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Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 415 records · Page 23Linked to original sources

Effects of KB-5492, a new anti-ulcer agent, on ethanol- and acidified aspirin-induced gastric mucosal damage in vivo and in vitro.

The effects of KB-5492, a new anti-ulcer agent with selective affinity for the sigma receptor, on ethanol- and acidified aspirin-induced gastric mucosal damage were studied in vivo and in vitro and compared with those of 16,16-dimethyl prostaglandin E2 (dmPGE2). In the in vivo study, KB-5492 (200 mg/kg, p.o.) as well as dmPGE2 (0.01 mg/kg, p.o.) significantly prevented the acute macroscopic lesions in rat gastric mucosa induced by oral administration of either absolute ethanol or 80 mM aspirin in 150 mM HCl. The light microscopic examination revealed that KB-5492 almost completely prevented the deep mucosal lesions induced by these necrotizing agents. KB-5492 also prevented the exfoliation of surface epithelial cells, but its preventive effect was incomplete. In the in vitro study, gastric epithelial cells, isolated from the rat stomach, were cultured for 6 days until they reached confluency. Subsequently, 51Cr was incorporated into the cells. Both 10 mM aspirin (at pH 5.0) and 12.5% ethanol (at pH 7.4) induced damage to the cells and markedly increased 51Cr release from the cells. KB-5492 at 0.3 and 1 mM and dmPGE2 at 0.3 and 1 microM significantly, but not completely, prevented both the aspirin- and ethanol-induced increases in 51Cr release from the cells. These findings indicate that KB-5492 as well as dmPGE2 may exert a direct but limited protective effect on the surface epithelial cells in vivo.

16,16-Dimethylprostaglandin E2↗

Effects of KB-5492, a new anti-ulcer agent with a selective affinity for the sigma-receptor, on aspirin-induced disruption of the rat gastric mucosal barrier.

The effect of KB-5492, a new anti-ulcer agent with a selective affinity for the sigma-receptor, on aspirin-induced disruption of the gastric mucosal barrier was studied in rats. Intragastric instillation of aspirin at 200 mg/kg rapidly decreased the gastric transmucosal potential difference (PD) in anesthetized rats. The PD recovered gradually following the removal of aspirin from the instillation solution. Aspirin, administered orally at 200 mg/kg, also reduced the amount of gastric covering mucus and induced a decrease in gastric H+ concentration and an increase in gastric Na+ concentration in pylorus-ligated rats. KB-5492, administered intraduodenally at 200 mg/kg, significantly prevented the aspirin-induced decrease in PD and accelerated the recovery of PD. In addition, KB-5492 at 200 mg/kg significantly prevented the reduction of gastric covering mucus, the decrease in gastric H+ concentration and the increase in gastric Na+ concentration induced by aspirin. These effects were similar to those of 0.01 mg/kg of 16,16-dimethyl prostaglandin E2 (dmPGE2). Teprenone at 200 mg/kg did not show any effect except for the inhibitory effects on the changes in gastric H+ and Na+ concentration. In the histological study, marked reduction of PAS-positive epithelial mucus and the exfoliation of surface epithelial cells were observed in the gastric mucosa exposed to aspirin. KB-5492 and dmPGE2 almost completely prevented the former, whereas both drugs prevented the latter incompletely. These findings indicate that KB-5492 protects the gastric mucosal barrier against the disruption by aspirin, which may be mainly exerted by retention of the gastric covering mucus.

16,16-Dimethylprostaglandin E2↗

Preparation of a new arabinoxylooligosaccharide from wheat bran hemicellulose and its structure.

A novel arabinoxylooligosaccharide was prepared from wheat bran and its structure was analyzed. Wheat bran hemicellulose was digested with a commercial Aspergillus japonicus hemicellulase preparation and an oligosaccharide was purified by carbon column and gel filtration chromatographies to be a single component. The oligosaccharide has D.P. of 6 and contains arabinose and xylose with a molar ratio of 2:1. Xylotetraose was formed as an intermediate hydrolyzate on acid hydrolysis of this oligosaccharide. Methylation analysis indicated that both reducing and non-reducing end xylose residues were free from arabinose residues and that there is only one xylose residue attached by two arabinose residues. The structure of this saccharide was finally identified by 13C NMR as beta-D-Xylp-(1-->4)[alpha-L-Araf-(1-->2)][alpha-L-Araf -(1-->3)]-beta-D- Xylp-(1-->4)-beta-D-Xylp-(1-->4)-D-Xylp.

