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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 775 records · Page 43Linked to original sources
PubMed1987

[Clinical experience of tegafur-uracil (UFT) against bladder cancer and renal cell carcinoma].

The safety of prolonged administration of UFT in which tegafur and uracil were mixed in a ratio of 1:4 in molar fraction was studied in 44 cases of bladder cancer and 10 cases of renal cell carcinoma. Daily doses of UFT were 300-600 mg, and average total doses administered were 102.0 g for bladder cancer and 116.6 g for renal cell carcinoma cases. Incidence of adverse effects were 25.0% in bladder cancer and 18.5% in renal cell carcinoma cases. Anorexia, nausea, vomiting and decrease in WBC were observed, but rates of having discontinued the administration of UFT were very low, being 9.1% in bladder cancer and 10.0% in renal cell carcinoma. Thus, UFT was considered to be tolerable during prolonged use in bladder cancer and renal cell carcinoma and also a drug in which more usefulness is expected in multidisciplinary treatments in future.

Adult↗
PubMed1986

N6-functionalized congeners of adenosine with high potency at A2-adenosine receptors: potential ligands for affinity chromatography.

Adenosine analogues substituted at N6 with spacer arms designed for attachment to soluble macromolecules or to solid supports for affinity chromatography are agonists at the A2-adenosine receptor that mediates coronary vasodilation in the dog. The most active analogues had spacer arms terminating in -NH2, -NHCH3 or in a biotin residue. Comparisons of coronary vasoactivity with affinity for brain A1 adenosine receptors identified one biotin-containing analogue as relatively selective for coronary A2 receptors. The complex of this analogue with avidin retained coronary vasoactivity.

Adenosine↗
PubMed1986

Immunohistochemical localization of apolipoprotein E in atherosclerotic lesions of the aorta and coronary arteries.

The distribution of apolipoprotein E (apo E) immunoreactive substances (IRS) in atherosclerotic lesions and lesion-free areas of the aorta and coronary arteries obtained from 17 autopsied cases was studied using a specific anti-apo E serum and the unlabeled peroxidase-antiperoxidase (PAP) method. In fatty streak lesions of the aorta, many cells containing apo E-IRS were found in the deeper layer of the intima and diffuse staining of apo E in the extracellular spaces was also noted. In more advanced lesions apo E-positive cells could not be found. Immunohistochemical findings of coronary arteries differed distinctly from those of the aorta in that the apo-E-positive cells were absent in the deeper layer of the intima. The endothelial cells of coronary arteries, but not those of the aorta, showed positive staining for apo E.

Adult↗
PubMed1986

Change in period of free-running rhythms determined by two different tools in blinded rats.

Drinking rhythm in 6 rats optically enucleated on the day of birth was determined every one to two weeks after weaning until the age of 28 weeks. Each rat was transferred repeatedly from a cage without a running wheel to one with a running wheel, and vice versa. During the periods when the rats were housed in the former cage, drinking rhythm delayed, while it advanced when they were housed in the latter. The rats, which had a period of free-running rhythm of motor activity longer than 24 hr when measured by an Automex device in a cage without a running wheel, showed a period shorter than 24 hr when measured by a running wheel. These results suggest that the difference in tools for determination of activity may influence the results of animal experiments for free-running rhythm, and warn investigators of risks being caused by the selection of tools.

Animals↗
PubMed1986

Periodic exposure to mother is potent zeitgeber of rat pups' rhythm.

To study the possibility and potency of periodic maternal deprivation (PMD) in entraining the circadian rhythm of rat pups, access to the natural mother of which pups were optically enucleated on the day of birth (day 1) was restricted to either light phase (L-group) or dark phase (D-group) for various durations beginning on various days during the nursing period. Drinking rhythm of both groups was determined once per one or two weeks between the 4th and 8th postnatal week. The corticosterone rhythm was determined to confirm the results obtained by the measurement of water intake. Both rhythms were clearly observed by 5 weeks of age, and a reversed phase relationship was observed even when PMD was performed for a short period during days 1-4 or days 15-21. On the other hand, no phase angle difference was observed between L- and D-groups, when pups were periodically exposed to their original mother either during days 1-2 or days 18-21. These facts indicate that periodic exposure to mother can set the phase of the blinded pups' rhythm and that the period required for entrainment of the rhythm is as short as 4 or 7 days in the early or late times during the nursing period respectively, showing the high potency of PMD in entraining the circadian rhythm of blinded pups.

