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Biomedical subjects

Y Ohta

Publications and source records attributed to Y Ohta.

At least 433 records · Page 24Linked to original sources

Pulmonary blood flow distribution during acute hypoxia in conscious resting rats.

The effect of hypoxia on pulmonary blood flow (PBF) distribution were studied in 11 conscious resting rats. Microspheres were infused into the inferior vena cava during normoxia (Nx), acute normobaric hypoxia (AHx, 10% O2, 30 min), and 30 min after removal of hypoxia (post-hypoxia, PHx). The lungs were cut into 28 samples, and relative scatter of specific PBF was calculated as (sample activity/sample dry weight)/(total activity/total lung dry weight). Changes in pulmonary arterial pressure (PAP) during AHx were determined in five additional rats. During Nx, PBF was distributed preferentially to the hilar, central regions, rather than to the periphery. AHx resulted in a decrease in PaO2 from 85.1 +/- 0.9 to 37.8 +/- 1.2 Torr (mean +/- SE). Mean PAP increased significantly from 14.9 +/- 0.6 in Nx to 21.2 +/- 1.0 Torr in AHx (mean +/- SE). However, PBF distribution remained unchanged. PHx restored arterial blood gases and PAP to control levels without changing PBF distribution. The results indicate that conscious resting rats do not demonstrate changes in PBF distribution during AHx.

Animals↗

Simple fluorescent enzyme immunoassay for detection and quantification of hepatitis C viremia.

The viral load of hepatitis C virus, as reflected by hepatitis C virus viremia, has been shown to have important clinical implications. In this study the hepatitis C virus core protein level in serum was evaluated for the detection and quantification of hepatitis C virus viremia. Hepatitis C virus core protein in serum was detected using a simple and sensitive fluorescent enzyme immunoassay. Hepatitis C virus core protein was quantitated in 100 healthy subjects, 258 patients with hepatitis C virus infection and 108 patients with non-hepatitis-C-virus-related chronic liver diseases. HCV-RNA was determined using the branched DNA (bDNA) assay and reverse-transcription polymerase chain reaction. The detection limit of this fluorescent enzyme immunoassay was found between 10(4) - 10(5) copies/ml HCV-RNA equivalent. There was a good correlation between the core protein and bDNA assay results (p <0.01). Hepatitis C virus core protein was detected in 81% of patients with hepatitis C virus infection (acute hepatitis 4/5, chronic hepatitis 85/104, cirrhosis 64/73 and hepatocellular carcinoma 56/76) but in none of the healthy subjects and patients with non-hepatitis C virus chronic liver diseases. The amount of hepatitis C virus core protein in patients with hepatitis-C-virus-related hepatocellular carcinoma was lower compared to chronic hepatitis and cirrhosis (p <0.05). All 26 patients treated with interferon-alpha showed parallel changes between HCV-RNA and core protein levels. This fluorescent enzyme immunoassay is simple and quick (assay time <3 h) with sensitivity at least matching the bDNA assay. Similar levels of hepatitis C virus core protein were detected in patients with chronic hepatitis and cirrhosis, but patients with hepatocellular carcinoma tended to have a lower level of hepatitis C virus core protein.

DNA, Viral↗

Sterility in neonatally androgenized female rats and the decidual cell reaction.

In female rats, administration of androgen during early postnatal life results in anovulatory sterility characterized by polyfollicular ovaries and persistent vaginal cornification in adulthood. In these androgen-sterilized rats, the acyclic male pattern of gonadotropin secretion results from permanent damage to hypothalamic centers normally responsive to steroid feedback. The capacity of the endometrium to differentiate into deciduoma in response to endometrial stimulation is markedly reduced in the uterus of the androgenized rats receiving an appropriate regimen of progesterone and estrogen injections. The hypothesis is presented that the lowered uterine responsiveness in the androgenized rats is largely ascribable to the effect of androgen given neonatally rather than to the influence of continued exposure to ovarian estrogen. This review deals with the nature of the uterine response to ovarian hormones and the deciduogenic stimulus in androgenized rats in order to verify the mechanism involved in androgen action on the neonatal uterus.

Androgens↗

Oligonucleotide-mediated modulation of mammalian gene expression.

