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Biomedical subjects

I Ninomiya

Publications and source records attributed to I Ninomiya.

At least 91 records · Page 5Linked to original sources

The amplitude and periodicity of synchronized renal sympathetic nerve discharges in anesthetized cats: differential effect of baroreceptor activity.

We applied a computerized peak detection algorithm to recordings of synchronized sympathetic nerve discharges from anesthetized cats to retrieve information about the characteristics of renal nerve activity (RNA) during changes in baroreceptor activity. The algorithm scanned the series of RNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RNA peak had been detected, its corresponding amplitude, width and peak-to-peak interval were calculated. The peak-to-peak interval periodicity showed two modes of synchronized discharge, one between 200-500 ms accounting for 47% of intervals, and a higher 20-180 ms frequency (49% of intervals). Baroreceptor stimulation decreased the occurrence of the high frequencies while increasing the probability of the lower frequency components. The overall occurrence of synchronized peaks per second fell linearly to zero with increases in blood pressure. The peak amplitude of RNA was unimodally distributed and was not affected by baroreceptor stimulation until an increase in mean arterial pressure reached a threshold (mean 142 +/- 5 mmHg) whereupon it fell quickly to zero. Sino-aortic vagal denervation did not affect the distribution of peak height. The width of synchronized discharges was also unimodal, mean 82 +/- 1 ms, and was almost unchanged during baroreflex stimulation acting in parallel with changes in the peak amplitude and decreasing at high blood pressures. Sino-aortic vagal denervation did not affect the synchronized width. There was no relationship between the periodicity and amplitude or width of synchronized discharges under all conditions. The results indicate that the periodicity and amplitude of renal synchronized discharges appear to be independent of each other and are differentially affected by baroreceptor input.

Animals↗

Effect of asphyxia on the frequency and amplitude modulation of synchronized renal nerve activity in the cat.

A computerized peak detection algorithm was used to retrieve new information about changes in the characteristics of renal nerve activity (RNA) with asphyxia in anesthetized cats. The algorithm scanned the series of RNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RNA peak had been detected, its corresponding amplitude, width, and peak-to-peak interval were calculated. The peak-to-peak interval showed two rhythms of synchronized discharge: one between 200-500 ms accounting for 38 +/- 3% of intervals and a higher 20-180 ms frequency (52 +/- 5% of intervals). Asphyxia did not change the periodicity distribution despite increases in arterial pressure. The peak amplitude of RNA, reflecting the number of active fibers, was unimodally distributed and was increased 39 +/- 9% with asphyxia. The shape of the distribution was unchanged. The width of the synchronized activity was also unimodally distributed, mean 79 +/- 3 ms, and increased by asphyxia to 99 +/- 5 ms. The results indicate that the control of the periodicity and amplitude of synchronized discharge appear to be independent and are differentially affected by chemoreceptor input.

Animals↗

A new approach to analysis of synchronized sympathetic nerve activity.

Renal sympathetic nerve activity (RSNA) recorded from the multifiber preparation is a continuously fluctuating variable in terms of period and amplitude, reflecting a coordinated tonic level of output from the vasomotor center. Yet current methods of analysis cannot simultaneously measure both of these parameters. A new accurate technique for assessing changes in global sympathetic activity is required. We made a novel application of a computerized peak detection algorithm (Cluster program) to recordings of synchronized sympathetic nerve discharges. The procedure was applied to this new area to retrieve information about the characteristics of synchronized RSNA. Peaks in synchronized RSNA activity were detected from short-term (20 ms) integrated recordings in which voltage changes had been digitized at 200 Hz and stored on computer. The program scanned the data series for significant increases followed by significant decreases in a small cluster of voltage values. The program permits the input of the cluster sample sizes for the test peaks and pre- and postpeak nadirs and also the minimum height to be defined as a peak. Once each synchronized RSNA peak had been detected, its corresponding amplitude, width, and peak-to-peak interval were calculated. The program successfully characterized RSNA in a group of eight cats and yielded results comparable to other analysis techniques. The peak-to-peak interval period showed two modes of synchronized discharge, one related to the cardiac cycle and a faster 8- to 14-Hz frequency. The synchronized peak amplitude and width showed unimodal frequency distributions. The relationship between each of the three variables was examined; only the peak height and width were significantly related to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Thromboxane A2/endoperoxide receptors mediate cholinergic constriction of rabbit lung microvessels.

