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Biomedical subjects

I Ninomiya

Publications and source records attributed to I Ninomiya.

At least 109 records · Page 6Linked to original sources

Immunocytochemical staining of proliferating cells in endoscopically biopsied tissues of gastric carcinomas with monoclonal antibody Ki-67.

The growth fractions in endoscopically biopsied materials from 121 patients with gastric carcinomas were determined by immunohistochemical staining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings and clinical outcome. The Ki-67 labeling rates ranged from 4.6 to 52% (mean: 22%). A significant correlation was found between Ki-67 labeling rates of biopsied materials and those of resected specimens. The tumors showing Ki-67 labeling rates of greater than 22% are more likely to have lymph node metastasis, lymphatic invasion of serosal invasion than those with the rates below 22%. In addition, Ki-67 labeling rates were closely associated with prognosis. Tumors with high Ki-67 labeling rates (greater than 22%) were related to poor prognosis, whereas those with low Ki-67 labeling rates were associated with favorable prognosis. The immunohistochemical staining of proliferating cells in endoscopically biopsied specimens of gastric carcinomas using the Ki-67 monoclonal antibody may be useful in assessing prognosis in carcinoma of the stomach.

Antibodies, Monoclonal↗

Constrictor response of small pulmonary arteries to acute pulmonary hypertension during left atrial pressure elevation.

Acute elevations in left atrial pressure (LAP) were induced by altering the volume of air within a balloon inserted into the left atrium; the changes in internal diameter (ID) of small muscular pulmonary arteries (100-600 microns ID) in response to the associated rises of pulmonary arterial pressure (PAP) were measured using an X-ray TV system on the in vivo cat lung. When LAP was elevated to 14 +/- 1, 24 +/- 1, and 30 +/- 1 mmHg, PAP was increased to 21 +/- 1, 30 +/- 1, and 37 +/- 1 mmHg, respectively. With PAP ranging from 16 (control value) to 21 mmHg the ID did not dilate significantly. With PAP of 30-37 mmHg significant ID dilation occurred. The magnitude of the ID dilation (16%) with PAP of 37 mmHg, however, was significantly smaller than that (20%) with PAP of 30 mmHg despite the greater pressure rise. When the elevated PAP of 30-37 mmHg was quickly returned to the control level by rapid balloon deflation, the ID constricted significantly below the control level. The magnitude of the ID constriction was proportional to the degree of the preceding PAP rise and was maximal in the arteries of 200-400 microns ID. A papaverine hydrochloride injection combined with the balloon deflation completely abolished the ID constriction. A phentolamine injection, on the other hand, significantly attenuated the constriction with approximately half of the constriction persisting. The results indicate that an increase in vascular smooth muscle tone occurred in the small muscular pulmonary arteries, particularly those of 200-400 microns ID, in response to the acute rise of PAP above 30 mmHg during the LAP elevation. In addition, the data suggest the partial participation of catecholamines in the active contraction of vascular smooth muscle. The arterial contraction may serve to protect the pulmonary capillaries from an excessive hydrostatic pressure and pulmonary edema.

Angiography↗

[In vitro chemosensitivity test using collagen gel matrix for human gastric carcinomas].

We evaluated the usefulness of in vitro human tumor culture system using a specialized collagen gel matrix derived from pigskin as a chemosensitivity test for human gastric cancer including scirrhous type. Seven xenograft tumors derived from human gastric cancers were examined with this system and compared with the data obtained by the nude mouse chemosensitivity assay. Xenograft tumors exhibited an in vivo like three-dimensional growth on the collagen gel matrix. There were very close associations between the results obtained by this assay and those obtained from the same drug by the nude mouse assay. Moreover, this system seemed to be useful for prediction of drug sensitivity for scirrhous type gastric cancers. This in vitro assay system has an advantage for chemosensitivity test, because of its convenience, rapidity, and in vivo like three-dimensional tumor growth.

Adenocarcinoma, Scirrhous↗

[Chemosensitivity test for gastric cancer by in vitro MTT assay].

In vitro MTT assay was applied for examining chemosensitivity with 104 samples; 56 primary tumors, 31 lymph node, 9 liver, and 8 peritoneal metastases, obtained from 87 patients with advanced gastric carcinoma. The rate of effectiveness of various anticancer drugs were as follows; etoposide, 87.7%; cisplatin, 55.1%; mitomycin C, 51.5%; pirarubicin, 50.0%; aclarubicin, 48.8%; carboquone, 31.8%; doxorubicin, 20.3%; and 5-fluorouracil, 12.9%. Etoposide was found to be most effective against gastric carcinoma in this test. Concerning with the metastatic lesions, liver metastases were resistant to all tested drugs. On the other hand, peritoneal metastases were sensitive to etoposide, mitomycin C, and pirarubicin. The results indicate heterogeneity of the chemosensitivity between primary and metastatic lesions, and it was supposed that etoposide might be useful against human gastric cancer.

