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Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 577 records · Page 32Linked to original sources
PubMed1987

Purified opioid mu-receptor is of a different molecular size than delta- and kappa-receptors.

Opioid mu-receptors were solubilized from rat brains with 0.5% Triton X-100 in the presence of 0.32 M sucrose and then purified with 6-succinyl morphine-Affi-Gel 102 column. Purified materials showed a major band with mol.wt. 58,000 Da and a minor band with mol.wt. 41,000 Da. Affinity cross linking with [3H]DAGO, a selective mu-opioid agonist, to the neural membranes and purified materials revealed that opioid mu-binding protein has a mol.wt. of 58,000 Da, a value totally different from that of delta- (mol.wt. 18,500 Da) and kappa- (mol.wt. 36,000 Da) binding protein.

Animals↗
PubMed1987

Mechanism of direct cardiostimulating actions of hydralazine.

The vasodilator, hydralazine, was reported to also exert a direct positive inotropic effect on the myocardium at high concentrations. In the present study we investigated the mechanism of this positive inotropic action by using the ventricular myocardium of isolated perfused chick hearts. Hydralazine (10(-3) M) enhanced contractile force and heart rate, and elevated the myocardial cyclic AMP level. To study the Ca2+-dependent slow action potentials, the fast N+ channels were voltage-inactivated with elevated K+ (25 mM), resulting in a loss of electrical excitability. Hydralazine (10(-4) M) rapidly (less than 3 min) allowed the generation of slow action potentials and accompanying contractions by electrical stimulation. These effects of hydralazine were only partially prevented by propranolol. The results suggest that the increase of myocardial contractility produced by hydralazine is the result, at least in part, of a direct effect on the myocardium to increase Ca2+ inflow. The increased Ca2+ influx and inward slow current is due partly to activation of beta-adrenoceptors, with resultant elevation of cyclic AMP, and partly to another mechanism.

Action Potentials↗
PubMed1987

Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering.

In this study we provide evidence that distinct DNA sequences within the 5'-flanking regions of the genes for interleukin-2 (IL-2) and its receptor (IL-2R) are involved in human T-cell-specific activation of transcription by p40x, a product of human T cell leukemia virus type I (HTLV-1). The same DNA sequences appear to be responsible for induction of the genes in a T cell line, Jurkat, by mitogens. Although the IL-2 gene sequences are activated by p40x with much lower efficiency than the IL-2R gene sequences, they are synergistically activated by the p40x expression and subsequent extracellular stimulation by Concanavalin-A or anti-T3. We propose a model for two-step activation of the IL-2 autocrine loop in ATL development.

Cell Line↗
PubMed1987

Retroviral expression of the human IL-2 gene in a murine T cell line results in cell growth autonomy and tumorigenicity.

In mature T lymphocytes (T cells) the regulated expression of the genes for interleukin-2 (IL-2) and its receptor (IL-2R) constitutes an essential part in controlling the cell growth. Evidence has been provided which suggests the involvement of an aberrant function of the IL-2 system in developing T cell neoplasms, particularly the adult T cell leukemia/lymphoma (ATL). As an approach to examine the extent of the IL-2 system contribution to T cell neoplasms, we created the experimental conditions wherein both IL-2 and IL-2R are expressed constitutively in a murine T cell line. We made use of a retroviral vector to infect an IL-2-dependent CTLL-2 line and lead to the expression of human IL-2. Here, we show that the virus-infected cells not only proliferate in vitro in the absence of exogenously supplied IL-2 under certain conditions, but also develop tumors (lymphomas) in nude and syngeneic mice.

Animals↗
PubMed1987

Development of cell systems to study viral gene transcription at the initial phase of Epstein-Barr virus infection.

