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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 505 records · Page 28Linked to original sources
PubMed1985

Quantitative analysis of development of mitochondrial ultrastructure in differentiating mouse hepatocytes during postnatal period.

Between birth and 10 days of age, the volume density (volume/unit cytoplasmic volume) of the matrix, and the surface density (area/unit cytoplasmic volume) of the inner membrane and cristae increased in both periportal and perihepatic hepatocytes, and did not differ significantly between the cells of the two zones. After 10 days of age, however, the volume density of the matrix decreased in perihepatic cells and remained unchanged in periportal cells, and, therefore, it became greater in periportal cells than in perihepatic cells in 20-day-old and adult animals. The surface density of the inner membrane and cristae decreased in the cells of both zones. Further, the hepatocyte volume increased markedly, especially in perihepatic zones between 20 days of age and the adult. The results show that, in postnatally differentiating hepatocytes, mitochondria are likely to develop during early postnatal period, then the structural heterogeneity of mitochondria arises, and hepatocyte volume increases markedly during late postnatal period after weaning. Thus, the process of postnatal hepatocyte differentiation includes such several phases of development.

Aging↗
PubMed1985

Human hepatocellular carcinoma is associated with quantitative and qualitative changes in glycolipids.

Changes of glycolipids in the naturally occurring human hepatocellular carcinoma tissues were studied. Neutral glycolipids (two fractions) and gangliosides from human hepatocellular carcinoma tissues and their adjacent uninvolved liver tissues from ten patients were purified and analyzed by high-performance thin-layer chromatography. Human hepatocellular carcinoma was shown to be associated with the extensive changes of the thin-layer chromatography patterns of both neutral glycolipids and gangliosides. Changes in neutral glycolipids were: (a) increased dihexaosylceramide with the concomitant decrease of trihexosylceramide and globoside, (b) increased ratio of the lower band of globoside to the upper band, and (c) increased expression of at least two "upper-phase" neutral glycolipids. Changes in gangliosides were: (a) increased expression of gangliosides migrating slower than GM3 on thin-layer chromatography with relative decrease of GM3, and (b) expression of tumor-associated new gangliosides, i.e., "neogangliosides".

Adult↗
PubMed1985

Effect of age on the hepatic clearance of propranolol in rats.

The effect of age on hepatic clearance of propranolol was investigated in male Wistar rats (3 to 104 weeks old). Pharmacokinetic analysis of the plasma propranolol data obtained after i.v. dosage (1.0 mg kg-1) indicated that both the elimination rate constant and the volume of distribution decreased with age between weeks 5 and 11, after when the distribution volume remained almost constant. The elimination rate constant was reduced consistently with age after 15 weeks. Total body clearance of the drug was reduced extensively with age between weeks 5 and 11 (94 to 43 ml min-1 kg-1) and decreased gradually thereafter. The plasma free fraction of propranolol also decreased with age, falling from more than 20% in 3 to 5 weeks-old rats to about 10% in rats of 52 to 104 weeks. In immature rats the renal clearance was approximately 5 to 12% of the total body clearance. Intrinsic hepatic clearance for unbound propranolol also decreased with age between weeks 7 and 24. As expected from the evidence that propranolol has a high extraction ratio, the extent of its hepatic clearance was significantly dependent on the liver blood flow. These data suggest that the age-dependent decrease in hepatic clearance of propranolol is largely due to a reduction of the elimination rate that might be accompanied by the age-dependent decrease in liver blood flow.

Administration, Oral↗
PubMed1985

Dose-dependent presystemic elimination of propranolol due to hepatic first-pass metabolism in rats.

Gastrointestinal first-pass elimination of propranolol and the effect of dose (1.0, 2.5, 5.0 and 10.0 mg kg-1) on its systemic availability were studied in male Wistar rats which received the drug intravenously, orally or intraportally. The plasma elimination half-life was not altered either by the route of administration or the dose. There was no gastrointestinal first-pass metabolism of propranolol, since the same systemic availability was obtained after oral and intraportal administration. Hepatic clearance was estimated to be constant at any dose. In contrast, the hepatic intrinsic clearance was found to be largely dependent on the portal dose.

Animals↗
PubMed1985

Increased angiotensin-converting enzyme in peripheral blood monocytes from patients with sarcoidosis.

