[Progress in clinical test methods on the protective function of the gastric mucosa; evaluation of mucosal epithelium blood flow by reflectance spectrophotometry].
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Biomedical subjects
Publications and source records attributed to T Kamada.
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Fibronectin is known to interact with fibrin, collagen, etc. We have labeled fibronectin with 131I, and measured its accumulation in the deendothelialized lesion in the rabbit aorta to evaluate it as a candidate for imaging atherosclerotic lesions and thrombi. Accumulation of [131I] fibronectin in the deendothelialized lesion was apparent at 48 hr, and increased at 72 hr after injection of the agent. Our results indicate that radiolabeled fibronectin may be a useful tracer for imaging early atherosclerotic lesion and thrombus.
The purpose of this study was to determine the differences in hepatic circulation and oxygen consumption in two groups: those with nonalcoholic obesity-related fatty live and those with alcoholic fatty liver. Although the histological degree of fatty infiltration was equal in the two groups, the delta Er569-650, as an index of the regional liver blood flow estimated by spectrophotometric method, was significantly lower in alcoholic fatty liver than in nonalcoholic fatty liver, and the in vivo hepatic oxygen consumption (VO2), also determined by hepatic reflectance spectrophotometry during peritoneoscopy, tended to be lower in alcoholic fatty liver than in nonalcoholic fatty liver. The oxygen saturation of hemoglobin in local liver blood (SO2) was, however, significantly higher in alcoholic fatty liver than in nonalcoholic fatty liver. These results suggest that an increase in oxygen extraction to maintain oxygen consumption, which was indicated by the lowering of the SO2, was not found in alcoholic fatty liver, in spite of a reduction of oxygen supply to the liver. It is concluded that the impairment of hepatic circulation and hepatic oxygen consumption was more serious in alcoholic fatty liver than in nonalcoholic fatty liver, possibly contributing to a different prognosis for the two forms of fatty liver.
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The existence of nerve fibers containing corticotropin-releasing factor (CRF)-like immunoreactivity (CRFI) in the rat superior cervical ganglion (SCG) was demonstrated by using immunocytochemistry. They were found to be extrinsic in origin, because no CRFI neurons were seen in the SCG and decentralization resulted in the disappearance of CRFI fibers in the SCG on the operated side. These findings were also confirmed by immunoelectron microscopic analysis; CRFI fibers contained a number of small clear synaptic vesicles but were devoid of large granular and agranular vesicles. These morphological characteristics are identical to those of the preganglionic fibers. The present immunoelectron microscopic analysis revealed that most of the CRFI fibers in the SCG make synaptic contact predominantly with the dendrites of the principal cells, partly with their somas and rarely with a non-CRFI terminal. Thus, the present study provides direct morphological evidence that CRF directly influences the function of the principal cells of the SCG and that CRFI fibers are preganglionic.
Normal erythrocyte morphology is necessary for proper distribution of blood-flow in the microcirculation. Erythrocyte shape was studied in 20 patients undergoing extracorporeal circulation (EC) during coronary bypass surgery. Crenated erythrocytes comprised a mean 64% of all erythrocytes during and 29% after EC. Free fatty acid (FFA) content of the erythrocyte membranes was significantly increased at both times, and FFA content correlated with the proportion of crenated erythrocytes. Washing crenated cells with defatted albumin solution transformed them back to discocytes, simultaneously removing more FFA than that removed from pre-EC discocytes. The plasma FFA to albumin ratio became disproportionately increased during EC; the increased level correlated with severity of erythrocyte crenation. Maintaining a higher level of albumin during EC by adding 50 g human albumin to the extracorporeal system prevented erythrocyte crenation. Entry of plasma FFA not bound to albumin into erythrocyte membranes during EC causes massive erythrocyte crenation.
Leucine-enkephalin (L-ENK)-like immunoreactive (L-ENKI) structures in the superior cervical ganglion (SCG) were first examined by using immunoelectron microscopy. L-ENKI neurons formed cell clusters and were small. They were filled with large granular or agranular vesicles and small electron lucent vesicles, and had nuclei that lacked a nucleolus. Since these morphological characteristics are identical to those of the small intensely fluorescent (SIF) cells, L-ENKI cells seemed to be a kind of SIF cell. Two types of L-ENKI fibers were identified, a large type filled with large granular or agranular vesicles and a small type filled with small electron lucent vesicles. The large fibers were located near the L-ENKI perikarya and often could be traced directly to the soma. These fibers remained intact after decentralization of the SCG. These findings indicate that the large L-ENKI fibers are processes of L-ENKI SIF cells. The fibers showed a close apposition to the blood vessels and rarely formed synaptic contact with dendrites of the principal cells. On the other hand, the small L-ENKI fibers were found to originate outside the SCG, because they disappeared after decentralization of the SCG. These L-ENKI fibers frequently formed synaptic contact with the dendrites of the principal cells. Thus, the present study demonstrated the presence of two discrete L-ENKI neuron systems in the SCG of the guinea pig, one an intrinsic SIF system and the other an extrinsic L-ENKI system.