Using an X-ray television system, we directly measured the internal diameter (ID; 100-1,000 microns) of small pulmonary arteries and analyzed the effects of cyclooxygenase inhibition and thromboxane A2/prostaglandin endoperoxide (TP) receptor blockade on the ID reductions in response to vagal nerve stimulation (VNS; 16 Hz) and injection of acetylcholine (ACh; 0.3 micrograms) in anesthetized rabbits. The ID reductions of the small arteries in response to VNS and ACh were completely abolished by pretreatment with cyclooxygenase inhibitors indomethacin and meclofenamate. Those reductions were also eliminated by pretreatment with TP receptor antagonists AA-2414 and Ono 3708. Both TP receptor antagonists abolished the ID reduction to thromboxane A2 mimetic U-46619 but did not affect the reduction to norepinephrine. The ID reductions in response to VNS and ACh were eliminated by atropine. The reduction in response to VNS was abolished by hexamethonium bromide, whereas the reduction in response to ACh was not altered by hexamethonium bromide. The results indicate that vasoconstrictions of the rabbit small pulmonary arteries in response to VNS and exogenous ACh are mediated by TP receptors as well as muscarinic receptors. The data suggest that during VNS endogenous ACh acts on muscarinic receptors to constrict the small arteries mainly by generating thromboxane A2 or prostaglandin endoperoxide.

Acetylcholine↗

Immunohistochemical detection of c-myc products in colorectal cancer and proliferative cell rate.

Expression of c-myc protein was studied immunohistochemically in colorectal cancers using a monoclonal antibody, MYC-1. Immunoblotting assays with cellular lysates demonstrated a band of the gene products at the level of 60 kDa. c-myc-protein-positive tumor cells were observed in 43 (43.4%) of 99 specimens of colorectal cancers. There was no significant correlation between the incidence of MYC-1-positive tumors and clinicopathological findings. The rate of MYC-1 proteins occurring in patients with liver metastasis was significantly higher than that in patients without the metastasis. The rate of occurrence of DNA polymerase-alpha-positive cells in MYC-1 protein-positive tumors was significantly higher than in MYC-1 negative ones. The results suggested that MYC-1 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers.

Adenocarcinoma↗

Interrelationship between transforming growth factor-alpha and epidermal growth factor receptor in advanced gastric cancer.

An immunohistochemical study for transforming growth factor-alpha (TGF alpha) and epidermal growth factor receptor (EGFR) was made with 167 primary tumors of advanced gastric cancer to demonstrate the potential existence of autocrine mechanism. TGF alpha stained positively in 87 (52%), and EGFR in 68 (41%) of the tumors. The authors classified the tumors into the following three groups: group 1 with neither TGF alpha nor EGFR staining positively (63 tumors); group 2 with either TGF alpha or EGFR staining positively (53 tumors); group 3 with both TGF alpha and EGFR staining positively (51 tumors). The incidence rates of macroscopically infiltrative tumors and large tumor measuring 6 cm or more in diameter were significantly higher for group 3 than for groups 1 and 2. The patients of group 3 had the poorest prognosis, with a 5-year survival rate of only 12%, while the 5-year survival rates were 45 and 36% for groups 1 and 2. There was a significant difference in survival between the patients of group 1 and those of group 3. Bromodeoxyuridine labeling indices were significantly higher in the tumors belonging to group 3 (median 15.8%) than in those of group 1 (median 10.8%). The results suggest that the autocrine mechanism between TGF alpha and EGFR may play an important role in the progression of gastric cancer, and that when such a mechanism becomes operative, prognosis may be poor.

Adenocarcinoma↗

Correlation of c-erbB-2 protein expression and lymph node status in early gastric cancer.

For the prediction of nodal status of early gastric cancer, sections of formalin-fixed, paraffin-embedded tissue from 220 early gastric cancers were analyzed immunohistochemically, using a polyclonal antibody against erbB-2 protein. The data of erbB-2 protein expression have been correlated with pathologic data, and a logistic regression analysis was made for the estimation of the significant factors responsible for lymph node metastasis. A pattern consistent with cell membrane staining was regarded as most specific for the erbB-2 expression. There were 22 (10%) cancers with evidence of erbB-2 protein expression. Positive staining was associated with only lymph node metastasis. The risk of lymph node metastasis was 3-fold greater in tumors having erbB-2 protein expression than in tumors without the expression. When the erbB-2 tissue status and clinicopathological parameters were entered into the logistic regression analysis, erbB-2 protein expression emerged as one of the independent significant factors for lymph node metastasis. These results indicate that early gastric cancer with erbB-2 protein expression may represent a potential risk of lymph node metastasis.