Aging↗
PubMed1986

Restricted access to natural mother shifted endogenous rhythm of rat pups.

For further investigation of the role of rat dams in setting the phase of pups' endogenous circadian rhythm, periodic maternal deprivation experiments were performed. Access of intact original mothers to blinded pups was restricted to light phase (L-Suckling pups) or dark phase (D-suckling pups) under 12-12 h light-dark alternation throughout the nursing period. Free-running patterns of drinking and corticosterone rhythms were determined for 3 consecutive weeks after weaning. In each determination of the rhythm, water consumption and corticosterone levels were measured every 4 hr. Both rhythms were clearly observed in both L- and D-suckling pups. Acrophase of water intake rhythm at 5 weeks of age in L-suckling and D-suckling groups were 0758 h and 1954 h while those of corticosterone rhythm were 0143 h and 0948 h respectively. Reversed phase relationship of rhythms between L- and D-suckling groups were observed throughout the period examined. These results indicate that suckling can act as a Zeitgeber for the endogenous rhythm of pups.

Age Factors↗
PubMed1986

Effect of dorsal midbrain lesion in infant rats on development of circadian rhythm.

To investigate the relationship between serotonergic system and development of the circadian rhythm, we made destruction of the dorsal region of midbrain including dorsal raphe nuclei in neonatal rat pups. Overt circadian rhythms of locomotor activity and water consumption were clearly observed at 4-6 weeks of age, in both the sham operated and the lesioned pups. However, amount of both activities in the lesioned pups was significantly larger than that of the sham operated pups during the light phase. This indicates that the circadian activity rhythm is altered by the lesion, although the degree of alteration is slight. This suggests the involvement of the serotonergic system in the full development of the normal circadian rhythm. An irregular drinking pattern was observed in the lesioned rats at 5 months of age, although a light-dark difference in water consumption was evident. It takes longer for lesioned adult rats to manifest a significant day-night difference in water consumption, than for sham operated rats after reversal of light-dark cycle. This suggests that a lesion in the dorsal midbrain made during the neonatal period may cause a permanent change in the circadian system.

Age Factors↗
PubMed1986

Dog coronary artery adenosine receptor: structure of the N6-aryl subregion.

Previous structure-coronary vasoactivity correlations of the N6-alkyladenosine analogues of N6-[(R)-1-phenyl-2-propyl]adenosine, 1, support the hypothesis that the coronary artery A2 adenosine receptor contains an N6 region of specialized structure. The part of this receptor region that binds the 2-propyl moiety of 1 determines stereoselectivity and contributes to coronary vasoactivity. The present study uses 92 adenosine analogues containing an aryl group in the N6 substituent to test the hypothesis that the N6 receptor region contains an aryl subregion that binds the phenyl moiety of 1 and thereby contributes to its coronary vasoactivity. N6-Aralkyladenosines are often more potent than their alkyl congeners. Two methylene residues seem to provide optimum separation of the aryl group from N6. Among adenosines with semirigid N6 substituents, N6-[(1R,2S)-trans-2-phenylcyclohexyl]adenosine was uniquely active, evidence that when 1 occupies the receptor, the axis of the propyl C-1 to phenyl C-1 bond is nearly in the plane described by N6 and propyl C-1 and C-2. The torsion angle around this bond is unknown. Replacing the phenyl group of N6-2-phenethyladenosine with a thienyl or a 3-pyridyl group raises activity. The structure-activity relationships of the N6-(arylethyl)-, the N6-(arylmethyl)-, and the N6-phenyladenosines differ strinkingly from each other. Taken together, such results support the idea that the N6 region of the dog coronary artery A2 adenosine receptor includes an aryl subregion.

Adenosine↗
PubMed1986

Metabolism of lipoproteins containing apolipoprotein B-100 in blood plasma of rabbits: heterogeneity related to the presence of apolipoprotein E.

