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Biomedical subjects

M Kinjo

Publications and source records attributed to M Kinjo.

At least 19 recordsLinked to original sources

Effect of Irsogladine on gap junctions in cerulein-induced acute pancreatitis in rats.

The capacity for intercellular communication (IC) via gap junctions is found in normal pancreatic acinar cells. The major role of IC is considered to be the maintenance of tissue homeostasis and the regulation of signal transmissions. Up to now, the participation of IC via gap junctions in acute pancreatitis has not been reported. We investigated the role of IC in cerulein (Cn)-induced acute pancreatitis in rats using irsogladine, an enhancer of IC via gap junction. Acute edematous pancreatitis was induced in rats by two intraperitoneal injections of 40 micrograms/kg Cn. Rats received various doses (25, 50, or 100 mg/kg body weight) of irsogladine orally, 15 and 2 h before the first Cn injection. The normal control group received only vehicle. The severity of pancreatitis was evaluated enzymatically and histologically 5 h after the first Cn injection. In Cn-induced acute pancreatitis, irsogladine significantly lowered the serum amylase level, the pancreatic wet weight, and the pancreatic amylase and DNA contents, in a dose-dependent manner. Particularly, the amylase content improved to the level of the normal controls. Histologically, the severity of pancreatitis was reduced significantly by treatment with irsogladine and no discernible vacuolization was seen in the group with 100 mg/kg irsogladine treatment. By immunofluorostaining pancreata with anti-connexin 32 (Cx32; a gap junction protein) antibody, we found that pancreatic acini were diffusely positive for Cx32 in the control group, but the number of Cx32-positive grains decreased markedly, to 19%, in the pancreatitis group. With 100 mg/kg irsogladine treatment, the number of Cx32 grains recovered to 70% of the normal control value. These findings indicate that IC via gap junction is disturbed in Cn-induced pancreatitis, which may result in the breakdown of tissue homeostasis and the progression of acute pancreatitis.

Acute Disease

Clinical and histopathological studies in children with supraventricular tachycardia.

To determine whether myocardial changes in patients with supraventricular tachycardia (SVT) are primary or secondary to persistent tachycardia, 11 patients with SVT were studied. These patients were divided into 2 groups with respect to the type of SVT. Group I consisted of 5 patients with incessant SVT and one with multifocal atrial tachycardia, while group II consisted of 4 patients with paroxysmal supraventricular tachycardia and one with short-run supraventricular premature contraction. All of the patients underwent electrophysiological study and endomyocardial biopsy from the right ventricle following routine cardiac catheterization. In group II, there were no significant abnormalities in the clinical and hemodynamic parameters. In group I, 3 patients had clinical features of dilated cardiomyopathy including abnormal ECG, chest X-ray and hypokinesis on left ventriculography. Induction and termination of SVT were possible in 2 patients in group I and in 4 of the 5 patients in group II. The only significant histologic difference between group I and group II was fibrosis. A high incidence of histopathological abnormalities, such as hypertrophy, degeneration, interstitial fibrosis and disarray was observed in both groups. The incidence of significant pathology was higher in group I than in group II. Almost all of the patients were given antiarrhythmic drugs. One patient underwent a successful surgical procedure and normal cardiac function returned after resection of the foci of the right atrium. Our present results suggest that patients with SVT who have incessant or recurrent SVT should undergo not only intracardiac electrophysiologic study but also endomyocardial biopsy for the evaluation of myocardial damage, since SVT might be the initial sign of cardiomyopathy.

Adolescent

[Flow cytometry analysis of the DNA content of the prostate cancer--study on the tumor heterogeneity in prostate cancer].

PURPOSE: Clinical significance of DNA ploidy pattern and its DNA heterogeneity is examined in prostate cancer. METHODS: Fresh needle biopsy specimens were analyzed with flow cytometry and were compared with histopathological findings in 42 patients. RESULTS: Seven patients had stage B (1 case of B1, 6 cases of B2), 14 had stage C and 21 had stage D disease respectively. Histopathologically, 18 of the cases were well, 12 were moderately and 12 were poorly differentiated adenocarcinoma. Diploid was observed in 20, aneuploid in 22. Though 22 cases showed no DNA heterogeneity, 14 had type A heterogeneity with aneuploid in association with diploid pattern, and 6 cases had type B heterogeneity in which multiple aneuploid patterns with different D.I. values were observed. The heterogeneity was observed in 28% of well, 58% of moderately and 67% of poorly differentiated adenocarcinoma, respectively, and also in 14% of stage B, 50% of stage C and 57% of stage D patients, respectively. CONCLUSION: We conclude that DNA heterogeneity in prostate cancer is more frequently seen in poorer differentiated ones on histologic grade and in more advanced ones on clinical stage.