Two infection systems have been introduced in order to study viral gene expression at the initial period of Epstein-Barr virus (EBV) infection which leads to immortalization. The data indicate that major viral gene expression in tonsil lymphocytes at 2 days post-infection (p.i.) with EBV is very similar to that observed in latently infected cells. Both tonsil lymphocyte and BJAB cell (lymphoblastoid cells free of EBV genome) infection with EBV induced similar viral gene transcription. Twelve cDNA clones were prepared from poly(A) RNA of tonsil lymphocytes infected with EBV 2 days p.i. by hybridization with BamHI fragments of EBV DNA. Some cDNAs were derived from primary transcripts of the BamHI-WYHK region, suggestive of splicing of a large transcript. It is possible that a number of cDNA clones may be derived from cellular genes. The derivation of these cDNA clones is being studied.

Bacteriophage lambda↗
PubMed1987

1H-NMR of human saliva. An application of NMR spectroscopy in forensic science.

1H-NMR was applied to the study of metabolites in human saliva specimens. Acetate, lactate, ethanol, glucose and some other substances were simultaneously identified and quantitated from the 1H-NMR spectra of saliva specimens treated with D2O. These experiments demonstrated the value of 1H-NMR as an analytical method in the field of forensic science and clinical pathology and toxicology.

Acetates↗
PubMed1987

Acute haemodynamic effect of taurine on hearts in vivo with normal and depressed myocardial function.

The acute haemodynamic effects of taurine were studied in normal and in beta blocker (propranolol) or calcium antagonist (diltiazem) treated rabbits and in rabbits with experimentally produced chronic aortic regurgitation. The administration of taurine (25 mg.kg-1) did not affect heart rate and left ventricular end diastolic pressure but produced significant increases in left ventricular dP/dtmax, cardiac output, and left ventricular systolic pressure in control hearts, indicating that intravascularly administered taurine substantially increased cardiac performance. In propranolol (1 mg.kg-1) treated rabbits taurine significantly improved left ventricular dP/dtmax and cardiac output, which were previously depressed by propranolol. Taurine had the same effect on diltiazem (1 mg.kg-1) treated rabbits. In rabbits with aortic regurgitation a bolus injection of taurine improved cardiac performance. Continuous infusion of taurine (100 mg.h-1) also produced a significant increase in left ventricular dP/dtmax. These results suggest that taurine has a unique action as an inotropic agent and that it may be useful in the treatment of patients with congestive heart failure.

Animals↗
PubMed1987

Clinical course and prognosis of chronic pancreatitis.

Course and prognosis of 125 patients with chronic pancreatitis (CP) were evaluated. Follow-up period ranged from 1-20 years with a median of 6.3 years. The following conclusions were obtained. Recent increase of CP in our clinics was ascribed to alcoholic CP and idiopathic CP in the aged. Of 106 patients with pain, 74 showed improvement or disappearance of pain. Drinking habit and observation period were the main factors determining the rate of pain relief. Serial endoscopic retrograde pancreatography (ERP) showed aggravation in 17/47 patients, cholecystokinin-pancreozymin (CCK-PZ) secretin test in 4/40 patients, and oral glucose tolerance test (OGTT) in 7/25 patients. Exocrine function showed improvement in five patients, whereas endocrine function showed none. Improvement or aggravation of exocrine function was closely related to drinking habit. Main complications included 15 cases of peptic ulcer, 19 of pancreatic pseudocyst, and 15 of bile duct stenosis. Twenty-six patients died, often due to malignant neoplasms and diabetic complications. Those who continued drinking as much showed a lower survival rate than those who discontinued or decreased alcohol intake. The socioeconomic status deteriorated often due to pain or alcoholism. Three patients had to degrade jobs and six fell into inactive social life.

Age Factors↗
PubMed1987

Dendritic activities of spinal motoneurones in pigs and rabbits enhanced through chronic stimulation of a dorsal root.

