[Endless voyage. The life of Ms. Shin Tanaka. 6. Chapter 2].
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Biomedical subjects
Publications and source records attributed to K Shima.
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In order to explore secretory mechanisms in peptic ulcer, the plasma secretin response to an intraduodenal load of gastric acid stimulated with tetragastrin was studied in 10 patients with duodenal ulcer, nine with gastric ulcer, and five young healthy volunteers. After the injection of tetragastrin plasma secretin level was significantly increased in all subjects. The integrated incremental secretin output significantly correlated with the incremental acid output in the duodenal ulcer group as well as the gastric ulcer group. THere was no significant difference in the integrated incremental secretin output among the three groups. However, the integrated incremental secretin output per unit amount of gastric acid loaded in the duodenum was significantly lower in the duodenal ulcer group than in the other two groups. These results suggest that in patients with duodenal ulcer the secretin release in response to an intraduodenal load of endogenous acid is impaired.
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A total of 50 neurons in the periaqueductal gray (PAG) of the cat were studied. Sixty percent of the units were excited by nociceptive pinch stimulation. These units were also excited by non-nociceptive stimulation such as tapping, hair movement and/or joint rotation. Non-nociceptive stimulation excited 20% of the units, whereas nociceptive stimulation did not drive these units. Their receptive fields were large, and often encompassed the entire body. Spontaneous discharges of PAG neurons revealed great irregularity.
Impulse discharges were recorded from 43 neurons in the nucleus raphe dorsalis of the cat. Of these neurons examine for spontaneous activity, 23 fired in remarkable regular rhythm (clock-like neurons); 18 fired irregularly (non-clock-like neurons); and 2 fired with an unclassified pattern. Almost all clock-like neurons were unresponsive to any kind of peripheral somatic stimuli, while the majority of non-clock-like neurons were excited by both nociceptive and non-nociceptive stimuli or by non-nociceptive stimuli. The somatic receptive fields were large, spanning the entire body.
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To clarify the mechanism of an increased response of diabetic D-cells to arginine, we studied the changes in responsiveness of pancreatic D-cell to this agent with the passage of time after the onset of diabetes and the effect of chronic insulin substitution on the altered D-cell function utilizing the perfused pancreas of streptozotocin diabetic rats. The magnitude of somatostatin (SRIF) response to arginine (10 mM) was progressively increased with the duration of diabetes. The integrated response of SRIF during a 20 min period of an arginine infusion one week after the injection of streptozotocin was not different from that in the normals, but it was increased by 240% at 8 weeks and by 390% at 15 weeks. The exaggerated pancreatic SRIF release observed in 8 week diabetic rats was partially ameliorated with the daily insulin replacement (15.0 +/- 1.0 units/kg of B.W.). This was accompanied by a partial recovery from growth failure. The integrated amount of SRIF secreted during an arginine-stimulated period (20 min) was inversely correlated with an increase in body weight during an 8 week period (r = -0.741, p less than 0.001). From these results, it might be concluded that the alteration in diabetic D-cell function may be related to the metabolic and hormonal abnormalities of diabetes, rather than insulin deficiency itself.
In order to study the pathogenesis of reactive hypoglycemia, the responses of plasma glucose, IRI, glucagon immunoreactivity (GI) and total glucagon-like immunoreactivity (GLI) to 100 g oral glucose load were investigated in twenty-six patients of normal weight with reactive hypoglycemia. Of these patients, nineteen exhibited a diabetic OGTT curve. The findings in these patients were compared to normal control subjects (N = 20) and to disease-matched patients controls (N = 43). The psychological status was assessed by Cornell Medical Index Health Questionnaire in most of the subjects, who also received an x ray examination of the upper gastrointestinal tract. In addition, IVGTT was performed in the hypoglycemic patients. No apparent difference in plasma IRI response to oral glucose was observed between the hypoglycemic patients and their respective controls. Plasma total GLI concentrations were significantly increased during OGTT in both hypoglycemic groups. Following an oral glucose load, plasma GI levels were suppressed in the hypoglycemic groups to an extent similar to that in the control despite an apparent fall in their plasma glucose levels to the hypoglycemic range in the former. Radiological alterations in the upper gastrointestinal tract; deformity of the duodenal cap, gastric and/or duodenal ulcer, were found more frequently in the hypoglycemic groups. However, no characteristic change in personality was noticed in the patients. During IVGTT, neither plasma glucose nor total GLI level of the hypoglycemics differed from that of each control. The pathogenic factors responsible for reactive hypoglycemia will be discussed.