The effects of misoprostol on human gastric mucosal hemodynamics were examined in a double-blind, placebo-controlled, parallel study in 12 healthy male volunteers. Six subjects received 200 micrograms of misoprostol and six received placebo. The index of mucosal blood volume and mucosal blood hemoglobin oxygen saturation (Hb-SO2) were measured at 20 locations in the stomach using reflectance spectrophotometry during endoscopy prior to and after administration of the study drug. Mucosal blood volume index increased by approximately 10 to 25 percent throughout the stomach without a significant change in mucosal Hb-SO2 following treatment with misoprostol. The increase in mucosal blood volume index was statistically significant for 16 of the 20 locations (p less than or equal to 0.05). Placebo produced no significant change in mucosal blood volume and mucosal Hb-SO2. These findings suggest that misoprostol may have the potential effect of accelerating gastric ulcer healing by improving gastric mucosal hemodynamics, in addition to its gastric acid antisecretory activity.
To clarify the signal transduction mechanism of angiotensin II in renal glomeruli, we studied the effect of the hormone on phospholipid metabolism using isolated rat glomeruli. Stimulation of the glomeruli pulse-chase labeled with [3H]glycerol by angiotensin II caused a rapid (within 15 s) breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) with a concurrent production of 1,2-diacylglycerol. This effect of angiotensin II was in a dose-dependent manner within the range from 10(-12) M to 10(-6) M, and was inhibited by saralasin. Angiotensin II also decreased the 3H radioactivity of PIP slightly only at 15 s and increased that of phosphatidic acid after 15 s, with no significant effect upon the labelings of phosphatidylinositol (PI), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) within 1 min. The change in phospholipid metabolism by angiotensin II was similar when the glomeruli were labeled with [32P]orthophosphate: the decrease in the labeling of PIP2 and the increase in the labeling of phosphatidic acid after 15 s. In addition, 32P labeling of PI increased after 2 min. These results suggest that angiotensin II, after binding to glomerular receptors, induces initial PIP2 hydrolysis to diacylglycerol and subsequent resynthesis of PIP2 through phosphoinositide turnover.
Angiotensin II-induced change in inositol phosphates were studied in cultured rat mesangial cells prelabeled with [3H]myo-inositol. By using anion-exchange high performance liquid chromatography, we could analyzed the change in inositol mono-, bis-, and tris-phosphate more rapidly and easily with higher resolution than the previously reported methods. Angiotensin II rapidly increased inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate within 15 sec, followed by an increase in inositol 1-monophosphate at 30 sec. Angiotensin II-induced increases in inositol phosphates were dose-dependent and completely blocked by saralasin. These results indicate that angiotensin II induces the production of inositol phosphates including inositol 1,4,5-trisphosphate, an intracellular Ca2+-releasing factor, in cultured rat mesangial cells.
We found that large cells in the dorsal root and trigeminal ganglia contained glutamate-like immunoreactivity. Immunoreactive neurons were not detected in the superior cervical or pterygopalatine ganglia. These findings indicated that glutamate is a neurotransmitter or neuromodulator of large cells of sensory ganglia.
The effect of glucocorticoid (dexamethasone) on insulin receptor mRNA was examined in the IM-9 cell line by dot hybridization analysis using insulin receptor c-DNA probe (phINSR 13-1). Insulin receptor mRNA was found in a dose- and time-dependent manner, to increase during a 24-h culture with glucocorticoid. Although there has been some dispute about the effect of glucocorticoid on degradation of the insulin receptor itself, we have found glucocorticoid had no significant effect on the degradation rate of insulin receptor mRNA. These results suggest that glucocorticoid has the effect of increasing de novo synthesis of insulin receptor mRNA. But the molecular mechanism of glucocorticoid's effect still needs to be investigated.
Urine from 5 renal transplant recipients treated with frusemide was analyzed for unchanged frusemide (F), glucuronidated frusemide (G) and 4-chloro-5-sulfamoylanthranilic acid (CSA) by HPLC. In 3 recipients, whose renal function recovered steadily and whose hepatic function was normal throughout, the ratio of frusemide to its metabolites, F/(F + G + CSA), increased steadily in conjunction with the recovery of renal function. In one patient, who received frusemide 200-400 mg/day i.v., the urinary CSA concentration was 64-102 micrograms X ml-1. In 2 patients who experienced shock and/or hepatic dysfunction after transplantation, the F/(F + G + CSA) ratio fluctuated.