Carbohydrate Sequence↗

Comparison of methods of cardiac output measurements determined by dye dilution, pulsed Doppler echocardiography and thermodilution in horses.

Cardiac output (CO) measurements by the three methods of dye dilution, pulsed Doppler echocardiography and thermodilution in horses under anesthetized conditions were compared. Although CO determined by the thermodilution method was slightly higher than those obtained by the other two methods, the measurements by all methods showed almost similar results. The coefficients of correlation between the dye dilution and thermodilution methods, the dye dilution and pulsed Doppler echocardiography methods, and the thermodilution and pulsed Doppler echocardiography methods were 0.87, 0.89, and 0.88, respectively (P < 0.01). These results indicate that pulsed Doppler echocardiography and thermodilution methods could be no less useful than the traditional dye dilution method for evaluating of CO in horses. The pulsed Doppler echocardiography method may offer some advantage over other two methods; it is non-invasive and enables continuous measurement of CO.

Animals↗

Cardiovascular effects of intermittent positive pressure ventilation in the anesthetized horse.

Intermittent positive pressure ventilation (IPPV) is useful method for compensate of respiratory function in anesthetized horses. However, IPPV may decrease cardiac output. Alterations in cardiac output of three groups (N = 5) healthy, halothane-anesthetized mares were determined and compared during a 120 min period of anesthesia. The groups were as follows: spontaneous ventilation (SV), controlled ventilation using an end-inspiratory pressure of 20 cmH2O (CV20) and a third group using 25 cmH2O (CV25) inspiratory pressure. In the CV groups, respiratory function was adequately maintained. Although, cardiac output tended to decrease over time in each group. After 105 min of anesthesia in the CV groups, the cardiac outputs decreased below 50 percent of pre-anesthetic values. In the CV25 group, cardiac outputs were significant difference (p < 0.05) from the SV group after 45, 90 and 120 min of anesthesia. There was no significant difference in cardiac output between SV and CV20 group over time. These values suggest that when long durations of anesthesia was used with the IPPV, decrease of cardiac output should be improved. In clinical use of halothane anesthesia, an end-respiratory pressure of 20 cmH2O seems to be appropriate because the mild decrease in cardiac output was observed even though a little high PaCO2.

Anesthesia, General↗

A case-control study on risk factors for leukemia in a district of Japan.

A case control study was performed with 142 leukemia patients and 284 controls matched for age and sex. Occupation, birth order, past medical history, and drinking and smoking habits were compared in these two groups. Persons born first or fourth were found to have a higher incidence of leukemia. History of a fracture was one of the risk factors for acute leukemia, and a history of gastroduodenal ulcer was a risk factor for chronic leukemia. This may suggest that extensive exposure to X-rays in diagnosis and treatment is a risk factor for leukemia. There was a significant dose-response relationship between the amount of smoking and the incidence of acute nonlymphocytic leukemia, but not between the amount of alcohol consumption and the incidence of leukemia. Thus, smoking was one of the risk factors for acute leukemia.

Aged↗

Effect of cerebral arterial occlusion on cerebral perivascular innervation: a histochemical and immunohistochemical study in the rat.

