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Biomedical subjects

H Ohta

Publications and source records attributed to H Ohta.

At least 415 records · Page 23Linked to original sources

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↗

[Clinical usefulness of tumor markers associated with pancreatic cancer].

Most of the recently developed tumor antigens detected by monoclonal antibodies are sugar chains and frequently associated with blood group substance. By immunohistochemical studies, we evaluated mainly the clinical usefulness and significance of the serum assay of CA-50 classified as a type 1 sugar chain, sialyl SSEA-1 as a type 2 sugar chain, and ST-439 with an undetermined structure, as well as their clinicopathological significance. In addition, the value of measurement of CA19-9, ST-439, and SLX in pure pancreatic juice (PPJ) was investigated. Furthermore, the clinical usefulness of K-ras mutation at codon 12 (KRM) in PPJ was studied. The incidence of serum CA19-9 among tumor markers was highest in pancreatic cancer (81%), but relatively high in benign diseases. On the other hand, both serological and immunohistological studies showed that sialyl SSEA-1 and ST-439 were highly specific for the tumor, whereas they appeared in serum or tumor less frequently than CA19-9 or CA-50 carrying the type 1 sugar chain. The accuracy of the tumor markers (CA19-9, sialyl SSEA-1, and ST-439) for pancreatic cancer, was almost equal (77% to 80%) and higher than that of CEA (69%). However, a highly positive correlation between sialyl SSEA-1 and ST-439 was revealed as well as among type 1 sugar chains in malignant diseases. Therefore, we conclude that the combination assay with CA19-9 or a similar tumor marker, sialyl SSEA-1 or ST-439, and CEA would be appropriate for the screening of pancreatic cancer. When the cut off value was set as the M + 2SD of the controls, significantly elevated concentrations of CA19-9 in PPJ were found in the secretory phase in 90% of the patients with pancreatic cancer (PC) and 66% of the patients with chronic pancreatitis (CP). Although increased concentrations of CA19-9 in PPJ have no cancer specificity, measurement of CA19-9 in PPJ can be used as a sensitive marker for some pancreatic disorders. On the other hand, concentrations of ST-439 and SLX in PPJ were significantly increased only in PC, and their incidences were 50% and 40%, respectively. They have a high tumor-specificity, but their incidences were not as high as initially expected.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗

[Osteoporosis after menopause and oophorectomy].

Characteristics of osteoporosis occurring after menopause and oophorectomy are described. Changes in hormone dynamics induced by menopause or oophorectomy lead to high metabolic turnover of bone, characterized by increased bone formation and resorption. The increase in bone resorption surpasses that of bone formation, resulting in decreased bone mineral density (BMD). Even before the onset of menopause, a transient decrease in estrogen concentrations can produce decreases in BMD that are comparable to those occurring after menopause or oophorectomy. Long-term observation of women undergoing premature menopause indicates that BMD progressively continues to decline in association with high bone metabolic turnover. There was no significant difference between BMD, 3 years after menopause, compared with that 3 years after oophorectomy, a time when the effect on BMD are fully evident. These findings indicate that osteoporosis, associated with either menopause or oophorectomy, can be managed in the same manner in a clinical setting.

Biomarkers↗

[A case of poorly differentiated hepatic cell carcinoma which showed 90% decrease in size after chemotherapy with intraarterial infusion of mitomycin C and oral administration of tegafur].

The patient was a 77-year-old man, admitted complaining of abdominal fullness and appetite loss. By ultrasonography and CT an 8 x 5 cm mass was discovered in S1 of the liver. Needle biopsy specimen from the lesion revealed poorly differentiated hepatic cell carcinoma. Because of his advanced age and the size of the tumor, surgical therapy was not used. Chemotherapy with intraarterial injection of mitomycin C 2 mg once a week and 800 mg of tegafur PO daily was given for 5 weeks until bone marrow suppression developed. After recovery of hematological data, tegafur 800 mg PO daily every other week was administered for a year. In the course of these therapies, the hepatic tumor became smaller, and the ultimate decrease rate was over 90% (PR). Thus far it seems that chemotherapy with tegafur might be tried in hepatic cell carcinoma cases in which surgery is not indicated.