The purpose of this study is to develop a useful gamma camera system for atraumatic rCBF measurement by the 133Xe intravenous injection (i.v.) method. A super high sensitivity slant hole (SHS-SL) collimator was designed for this purpose. The gamma camera used with this collimator was able to move close to the patient's head and obtain satisfactory count rates (130 kcpm-178 kcpm in a hemisphere) with a low dosage (10 mCi) of 133Xe. To validate this rCBF measurement system three studies were carried out: a comparative evaluation was performed against the flow values with the intracarotid 133Xe injection (i.c.) method, reproducibility of flow values was assessed from two serial i.v. measurements, and flow values were compared with clinical severity of the patients. The comparative study showed good correlation in the hemispheric and regional values between the two methods; r values 0.98 and 0.64-0.93 for gray matter flow and 0.96 and 0.78-0.93 for initial slope index. In the reproducibility study, the variation coefficients in the hemispheric and regional values between the two serial measurements were 5.0% and 7.3%-14.2% for gray mater flow, 5.2% and 7.9%-12.9% for initial slope index. The reproducibility in this study was as good as those with the i.c. method reported previously. The hemispheric flow values from our gamma camera system correlated well with the clinical severity of cerebrovascular disease. These results show that the gamma camera system with the SHS-SL collimator is useful for atraumatic rCBF measurement.
We studied the three-dimensional distribution of structures with calcitonin gene-related peptide-like immunoreactivity (CGRPI) in the rat stomach and duodenum, including the origins of these structures, using indirect immunofluorescence in both muscle strips and frozen sections. There was a very dense meshwork of CGRPI fibers in the circular and longitudinal muscle layers, and also in the myenteric and submucous plexuses of the stomach and duodenum. No CGRPI neurons were seen in the stomach, even in rats treated with colchicine; in the duodenum, there was a group of CGRPI cells in the myenteric and submucous ganglia. No regional differences were seen in the stomach and duodenum. We found by experimental manipulations that CGRPI fibers in the stomach were exclusively extrinsic in origin; some of such fibers in the duodenum were intrinsic in origin, though most were supplied by CGRPI cells outside the duodenum.
To investigate whether disseminative coronary embolization with microspheres brings about a pathophysiological mimicking of the syndrome of exertional angina with a normal coronary arteriogram, 25 dogs were studied immediately and 2 weeks after the coronary embolization with microspheres 15 micron [2.5 X 10(5) or 5.0 X 10(5)/regional flow (ml/min)] and 25 micron [2.0 X 10(5)/regional flow (ml/min)] in diameter. Two weeks after embolization with the 15-micron microspheres, the resting coronary blood flow recovered to the control (preembolization) level with the absence of myocardial necrosis, but the coronary flow reserve was significantly lower. In ten dogs receiving the larger dose embolization (5 X 10(5)/regional flow (ml/min], lactate production or a marked decrease in lactate extraction was observed during rapid atrial pacing. In five dogs subject to 25-micron microsphere embolization, however, disseminative patchy myocardial necrosis was observed and the coronary flow reserve remained normal. These results indicate that the chronic state after microembolization with a large dose of 15-micron microspheres mimics the syndrome of exertional angina with a normal coronary arteriogram, whereas 25-micron microsphere embolization does not. Thus, the condition of some patients with a normal coronary arteriogram but with reduced coronary flow reserve may be attributable to microcirculatory disturbances in the coronary arterioles or smaller vessels. Moreover, we observed that the coronary flow at the induction of myocardial ischemia by pacing was much less than the reactive hyperemic flow. This discrepancy may be a characteristic feature in this syndrome.
The effects of ranitidine on plasma clearance of ICG were investigated in 68 cirrhotic patients (9 were positive for HBsAg, 33 were alcoholics and 26 had cryptogenic cirrhosis). The ICG clearance test was performed before and after ranitidine administration. In 31 patients treated with ranitidine (150 mg perorally), the plasma ICG clearance were 233.6 +/- 20.4 ml/min (mean +/- S.E.) and 239.2 +/- 20.5 ml/min before and after ranitidine, respectively. In the 37 treated with intravenous ranitidine 50 mg, the corresponding values were 205.4 +/- 17.7 ml/min and 206.4 +/- 17.9 ml/min. There was no significant change in the plasma clearance of ICG or the elimination rate constant after ranitidine administration. Even in patients with decompensated liver cirrhosis, no significant change was demonstrated in the plasma ICG clearance after ranitidine. These results led to the conclusions that ranitidine does not reduce the hepatic blood flow and that it is a safe and useful drug for the treatment of gastrointestinal tract bleeding in patients with liver cirrhosis.