1. The L6 or L7 dorsal root in 7-10-day-old pigs was chronically stimulated for 3 or 4 h a day for 4 days/week. The stimuli were 50 or 500 Hz pulse trains delivered at 0.5/s. The induced movements were limited to the hip and hind leg on the stimulated side without any sign of pain. There was evidence that not only the monosynaptic, but also polysynaptic pathways to the motoneurones were chronically stimulated. After 2-6 days of chronic stimulation, all pigs were studied in acute experiments either under pentobarbitone (Nembutal) anaesthesia or in the decerebrated state. Normal (unstimulated) 15-28-day-old pigs were also studied in acute experiments under similar conditions, as the controls. 2. In thirty-three out of fifty-six motoneurones of normal pigs there were all-or-none potentials of 2-6 ms duration and 1-5 mV amplitude. These have been named D-spikes. They occurred in response to tibial nerve and/or dorsal root stimulation and/or spontaneously. They could be abolished by injection of a hyperpolarizing current. These results show that D-spikes are different from any of the well-established all-or-none events of the motoneurone, i.e. the spikes of the axon, initial segment, soma and unitary excitatory post-synaptic potentials. Several kinds of D-spikes could exist in the same motoneurone, as judged from their wave forms and thresholds. This argues for the dendrites as the sites of origin for D-spikes, because only the dendrites can have multiple sites for spike generation. D-spikes were shown to summate to form a larger depolarization. 3. In pigs chronically stimulated with 500 Hz pulses seventy-five motoneurones were studied in acute experiments. In sixty-one motoneurones D-spikes were observed. This indicated that D-spike occurrence was enhanced in the chronically stimulated motoneurones as compared with controls. 4. Characteristic of the chronically stimulated motoneurone was the presence of a depolarization of all-or-none nature which was more than 10 ms in duration and 2-12 mV in amplitude. The depolarization is referred to as the D-wave. The D-wave was similar in properties to the D-spike described above, except that it was of longer duration. Consequently, it is assumed that the D-wave is summed D-spikes. D-waves were observed in nineteen motoneurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

A new uricosuric diuretic, S-8666, in rats and chimpanzees.

5-Dimethylsulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxyli c acid (S-8666) was studied as a possible new uricosuric diuretic agent using rats and chimpanzees. Various new compounds belonging to the 5-sulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acids were clearly diuretic with uricosuric activity in intraperitoneally oxonate-treated rats. S-8666 was chosen as a favorable candidate because its uricosuric activity due to the effects of tubular transport of uric acid were apparently more marked than those of known uricosuric agents such as probenecid, benzbromarone, tienilic acid and indacrinone in oxonate-treated rats. S-8666 was also uricosuric in rats not given urate oxidase inhibitor. The diuretic effect of S-8666 in oxonate-treated rats was as high-ceilinged as that of furosemide, while those of tienilic acid, indacrinone and a known compound of a 5-carbonyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acid were rather low-ceilinged. These uricosuric and diuretic activities of S-8666 were manifested by two enantiomers, of which the (+)-enantiomer displayed predominantly uricosuric activity and the (-)-enantiomer, diuretic activity like furosemide. The new compound was also uricosuric and diuretic in chimpanzees, although the potency of the uricosuric activity was similar to that of probenecid and less than that of indacrinone. Thus, it seems that S-8666 is a different type of uricosuric diuretic from known agents which have already been tried in humans.

Animals↗
PubMed1987

A new diuretic that does not reduce renal handling of uric acid in rats, S-8666.

The uric acid-retaining effects of diuretics were studied using sodium-restricted spontaneously hypertensive rats. Test agents were administered orally once a day for two weeks. Diuretic thiazides such as trichlormethiazide and hydrochlorothiazide and loop diuretics such as furosemide and indacrinone clearly reduced the renal function for uric acid excretion in treatment which produced major effects such as diuresis, saluresis and hypotension. However, a new diuretic with uricosuric activity, S-8666, developed in our laboratories, had no effect on the renal handling of uric acid at doses which showed major effects similar to those of other diuretics. The results should aid the understanding of the utility of S-8666 as a new diuretic antihypertensive which does not cause hyperuricemia during therapy.

Animals↗