. The gain was 0.61 +/- 0.34 and 0.23 +/- 0.18 in young and old rats, respectively. The difference in the gain was statistically significant (p < 0.05). We concluded that the gain of baroceptor-sympathetic nerve system in acute arterial hemorrhage is attenuated with aging.

Aging↗

PubMed1996

Identification of cholesta-3,5-dien-7-one by gas chromatography-mass spectrometry in the erythrocyte membrane of alcoholic patients.

Lipids and oxidized lipids were analyzed by gas chromatography-mass spectrometry in the erythrocyte membranes of alcoholic and control subjects. Cholesta-3,5-dien-7-one and cholesta-trienes were detected in alcoholic samples examined, but not in significant amounts in controls. Levels of polyunsaturated fatty acids (arachidonic acid, 20:4; docosahexaenoic acid, 22:6; and docosatetraenoic acid, 22:4) in alcoholic samples declined significantly, whereas cholesta-3,5-dien-7-one levels increased. A high level of total bilirubin was observed in most patients. A possible mechanism of the accumulation of cholesta-3,5-dien-7-one in the erythrocyte membrane of alcoholics is discussed.

Adult↗

PubMed1996

Regional myocardial interstitial norepinephrine kinetics during coronary occlusion and reperfusion.

We investigated myocardial interstitial norepinephrine kinetics in both the ischemic and nonischemic regions during reperfusion after 40 min of coronary occlusion in anesthetized cats. By use of a cardiac dialysis technique, dialysate norepinephrine contents from both regions were monitored as an index of myocardial interstitial norepinephrine levels. For vehicle perfusate (n = 8), the accumulated dialysate norepinephrine level in the postischemic region decreased from 3,010 +/- 923 pg/ml at 30-40 min of occlusion to 957 +/- 178 pg/ml at 0-10 min of reperfusion and returned to near control level at 30-40 min of reperfusion. After 40 min of reperfusion, there were no significant differences in tyramine (100 micrograms/ml, norepinephrine-releasing sympathomimetic amine)-induced norepinephrine release between both regions. For perfusate containing 100 microM desipramine (neural uptake inhibitor, n = 6), at 0-10 min of reperfusion, the dialysate norepinephrine in the postischemic region did not significantly decrease. The dialysate norepinephrine then returned to near preocclusion level at 30-40 min of reperfusion. These data suggest that reperfusion rapidly returns accumulated myocardial norepinephrine to the preischemic level and neuronal norepinephrine uptake greatly contributes to this return in the early phase of reperfusion. Forty minutes of coronary occlusion cause neither norepinephrine exhaustion nor irreversible impairment of norepinephrine uptake function in nerve terminals.

Animals↗

PubMed1996

Inhaled nitric oxide: diameter response patterns in feline small pulmonary arteries and veins.

Using an X-ray television system on the in vivo cat lung, we directly measured internal diameter (ID) changes in the small pulmonary arteries and veins (100-1,100 microns ID) in response to 5, 15, and 40 ppm nitric oxide (NO) inhalations. We also measured to what extent 40 ppm NO inhalation can attenuate large ID constrictions at the different serial segments of the small vessels due to unilobar anoxic (0% O2) exposure. Under normoxic conditions, 5-40 ppm NO inhalations significantly increased the ID of both arteries and veins less than approximately 900 microns dose dependently but caused no significant, or only slight, ID increases in the vessels larger than this, if any at all. The ID increase in the serially connected arteries was nonuniform (4-18, 8-28, and 7-35% with 5, 15, and 40 ppm NO inhalations, respectively), whereas that for the veins was relatively uniform (4-9, 6-17, and 7-18% with 5, 15, and 40 ppm NO, respectively). The maximum ID increase occurred in the 200- to 500- and 200- to 700-microns arteries in response to 5-15 and 40 ppm NO, respectively. Unilobar anoxic exposure significantly decreased the ID of the 100- to 700-microns arteries and veins, but not the ID of the other-sized vessels. The ID decrease in the serially connected arteries was nonuniform (13-29%) but relatively uniform in the veins (8-12%). The maximum ID decrease occurred in the 200- to 300-microns arteries. However, adding 40 ppm NO to the lobe completely eradicated the ID decreases at all segments of the arteries and veins and, instead, caused significant ID increase (11-21%) in the arteries and (10-12%) in the veins. The data indicate that, according to dosage, 5-40 ppm NO inhalations cause selective dilation of approximately 100- to 900-microns pulmonary arteries and veins, particularly the 200- to 700-microns arteries. During anoxic exposure, the vasodilator effect of NO is preserved and can completely reverse the marked pulmonary vasoconstriction.