The notion that oligonucleotides can modulate gene-specific expression was established more than a decade ago. Recent advances in molecular genetics have broadened the armamentarium used to manipulate gene expression in biological systems including triplex DNA, antisense RNA/DNA, and ribozymes (catalytic RNA). These oligonucleotides demonstrated important early application to the elucidation of cellular signaling pathways. More recently, studies with these agents have probed their utility as potential therapeutic agents, especially in the realm of cancer. With the implementation of gene therapy in early clinical trials, oligonucleotide-mediated suppression of gene expression has emerged as an important strategy for gene therapy. This review will discuss the current knowledge in this field, focusing on the biology of triplex DNA, antisense oligonucleotides, and ribozymes.

Animals↗

Activity changes in rat raphe magnus neurons at different concentrations of fentanyl in vitro.

The nucleus raphe magnus (NRM) is an important descending pain inhibitory system. We postulated that the analgesic action of supraspinally administered opiates results from increased descending inhibitory control of the NRM. We tested whether fentanyl activates NRM neurons in the rat slice preparation using extra-cellular recording. Eighty-seven percent of NRM neurons (total number = 68) tested were spontaneously active with firing frequencies of 0.2-4 spikes/s in artificial cerebrospinal fluid. Application of fentanyl (0.25, 0.5, and 1 mumol/L) increased firing frequencies in 12 of 59 (20%) spontaneously active neurons. In 6 of 9 (67%) silent neurons, fentanyl induced firing activities. Naloxone (1-2 mumol/L) antagonized the increased or induced activities by fentanyl in three neurons. In 13 of 59 (22%) spontaneously active neurons, fentanyl decreased the firing frequencies. Although fentanyl was associated with increased activity in a total of 18 NRM neurons, fentanyl at a higher concentration significantly increased the number of inhibited neurons. The results indicate that fentanyl partly activates the descending inhibitory system originating from the NRM; however, at higher concentrations, it appears also to inhibit this same system.

Action Potentials↗

The effect of isoflurane and temperature on the actions of muscle relaxants in rat in vitro.

Hypothermia and isoflurane alone increase the potencies of steroidal muscle relaxants (MRs). We studied the combined influence of isoflurane and hypothermia on MR potency. Phrenic nerve-hemidiaphragm preparations of rats were mounted in modified Krebs' solution and aerated with 5% CO2-95% O2 gas mixture at 37 degrees C and 4% CO2 at 27 degrees C to maintain the CO2 content constant. Phrenic nerves were stimulated with 0.1 Hz supramaximal impulses and elicited tension of the diaphragm was recorded. Isoflurane 1% was added after stabilization of twitch tension and MR was added 60 min later. Twitch tension was reduced by 20% +/- 2.5% at 37 degrees C and 3.5% +/- 0.7% at 27 degrees C from control with only isoflurane. The IC50 (inhibitory concentration, 50%) values of the MRs decreased significantly (P < 0.05) with isoflurane at both temperatures. The ratios of the IC50 values without and with isoflurane of the benzylisoquinolinium MRs were significantly more at both temperatures (P < 0.05) indicating the enhancement of potentiation of their action by isoflurane over steroidal MRs. When the soluble concentration of isoflurane at 27 degrees C was kept similar to that of at 37 degrees C, the ratios of all the MRs were reduced significantly from the ratios at 37 degrees C, indicating a reduction of potentiation. When the partial pressure of isoflurane was kept constant at 37 degrees C and 27 degrees C, the potentiating action of the MRs by isoflurane was similar. But when the partial pressure was decreased to keep the concentration of isoflurane constant, the potentiation was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ocular fundus changes in malignant or precocious stroke-prone spontaneously hypertensive rats after administration of antihypertensive drugs.

1. Malignant or precocious stroke-prone spontaneously hypertensive rats (M-SHRSP) showed hypertensive ocular fundus changes with severe hypertension, but various anti-hypertensive drugs given over a proper period improved funduscopic findings. 2. We treated a M-SHRSP with SQ29,852 (an angiotensin converting enzyme inhibitor, ACEI) or manidipine (a calcium antagonist) and observed hypertensive vascular changes in the fundus. 3. The M-SHRSP treated with anti-hypertensive drugs lived longer and the hypertensive fundic changes improved in both groups. But there were some differences of histochemical staining reaction on the endothelial cell-surface and mucopolysaccharides accumulations between the treated group of ACEI and the group treated with the calcium antagonist. 4. In the treated group with calcium antagonist, the anionic ion functions of the endothelial cell-surface were impaired and organic retinal or choroidal damages appeared to have deteriorated.