Administration, Oral↗

The effect of castration on dopamine receptor sensitivity in male young rats: behavioral and neurophysiological studies.

The effect of castration on the sensitivity of dopamine (DA) receptor to low doses of apomorphine was investigated using drug discrimination task and neurophysiological recording of the firing rate of DAergic neuron in the substantia nigra pars compacta in male young Wistar rats. In the behavioral study, castration did not change the dose-response curve for apomorphine (ip) discrimination (the ED50 values in sham-operated and castrated animals were 45.2 and 47.1 micrograms/kg, respectively). In the neurophysiological study, the inhibitory effect of apomorphine (iv) on the firing rate of DAergic neuron in the substantia nigra pars compacta was significantly enhanced by castration (the ED50 values in sham-operated and castrated animals were 6.15 and 2.96 micrograms/kg, respectively). These results suggest that castration does not change post-synaptic DA receptor sensitivity, whereas it potentiates the sensitivity of pre-synaptic DA receptor to low doses of apomorphine in the substantia nigra.

Action Potentials↗

The interaction between central cholinergic and peripheral beta-adrenergic systems on radial maze performance in rats.

The interaction between cholinergic and beta-adrenergic systems on radial arm maze performance was investigated. Scopolamine significantly disrupted radial maze performance. Although neither propranolol (a centrally and peripherally acting beta-antagonist), nor atenolol (a peripherally acting beta 1-antagonist) affected the maze performance, both antagonists significantly augmented the scopolamine disruption. These results suggest the importance of the interaction between central cholinergic and peripheral beta-adrenergic systems on radial maze performance.

Acetylcholine↗

Spermidine and cardiovascular control in nucleus tractus solitarii in rat.

Cardiovascular effects elicited by unilateral microinjection of polyamines into the nucleus tractus solitarii (NTS) were tested in anesthetized rats. Spermidine (50-900 pmol) produced dose-dependent depressor and bradycardiac responses that were similar to those elicited by N-methyl-D-aspartate (NMDA; 0.1-1.2 pmol). The polyamines, putrescine and spermine, did not produce significant cardiovascular responses. The cardiovascular responses induced by spermidine and NMDA were almost eliminated by prior injection of the noncompetitive NMDA antagonist MK801 into NTS. On the other hand, a competitive antagonist 2-amino-5-phosphonovaleric acid (APV) blocked responses to NMDA but only attenuated those to spermidine. These findings support an action of the polyamine spermidine at the NMDA receptor complex in NTS where it could participate in modulating cardiovascular activity.

2-Amino-5-phosphonovalerate↗

A putative transcription factor binding to the upstream region of the puf operon in Rhodobacter sphaeroides.

Gel shift assays of the upstream region of the puf operon in Rhodobacter sphaeroides were performed using cell-free extracts from cells grown under various culture conditions. The results suggested that a protein binding to the upstream region functioned as a repressor-like substance of the expression of the operon by oxygen tension or light. The density of the shifted band of cell-free extracts from cells irradiated with blue light under semi-aerobic conditions was higher than that with red light. Phosphatase treatment of the cell-free extracts strongly increased the DNA-binding affinity of the protein.

Base Sequence↗

N200 component of event-related potentials in depression.

Event-related potentials (ERPs) recorded during a two-tone discrimination (oddball) task were examined in 36 drug-free depressed patients and 36 control subjects. At remission, the ERPs of 12 of the depressed patients were reexamined. In the depressed patients, although a group difference was not detected in the peak latency and amplitude of N200 to rare stimuli, the mean amplitude for the N200 latency range in the difference waves was smaller than in the control subjects. Mismatch negativity (N2a), which was elicited by rare stimuli, was reduced in amplitude; but N2b may have been evoked to frequent stimuli more in the patients than in the control subjects. Depressed subjects may have a deviance in the fully automatic cerebral mismatch process that is assumed to be related to mismatch negativity and provoke the controlled mismatch detection process (presumed to be associated with N2b) even to nontarget frequent stimuli. These findings were observed during remission; however, there was a tendency for the N2b amplitude to decrease and recover toward the level of the control subjects.