Biomarkers, Tumor↗

[A multichannel telemetry system for autonomic neural signals, blood flow velocity, blood pressure, and ECG measurements].

A radio multichannel telemetry system has been developed for use with chronically instrumented, unrestrained, small animals. The system can simultaneously record autonomic neural signals, blood flow velocity, blood pressure, and ECG. The system is time-multiplexed and pulse width modulation (PWM)/FM device, which employs two sampling frequencies. The system is designed with 10 standard low power integrated circuits, a 3 terminal voltage regulator, and a transistor. The size is 53 x 42 x 20 mm, and the weight, including two batteries is 40 grams. The system is powered by two lithium cells, which provide 60 hours of continuous operation.

Action Potentials↗

Heterogeneity of DNA ploidy in gastric cancer.

Heterogeneity of DNA content was analyzed in 389 samples from 65 resected gastric cancers. Analysis of the samples revealed that there were 14 homogeneously diploid tumours. Six tumours were uniformly DNA aneuploid, each tissue block containing the same DNA index. The other 45 tumours (69%) varied in DNA content heterogeneity. In 39 of 45 tumours, there was a mixture of diploid and aneuploid samples, and 25 of the 39 tumours had a single aneuploid stemline. In 14 out of 39 tumours, there was also a mixture of diploid and aneuploid samples having two or more DNA aneuploid stemlines. In the remaining six tumours, different DNA aneuploid stemlines were contained in different samples without evidence of diploidy. When four or fewer samples were analyzed, only 50% of the tumours were diagnosed as having DNA content heterogeneity. On the other hand, 78% of the tumours showed DNA heterogeneity when 5 or more samples were analyzed. If the tumours had not been widely sampled, about a quarter of the tumours would have been mislabeled as diploid. The patients with tumours showing homogeneous diploidy survived longer than those with tumours showing a mixture of diploid and aneuploid stemlines. The survival rate was lowest for the patients with tumours having a mixture of diploid and multiple aneuploid stemlines, compared with those showing homogeneous diploid or a mixture of diploid and single aneuploid stemlines. The data from the current study clearly demonstrate the importance of adequate sampling in assessing the ploidy status of gastric cancers to identify groups of patients running different clinical course and prognosis.

DNA, Neoplasm↗

Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma.

Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c-erbB-2 tissue status emerged as independent prognostic variables. The results suggested that c-erbB-2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c-erbB-2 protein is an indicator of poor short-term prognosis.

Adult↗

Determination of beta-carbolines in foodstuffs by high-performance liquid chromatography and high-performance liquid chromatography-mass spectrometry.

A high-performance liquid chromatographic method combined with fluorimetric detection is described for the determination of beta-carboline (norharman) and 1-methyl-beta-carboline (harman). The analysis of foodstuffs for the identification of beta-carbolines is facilitated by clean-up samples using Bond Elut PRS cartridges. Recoveries were excellent. Further, a high-performance liquid chromatographic-mass spectrometric method was also developed for their identification. The concentration of beta-carboline among the foodstuffs and alcoholic beverages varied greatly. Also, norharman and harman were observed in uncooked foodstuffs, whereas acetaldehyde was found in most fermented food. The toxicological implication of beta-carbolines in foodstuffs is discussed.

Acetaldehyde↗

Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer.

Using a polyclonal antibody that is monospecific for the erbB-2 oncogene product, an immunohistochemical study of the expression of erbB-2 protein was performed in formalin-fixed paraffin-embedded tissue sections from 260 primary gastric cancers. erbB-2 protein expression in which the reaction was localized to the cell membranes was observed in 31 (11.9%) cancers. All nontumor cells and normal gastric epithelium were negative for membrane staining. There was not a significant association between erbB-2 staining and histological type or venous invasion. erbB-2 protein expression was associated with serosal invasion, lymph node metastasis, and lymphatic invasion. In addition, erbB-2 protein expression correlated with a high number of lymph node metastases. Furthermore, the risk of recurrence in lymph node was over 3 times higher in patients with erbB-2 protein-positive tumors than in those with erbB-2 protein-negative ones. When erbB-2 protein expression and the clinical parameters were entered simultaneously into the Cox regression model, erbB-2 protein expression emerged as an independent prognostic indicator. Patients with erbB-2 protein-positive tumors had 5-fold greater relative risk of death, as compared with those with erbB-2 protein-negative tumors. These results indicate that erbB-2 protein expression is an important independent prognostic indicator in gastric cancer. The high malignant potential of erbB-2 protein-positive tumors may be associated with the very high potential for lymph node metastasis.