Angiotensin-Converting Enzyme Inhibitors↗

Influence of hypertensive vascular changes in intratesticular arteries on spermatogenesis in SHRSP.

1. The process of the spermatogenetic damage induced by hypertensive vascular changes was studied with stroke-prone spontaneously hypertensive rats (SHRSP). 2. In SHRSP, hypertensive changes in intratesticular arterioles developed from 19 weeks of age. 3. At 23 weeks of age, a severe reduction in the number of mature and immature spermatids was observed. 4. The transferrin concentration in testicular cytosol was decreased at 23 weeks of age, suggesting that Sertoli cell function in SHRSP had regressed. 5. In conclusion, it was suggested that the decline in Sertoli cell function as a result of hypertensive vascular changes is part of the mechanism whereby spermatogenic damage occurs in SHRSP.

Animals↗

Temporal and spatial properties of slow waves in the electroencephalogram of spontaneously hypertensive rats.

1. Electroencephalogram (EEG) of stroke-prone spontaneously hypertensive rats (SHRSP) and M(malignant)-SHRSP were analysed for excitability changes in the cerebral neuronal circuit using power spectral comparisons. 2. EEG in hypertensive SHRSP and M-SHRSP showed the emergence of slow wave bursts parallel to the development of hypertension. 3. These bursts were composed of spikes and sharp waves, and became dominant in the later stages of hypertension. 4. Bursts were interposed by a silent period indicating a strongly depressed state of neuronal activities. The ratio of the periods of the depressed to the burst increased with the progress of the hypertension. 5. A shift of the major component toward a lower frequency band also indicated decreased cerebral activity.

Animals↗

Long-term therapeutic effects of ace inhibitor and calcium antagonists on hypertensive vascular lesions in M-SHRSP.

1. Our results indicate that the drugs used in this study are very effective in malignant hypertension therapy. 2. For M-SHRSP treated with highly effective antihypertensive drugs, if blood pressure remains under 200 mmHg over the long-term, the structures of the small arteries and/or arterioles stay as well preserved as they do in WKY. 3. For M-SHRSP treated with drugs with a lower antihypertensive effect, the occurrence of cerebrovascular lesions and angionecrosis in the various organs are suppressed significantly, even though blood pressure remains over 250 mmHg over the long-term. Based upon effect alone, there is no difference between ACEI and a calcium antagonist. However, inhibition of the proliferation of vascular smooth muscle cells is more potent in the former than in the latter. 4. These results suggest that ACEI might have the potential to suppress smooth muscle cell proliferation independent of high blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗

Suppressive effects of benidipine on the development of hypertension and renal lesions in salt-loaded stroke-prone spontaneously hypertensive rats.

1. The effects of benidipine hydrochloride (benidipine), a long-acting dihydropyridine calcium antagonist, on the development of hypertension and renal lesions were examined in stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were fed with 8% NaCl diet for 3 weeks from 13 weeks of age, and benidipine (1 or 3 mg/kg per day) was orally administered during the same period. 3. The high salt diet accelerated an increase in urinary excretions of total protein and albumin, and caused marked arteriole, glomerular and tubular lesions in the kidney. 4. Benidipine significantly inhibited these changes, and also suppressed the elevation of blood pressure in salt-loaded SHRSP. 5. These results reveal that benidipine has protective effects against the development of hypertension and the progression of renal lesions induced by the high salt diet in SHRSP.

Animals↗

Protective effects of manidipine on spermatogenesis in stroke-prone spontaneously hypertensive rats.