Adolescent↗

Antigenic properties of Campylobacter rectus (Wolinella recta) major S-layer proteins.

The antigenic properties of the surface layer (S-layer) proteins of various Campylobacter rectus strains including 24 clinical isolates and the type strain ATCC 33238 were examined. S-layer proteins were extracted from whole cells by acid treatment according to the method of McCoy et al. (Infect. Immun. 11, 517-525, 1975). The acid extracts from 23 of the isolates and ATCC 33238 contained two major proteins with molecular masses of 130 kDa and 150 kDa, both of which were identified as subunits of the S-layer after comparison with the protein profiles of acid-treated (S-layer-deficient) cells. An S-layer protein from one isolate (CI-808) demonstrated a different molecular mass (160 kDa). Both the 150-kDa proteins of ATCC 33238 and isolate CI-306 and the 160-kDa protein of CI-808 were purified by ion-exchange chromatography in the presence of urea. In Ouchterlony immunodiffusion experiments with these purified proteins and rabbit antiserum raised to each purified protein, both common and strain-specific antigenic determinants were identified in the C. rectus S-layer proteins.

Antigens, Bacterial↗

Effects of K+ channel openers on ischemic dysfunction and metabolic disturbance in isolated perfused rat heart.

The effects of two structurally different K+ channel openers, KRN2391 and cromakalim, on cardiac mechanisms during ischemia and reperfusion were studied in isolated perfused rat hearts. Isolated buffer-perfused rat hearts pretreated with KRN2391, cromakalim and vehicle were subjected to 25 min of ischemia followed by 30 min of reperfusion. Before ischemia, KRN2391 (1-10 microM) and cromakalim (1-10 microM) increased coronary flow, but did not modify cardiac function or biochemical parameters (adenine nucleotides, energy charge potential: ECP, lactate). During ischemia, KRN2391 (3, 10 microM) and cromakalim (10 microM) significantly accelerated the reduction in cardiac function and attenuated the decreased levels of ATP and ECP, but did not change the lactate content. After 30 min of reperfusion, pretreatment with KRN2391 and cromakalim resulted in a significant improvement in cardiac function, ischemic contracture and biochemical parameters. Thus, both KRN2391 and cromakalim have beneficial effects on biochemical parameters during ischemia and reperfusion, effects which may be related to cardiodepression during ischemia.

Animals↗

Immunohistochemical analysis of rat liver using a monoclonal antibody (HAM8) against gap junction.

Four monoclonal antibodies were raised against crude gap junction fractions of rat liver to clarify the distribution of gap junctions during animal development and to analyze gap junction expression in vivo and the polarity of hepatocytes in vitro. Among the monoclonal antibodies obtained, HAM8 antibody recognized the 27-kDa rat liver gap junction protein connexin 32. This antibody recognized gap junctions at the contiguous faces of hepatocytes, and the antigen was also observed in exocrine pancreas and salivary gland but not in kidney, heart, esophagus, or thymus. HAM8 did not react with amphibian or fish liver, heart, esophagus, stomach, or intestine as assessed via the immunofluorescence method on frozen sections. A few hepatocytes and many hemopoietic cells were seen in rat fetal liver at 15 days of gestation. HAM8 antigen was expressed on some hepatocytes but not on any hemopoietic cells. As the fetus grew, the number of hepatocytes in the liver increased gradually, together with the amount of HAM8 antigen. The distribution of HAM8 antigen at 25 days after birth was similar to that in adult liver. When the expression of HAM8 antigen was examined in primary cultured hepatocytes using the immunofluorescence method, the antigen was observed clearly between the hepatocytes. However, most of the HAM8 antigen on the free surface of hepatocytes disappeared within 4 hr. HAM8 antigen was not expressed on AH-7974 rat hepatoma cells when they formed small islets in the rat peritoneal cavity or within the liver. When HAM8 IgG antibody was injected intravenously, the HAM8 signal was expressed in the liver.