Adenocarcinoma

[The spread of contrast medium in the epidural space and the analgesic area in epidural anesthesia in elderly patients].

We evaluated the relationship between the spread of contrast medium in epidural space and the analgesia area in epidural anesthesia in elderly patients. The spread of contrast medium was examined radiographically after the injection of iotrolan 5 ml through the epidural catheter and the analgesia area was examined by pin prick following the epidural injection of the same volume of 1% lidocaine. In lumbar group (group L) (n = 10), the radiographic spread was 10.4 (4-17) segments (mean, minimum-maximum) and the analgesic area was 8.5 (4-15) dermatomes. In cervical or thoracic group (group C/T) (n = 10), the radiographic spread was 12.4 (8-17) segments and the analgesic area was 10.4 (6-15) dermatomes. The dose of local anesthetics required to get analgesia per. one dermatome was 0.7 (0.3-1.3) ml in group L and 0.5 (0.3-0.8) ml in group C/T. The spread of contrast medium correlated well with the analgesic area in both groups (group L:Y = 0.79X + 0.31, r = 0.92, group C/ T:Y = 0.80X + 0.52, r = 0.79). The mean dose of local anesthetics required for analgesia was smaller than that of previous reports although individual variations were large. We conclude that the spread of contrast medium is useful for predicting the spread of epidural block.

Aged

Ultrasensitive hybridization analysis using fluorescence correlation spectroscopy.

The hybridization of fluorescently tagged 18mer deoxyribonucleotides with complementary DNA templates was analysed by fluorescence correlation spectroscopy (FCS) in a droplet under an epi-illuminated fluorescence microscope at the level of single molecules. The interaction can be monitored by the change in the translational diffusion time of the smaller (18mer) primer when binding to the bigger (7.5 kb) DNA containing the complementary sequence. The hybridization process in the presence of template M13mp18 ssDNA was monitored in a small volume (2 x 10(-16)I) at various temperatures. The Arrhenius plot of the association rate constant shows that the activation energy was 38.8 kcal/mol, but the hybridization process may involve several components. The titration experiment suggested that approximately 2 primers can be associated with one template DNA at 40 degrees C. Results of a simple homology search for the sequences complementary to the primer indicate the existence of additional sites of lower specificity.

Base Sequence

New chronic pancreatitis model with diabetes induced by cerulein plus stress in rats.

To establish a new experimental model of chronic pancreatitis (CP) with diabetes, we investigated pancreatic endocrine function, blood flow, and histopathology in CP induced by repetition of cerulein injection plus water immersion stress in rats. CP rats were treated with water immersion stress for 5 hr and two intraperitoneal injections of 20 micrograms/kg body weight of cerulein once a week for 16 weeks. In the CP group, pancreatic contents of protein, amylase, elastase, and lipase significantly decreased to 64, 38, 23, and 68% of the control group, respectively. In oral glucose tolerance test (glucose 2 g/kg body wt), blood glucose level in the CP group was 212.1 +/- 97.8 mg/dl (mean +/- SD) at 30 min and was significantly higher than the control group (126.3 +/- 15.4 mg/dl)(P < 0.05). Two of seven rats in the CP group showed an obvious diabetic insulin in the CP group was 640.1 +/- 148.7 pM, significantly lower than in the control group (1133.4 +/- 242.0 pM)(P < 0.001). However, insulin content in the pancreas was 12.37 nmol/pancreas). In CP rats, winding and dilatation of surface blood vessels and gland atrophy were evident. Marked fibrosis, fatty changes, and destruction of lobular architecture were also demonstrated microscopically, although the structure of each pancreatic islet was preserved and each islet was fully stained with anti-insulin antibody. In the CP group, pancreatic blood flow by the hydrogen gas-clearance method was 197.6 +/- 33.0 ml/min/100 g, which was significantly less than the control group (276.2 +/- 19.1 ml/min/100 g) (P < 0.001). Thus, we conclude that the CP model induced by cerulein plus stress is a new CP model with diabetes in rats, in which the glucose tolerance was impaired without loss of insulin reserve.

Amylases

Two cases of urogenital malignancies in male patients undergoing maintenance haemodialysis.