Administration, Inhalation↗

PubMed1995

Periodicity, amplitude and width of synchronized cardiac sympathetic nerve activity in anaesthetized cats.

Using a recently developed method, we studied periodicity, amplitude and width of synchronized cardiac sympathetic nerve activity (CSNA) at various intervals of periodic baroreceptor input in anaesthetized cats. ECG, aortic pressure and CSNA were recorded when cardiac interval was changed by artificial pacing, or when the aortic nerve was stimulated after baroreceptor denervation. The periodicity of synchronized CSNA showed mainly two modes: one was 8-14 Hz rhythmicity (Tc) and the other was related to cardiac cycle (Tb). The Tc mode was almost constant and independent of cardiac interval or stimulation. The probability of the Tc mode increased as pacing interval increased. The Tb mode reflected the interval of inhibition in CSNA due to pulsatile baroreceptor input. The mode of inhibitory rhythm (Ts) related to the stimulation of the aortic nerve was almost constant and independent of the stimulation interval. The probability of the Ts mode was highest at a 250-ms interval and decreased with increase in stimulus interval. The mean peak height or mean peak width did not changed significantly during pacing the heart at various intervals nor after baroreceptor denervation. The peak height and peak width had a significant linear relationship at any cardiac interval or after baroreceptor denervation, whereas no relationship between the peak-to-peak interval and the peak height or peak width was found. These results indicate that the cardiac-related rhythm is produced by inhibition of transmission of the fundamental rhythm by periodic baroreceptor input. Our results suggest also that the amplitude and periodicity of synchronized CSNA are separately regulated.

Algorithms↗

PubMed1995

E-cadherin and urokinase-type plasminogen activator tissue status in gastric carcinoma.

BACKGROUND: E-cadherin (ECD) is known to be an invasion suppressor gene, and urokinase-type plasminogen activator (uPA) plays a central role in infiltration of solid cancers. METHODS: To elucidate the relationship between expression of these factors and metastasis in patients with gastric cancer, the authors examined immunohistochemically a combination analysis of uPA and E-cadherin expression in 98 primary tumors, and the results were correlated with several parameters related to metastasis. RESULTS: Among 125 tumors, 42 (34%) were evaluated as having E-cadherin expression (E-cadherin-positive), and the other 83 (66%) were defined as having reduced E-cadherin expression (E-cadherin-negative). uPA immunoreactivity was observed in 82 tumors (66%). There were four subtypes of patterns of uPA and E-cadherin expression: 22 uPA-negative/E-cadherin-positive, 17 uPA-negative/E-cadherin-negative, 21 uPA-positive/E-cadherin-positive, and 65 uPA-positive/E-cadherin-negative, uPA overexpression and reduced E-cadherin expression were associated with lymph node metastasis, vessel invasion, serosal involvement, and poor prognosis. In addition, uPA-positive/E-cadherin-negative tumors were associated significantly with large tumors, positive serosal invasion, lymph node involvement, and poor prognosis. Patients with uPA-positive/E-cadherin-negative expression had the poorest prognoses, compared with the three other groups of patients uPA-positive/E-cadherin-negative tumors had a fourfold relative risk of death when compared with uPA-negative/E-cadherin-positive tumors. A Cox proportional hazard model projected lymph node status as the strongest of the prognostic variables followed by DNA ploidy patterns and uPA/E-cadherin tissue status. CONCLUSIONS: These results indicate that immunohistochemical combination analysis of uPA and E-cadherin expression may be a powerful aid in evaluating metastatic potential or the prognosis of patients with gastric cancer.

Adult↗

PubMed1995

Effects of baroreceptor reflex on efferent pulmonary sympathetic nerve activity in anesthetized cat.