The effect of acute cerebral occlusion on the distribution of cerebral perivascular nerves containing catecholamine, neuropeptide Y, and vasoactive intestinal peptide was studied in the three commonly used rat models of cerebral ischemia: Unilateral permanent middle cerebral artery (MCA) occlusion induced with an intraluminal thread technique; unilateral MCA occlusion produced by extraluminal electrocoagulation of the MCA; and transient arterial occlusion of the whole brain induced extracranially by the four-vessel clasp occlusion method for 30 minutes. Animals were sacrificed 3 days after occlusion and the distribution of the perivascular nerves of the MCA studied. Intraluminally occluded MCAs showed a similar distribution of perivascular nerves to those of contralateral and sham-operated MCAs. Extraluminally occluded MCAs demonstrated a marked decrease in perivascular nerves containing catecholamine and peptides while the contralateral MCAs showed normal distribution of the nerves. Extracranial occlusion caused no discernible change in the distribution of perivascular nerves in occluded and sham-operated animals. This study indicates that the different methods of cerebral arterial occlusion have variable effects on the perivascular innervation. Arterial occlusion induced by intraluminal or transient extracranial procedures does not impair cerebral perivascular innervation at least up to 3 days post-occlusion. In contrast, cerebral arterial occlusion by extraluminal electrocoagulation diminishes the perivascular nerves around the occluded cerebral artery.

Animals↗

Effects of dietary supplementation with lactosucrose (4G-beta-D-galactosylsucrose) on cecal flora, cecal metabolites, and performance in broiler chickens.

The effects of dietary lactosucrose on cecal flora, cecal metabolites, and performance were studied in eight 20-d-old and eight 62-d-old broiler chickens fed a basal diet (control) or a diet with .15% lactosucrose added. On Day 20 of age, the frequency of occurrence of lecithinase-negative clostridia were decreased (P < .05) by lactosucrose consumption. On Day 62 of age, the numbers of bifidobacteria were increased (P < .05) by lactosucrose consumption, but the counts of lecithinase-positive clostridia, including Clostridium perfringens, bacteriodaceae, and staphylococci, total anaerobic bacteria, and the frequency of occurrence of pseudomonads were decreased (P < .05). No detectable change was observed in counts of other organisms throughout the experimental period. Cecal concentration of ammonia (P < .01), phenol (P < .05), and cresol (P < .05) were decreased on Day 62 of lactosucrose consumption. Acetic acid and butyric acid were increased (P < .01 and P < .05, respectively) on Day 62 of lactosucrose consumption. Environmental ammonia and odor of chicken ceca were greatly reduced by lactosucrose consumption.

Ammonia↗

[Equilibrium of small animals in "drop shaft" experimentation--preliminary study on the frog with vestibular neurectomy].

We have newly designed instruments for equilibrium experimentation, using a drop shaft, and studied the behavior and EMG Patterns of frogs with or without unilateral vestibular neurectomy, as a preliminary study at JAMIC (Japan Microgravity Center). The results are reported herein and the efficacy of the drop shaft in equilibrium experimentation is also documented. 1) In unilateral vestibular neurectomized frogs, posture--head tilt, leg flexion on the affected side, and leg extension on the opposite side--is maintained and persists under microgravity. Rolling to the affected side was also observed. 2) The latencies of the EMG responses from M. tibialis anticus and M. longissimus dorsi were prolonged on the affected side. 3) The frog is suitable for use in equilibrium experiments utilizing a drop shaft. 4) The JAMIC drop shaft can be used to obtain constant and stable microgravity, 10(-4) G for 10 sec, which is similar to that in space. Drop shafts are suitable for equilibrium experimentation.

Animals↗

A new thymopoietin precursor gene from human thymus.

Thymopoietin-related peptide (TPRP) gene was identified and cloned from a human thymus cDNA library. The cloned cDNA encoded a mature TPRP including the active site of thymopoietin (TP) (residues 32-36). TPRP and bovine TP were very similar in amino acid sequence, each being a 49 amino acid linear polypeptide. TPRP differed in only one residue from bovine putative TP and in only five residues from bovine TP I; whereas TPRP differed much more, at 12 amino acid residues, from human TP from thymus. This suggests that TPRP is a novel peptide and a genuine counterpart of the bovine TP.

Amino Acid Sequence↗

Induction of asymptomatic HBeAG carrier state in a patient with Down's syndrome following human bite.