Angiotensin-converting enzyme (ACE) activity was measured in isolated peripheral blood monocytes and culture medium from 28 patients with sarcoidosis and compared with values obtained from monocytes of 25 normal control subjects. ACE activity was determined by radioimmunoassay of angiotensin II produced from angiotensin I. While there was no measurable ACE activity in monocytes or culture medium from normal controls under the conditions of our study, monocytes from patients with sarcoidosis all showed activity both in cells and culture medium. The mean ACE activity of monocytes from patients with sarcoidosis was 2.0 pg angiotensin II formed/min per 10(5) cells, and that released into medium over a 24-h interval was 30.4 pg angiotensin II/min per 10(5) cells. The monocyte ACE from patients with sarcoidosis was activated by chloride ions and inhibited by EDTA, captopril, and rabbit antiserum to purified human plasma ACE, indicating that enzymatic activity was effected specifically by ACE. Thus, our studies show a significant elevation and release of ACE by peripheral blood monocytes of patients with sarcoidosis under conditions where monocytes of normal control subjects do not demonstrate ACE activity.

Adult↗
PubMed1985

Dose-dependent disposition of fractionated 3H-heparin in rats.

To investigate the disposition of fractionated 3H-heparin, commercial 3H-heparin was fractionated by affinity chromatography on protamine-Sepharose and subsequently by Sephadex G-100 chromatography. Effect of dose on the disposition of fractionated 3H-heparin was studied. At an early stage following the intravenous administration of fractionated 3H-heparin which had either affinity or non-affinity for protamine-Sepharose, elimination of the radioactivity from plasma was delayed with increasing dose. Even at 5 h after the administration when most radioactivity in plasma disappeared, the cumulative urinary recovery was only 4.8 to 8.4% of dose (1 to 15 microCi/kg), and 61 to 43% of dose was found in liver. Therefore, it was suggested that tissue (liver) distribution of radioactivity might be a predominant factor for the dose-dependent disappearance of the radioactivity from plasma at an early stage following the administration of fractionated 3H-heparin. Plasma radioactivity levels tended to be pseudo-steady state or to increase slightly after about 1 to 2 h following the administration of fractionated 3H-heparin. Participation of entero-hepatic circulation in this tendency was rejected.

Animals↗
PubMed1985

The change of p-aminohippuric acid disposition kinetics accompanied by growth in mice.

The change of disposition kinetics for p-aminohippuric acid (PAH) was studied following intravenous administration of p-[glycyl-1-14C]aminohippuric acid to 1-day-old, 1-week-old, 3-week-old and 8-week-old mice. The expiratory excretion of 14CO2 in 24 h following the administration was almost negligible in 1-day-old and 1-week-old mice in contrast to 3-week-old (6.8 +/- 1.8%) and 8-week-old (8.8 +/- 1.9%) mice. The ability to metabolize PAH may not be developed in these infant mice. The elimination of blood radioactivity following the administration was considerably delayed in 1-day-old and 1-week-old mice, especially in 1-day-old mice, suggesting that the renal tubular secretory function for PAH might not have been developed in the infant mice. Whole-body autoradiographic data showed that the transfer of PAH from blood to muscle was enhanced in 1-day-old and 1-week-old mice, especially in 1-day-old mice, compared to 3-week-old and 8-week-old mice. The enhanced muscular cell membrane permeability to PAH in 1-day-old and 1-week-old mice was considered to be the most plausible explanation for this result.

Age Factors↗
PubMed1985

Involvement of different receptor subtypes for the production of in vitro and in vivo effects in a series of synthetic enkephalin analogues.