Antineoplastic Agents↗

[In vitro chemosensitivity test using collagen gel matrix for human gastric carcinomas].

The usefulness of an in vitro human tumor culture system using a specialized collagen gel matrix derived from pig skin was retrospectively evaluated as a chemosensitivity test for human gastric carcinomas. Seven xenograft tumors derived from human gastric cancers were examined by this system (CGM assay) and compared with the data obtained by a nude mice assay (NM assay) and a succinic dehydrogenase inhibition test (SDI test). Xenograft tumors had three-dimensional growth on the collagen gel matrix like that in vivo. There was increasing cell kill with rising cytotoxic drug concentration. When drug sensitivity was evaluated as effective based on an inhibition rate of 40% or more in the CGM assay, drug sensitivity as measured by the CGM assay corresponded with that measured by the NM assay for all xenograft tumors but not the SDI test. This system could be applied for chemosensitivity test of scirrhous gastric carcinomas. It was suggested that the CGM assay may be more like an in vivo like chemosensitivity test and clinically useful testing for the patients with gastric cancer, including scirrhous one.

Animals↗

Growth fractions in gastric carcinomas determined with monoclonal antibody Ki-67.

The growth fractions of 101 gastric carcinomas were determined in situ by immunostaining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings, bromodeoxyuridine (BrdU) labeling index, and DNA ploidy pattern. DNA ploidy patterns were determined by flow cytometric analysis. The Ki-67 labeling rates are rated from 4.6% to 82% (mean, 22%). A significant correlation was found between Ki-67 labeling rates and BrdU labeling indices. Sixty-seven percent of tumors with lymph node metastases showed Ki-67 labeling rates of less than 22%, whereas 33% of tumors without lymph node metastases showed Ki-67 labeling rates of less than 22%. There was a significant correlation between these two groups. Tumors with vessel invasion more often have higher Ki-67 labeling rates than those without vessel invasion. By the DNA ploidy classification, the mean Ki-67 labeling rates of aneuploid tumors was significantly higher than that of diploid tumors. This method yielded similar results to those obtained by BrdU labeling and flow cytometric study. The measurement of Ki-67 labeling rates may be useful to decide the therapeutic modalities.

Antibodies, Monoclonal↗

Mechanism of cardiac-related synchronized cardiac sympathetic nerve activity in awake cats.

To examine the mechanism of cardiac-related sympathetic discharge, the periodicity of synchronized cardiac sympathetic nerve activity (CSNA) was measured in awake cats before and after baroceptor denervation using an interval histogram. We found two major periodicities, i.e., Tc = 48-164 ms (20-6 cycles/s) and Tb = 164-512 ms (6-2 cycles/s). In the baroceptor-intact state, the modes of Tc (C) and Tb (B) were 96 ms (10 cycles/s) and 368 ms (2.7 cycles/s), respectively, whereas the cardiac interval (CI) was 366 ms (2.7 cycles/s). Probability of B mode was larger than that of C mode. During tachycardia by atropine, B mode decreased to 304 ms in proportion to CI of 308 ms, whereas C mode remained the same. Probability of B and C modes decreased reflexly by hypertension. Under baroceptor denervation, C mode remained unchanged but its probability increased significantly. A 2-6 cycles/s Tb rhythm could be found, but its probability decreased significantly. Tb periodicity consists of 2Tc, 3Tc, and 4Tc. These results suggest that C mode may reflect a fundamental periodicity of central origin and that B mode reflects a periodicity of cardiac-related synchronized CSNA, which is produced in a probabilistic manner by reflex inhibition of fundamental rhythm due to periodic baroceptor input.

Animals↗

Anesthetic effects on tonic and reflex renal sympathetic nerve activity in awake cats.