A 56-year-old Japanese male patient with Down's syndrome was bitten by a hepatitis B envelope antigen (HBeAg) carrier and become an asymptomatic HBeAg carrier without seroconversion. His mitogen response of T cells was poor compared with that of healthy controls. An impaired T cell response to hepatitis B virus infection may be responsible for the HBeAg carrier with Down's syndrome.

Bites and Stings↗

Immunohistochemical study on blood-brain barrier in congenitally hydrocephalic HTX rat brain.

The purpose of the present study is to examine the blood-brain barrier in brain of congenital hydrocephalus HTX rats. We investigated the rat brain from postnatal day 1 to 44 using light and electron microscopy and immunohistochemical methods with monoclonal anti-blood-brain barrier (BBB) antibody. HTX rats developed hydrocephalus at 1-2 days after birth. Most rats succumbed to brain changes within 4-5 weeks. Among 136 HTX rats examined, 45 rats succumbed within 1 week after birth, 29 rats between 1-2 weeks, and 4 rats 27-44 days after birth. Out of 88 hydrocephalic rats 54 showed a marked ventricular dilatation, and 34 showed a mild dilatation. Dilatation of lateral ventricles was mild in the rats at 1-2 days after birth, but 3-14-day-old rats showed moderate or marked dilatation. 15-30 days after birth the rats developed mostly marked dilatation of lateral ventricles and third ventricle. Lateral ventricles and third ventricle showed a symmetric dilatation, but ependymal cell layers were well preserved. Aqueduct exhibited no dilatation in any rat. There were spongy appearances and cystic cavities in the white matter around the lateral ventricles. There were glial fibers and capillaries across the cystic cavities. Cystic lesions were also found in the deep subcortical white matter, consisting of spongy changes with extended extracellular spaces and microcysts in the white matter. Immunohistochemically, the anti-BBB reactivity in the normal control rats was at first weak at 2 weeks after birth and increased with the course of development, prominently 4 weeks after birth. Three- and four-week-old HTX rats with hydrocephalus showed moderate positive anti-BBB reaction in the cerebral cortex, the basal ganglia, and around the aqueduct but only a very weak reaction in the deep subcortical white matter and in the subependymal area of lateral ventricles. Laminin immunoreactivity was not different in the capillaries of hydrocephalic brain as compared with normal brain. Electron microscopically, tight junctions were well formed between endothelial cells of capillaries in the subcortical white matter. Occasionally capillaries with partial defect of basal membrane could be found, where the cytoplasm of endothelial cell was protruding between pericytic cytoplasm. Swelling of astrocytic end-feet were found around the microvessels. The results suggest that at the site of the lesion there is underdevelopment or immaturity of the blood-brain barrier.

Aging↗

Generation of self HLA-DR-specific CD3+CD4-CD8+ cytotoxic T cells in chronic graft-versus-host disease.

To analyze the mechanism of chronic graft-versus-host disease (GVHD) characteristic of autoimmune disease, we used a cell-mediated lympholysis assay to study the autoreactivity of PBL from two patients after MHC-matched BMT. Our data indicate the induction of CD3+CD4-CD8+ autoreactive cytotoxic T lymphocytes (CTL) in the one patient with chronic GVHD and an important role for allo-non-MHC (minor histocompatibility) antigen-specific CD3+CD4+CD8- helper T cells in this induction. Experiments using HLA-DR gene-transfected mouse L cells as target cells and blocking assays with anti-HLA class I and class II antibodies provided evidence that autoreactive CTL recognized HLA-DR antigen on autologous cells. Analysis of antigen-specific T cell proliferative responses in these patients to examine the effect of self HLA-DR-specific CTL on the antigen presenting cell (APC)-T cell interaction suggested that donor bone marrow-derived self HLA-DR-specific CTL are responsible for the decreased antigen-presenting ability of the patient's APC. These results suggest a new interpretation of the induction mechanism of chronic GVHD and its associated immunosuppression after MHC-matched BMT based on diminished APC function.

Antibodies, Monoclonal↗

Serum and urinary type IV collagen concentrations in the assessment of diabetic microangiopathy.