We report two cases of urogenital malignancies, prostatic cancer in a 72-year-old man and urinary bladder carcinoma in a 50-year-old man, that developed during maintenance haemodialysis. The former patient responded to hormonal therapy with diethylstilboestrol and is still alive on maintenance haemodialysis, but the latter patient did not respond to treatment, being past cure in the far advanced stage. There are few clinical symptoms suggesting the existence of urogenital malignancies in dialysis patients and screening methods such as urine cytology or roentgenology must be restricted because of extremely reduced urine volume. However, the high incidence of urogenital malignancies in such patients is well recognized. Screening examinations with ultrasonography and/or CT scan following digital rectal examination or testing for serum prostate-specific antigen should be performed at least every 6 months.

Aged

Ultrastructural study of the effects of stress on the pancreas in rats.

We studied morphologic changes in a rat model of acute hemorrhagic pancreatitis in order to investigate the mechanism by which water immersion stress injures the pancreas. Acute hemorrhagic pancreatitis was induced by two intraperitoneal injections of 40 micrograms/kg body weight of caerulein at 1-h intervals under water immersion stress for 5 h at 23 degrees C. Light microscopy showed interstitial edema with inflammatory cell infiltration, degeneration and necrosis of acinar cells, and bleeding. Electron microscopy showed large autophagic vacuoles, decreased zymogen granules, and dilated rough endoplasmic reticulum in acinar cells. Basolateral exocytosis of large vacuoles and phagocytosis of the degenerated acinar cells were observed. In addition, microvascular damage, including the destruction of the capillary endothelial cells, capillary thrombosis, and the extravasation of blood cells, was seen. In contrast, in a pancreatitis model induced by caerulein injection alone, there was no bleeding, no remarkable vascular change, and no thrombosis. Degeneration and necrosis of acinar cells were less severe. In the pancreas under stress alone, microvascular damage and degeneration of acinar cells were observed. These findings demonstrate that stress injures the pancreas and worsens the pancreatitis by causing microcirculatory disturbances, such as vascular damage, thrombosis, increased vascular permeability, and bleeding. These results suggest that chemical mediators, such as free radicals and platelet-activating factor (PAF), which are produced by vascular damage and thrombosis, may accelerate the activation of zymogen proteases in acinar cells in caerulein-induced pancreatitis, leading to hemorrhagic pancreatitis.

Acute Disease

Time course of changes in phospholipid in cardiac mitochondria from rats recovering from prolonged swimming.

The time course of the recovery of cardiac mitochondrial phospholipids was investigated in rats subjected to a 3 hour loaded swim. The 3 hour swim caused a 50% reduction in mitochondrial phospholipids compared with the level in sedentary controls. During the first 12 hours of the recovery period, phospholipids tended to increase but fell again before reaching control values by 120 hours after the swim ended. Phospholipid recovery in microsomes was completed in 12 hours. Total mRNA in cardiac tissue decreased by about 15% in rats subjected to a 3 hour loaded swim but recovered to control levels in the first 12 hours of the sedentary recovery period. Thus, fluctuations in cardiac mitochondrial phospholipids do not parallel the changes in total mRNA in cardiac tissue.

Animals

The effectiveness of pressure support ventilation for mechanical ventilatory support in children.

BACKGROUND: The rapid respiratory frequency of children may lead to patient-ventilator asynchrony and increase the work of breathing during mechanical ventilation, and the use of a small endotracheal tube and a demand valve can further increase this work of breathing. Although pressure support ventilation (PSV) is well known to reduce the work of breathing in adults, there are no reports regarding clinical studies of PSV in children. Therefore, the effect of PSV on breathing patterns and the work of breathing in children was studied. METHODS: Six children (3-5 yr of age) were studied in the immediate postoperative period. Three levels of PSV, 0, 5, and 10 cmH2O, were employed. Airway pressure, flow, tidal volume, minute ventilation, and respiratory frequency were measured. To assess the work of breathing, the negative deflection of esophageal pressure (delta Pes) caused by inspiratory effort was measured. The inspiratory work of breathing was also estimated directly by measuring the esophageal pressure-volume loop using the Campbell technique. RESULTS: Although minute ventilation did not change with PSV, tidal volume increased and respiratory frequency decreased with increasing levels of PSV. The delta Pes decreased markedly from 8.9 cmH2O with PSV of 0 cmH2O to 5.7 cmH2O with PSV of 5 cmH2O and 2.7 cmH2O with PSV of 10 cmH2O. The mechanical work of breathing also decreased from 0.743 Joules/l with PSV of 0 cmH2O to 0.463 Joules/l with PSV of 5 cmH2O and 0.196 Joules/l with PSV of 10 cmH2O. CONCLUSIONS: It was concluded that PSV can effectively augment spontaneous breathing and reduce the work of breathing in children.