Renal sympathetic nerve activity (RNA), arterial blood pressure (AP), and heart rate (HR) were simultaneously measured before and after administration of pentobarbital sodium (PB), chloralose (CHL), or urethan (URE) in conscious cats. We examined the time courses and magnitudes of the changes in RNA, AP, and HR over a period of 5 h under anesthesia with spontaneous or artificial respiration. In both respiratory conditions, PB initially decreased and then increased RNA, AP, and HR; CHL sustainedly increased RNA but had almost no effect on AP and HR. Under artificial respiration, URE transiently decreased RNA but had no effect on AP and HR. To examine the baroreflex response of RNA, AP was increased to 150 mmHg by norepinephrine and decreased to 65 mmHg by nitroprusside. RNA responded inversely to the alterations of AP in both awake and anesthetized states. Compared with the awake state, the inverse AP-RNA relationship curve initially shifted downward and then upward under PB, and the slope of the relation curve was initially decreased. On the other hand, under CHL the relationship curve shifted only upward, and the slope increased. Thus the anesthetic drugs affected differently and time dependently tonic and reflex renal sympathetic nerve activity in the conscious cat.

Animals↗

Renal sympathetic nerve activity and plasma catecholamines during eating in cats.

We measured renal sympathetic nerve activity (RNA) and arterial plasma concentration of norepinephrine (NE) and epinephrine (EPI) before, during, and after eating in six conscious cats. Eating continued for a period of 5 min. RNA, heart rate (HR), and arterial blood pressure (AP) increased almost simultaneously with the onset of eating and reached a maximum value of 192%, 221 beats/min, and 121 mmHg at 2.5-5 min after the onset of eating, respectively. The plasma NE level increased significantly (P less than 0.05) during eating from the control value of 0.56 ng/ml and reached a maximum value of 1.33 ng/ml at 4.5-5 min, whereas the plasma EPI level did not change significantly from the control value of 0.12 ng/ml. The plasma levels of NE and EPI were unaffected by the blood samplings. The relationship between the changes in RNA and the plasma NE level during eating had a significant (P less than 0.05) positive correlation (r = 0.52). The result suggests that plasma NE concentration tends to increase with the rise in RNA during eating.

Animals↗

Fundamental rhythm of cardiac sympathetic nerve activity in awake cats at rest and during body movement.

Cardiac sympathetic nerve activity (CSNA in imp/s) was measured in the postganglionic fibers of awake cats at rest, during body movement, and with excitement. The CSNA showed synchronized discharges with various periodicities. Rhythms of the synchronized CSNA were analyzed by an interval histogram (IIH). The IIH showed a multimodal distribution. The first model interval (Tc) was in a range of 75 to 125 ms. An 8-12 cycle/s Tc rhythm, i.e., inverse value of Tc, was always observed in the awake cat at rest and during body movements. Probability of the 8-12 cycle/s Tc rhythm was smallest at rest, increased during body movement, and was largest with excitement. These results suggested that the 8-12 cycle/s Tc rhythm, observed in all states in the conscious cat, is a fundamental rhythm of central cardiovasomotor origin. The subsequent model distribution (Tb = 2 x Tc, 3 x Tc, 4 x Tc, or 5 x Tc) ranged from 150 to 700 ms, mostly 200 to 500 ms. A 2-5 cycle/s Tb rhythm, i.e., inverse value of Tb, appeared more frequently at rest than that during body movement or with excitement. A new model concerning a mechanism to cause the 2-5 cycle/s Tb rhythm is suggested.

Animals↗

Changes in AdSNA and arterial catecholamines to coronary occlusion in cats.

The relationship between adrenal (preganglionic) sympathetic nerve activity (AdSNA), cardiac sympathetic nerve activity (CSNA), and arterial catecholamines, i.e., epinephrine (Epi) and norepinephrine (NE), were analyzed during 200 s of occlusion of left anterior descending coronary artery in anesthetized cats. With coronary occlusion, AdSNA maximally increased to 168 +/- 20% (mean +/- SE) of the control value at 20 s and gradually decreased to 149 +/- 10% at 200 s. Mean CSNA (MCSNA), mean arterial pressure, and heart rate decreased significantly because of coronary occlusion. Arterial NE and Epi progressively increased from 0.54 +/- 0.05 and 0.29 +/- 0.03 ng/ml to 1.41 +/- 0.16 and 0.59 +/- 0.08 ng/ml at 3 min after the onset of occlusion, respectively. The correlation between AdSNA and arterial Epi (r = 0.71; P less than 0.01) and between AdSNA and arterial NE (r = 0.57; P less than 0.05) were significant, but the correlation between CSNA and arterial NE was not significant. On the other hand, in adrenalectomized cats, the increases in arterial Epi and NE did not appear during coronary occlusion. We concluded that, with coronary occlusion, AdSNA increased and, in turn, caused an increase in arterial Epi and NE.

Adrenal Glands↗

Diameter and flow velocity changes in small pulmonary vessels due to microembolization.