1. We evaluated the protective effects of manidipine on spermatogenic damage induced by the hypertensive vascular changes in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Blood pressure reached more than 250 mmHg in SHRSP at 15 weeks of age, and thereafter the hypertensive changes in testicular arterioles developed. Manidipine reduced both the blood pressure and the hypertensive vascular changes. 3. Although immature and mature spermatids greatly diminished in SHRSP at 23 weeks of age, manidipine could preserve almost normal spermatogenesis even at 23 weeks of age. Transferrin concentration in testicular cytosol, which was considered to be indicative of the Sertoli cell function, in SHRSP with manidipine administration was significantly higher than that in SHRSP with no treatment at 23 weeks of age. 4. In conclusion, manidipine could prevent the development of the hypertensive changes in intratesticular arterioles and maintain normal Sertoli cell function. As a result, manidipine protected spermatogenic damage in SHRSP.

Animals↗

Electroencephalographic evaluation of the therapeutic efficiency of antihypertensive agents on M-SHRSP.

1. In order to evaluate the therapeutic effects of antihypertensive agents on malignant hypertension in M-SHRSP, EEG were performed as a non-invasive, therapeutic index. 2. Under pentobarbital anaesthesia, the EEG pattern of rats with severe hypertension and/or cerebrovascular lesions showed alternate short-active and long-depressive phases with spike and sharp waves. 3. When M-SHRSP were treated with an angiotensin converting enzyme inhibitor (SQ 29,852) or a calcium antagonist (manidipine), the depressive phases became shorter and active phases longer. These changes were more prominent in manidipine treated rats than in SQ 29,852 treated rats. 4. The EEG spike- and sharp-wave complex seems to be a convenient index for evaluating cerebrovascular lesions and cerebral activity in M-SHRSP.

Angiotensin-Converting Enzyme Inhibitors↗

Myoepithelial carcinoma in pleomorphic adenoma of salivary gland type, occurring in the mandible of an infant.

A rapidly growing mandibular tumor occurred in a 17 month old female infant. Tumor outgrowth showing a periosteal reaction was radiographically seen on the lower surface (base) of the mandible. Under the biopsy diagnosis of osteosarcoma, high-dose chemotherapy with methotrexate was performed, resulting in little effect. The right hemimandibulectomy specimen disclosed intraosseous infiltrative growth of pleomorphic adenoma of salivary gland type, associated with chondroid stroma and reactive bone formation. The highly proliferative small-sized cells retained immunohistochemical features of myoepithelial cells, with positive reactivity of cytokeratin, vimentin, S-100 protein, alpha-smooth muscle actin, epithelial membrane antigen, CA15-3, type IV collagen, laminin and p53 protein. No heterotopia of the salivary gland was identified within the bone tissue. The tumor recurred 2 months later. Due to uncontrollable local growth, the patient died 8 months after operation. At autopsy, reactive ossification was closely associated with malignant myoepithelial proliferation. No distant metastasis was noted. This osteosarcoma-like tumor can be regarded as myoepithelial carcinoma in pleomorphic adenoma, originating from intramandibular heterotopic salivary gland tissue.

Adenoma, Pleomorphic↗

Prediction of prognosis of primary biliary cirrhosis in Japan.

The clinical profile of primary biliary cirrhosis in Japan was clarified on the basis of data on 1066 patients attending 212 hospitals and institutions in this country. Six hundred and twelve patients (57.4%) were asymptomatic. The majority of the patients were middle-aged women. Pruritus was the most frequent initial symptom of symptomatic primary biliary cirrhosis. Antimitochondrial antibodies were positive in 877 patients (82.5%). Sjögren's syndrome was the most common associated autoimmune disease. Liver biopsy was performed in 753 patients at the time of diagnosis, and histological staging by Scheuer's classification indicated that 307 (43.7%) patients were in stage I and 222 (31.6%) were in stage II. The most frequent causes of death were hepatic failure and/or gastrointestinal bleeding, which affected 166 (78.3%) of the 212 patients who died. Statistical analysis using Cox's regression method revealed that the patient's age and the serum bilirubin, albumin, and total cholesterol concentrations were significant predictors of the prognosis. A prognostic index was also calculated that could be used to predict the duration of survival for patients with primary biliary cirrhosis.

Adult↗

Preventive effect of dai-saiko-to (da-chai-hu-tang) extract on disrupted hepatic active oxygen metabolism in rats with carbon tetrachloride-induced liver injury.