Animals↗

Antigenic and molecular properties of Murayama virus isolated from cynomolgus monkeys: the virus is closely related to avian paramyxovirus type 2.

A new virus that belonged to a member of paramyxovirus was isolated from cynomolgus monkeys showing respiratory disorders about 20 years ago and was named Murayama virus (MrV). Interestingly, it showed no serological relationship with the mammalian paramyxoviruses tested. On the other hand, it was related to Yucaipa (YuV) and Bangor virus (BaV) belonging to avian paramyxovirus type 2 (PMV2). In analysis using anti-MrV monoclonal antibodies, MrV showed the closest relationship with YuV, and furthermore some conserved epitopes were found among avian paramyxovirus, MrV, YuV, BaV, and Newcastle disease virus (NDV). Subsequently, the nucleotide sequences of the F and HN genes of MrV were determined. In comparison with the deduced amino acid sequence of MrV and other paramyxoviruses, MrV showed the highest homology with NDV and higher similarity to HPIV2 group rather than to HPIV1 group. The present study clearly indicates that MrV belongs to PMV2 adapting to monkeys.

Amino Acid Sequence↗

Relationship between myoglobin contents and increases in cyclic GMP produced by glyceryl trinitrate and nitric oxide in rabbit aorta, right atrium and papillary muscle.

Effects of glyceryl trinitrate (GTN) and nitric oxide (NO) on the cardiac functions and myocardial cyclic GMP (cGMP) contents were examined in comparison with those in the aorta and correlated with myoglobin (an inhibitor of soluble guanylate cyclase) contents using the preparations isolated from the reserpinized rabbit. GTN (10(-10)-10(-4) mol/l) produced a dose-dependent relaxation in the aorta. However, this compound exerted no effect on the rate of the spontaneous beat of the right atrium and the contraction of the papillary muscle. A transient and significant increase in cGMP was observed in the aorta with GTN (3 x 10(-6) mol/l). Although the increase was also observed in the right atrium, it was much smaller. No definite change was observed in papillary muscle. Increases in cGMP produced by NO (3 x 10(-6) mol/l) were larger and significant in all tissues; (AUCcGMP(GTN)/AUCcGMP(NO)) ratio was 30.1 for the aorta, 65.0 for the right atrium and 16.3% for the papillary muscle. Although higher concentrations of NO were necessary in the right atrium and papillary muscle to induce increases in cGMP, no differences were noted in the three tissues as regards the maximum accumulation of this substance. Furthermore, kinetic analysis of NO-induced increases in tissue cGMP indicated no marked difference in the production rate among the three tissues, while the rate of elimination of cGMP was lower in the aorta than in the atrium or the papillary muscle. The increases in cGMP observed in these three tissues were inversely related to the contents of myoglobin in respective tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗

Renal effects of manidipine hydrochloride. A new calcium antagonist in hypertensive patients.

The renal effects of manidipine hydrochloride were investigated in ten hospitalised patients with mild-to-moderate essential hypertension. After a one-week placebo period, manidipine was given for 1 week in a dose rising from 5 mg to 10 mg or 20 mg daily to normalise the mean blood pressure measured after 2 h. Blood pressure had decreased from 171/101 to 147/86 mm Hg at the end of manidipine treatment. The pulse rate was unaltered. Renal vascular resistance decreased from 1.90 to 1.33 dyn.s.cm-5/1.48 m2 x 10(4), and renal blood flow and glomerular filtration rate increased from 522 to 662 ml.min-1 x 1.48 m-2 and from 81 to 93 ml.min-1 x 1.48 m-2, respectively, in spite of a fall in renal perfusion pressure. Manidipine reduced the filtration fraction from 0.260 to 0.243, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium and potassium did not change. Manidipine did not produce any significant alteration in plasma renin activity or in the plasma aldosterone concentration. The results indicate that manidipine has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension.

Adult↗