Apolipoprotein B-100 is a constant component of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) in mammalian blood plasma. We have found that each of these classes of lipoproteins includes particles that contain apolipoprotein E (B,E particles) as well as particles that lack this protein (B particles). These two species can be separated by immunosorption on columns of anti-apolipoprotein E bound to Sepharose. We have injected radioiodinated VLDL, IDL, and LDL intravenously into recipient rabbits and have determined the concentration of radioiodine in apolipoprotein B-100 in B,E and B particles in whole-blood plasma obtained at intervals for 24 hr. We have developed a multicompartmental model that is consistent with this new information and with current concepts of lipoprotein metabolism. The model indicates that all apolipoprotein B-100 enters the blood as VLDL, of which about 90% is in B,E particles. Most VLDL B,E particles are removed rapidly from the blood, and only a small fraction is converted to IDL and eventually to LDL (overall conversion is approximately 2%). By contrast, a much smaller fraction of VLDL B particles is removed directly, and approximately 27% is converted to LDL. In addition, some B,E particles are converted to B particles as VLDL are converted to LDL, so that most LDL particles lack apolipoprotein E. Fractional rates of irreversible removal of B,E and B particles in IDL and LDL are similar. Our results indicate that the presence of apolipoprotein E is a major determinant of the metabolic fate of VLDL particles and support the hypothesis that polyvalent binding of particles containing several molecules of apolipoprotein E promotes receptor-dependent endocytosis of hepatogenous lipoproteins and limits their conversion to lipoproteins of higher density.

Animals↗
PubMed1986

Lipid metabolism in endotoxic rats: decrease in hepatic triglyceride lipase activity.

Studies were conducted to investigate the effect of E. coli endotoxin administration on hepatic triglyceride lipase (H-TGL) activity in rats, since H-TGL activity is known to behave differently from lipoprotein lipase (LPL) activity in various situations. Plasma triglyceride and free fatty acid concentrations were markedly elevated in animals after injection of endotoxin. Cholesterol and phospholipids were also increased significantly. Lipoprotein analysis by ultracentrifugation showed that the most pronounced increase of lipoproteins was in the VLDL and IDL fractions. Triglyceride lipase activities in post-heparin plasma were markedly decreased. A selective assay for H-TGL activity using a specific antibody revealed that this enzyme as well as LPL is significantly decreased (26% of control) in endotoxic animals. Thus, the increase of VLDL and IDL appears to result from the decrease of both of LPL and H-TGL.

Animals↗
PubMed1986

Studies on 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG) levels in human urine, plasma and cerebrospinal fluids, and their significance in studies of depression.

Both concentrations of total 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG) in the human urine, plasma and CSF were determined with a high-pressure liquid chromatography with electrochemical detection in order to clarify the dynamic change in these noradrenaline metabolites. Three different biological fluids were collected simultaneously from 16 orthopedic patients who were regarded clinically as substitutes for normal subjects. In the urine, the MHPG concentrations were 1.67 +/- 0.65 micrograms/mg creatinine (mean +/- S.D.) and DHPG 0.39 microgram/mg creatinine +/- 0.21. The plasma levels were 21.16 ng/ml +/- 9.58 for MHPG, and 19.58 ng/ml +/- 8.13 for DHPG. The CSF levels of MHPG and DHPG were 24.08 ng/ml +/- 8.10 and 34.76 ng/ml +/- 11.46, respectively. The CSF levels of these metabolites were correlated significantly with those in the plasma (r = 0.852, p less than 0.001 for MHPG; r = 0.799, p less than 0.001 for DHPG), while no significant correlations were found between the urinary levels and either the plasma or CSF levels of these metabolites. In the urine, the MHPG levels were proportional to the DHPG levels, while the former were inversely proportional to the latter in the plasma or CSF. Neither the MHPG nor DHPG levels in the urine from depressed patients revealed to have any significant correlation with their clinical assessments using the Hamilton Rating Scale Score (HRS). The patients were treated with an antidepressant active selectively on the noradrenergic system, and no significant changes in urinary excretion of these metabolites were observed before and after the drug treatment. These findings suggest that in the case of psychiatric disorders such as depression, these compound levels in the plasma or CSF would provide more important information than those in the urine.

Adult↗