In order to clarify the preventive action of Dai-Saiko-to (Da-Chai-Hu-Tang) extract (TJ-8) on the progression of acute liver injury in rats intoxicated with carbon tetrachloride (CCl4), we examined the effect of post-oral TJ-8 administration on hepatic active oxygen metabolism following the progression of this liver damage. When TJ-8 (1.0 g/kg body weight) was administered orally to male Wistar rats aged five weeks 2 hrs after i.p. injection of CCl4 (1.0 ml/kg body weight), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found at 24 hrs after injection, judging from the activities of serum transaminases, indexes of liver cell damage. Liver cytosolic superoxide dismutase (SOD) activity decreased 2 and 24 hrs after CCl4 injection, while liver cytosolic catalase and glutathione reductase (GSSG-R) activities decreased 24 hrs after the injection. At 2 and 24 hrs after CCl4 treatment, liver cytosolic Se-containing glutathione peroxidase (GSH-px) activity did not change and liver cytosolic glucose-6-phosphate dehydrogenase (G-6-PDH) activity increased. Post-oral TJ-8 administration significantly ameliorated decreases in liver SOD, catalase, and GSSG-R activities at 24 hrs after CCl4 injection, but did not affect liver Se-GSH-px and increased liver G-6-PDH activities at 24 hrs after the injection. Although increased liver lipid peroxide level and decreased liver reduced glutathione and ascorbic acid levels were observed 2 and 24 hrs after CCl4 injection, post-oral TJ-8 administration significantly prevented these changes found at 24 hrs after injection. These results indicate that post-oral TJ-8 administration can prevent the progression of acute liver injury in CCl4-injected rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.

Administration, Oral↗

Distribution of mRNAs for natriuretic peptides in RV hypertrophy after pulmonary arterial banding.

It has been unclear whether the increases in transcript accumulation for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) during pressure overload are caused by the direct hemodynamic stress imposed on the myocytes or mediated by systemic hormonal factors. We examined the levels and regional distributions of ANP and BNP mRNAs in the hypertrophied right ventricle produced by experimental coarctation of main pulmonary artery (PA) in rats and compared them with those of skeletal alpha-actin mRNA, which is known to be a genetic marker for cardiac hypertrophy. In this experimental model, the left ventricle was free from the influence of pressure overload. By Northern blot analysis, remarkable increases in mRNAs for ANP and BNP, as well as skeletal alpha-actin, were observed in the right ventricle at 1 day after PA banding. Changes of expression of these genes were minimal in the left ventricle. ANP mRNA levels in the right ventricle increased further at days 3 and 7, whereas BNP mRNA remained at its day 1 level through 7 days. Increased expression of ANP, BNP, and skeletal alpha-actin mRNAs occurred exclusively in the right ventricular (RV) free wall and in the junctional region between the RV free wall and the interseptal wall as determined by in situ hybridization. These data suggest that local stimuli caused by hemodynamic overload induce cardiac hypertrophy and its associated increases in ANP and BNP expression in the RV free wall.

Actins↗

Muscle energy metabolism and nutritional status in patients with chronic obstructive pulmonary disease. A 31P magnetic resonance study.

We investigated the relationship between nutritional status and muscle energy metabolism during exercise in 18 male patients with chronic obstructive pulmonary disease (COPD) and 15 male control subjects using 31P nuclear magnetic resonance spectroscopy (31P-MRS). The patients and control subjects were further categorized as in either a well-nourished (% ideal body weight, % IBW > or = 90) or malnourished (% IBW < 90) state. Muscle energy metabolism was evaluated by determining the ratios PCr/(PCr + Pi) (PCr, phosphocreatine; Pi, inorganic phosphate), and ATP/(PCr + Pi + ATP). The exercise consisted of repetitive hand grips performed against a load. The work rate was normalized for the individual's lean muscle mass by dividing work performed by the forearm fat-free cross-sectional area, which was calculated using 1H-MRS. The PCr/(PCr + Pi) values during exercise did not correlate with the % IBW in any of the groups of control subjects or COPD patients. Furthermore, the PCr/(PCr + Pi) did not correlate with the normalized work rate in either the well-nourished or malnourished subject groups. However, there were correlations within the groups of control subjects and COPD patients. The PCr/(PCr + Pi) values for the normalized work rate were consistently lower in the COPD patients than in the control subjects. These findings suggest that the altered muscle metabolism in COPD patients is not affected by their nutritional status.

Adenosine Triphosphate↗