Antisera having a strong and strictly constant cross-reactivity for gut-GLI were raised in seven rabbits immunized with immunogen, a conjugate of BSA and des-Asn28, Thr29, Homoser27 -glucagon (CNBr-glucagon). All of the anti-CNBr-glucagon sera exhibited titer and affinity for glucagon sufficiently high enough to develop a sensitive radioimmunoassay. The relative crossreactivity of the antisera to gut-GLI was comparable to that of antiserum K-4023 which strongly crossreacted with gut-GLI. One of the anti-CNBr-glucagon sera, OAL-196, did not react with the glucagon 19-29 fragment at all. The intra- and inter-assay coefficients of variation were 3.8-5.0 and 6.0-7.3%, respectively, in the radioimmunoassay system for total GLI in human plasma using OAL-196. The fasting plasma total GLI was 374 +/- 18 pg/ml. The plasma total GLI during 50 g oral glucose load in normal subjects increased significantly, whereas the plasma IRG level measured with the anti-glucagon 19-29 serum, OAL-123, assay system was lowered. In the gastrectomized subjects, plasma total GLI measured with the present assay system elicited a marked increase following an oral glucose load. These results suggest that the radioimmunoassay using anti-CNBr-glucagon sera will be useful in measuring plasma total GLI.
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In this pancreatic-glucagon-specific radioimmunoassay we used C-terminal-region-specific antiserum. OAL-123, produced against a 19-29 C-terminal fragment of porcine glucagon. On measurement of pooled plasma the ranges for intra- and inter-assay coefficients of variation were 4.8-8.1% and 7.5-10.7%, respectively. The concentration of immunoreactive glucagon in plasma of healthy subjects, as measured with the OAL-123 assay system, was 87.9 (SD 23.8) ng/L. Measurement of the same plasma samples with the 30K assay system (30K being an antiserum highly specific for pancreatic glucagon) showed a comparable value, 86.2 (SD 26.3) ng/L. We followed changes in human and dog plasma immunoreactive glucagon concentrations on arginine infusion and after glucose load, using the OAL-123 and the 30K assay systems, with identical results. Combining other results of comparative immunochemical characterization of the OAL-123 and 30K assay systems, we confirmed that the antisera raised against the C-terminal fragment of glucagon can be used in radioimmunoassay of pancreatic glucagon.
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Studies were conducted to investigate the relationship between development of fibrosis and hemodynamic changes in the pancreas in dogs. The basal blood flow rate in the atrophied, fibrotic pancreas was preserved at almost the same level as in the normal pancreas. Fibrotic pancreas responded to VIP with increased blood flow, but not to administration of secretin. On the other hand, normal pancreas showed a brisk increase of blood flow in response to both of these agents. Our findings suggest that direct arterial acinar blood flow per gram of acini decreases prominently, whereas direct arterial flow to the islets per gram of islet is well maintained after the development of pancreatic fibrosis. It is also suggested that secretin acts indirectly by stimulating metabolic activity of the acinar cells with a secondary increase in blood flow, whereas VIP has a direct effect on the pancreatic vasculature.
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Plasma immunoreactive motilin (IRM) concentrations were strikingly higher in patients with chronic renal failure (CRF) than in normal subjects. IRM in azotemic plasma was heterogeneous in gel-filtration profile. The first peak eluted in the void volume of the column and the second and the third one, comprising a major portion of IRM content, came out coincidentally with insulin and authentic motilin, respectively. By contrast, no discernible amount of IRM was found in the region corresponding with the second peak in gel-filtration of the plasma from normals and very little in a patient with ileus whole plasma IRM level was elevated. The hypermotilinemia and the accumulation of this high molecular weight motilin in patients with CRF suggest that the kidney plays some role in the elimination of motilin, and further, that the clearance of the high molecular motilin is more dependent on renal function than that of authentic motilin. The present paper emphasizes the necessity for clarifying the significance of the heterogeneity of IRM in CRF.
Effects of intravenously administered morphine on the evoked potentials of the amygdala elicited by tooth pulp stimulation were examined in cats. The various evoked potentials were observed in regions of the amygdala such as nucleus amygdaloideus centralis (pars lateralis), nucleus amygdaloideus basalis (pars magnocellularis), nucleus amygdaloideus basalis (pars parvocellularis) and nucleus amygdaloideus lateralis. Evoked potentials were significantly decreased by morphine in four of the recorded regions. Morphine had no effect on the latency at any site of the amygdala observed. Depressant effects of morphine on evoked potentials were antagonized by naloxone in all 14 cats. This study indicates that there is a receptive field of pain in the amygdala which undoubtedly plays a role in emotion.