We investigated the role of measurement of serum and urinary type IV collagen (IV-C) levels in monitoring diabetic microangiopathy. Furthermore, we compared these levels in diabetic nephropathy and non-diabetic renal disease (NDRD). A one-step sandwich enzyme immunoassay was used to measure IV-C levels in 82 diabetic patients, 33 NDRD patients and 20 healthy non-diabetic control subjects. The diabetic patients were classified into four groups according to urinary albumin/creatinine index (ACI) (mg/g) and serum creatinine (s-Cr) (mg/dl): normoalbuminuria (ACI < 30), microalbuminuria (ACI 30-300), albuminuria (ACI > 300, s-Cr < 1.99 mg/dl) and renal insufficiency (s-Cr > 1.99 mg/dl). Serum and urinary IV-C levels were significantly elevated even in diabetic patients without clinical evidence of microangiopathy compared with control subjects (p < 0.05 and p < 0.01, respectively). Both levels were significantly higher in normoalbuminuric patients than in the control subjects, and in patients with microalbuminuria, albuminuria or renal insufficiency than in normoalbuminuric patients, with significant differences between these groups (serum and urinary IV-C, both p < 0.0001 by ANOVA). Urinary IV-C and albumin levels were significantly correlated, even in normo- and microalbuminuric patients (r = 0.55, p < 0.0001). Serum IV-C in normoalbuminuric patients rose significantly as the degree of retinopathy progressed from background to proliferative stages (p < 0.05). Neither serum nor urinary IV-C levels were influenced by glycemic control. Albuminuric diabetic patients (with and without renal insufficiency) had significantly higher levels of serum IV-C compared with those in proteinuric NDRD patients (p < 0.005), though there was no significant difference in the urinary IV-C level. However, the urinary IV-C/albumin ratio was significantly higher in albuminuric diabetic patients than in proteinuric NDRD patients, even after adjusting for s-Cr and creatinine clearance (p < 0.0001). In conclusion, we suggest that measured serum and urinary IV-C concentrations may serve as new markers for monitoring the development and progression of diabetic microangiopathy, particularly nephropathy. Furthermore, the measurement of serum IV-C concentrations and urinary IV-C/albumin ratios in diabetic patients may allow diabetic nephropathy and non-diabetic renal disease to be differentiated.

Adolescent↗

Effects of an angiotensin II receptor antagonist, TCV-116, on renal haemodynamics in essential hypertension.

The renal effects of a nonpeptide angiotensin II receptor antagonist, TCV-116, were investigated in 12 hospitalised patients with mild-to-moderate essential hypertension. After a 2-week placebo period, TCV-116 was given for 2 weeks in increasing doses from 4 mg to 8 mg daily to normalise the mean blood pressure. Blood pressure fell from 156 +/- 9/93 +/- 3 mmHg at the end of the placebo period to 140 +/- 9/85 +/- 4 mmHg after TCV-116 treatment. The pulse rate was unchanged. Renal vascular resistance fell from 1.62 +/- 0.20 to 1.37 +/- 0.17 dyne.s.cm-5 . 1.48 m2 x 10(4), renal plasma flow increased from 329 +/- 19 to 367 +/- 27 mL.min-1.1.48 m-2, and GFR was unchanged despite a fall in renal perfusion pressure. TCV-116 reduced the filtration fraction from 0.302 +/- 0.019 to 0.258 +/- 0.009, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium, potassium, and urate did not change. An increase in plasma renin activity (from 1.1 +/- 0.3 to 2.2 +/- 0.7 ng.mL-1.h-1) and a fall in the plasma aldosterone concentration (from 6.2 +/- 0.8 to 4.5 +/- 0.7 ng.dL-1) were also seen. These results indicate that TCV-116 has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension.

Adult↗

[Limb myokymia with involuntary finger movement caused by peripheral neuropathy due to systemic lupus erythematosus (SLE)--a case report].

