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Biomedical subjects

S Kubo

Publications and source records attributed to S Kubo.

At least 469 records · Page 26Linked to original sources
PubMed1983

Cardiovascular effects of a newly synthesized cardiotonic agent (TA-064) on normal and diseased hearts.

A new inotropic agent, TA-064, (-)-alpha-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzylalcohol, was shown to have strong effects in experimental animals. Its effectiveness and associated adverse effects were tested in humans invasively (n = 6) and noninvasively (n = 17). Increasing doses of intravenous infusion (1, 2, and 4 micrograms/kg/min) increased plasma levels to 15, 35, and 82 ng/ml, respectively, resulting in marked increases in the peak rate of left ventricular pressure rise (dP/dt) (1,450 +/- 63 to 3,042 +/- 349 mm Hg/s) (mean +/- standard error of the mean [SEM], p less than 0.01) and the ratio of dP/dt to left ventricular pressure at a developed pressure of 40 mm Hg (25 +/- 3 to 39 +/- 2 s-1) (p less than 0.01), with a reduction in left ventricular end-diastolic pressure (12 +/- 2 to 4 +/- 1 mm Hg) (p less than 0.01). Minimal or no changes were seen in heart rate and left ventricular systolic pressure. After a single oral dose (10 mg), the plasma level reached its peak at 90 minutes (16 +/- 9 ng/ml, n = 17). A positive inotropic effect was confirmed echocardiographically in both healthy volunteers (n = 8) and patients with congestive heart failure (CHF) (n = 9) who were maximally treated with conventional regimens: increase in mean velocity of circumferential fiber shortening (healthy volunteers: 1.29 +/- 0.05 to 1.60 +/- 0.11 circ/s [p less than 0.05]; patients with CHF: 0.69 +/- 0.08 to 0.93 +/- 0.09 circ/s [p less than 0.01]), ejection fraction (healthy volunteers: 68 +/- 2 to 75 +/- 2% [p less than 0.05], patients with CHF: 37 +/- 4 to 45 +/- 5% [p less than 0.01]) without change in heart rate. The cardiac index was increased only in the CHF group (2.71 +/- 0.22 to 3.21 +/- 0.24 liters/min/m2) (p less than 0.05). No significant untoward effects were observed. Thus TA-064 is a potent inotropic agent and can be used either parenterally or orally. Salutary effects can be expected in patients with congestive heart failure who are treated with digitalis and diuretic agents.

Adult↗
PubMed1983

Some cellular characteristics of somatostatin neurons and terminals in the periventricular nucleus of the rat hypothalamus and median eminence. Electron microscopic immunohistochemistry.

Somatostatin neuronal perikarya and their processes, presumably dendrites, in the periventricular nucleus of the rat hypothalamus and terminals in the median eminence were observed by electron microscopic immunohistochemistry. Neuronal perikarya and processes contained immunoreactive dense granules (100-120 nm in diameter) and other cellular components such as polysomes, rER membranes occasionally showed high electron density. Few axo-somatic terminals were found on the somatostatin neurons, but we could detect a number of preterminal axons on immunoreactive processes, presumably dendrites. Therefore, we considered that somatostatin neurons receive mainly neuronal input through axo-dendritic synapses rather than through axo-somatic ones. In the somatostatin terminals in the external layer of the median eminence immunoreactivity was completely restricted on the granules.

Animals↗
PubMed1983

Binding of Clostridium botulinum type C neurotoxin to rat brain synaptosomes.

The binding of Clostridium botulinum type C neurotoxin to rat brain synaptosomes was determined by the use of 125I-neurotoxin. The binding was independent of the incubation temperature (0 degrees C and 37 degrees C) and was equilibrated in 10 min. The dose dependent of 125I-toxin binding to synaptosomes at 0 degrees C showed that there were two kinds of toxin receptors on the synaptosomal membrane; the association constants and maximum binding values were 1.05 x 10(10 M-1, 5.25 x 10(-13) mol/mg of synaptosomal protein and 5.00 x 10(6) M-1, 5.00 x 10(-12) mol/mg of synaptosomal protein, respectively. When the incubation of toxin with synaptosomes was continued at 37 degrees C after 125I-toxin had been pre-incubated with synaptosomes at 0 degrees C for 10 min, the displacement of labeled toxin by the addition of excess amounts of unlabeled toxin decreased slightly with increasing incubation time, and finally 0.4% of the bound 125I-toxin was not displaced from synaptosomes. The binding of 125I-toxin to synaptosomes was inhibited by anti-heavy chain IgG and a monoclonal antibody which neutralized toxin and recognized heavy chain. These results suggest that the binding sites of toxin to synaptosomes are localized on heavy chain and a small amount of the bound toxin is incorporated into the synaptosomal membrane or synaptosomes.

Animals↗
PubMed1983

Predictors of future established hypertension and diurnal blood pressure variability in borderline hypertension.

Among 157 patients with borderline hypertension 33.8% developed established hypertension (H), 28.6% became normotensive (N), and 37.6% still had borderline hypertension (BH) during a 3 to 10 year follow-up period (an average of 6.4 years). Significant differences in the clinical data among these 3 groups at the first examination were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), age, obesity, known duration of hypertension and SV1 + RV5 on an electrocardiogram. Analysis of variance showed that SBP increased with age in both sexes, while DBP of men less than 49 years of age was higher in the H group than in the other groups. Obesity and duration of hypertension appeared to contribute to the later development of hypertension because of a higher blood pressure. Obese men in the H group generally had higher DBP than nonobese patients in the other groups. Men with a longer history of hypertension in the H group also had a higher initial blood pressure. SV1 + RV5 in many of the subgroups of the H group was often higher in similar subgroups of the other groups. These inter-subgroup differences may affect the statistical differences in the above-mentioned parameters among the 3 groups. The mean value and standard deviation of SBP and DBP of diurnal blood pressure measurements were in the order of established hypertensives, borderline hypertensives and normotensive subjects when power-normal distribution was applied. There was no evidence that lability of blood pressure was a characteristic feature of borderline hypertension.

Adult↗
PubMed1983

[Sequential changes of the activities of the dog tracheal secretory cells caused by intraduodenal application of brovanexine].

The effects of brovanexine (BvX) on secretory activities of tracheal secretory cells and on behavior of mucus glycoprotein in these cells were investigated histologically and histochemically using the biopsy technique. When BvX was given at 10 or 20 mg/kg intraduodenally to anesthetized dogs, the thickness of the acini of submucosal glands (SG) and the ratio of the acinar inner diameter to the tracheal wall thickness (A1WR) markedly increased dose-dependently after 2 to 6 hr. The numbers of goblet cells (GC) and glandular cells showing a stain index B&P with a combination of alcian blue (AB) at pH 2.5 or pH 1.0 and periodic acid-Schiff (PAS) were reduced dose-dependently after 1 to 6 hr, while the number of cells with a stain index R were increased. Both the BvX-induced histological changes in SG and histochemical changes in GC and SG reached a peak after 4 hr. These histological and histochemical changes were also found for the BR-227-, a metabolite of BvX, and bromhexine (BH)-treated groups. BR-227- or BH-induced histological changes were to the same degree as those induced by BvX, but BvX- or BR-227-induced histochemical changes were slighter than those induced by BH. The total number of GC stained positively with a combination of AB at pH 2.5 and PAS was unaffected by BvX or BH treatment, while BR-227 tended to decrease it. These findings suggest that BvX both has a secretagogic action selectively on SG and a mucolytic action toward acid glycoprotein in granules of secretory cells in vivo, and these actions are durable.

Animals↗