We analyzed the baroceptor reflex effect on efferent pulmonary sympathetic nerve activity (PSNA) in anesthetized cats. PSNA was recorded from the central end of the cut nerve bundle, which was isolated from the lobar artery supplying the diaphragmatic lobe. Renal sympathetic nerve activity (RSNA) and aortic blood pressure (AP) were also simultaneously measured. There were grouped discharges synchronous with cardiac cycle and its respiratory modulation in PSNA. In a given cardiac cycle, the discharge patterns differed between the pulmonary and renal nerves. Average sympathetic nerve activity and AP obtained from 100 consecutive cardiac cycles showed that the baroreceptor reflex delay time on the pulmonary nerve (266 ms) was longer than that on the renal nerve (195 ms). The data indicate nonuniformity in the cardiac-related PSNA and RSNA. The grouped PSNA disappeared with hexamethonium bromide, indicating that PSNA originates from postganglionic efferent fibers. To examine the baroreflex response of PSNA, AP was increased by 70 mmHg with phenylephrine and decreased by 70 mmHg with nitroprusside. PSNA changed inversely to the changes in mean aortic pressure (MAP). In the delta MAP-delta PSNA curve, delta PSNA reached the maximum level (74%) and the noise level at -56 +/- 4 and 58 +/- 4 mmHg, respectively. The mean slope of the curve was 1.5 +/- 0.1%/mmHg. RSNA also responded inversely to the MAP change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Changes in efferent pulmonary sympathetic nerve activity during systemic hypoxia in anesthetized cats.

Changes in efferent sympathetic nerve activity to the pulmonary vessels during systemic hypoxia have yet to be elucidated. The purpose of this study was to determine the pulmonary sympathetic nerve activity (PSNA) changes in response to acute systemic hypoxia before and after sinoaortic denervation plus vagotomy in anesthetized cats. The denervation was performed to estimate the central nervous system-mediated peripheral chemoreceptor- and baroreceptor-independent PSNA change. PSNA was recorded from the central end of the cut nerve bundle, which was isolated from the lobar artery supplying the diaphragmatic lobe. Renal sympathetic nerve activity (RSNA) and systemic and pulmonary arterial pressures were also measured simultaneously. The animals were submitted to approximately 3-min periods of graded hypoxia (16, 12, 8, 5, and 3% O2 inhalations). PSNA did not change from normoxia down to an arterial O2 partial pressure (PaO2) of approximately 45 Torr (with 12-21% O2 inhalations). Below this level, PSNA began to increase, and markedly so (approximately 2.5-fold) at a PaO2 of approximately 15 Torr (with 3% O2). The hypoxic PSNA increase was significantly larger than that for RSNA, with a PaO2 of less than approximately 30 Torr (with 3-8% O2). Particularly at a PaO2 of approximately 15 Torr, the magnitude of the PSNA increase was two times greater than that for RSNA. After denervation, the hypoxic PSNA increase was significantly attenuated at a PaO2 of approximately 25 to approximately 45 Torr (with 5-12% O2), but the attenuation was very small; therefore most of the PSNA increase persisted. The hypoxic RSNA increase, in contrast, was mostly abolished after denervation. The data indicate that the neural reflex effect of systemic hypoxia on PSNA is significantly greater than that on RSNA and suggest that the hypoxic PSNA increase is mostly mediated by central mechanisms, whereas that for RSNA is chiefly caused by peripheral chemoreceptors.

Animals↗

PubMed1995

[Inhibition of tumor cell metastasis in chick embryo by beta 1 integrin antisense oligonucleotide].

The antimetastatic effect of integrin beta 1 subunit antisense oligonucleotide on human fibrosarcoma cell (HT-1080) in chick embryo was examined. Phosphorothioate modified antisense oligonucleotide (B1-1) was designed to hybridize specifically to integrin beta 1 subunit mRNA. Pretreatment of HT-1080 cells with B1-1 decreased the metastatic ability in chick embryonic liver and lung, while B1-1 showed no toxicity to HT-1080 nor chick embryo. Western blot analysis showed a reduction of the amount of cell surface integrin beta 1 subunit. B1-1 also inhibited HT-1080 attachment to laminin and fibronectin. These results indicate that the inhibition of tumor cell attachment by antisense oligonucleotide might be a good approach to the prevention of cancer metastasis.

Animals↗

PubMed1995

[Comparison of the pattern of integrin expression between primary tumors and liver metastasis of gastric and colorectal cancers].

To investigate the interrelationship between integrin VLA3 overexpression and liver metastasis, immunohistochemical studies of VLA3 were made in 73 cases of gastric cancer (66 cases without liver metastasis, 7 cases with liver metastasis) and 15 cases of colorectal cancer (3 cases without liver metastasis, 12 cases with liver metastasis). The rate of integrin VLA3 expression in 69 primary gastric and colorectal cancers without liver metastasis was 41%, that was higher than that (0%) in the 19 primary tumors of gastric and colorectal cancers with liver metastasis. In contrast, the positive rate for integrin VLA3 staining in 19 cases involving liver metastasis of gastric and colorectal cancers was 58% (11/19), which was higher than that (0%) in primary tumors. These findings suggest that VLA3 may play an important role in the process of liver metastasis of gastric and colorectal cancers.