A 24-year-old woman with SLE since the age of 12 developed sensory-motor peripheral neuropathy in 1990. Her sensory neuropathy was symmetrical in all limbs and distally dominant. Electrophysiological study showed marked reduction of motor and sensory conduction velocities. Sural nerve biopsy revealed vasculitis and axonopathy. Symptoms of neuropathy and nerve conduction velocities were improved by high dose steroid treatment. After one year she had a fever of unknown origin, and then presented limb myokymia with involuntary finger movement which was fine, irregular, and continuous. Needle EMG revealed myokymic discharge at dorsal interosseous and flexor pollicis brevis muscles. Because myokymia was increased by hyperventilation and suppressed by local anesthesia at the wrist, her myokymia was thought to originate in the peripheral nerve. This is the first case report of limb myokymia with finger involuntary movement caused by peripheral neuropathy due to SLE.

Adult↗

N-ras mutation: an independent prognostic factor for aggressiveness of papillary thyroid carcinoma.

BACKGROUND: The clinical importance of point mutations of ras oncogene in differentiated thyroid cancers has not been fully clarified. The purpose of this study is to determine the prognostic importance of ras mutation in papillary thyroid carcinoma. METHODS: Tumors of 91 patients with papillary carcinoma were studied; mean follow-up was 14.1 years (range, 1 to 40 years). Patients were grouped as follows: class I, intrathyroidal disease, n = 21; class II, cervical node metastases, n = 22; class III, extrathyroidal disease, n = 19; and class IV, distant metastases, n = 29. DNA was analyzed with polymerase chain reaction, oligonucleotide hybridization, and DNA sequence analysis techniques. RESULTS: Thirteen (14.3%) of 91 tumors showed an N-ras point mutation: 4.8% (1 of 21) patients in class I; 4.5% (1 of 22) patients in class II; 15.8% (3 of 19) patients in class III; and 27.8% (8 of 29) patients in class IV. Each mutation changed codon 61 from glutamine to arginine. Patients with distant metastases (8 of 29) had a significantly higher incidence of ras mutations than others (5 of 62, p = 0.01). Patients in classes III and IV also had a higher incidence of mutations (11 of 48) than patients in classes I and II (2 of 43, p = 0.01). The incidence of ras mutations was significantly higher in patients who died of papillary cancer (5 of 15, 33.3%) than in patients who are still alive (8 of 76, 10.5%) (p = 0.02). Kaplan-Meier survival curves also showed a greater mortality from tumor (p < 0.05) and a higher recurrence rate (p < 0.01) in ras-positive tumors than in the ras-negative group. Finally, in studies by multivariate analyses, positive ras mutation and age were shown to be two independent prognostic factors for prediction of death from papillary cancer and recurrence of cancer. CONCLUSIONS: Mutation of N-ras gene at codon 61 is an independent prognostic factor for aggressiveness of papillary thyroid carcinomas.

Adolescent↗

[Autoimmune mechanism in HAM/TSP].

Identification of the localization of HTLV-I proviral DNA in the central nervous system (CNS) is crucial to elucidate the pathogenesis of HTLV-I associated myelopathy (HAM)/Tropical spastic paraparesis (TSP). We have developed a new sensitive detection method, called two-step PCR in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin embedded spinal cord tissue sections from HAM/TSP. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I is unlikely as a result of viral infection of oligodendrocytes or neuronal cells. The sequence of T-cell receptor (TCR) V beta genes of the lymphocytes in the spinal cord lesions from the same HAM/TSP autopsy cases revealed an unique CDR3 motif, LCASSLXGG (one letter amino acid. X is any amino acid) which is identical to those found in mice encephalitogenic T-cell clones specific for myelin basic protein (MBP) peptide and two more motifs of LCASSPT (G), LCASSGRL were identical to those described in brain lesions of multiple sclerosis and in a rat T-cell clone from experimental allergic encephalomyeilitis (EAE) lesions, respectively. Taken together, the present results demonstrated that T-cells, which are reactive to the myelin component, such as MBP or PLP, may be activated by HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients and suggested that an autoimmune mechanism may be involved in the pathogenesis of HAM/TSP.

Amino Acid Sequence↗