Child, Preschool

Acute pancreatitis induced by cyclosporin A under stimulation of pancreas by caerulein.

Our purpose was to investigate enzymatically and morphologically the acute effect of the immunosuppressive agent cyclosporin A (CsA) on the exocrine pancreas of rats. The intravenous injection of CsA 10 and 20 mg/kg body weight (BW) increased the content of pancreatic amylase and protein and decreased the content of pancreatic DNA. Histologically, we observed intraacinar vacuolization and individual cell necrosis. Under stimulation of the pancreas by two intraperitoneal injections of caerulein 5 micrograms/kg BW at 1-h intervals (which did not induce any evident change in the pancreas), CsA induced a significant increase in serum amylase and in pancreatic wet weight in a dose-dependent manner. CsA at doses of 10 and 20 mg/kg BW produced a significant increase in the content of pancreatic amylase and protein. Macroscopically, we observed marked pancreatic edema, venous dilatation, and patchy hemorrhage. Histologically, there were significant differences in the severity of intra-acinar vacuolization, interstitial edema, neutrophil infiltration, individual cell necrosis, and hemorrhage, severity of which was dose dependent. Pancreatic ductal erosion was particularly marked following treatment with CsA 20 mg/kg BW. These findings indicate that CsA accelerates abnormal pancreatic enzyme secretion and suggest that the therapeutically recommended doses of CsA can induce acute pancreatitis under stimulation of the pancreas.

Acute Disease

[A prospective study on necessary and sufficient retinal photocoagulation for diabetic retinopathy].

The present studies were performed to determine whether slight photocoagulation was better than heavy photocoagulation for the early stage of progressive proliferative diabetic retinopathy (PDR). The authors selected 17 patients who had bilateral PDR of equal severity (BI or BII stage according to Fukuda's classification). In every case, we randomly performed heavy photocoagulation (laser burns were 1142 +/- 179) to one eye and slight photocoagulation (405 +/- 166) to the other eye. More than 6 months after the last photocoagulation, the effects of these treatments were compared in both eyes by fundus pictures, visual acuity and posterior vitreous fluorophotometric values. The results of judgement by fundus pictures and by vitreous fluorophotometric values were in perfect agreement. Eight cases (47%) in whom eyes received slight photocoagulation showed result better than the other eye. Two cases (12%) which received heavy photocoagulation were better than the other eye. Seven cases (41%) showed the same level of severity. No significant differences were found between slight and heavy photocoagulation.

Adult

Suppressive effect of coenzyme Q10 on phospholipase A2 activation in cardiac cells after prolonged swimming.

Phospholipase A2 (PLA2) activity is elevated in cardiac microsomal fractions and phospholipids (PL) are much reduced in both the cardiac mitochondria and microsomal fractions from rats subjected to prolonged swimming. Preadministration of coenzyme Q10 (CoQ10 i.v. 30 mg/kg) significantly suppressed these changes. Two groups of 8-week-old male Wistar rats were trained to swim, receiving 30 min of training for 4 days. On the fifth day they were given an intravenous injection of either 30 mg/kg CoQ10 in saline or 1 ml saline. Thirty minutes later they began to swim for 3 hours carrying a weight representing 3% of body weight. On completion of the swim they were sacrified by instantaneous decapitation, and cardiac mitochondria were isolated. Mitochondria were also prepared from saline injected, unexercised control rats. Phosphatidylethanolamine (PE) and phosphatidylcholine (PC) concentrations were measured with HPLC and PLA2 activity was assayed fluorometrically. The mitochondrial concentrations (means +/- SEM, n = 6) of PE and PC were respectively 126 +/- 22 and 140 +/- 22 nmol/mg protein in the exercise-CoQ10 group against 66 +/- 4 and 50 +/- 10 nmol/mg protein in the exercise-saline group. The specific PLA2 activities (expressed as nmol degraded dipyrene phosphorylethanolamine substrate/hr/mg protein) in the microsomes was 0.20 +/- 0.02 in the exercise-CoQ10 group against 0.30 +/- 0.02 in the exercise-saline group. These results suggest CoQ10 has a protective effect against an excessive reduction in mitochondrial membrane phospholipids during prolonged exercise.