Biomarkers, Tumor↗

A new nonoperative method of percutaneous transgastric fistulo-drainage for an intractable external pancreatic fistula--a case report.

The external pancreatic fistula is a well-known complication of pancreatectomy and is conventionally classified as either a partial fistula or a total fistula. A partial fistula usually closes spontaneously and operative intervention is rarely needed, whereas, a total fistula on the other hand, very often does not close and may therefore require surgical intervention. We report herein, a case of an intractable total pancreatic fistula following pancreatoduodenectomy which was successfully repaired by a new non-operative method of percutaneous transgastric fistulo-drainage (PTFD). This technique, performed under the control of a two-way X-ray television system, is safe and considered useful for the treatment of an intractable total pancreatic fistula. In the future, this may be the method of choice for the management of such refractory total pancreatic fistulae.

Adult↗

Identification of tetrahydro-beta-carboline-3-carboxylic acid in foodstuffs, human urine and human milk.

1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA), both precursors of mutagenic N-nitroso compounds (N-nitrosamines, 1-methyl-2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid and 2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid), were detected in various food-stuffs, urine from healthy human subjects and human milk. A purification procedure, involving a chemically-bonded material followed by HPLC combined with fluorometric detection, was used for the quantitative determination of these compounds, allowing the separation of two diastereoisomers of MTCA. An HPLC and mass spectrometry method was also developed for their identification. Comparing the concentration of MTCA and TCCA in fermented products and raw materials suggested that tetrahydro-beta-carbolines may have been produced through fermentation or by condensation of tryptophan and acetaldehyde formed from ethanol added as a food preservative. This is the first report of excretion of tetrahydro-beta-carbolines in human urine and human milk. A comparison of the concentrations of tetrahydro-beta-carbolines in urine from human infants and human milk indicates that tetrahydro-beta-carbolines may be synthesized endogenously in humans. A possible pathway of tryptophan metabolism in plants and animals is presented.

Adult↗

In vivo monitoring of myocardial interstitial norepinephrine by dialysis technique.

To estimate local sympathetic nerve activity of the heart in vivo, we applied a dialysis technique to the heart and attempted to monitor norepinephrine levels in local myocardial interstitial fluid. The dialysis probe consisted of an 18 x 0.31 mm dialysis fiber with a 50,000-mol wt cutoff. When the probe was perfused at 5 microliters/min in vitro, the average relative recovery rate of norepinephrine was 31.3 +/- 0.6%. Dialysis probes were implanted in the left ventricular lateral wall of the beating heart in anesthetized cats and perfused with Ringer solution at 5 microliters/min. Dialysate norepinephrine concentration was measured using high-performance liquid chromatography with electrochemical detection. 1) After probe implantation, dialysate norepinephrine concentration decreased over the first 120 min and then reached an almost steady level (41.1 +/- 4.7 pg/ml). 2) Electrical stimulation of the left stellate ganglion increased dialysate norepinephrine concentration significantly, from control level of 39.0 +/- 5.8 to 82.0 +/- 7.7 pg/ml (P less than 0.01). After stimulation, dialysate norepinephrine concentration returned to the prestimulation level. The dialysis technique using high-performance liquid chromatography permits monitoring of norepinephrine levels in local myocardial interstitial fluid and detection of changes in local cardiac sympathetic nerve activity in vivo.

Analysis of Variance↗

Expression of c-myc gene product in gastric carcinoma.

The expression of c-myc oncogene product was studied in 213 cases with gastric carcinoma by an immunoperoxidase method using a monoclonal antibody (MYC-1). Fifty (23.5%) of 213 tumors showed immunoreactivity to MYC-1. The distribution of c-myc-product-positive cells was observed mainly at the marginal area of the tumor. Excess reactivity to c-myc product occurred more frequently in invasive cancers than in localized cancers, and c-myc production expression in cancer tissue correlated well with peritoneal dissemination. Patients with c-myc-protein-positive tumor had significantly poorer prognosis than those with c-myc-protein-negative tumor in invasive gastric carcinomas, and the c-myc product status correlated well with the recurrence of cancer by peritoneal dissemination. These results suggest that the expression of c-myc gene product might be related to the proliferative activity of gastric carcinoma and serve as a new biologically relevant tumor marker for determining the prognosis.

Animals↗