Colorectal Neoplasms↗

PubMed1995

[Correlation of DNA ploidy, c-erB-2 protein tissue status, level of PCNA expression and clinical outcome in gastric carcinomas].

One-hundred and sixty-four patients with gastric carcinomas, who underwent gastrectomy during 1979-1985, were studied. The nuclear DNA contents were measured by cytofluorometry, and immunohistochemical study on the expression of c-erbB-2 protein was performed using a monoclonal antibody against the c-erbB-2 oncogene product. Furthermore immunohistochemical detection of proliferating cell nuclear antigen (PCNA) was performed using a monoclonal antibody against the PCNA. The patients with aneuploid tumor had a significantly worse prognosis than those with diploid tumor. The group with positive staining for c-erbB-2 had a significantly worse prognosis than negative one. The higher group of PCNA indices had a worse prognosis. The patients with tumor showing both aneuploid and positive staining for c-erbB-2 tissue status and PCNA indices. But no correlation was formed between c-erbB-2 tissue status, PCNA indices and DNA contents. From these results, it can be concluded that DNA ploidy, c-erbB-2 protein, and PCNA may reflect the malignant potential of gastric carcinoma.

Aneuploidy↗

PubMed1995

Lymph node metastasis and surgical management of gastric cancer invading the esophagus.

In 88 resected patients with esophagus-invading gastric cancer, the factors determining the prognosis of this disease were investigated by multivariate analysis. Neither, age, sex, macroscopic type, thoracotomy, nor histological type proved to be independent prognostic factors. The presence or absence of lymph node metastasis, serosal invasion, tumor size, and the extent of esophageal invasion were found to be significant independent prognostic factors. Among lymph node metastases, involvement of para-aortic lymph nodes was especially important. The prognosis was significantly better in cases in which these nodes were carefully dissected (R4 gastrectomy), than in cases in which selected dissection was performed (R2). However, no patient with mediastinal lymph node metastasis survived for any lengthy period, and thus the mediastinal lymph nodes seemed to be nodes, the dissection of which brought little effect. Postoperative results were very poor in cases in which the extent of the esophageal invasion was 3 cm or more. These patients should be treated with multi-modal therapy such as neoadjuvant chemotherapy.

Adenocarcinoma↗

PubMed1995

Decreased E-cadherin expression correlates with poor survival in patients with gastric cancer.

E-cadherin, Ca(2+)-dependent intracellular adhesion molecule, is known to be an invasion suppressor gene. To elucidate the correlation between E-cadherin expression and invasion or metastasis in gastric cancer, we examined E-cadherin tissue status immunohistochemically. Ninety-eight primary gastric cancer, prepared by AMeX method, were retrospectively analyzed with anti-E-cadherin monoclonal antibody. In normal gastric epithelium, E-cadherin is expressed homogeneously with a typical membranous staining at cell-cell borders. Decreased and heterogeneous expression is found in 70 of 98 tumours. Tumours with decreased E-cadherin expression had a tendency to infiltrate more deeply in stomach wall, and metastasize in lymph nodes or peritoneal surface. More importantly, decreased E-cadherin expression correlates with shorter survival (z = 3.98, P = 0.00086). These results may indicate that E-cadherin tissue status is a powerful prognostic indicator in gastric cancer. The high malignant potential of tumours with decreased E-cadherin expression may be associated with high potential of lymph node metastasis and peritoneal dissemination.

Cadherins↗

PubMed1994

Diameter and flow velocity changes of feline small pulmonary vessels in response to sympathetic nerve stimulation.

Using an X-ray television system, we measured directly changes in the internal diameter (ID), flow velocity, and volume flow of the small pulmonary vessels (100-500 microns ID) in response to electrical sympathetic nerve stimulation (SNS) in anaesthetized cats before and after adrenergic receptor blockade. Flow velocity was obtained by measuring the distance that the leading edge of the contrast medium moved per 0.1 s in the small arteries. Volume flow was obtained from the product of flow velocity and cross-sectional area calculated from the ID of the small arteries. SNS was accomplished with 10- to 15-V square-wave pulses of 2-ms duration at 20-30 Hz for 20-s periods. In response to SNS, arterial ID decreased significantly by 8-13% in the 200- to 500-microns vessels but not in the 100- to 200-microns vessels. In the veins, on the other hand, there was no significant ID decrease in any of the 100- to 500-microns vessels. After alpha-receptor blockade (phentolamine, 2 mg/kg i.v.), there were significant ID increases (4-9%) in the 100- to 500-microns arteries in response to SNS, the maximum increases being in the 100- to 200-microns arteries. After beta-blockade (propranolol, 2 mg/kg i.v.), the ID decrease due to SNS in the 200- to 500-microns arteries was enhanced (24-27%) and, in addition, the 100- to 200-microns arteries exhibited a significant ID decrease (18%). Combined alpha- and beta-blockade completely abolished the ID decrease due to SNS. In the veins, on the other hand, no ID change occurred even after alpha- or beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Surgical results of performing R4 gastrectomy for gastric cancer located in the upper third of the stomach.

Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.

Female↗

PubMed1994

Origin of cardiac-related synchronized cardiac sympathetic nerve activity in anaesthetized cats.

To study the origin of cardiac-related rhythm in cardiac sympathetic nerve activity (CSNA), ECG, aortic pressure and CSNA were recorded when cardiac interval was changed by artificial pacing, or when the aortic nerve was stimulated after baroreceptor denervation in anaesthetized cats. CSNA was averaged by using the R-wave of ECG, or stimulus pulse as a trigger. Delay times from arterial pulse or stimulus pulse to the onset and half amplitude of inhibition and to the maximal inhibition were measured from the averaged data. The delay of inhibition in CSNA was constant and independent of pacing interval. Stimulation of the aortic nerve with single shocks caused an inhibition in averaged CSNA. The delay of inhibition was constant and independent of stimulus frequency. These results indicate that the cardiac-related rhythm in CSNA is produced reflexly by inhibiting the transmission of the fundamental rhythmicity due to periodic baroreceptor input.

Anesthesia↗

PubMed1994

Increase in myocardial interstitial norepinephrine during a short period of coronary occlusion.

The neurally intact in vivo beating hearts of cats were used to examine the influence of a short period of coronary occlusion on regional myocardial norepinephrine levels. Using a cardiac dialysis technique, dialysate norepinephrine levels were measured as an index of myocardial interstitial norepinephrine levels, and the left anterior descending coronary artery was occluded for 10 min. In anesthetized cats, 10 min occlusion increased the dialysate norepinephrine level in the ischemic region but not in the non-ischemic region. To investigate the influence of neuronal norepinephrine uptake on occlusion-induced dialysate norepinephrine response, a neuronal uptake inhibitor (desipramine) was locally administered to both regions with the dialysis perfusate. In the ischemic region, 10 min occlusion significantly increased the dialysate norepinephrine level from the control level in the presence of desipramine. We concluded that 10 min coronary occlusion was associated with an increase in the myocardial interstitial norepinephrine level in the ischemic region. This increase in the early phase of ischemia was not attributed to attenuation of neuronal norepinephrine uptake function.

Animals↗

PubMed1994

In vivo detection of endogenous acetylcholine release in cat ventricles.

To detect and monitor endogenous acetylcholine (ACh) release in the in vivo heart, we applied a dialysis technique to the hearts of anesthetized cats. Dialysis probes were implanted in the left ventricular myocardium and were perfused with Krebs-Henseleit solution containing Eserine (10(-4) M) at 3 microliters/min. Dialysate ACh concentration was measured with high-performance liquid chromatography. In four cats, the response to vagal stimulation was studied. Electrical stimulation of efferent vagal nerves (10 Hz) significantly increased dialysate ACh concentration from 596 +/- 118 (control) to 12,210 +/- 1,661 pM. After stimulation, dialysate ACh concentration significantly decreased to 382 +/- 80 pM below control. The influence of ganglionic blocker was determined in six cats. Control vagal nerve stimulation (10 Hz) increased dialysate ACh concentration from 582 +/- 136 to 9,102 +/- 754 pM. Local perfusion of hexamethonium (10(-4) M) did not affect this nerve stimulation-induced ACh increase (8,611 +/- 1,189 pM), and intravenous administration of hexamethonium (20 mg/kg) prevented this increase (340 +/- 88 pM). We examined the response to vagal nerve stimulation at different frequencies in three cats. Vagal nerve stimulation increased dialysate ACh concentration from a control of 588 +/- 211 to 1,227 +/- 195 pM at 2 Hz, 3,946 +/- 1,059 pM at 5 Hz, and 9,366 +/- 1,873 pM at 10 Hz. Dialysate ACh concentration reflects ACh release from postganglionic vagal nerves innervating the left ventricular myocardium; the dialysis technique permits estimation of relative changes in efferent cardiac vagal nerve activity.

Acetylcholine↗