Animals

Effects of stress on the development of chronic pancreatitis.

In this study, the effects of chronic water immersion stress on the pancreas were investigated in four groups of rats (each group, n = 9): stress + cerulein group, stress group, cerulein group, and control group. Stress + cerulein rats were treated with water immersion stress for 5 h and two intraperitoneal injections of 20 micrograms/kg body wt of cerulein once a week for 16 weeks. In the macroscopic findings of the pancreas, all rats in the stress+cerulein group exhibited moderate or distinctive congestion of blood vessels, gland atrophy, and fatty changes, while some of them showed bleeding. Microscopically, they all exhibited moderate or severe fibrosis, inflammatory cell infiltration, fatty changes, destruction of lobular architecture, and hemosiderin deposits, while some of them also showed bleeding. The stress group without treatment with cerulein injections showed slight fibrosis, hemosiderin deposits, and bleeding. The cerulein group without stress treatment showed fatty changes, but no inflammatory cell infiltration or fibrosis. In the stress + cerulein group only, the contents of digestive enzymes and protein in the pancreas were approximately 55% lower than those of the control group, whereas those in other groups did not show significant reduction. These findings suggest that stress plays some role in the development of chronic pancreatitis, perhaps by causing circulatory disturbance and blood vessel injury.

Amylases

Effectiveness of pressure support ventilation for mechanical ventilatory support in patients with status asthmaticus.

We compared the effects of pressure support ventilation (PSV) with those of assist control ventilation (ACV) on breathing patterns and blood gas exchange in six patients with status asthmaticus. Both PSV and ACV delivered adequate minute ventilation (PSV: 7.5 +/- 1.4 l/min/m2, ACV: 7.3 +/- 1.3 l/min/m2) to correct respiratory acidosis (pH = 7.33 +/- 0.12 during both PSV and ACV) and prevent hypoxia. Peak airway pressure during PSV was significantly lower with the same tidal volume than that during ACV (PSV: 30 +/- 10 cmH2O (2.9 +/- 1.0 kPa), ACV: 50 +/- 13 cmH2O (4.9 +/- 1.3 kPa)). The lower airway pressure during PSV was due to persistent inspiratory muscle activity. The oxygen cost of breathing estimated by oxygen consumption was equivalent in both modes. We conclude that PSV is effective in supplying tidal volumes adequate to improve hypercarbia at markedly lower airway pressures than ACV.

Adolescent

Intratumoral heterogeneity in DNA ploidy of bladder carcinomas.

In order to investigate whether DNA ploidy in a single area of a tumor could be representative of the entire tumor, flow-cytometric DNA analysis was performed for multiple samples (an average of 7 samples) obtained from the same tumor in 9 cases of transitional cell carcinoma of the urinary bladder. The incidence of DNA aneuploidy was 88.9% (8 out of 9 cases) and, furthermore, in 7 of these, intratumoral regional heterogeneity in DNA ploidy was evident. With high frequency, bladder carcinoma consisted of heterogeneous cell populations with different ploidy. There were 2 cases in which the tumor consisted of mixed subpopulations of diploid and aneuploid clones which were located in different parts of the same tumor. In such cases, an aneuploid line could not have been detected in a single specimen from the tumors.

Adult

Flow-cytometric deoxyribonucleic acid analysis of the human bladder cancers with reference to histopathological findings.

Flow-cytometric (FCM) DNA analysis was performed in 534 samples from 140 bladder tumor cases and was compared with histopathological findings. Frequency of DNA aneuploidy was closely correlated with tumor grade. Namely the incidences of DNA aneuploidy were 20% in grade 0 (papilloma), 25.6% in grade 1, 57.7% in grade 2 and 95.7% in grade 3. Invasive tumors showed a significantly higher incidence of DNA aneuploidy than superficial papillary tumors. Frequency of DNA aneuploidy of CIS was between them. Nonpapillary tumors showed a significantly higher incidence of DNA aneuploidy than papillary tumors. Tumors with vessel invasion did show a similarly higher incidence than those without. Approximately 10% of histologically normal mucosa taken from the bladder tumor patients showed DNA aneuploidy. The present study could support possibilities that FCM findings were highly correlated with tumor malignant potentials and were also able to predict precancerous lesions on histologically normal mucosa.

Adenocarcinoma