Enkephalin analogues of tyrosyl group on the N-terminal and Phe-ol or phenylethylamine (PHA) group on the C-terminal which are connected with different chain length were tested for their activities in vitro and in vivo. The inhibitory effect of the synthetic peptides on the electrically evoked contractions of isolated longitudinal muscle strips of guinea pig ileum were weaker than that of morphine or Leu-enkephalin and tended to decrease by increasing the number of methylene group,-(CH2)n-, n = 1-5, between N- and C-terminal. Compounds with PHA group on the C-terminal, n = 4 and 5, showed the least activity. The effect of peptides with short chains of methylene groups, n = 1 or 2, and Phe-ol on the C-terminal were antagonized by naloxone but others were insensitive to naloxone. Differing from in vitro activity, compounds with PHA on the C-terminal with a chain of 4 methylene groups produced short lasting analgesia after i.c.v. injection as well as the compounds with Phe-ol on the C-terminal and 1 or 2 methylene groups. The analgesic effect of these compounds were completely antagonized by naloxone. At a high i.c.v. dose, all the synthetic peptides, except the one with PHA on the C-terminal with a chain of 4 methylene group, produced convulsions and/or ipsilateral rotation to the injection side. These behavioral effects were not antagonized by naloxone. Thus, minor alterations in the chemical structure of enkephalin analogues resulted in the changes of their receptor selectivity and potencies in vitro and in vivo.

Analgesia↗
PubMed1985

A new indirect method for measurement of sinoatrial conduction time and sinus node return cycle.

We developed a new indirect method for the measurement of sinoatrial conduction time (SACT) and the sinus node return cycle (SRC) with a transvenous catheter technique. Two early premature stimuli, at intervals 50 msec longer than the effective refractory period (ERP), were given to the right atrium. These early stimuli were followed by eight constant stimuli. The interval of the constant stimuli was a little shorter than the basic cycle length (BCL). The return cycle A1Ar was measured and plotted on the abscissa; the next interval ArA3, was measured and plotted on the ordinate. This was called the "base point". A new stimulus, A2, was then added to the train of stimulations, first at a point simultaneous with Ar. It was then shifted toward the last constant stimulus at 10-20 msec intervals until A2 met the ERP. The relationship between A1A2 and A2A3 was obtained by the repetition of the procedures with various A1A2 intervals. It had two zones, compensatory and non-compensatory. We postulate that the atriosinus conduction time of the last of the eight stimuli was equal to that of A2 when the stimulus A2 first captured and reset the sinus nodal pacemaker cells, as indicated by the transition point of the two zones. Based on this supposition, SACT and SRC could be measured as the intervals from the base point to the transition point and from the transition point to the eighth stimulus, respectively.

Aged↗
PubMed1985

Effects of coronary artery stenosis on left ventricular end-ejection pressure-ejected volume relationships in isolated perfused canine hearts.

We investigated the behavior of the left ventricular end-ejection pressure-ejected volume relation with and without left circumflex coronary stenosis in isolated perfused canine hearts. To change ventricular afterload pressure, the peripheral resistance of the hydraulic model attached to the aortic root of the excised hearts was changed in a stepwise fashion to five different levels. The end-ejection pressure-ejected volume relationship was nearly linear in both pre-ischemic and ischemic states. The slope changes following left circumflex coronary stenosis differed among the hearts used in the present study, and there was no significant difference in average slope (n = 10) between the pre-ischemic and ischemic states (i.e., -7.4 +/- 1.0 and -8.4 +/- 1.2 mmHg/ml, respectively). Therefore, the, slope of the relation was not useful in judging the presence of depressed ventricular function induced by coronary stenosis. In contrast, the ejected volume axis intercept decreased significantly from 16.5 +/- 1.1 ml to 13.6 +/- 1.1 ml (p less than 0.05) with regional ischemia.

Animals↗
PubMed1985

Inhibitory effect of colchicine and vinblastine on transport of glucagon receptors to the plasma membrane in cultured rat hepatocytes.

The role of microtubules in the regulation of glucagon receptors on cultured rat hepatocytes was studied. Antimicrotubular reagents, colchicine and vinblastine, did not affect the binding of 125I-labelled glucagon to hepatocytes at 4 degrees C. At 20 and 37 degrees C, however, the reagents reduced the binding after 60 or 90 min of incubation. Scatchard analysis indicated that the reduction in the binding was due to loss of glucagon-receptor populations. If hepatocytes were preincubated with both unlabelled glucagon and the reagents at 37 degrees C, the binding of the ligand to the cells decreased markedly after a certain delay. The reagents did not inhibit the internalization of the ligand in the cells until 30 min of incubation at 37 degrees C. The results suggest that the microtubule system plays a role in the transport of glucagon receptors to the plasma membrane, which is followed by their internalization.

Animals↗