The pulmonary vascular bed was embolized with glass beads in small doses that induced no significant changes in pulmonary arterial pressure in anesthetized cats. We analyzed changes in internal diameter (ID), flow velocity, and volume flow of embolized and nonembolized arteries simultaneously with ID changes of small veins. In embolized arteries, with 180-, 300-, and 500-microns beads, ID constricted maximally in just proximal portions of the plug by 22, 23, and 17%, respectively, but with 840-microns beads, no ID constriction occurred. With 50-microns beads, the maximum ID constriction occurred in arteries of 200-300 microns but not in those of 100-200 microns. The constriction decreased in the upstream larger arteries and disappeared in those greater than 800 microns ID. In the nonembolized arteries no ID change occurred. Veins constricted slightly compared with arteries. By heparin pretreatment, ID constriction was slightly attenuated in arteries and was almost abolished in veins, whereas it was not affected with hexamethonium bromide. At a branching site, volume flow to an embolized artery decreased because of a decrease in ID and flow velocity, whereas volume flow to a nonembolized artery increased because of an increase in flow velocity. We concluded that pulmonary microembolization induced a vasoconstriction chiefly in small pulmonary arteries upstream to the plug. After embolization, blood flow was locally redistributed from an embolized to a nonembolized artery at a branching site. Arterial vasoconstriction may be mediated chiefly by local mechanical factors.

Animals↗

Effects of baroceptor reflex on cardiac and renal sympathetic nerve activity before and after atropinization in awake cats at rest.

The effects of baroceptor reflex on mean cardiac (MCSNA) and renal sympathetic nerve activity (MRNA) were analyzed before and after atropinized (0.1 mg/kg, i.v.) states in conscious cats at rest. Resting values of MCSNA, MRNA, mean aortic pressure (MAP), and heart rate (HR) were 85 +/- 6 imps/s, 76 +/- 11 imps/s, 100 +/- 4 mmHg, and 164 +/- 10 beats/min, respectively. Both MCSNA and MRNA changed almost inversely to changes in the absolute MAP in the range of 90-140 mmHg. Within this pressure range the gain of baroceptor-sympathetic system to the heart and kidney was 2.31 and 1.84, respectively. MCSNA as well as MRNA was reduced to the noise level at the MAP of 142 and 150 mmHg, respectively. With atropine, MCSNA and MRNA were inhibited centrally whereas HR increased to 192 beats/min. The increase in MAP caused by norepinephrine (2.1 micrograms/kg, i.v.) was enhanced to 75 +/- 7 mmHg by atropine from 31 +/- 4 mmHg in control. The piecewise linear MAP-MCSNA and MAP-MRNA relationships changed to a remarkable clockwise hysteresis loop. During the rising MAP period, the gain of the baroceptor-sympathetic system decreased to 0.91 and 0.97 in MCSNA and MRNA, respectively. During the returning MAP period, a delayed activation in MCSNA and MRNA occurred centrally. We conclude that the baroceptor reflex effect on MCSNA is larger than those on MRNA, and that the baroceptor control of MCSNA and MRNA is modified centrally by atropine in the awake cat at rest.

Animals↗

Central and baroreflex control of sympathetic nerve activity to the heart and kidney in a daily life of the cat.

We measured simultaneously and continuously the sympathetic nerve activity to the heart (CSNA) and kidney (RNA) together with heart rate (HR) and arterial blood pressure (AP) in conscious cats. The time course and magnitude of their responses to behavioral stimuli and norepinephrine iv administration were analyzed quantitatively. The increases in CSNA and RNA occurred almost simultaneously with the onset of standing, walking or eating behavior. The abrupt increases in CSNA and RNA were not preceded by a decrease in AP so it was unlikely to have been a reflex initiated by baroceptors. Rather, the increases in CSNA and RNA were followed by increases in HR and AP. The lag time ranged from 2 to 10 sec. Relative response magnitude of CSNA differed significantly from that of RNA. Thus, when AP increased spontaneously by behavioral stimuli, there was always preceding nonuniform increases in CSNA and RNA. On the other hand, when AP was elevated by norepinephrine iv administration, CSNA and RNA were inhibited proportionally to a rise in AP due to baroreflexes. At rest, the baroreflex effect on CSNA was greater than that on RNA. Cardiac-related discharges of CSNA and RNA, which were induced reflexly by baroceptor input, occurred dominantly at rest. However, with excitement or at the onset of body movements, they were diminished significantly. Our results suggested that AP adjustment associated with various behavior was made directly by a nonuniform central activation of the sympathetic nerve activity to the heart and blood vessels and partly by a central modulation of the baroceptor input.

Animals↗