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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 685 records · Page 38Linked to original sources

Cachectin/TNF kills or inhibits the differentiation of 3T3-L1 cells according to developmental stage.

The effects of cachectin/tumor necrosis factor (TNF) on growth and differentiation of 3T3-L1 cells were examined. This fibroblastic cell line can be induced to differentiate into a mature cell type having the biochemical and morphological characteristics of normal adipocytes. At various stages of growth and differentiation, 3T3-L1 cells were exposed to 2.5 x 10(-16) to 2.5 x 10(-8) M (4.2 fg/ml to 420 ng/ml = ca. 1.2 x 10(-14) to 1.2 x 10(-16) U/ml) recombinant human cachectin/TNF for 24 hr, after which cytotoxicity or differentiation was evaluated. During log-phase cell growth, cachectin/TNF had no significant effect on cell viability, and the preadipocytic cells were also resistant to the cytotoxic effect of cachectin/TNF at the contact-inhibited confluent stage. However, when cachectin/TNF was added to the cells during induced differentiation, only 20% of the cells survived. After differentiation into adipocytes, cells regained their resistance to cachectin/TNF-induced cytotoxicity. Cachectin/TNF also markedly affected the differentiation of 3T3-L1 cells into adipocytes. When cells in the confluent phase of growth were exposed to cachectin/TNF for 24 hr, their subsequent hormone-induced differentiation to adipocytes was inhibited. Like cachectin/TNF, IL-1 also induces suppression of lipoprotein lipase and enhances lipolysis in differentiated 3T3-L1 adipocytes; however, in contrast to cachectin/TNF, IL-1 had no effect on the viability or differentiation of pre-adipocyte 3T3-L1 cells. These results indicate that the cytotoxic action of cachectin/TNF varies in the same cell type depending on the stage of growth or differentiation. The results also imply that cachectin/TNF may play a normal role in controlling the differentiation of certain types of cells in vivo including adipocyte lineages.

Animals↗

Cerebral vascular malformations: applications of magnetic resonance imaging to differential diagnosis.

Twelve patients with cerebral vascular malformations (5 cavernous angiomas, 1 thrombosed arteriovenous malformation, and 6 venous angiomas) were studied with magnetic resonance (MR) imaging. All lesions were clearly depicted. Characteristic MR findings were obtained mainly on T2-weighted images: a markedly low intensity area was always seen. The margins of arteriovenous malformation (AVM) and venous angioma were irregular while those of cavernous angioma were smooth in all planes on T2-weighted images. Gradient-echo (GrE) pulse sequences were more sensitive than T2-weighted spin echo (SE) in lesion detection. MR imaging could play an important role in the differential diagnosis of cerebral vascular malformations.

Adult↗

A neonatal case of apolipoprotein C-II deficiency.

A neonatal case of apo C-II deficiency with hypertriglyceridaemia and xanthomas is presented. The patient responded well to a special diet formula containing medium-chain triglycerides (MCT). This is the first case of apo C-II deficiency to be discovered during the neonatal period.

Apolipoproteins C↗

A rapid electrophoretic method for the detection of serum Lp(a) lipoprotein.

A rapid electrophoretic method detecting serum lipoprotein(a) (Lp(a)) was described. When serum lipoproteins were electrophoresed using an agarose gel film containing 0.6% agarose and 3% sucrose, a distinct extra-band was frequently detected between beta- and prebeta-bands. This lipoprotein band was identified as Lp(a) by immunoblotting technique using anti-Lp(a) serum. Using this electrophoretic method, we studied 1,353 subjects with a variety of diseases. The Lp(a)-positive subjects accounted for 8.4% of all. Neither sex nor age influenced the frequency of Lp(a) positivity. Frequencies of definite myocardial infarction in Lp(a)-positive subjects did not differ significantly from those in Lp(a)-negative ones. Those of cerebral infarction in Lp(a)-positive subjects were significantly higher than those in Lp(a)-negative ones. An electrophoretic method described herein is very useful for the rapid detection and screening of Lp(a), and hence for large-scale clinical studies of atherosclerotic risk assessment.

Adult↗

Plasma apolipoproteins in patients with multi-infarct dementia.

We examined 27 elderly patients with multi-infarct dementia developed on the basis of cerebral arteriosclerosis. The levels of plasma cholesterol and triglyceride in the patients were 177 +/- 48 and 91 +/- 27 mg/dl (mean +/- SD), respectively. Despite normal plasma lipid levels, the patients had significantly higher plasma apo B (102 +/- 30 vs. 82 +/- 21 mg/dl for controls, P less than 0.01) and lower plasma apo A-I levels (104 +/- 25 vs. 130 +/- 22 mg/dl for controls, P less than 0.01) than the controls. Isoelectric focusing of apo E showed a 2-fold higher relative frequency for the epsilon 4 allele in patients than in Japanese controls (20.8 vs. 8.6-11.7% of total, P less than 0.05). The patients with phenotypes of E4/4 (n = 1) and E4/3 (n = 8) had higher plasma cholesterol levels than those with E3/3 (n = 15) (196 +/- 45 vs. 169 +/- 43 mg/dl). The results indicate that the patients had abnormalities in plasma lipoprotein metabolism and this may contribute to the development of cerebral arteriosclerosis.

Aged↗

Determination of the lysosomal role in tumor accumulation of 67Ga by dual-tracer studies.

The lysosomal role in tumor accumulation of 67Ga was determined by dual-tracer (67Ga and 46Sc) studies. It became clear that 67Ga essentially did not accumulate in the tumor lysosome, and that the lysosome did not play a major role in tumor accumulation of 67Ga. In addition, it was revealed that tumor lysosome was hardly disrupted at all in some phases of fractionation procedures.

Animals↗

Increased clearance of plasma cholesterol after injection of apolipoprotein E into Watanabe heritable hyperlipidemic rabbits.

Apolipoprotein E (apoE) is known to play an important role in lipoprotein metabolism. We have studied the effect of apoE on the metabolism of plasma cholesterol by injecting apoE intravenously into rabbits deficient in low density lipoprotein receptors [Watanabe heritable hyperlipidemic (WHHL) rabbits]. Approximately 30 mg of apoE was injected per rabbit; a total of five WHHL rabbits were used. One hour later, plasma cholesterol levels fell 8.3% (from 488 +/- 192 to 446 +/- 174 mg/dl). After 3 hr, cholesterol levels had fallen by 19% (to 392 +/- 152 mg/dl). The reduced levels were maintained for at least 8 hr after injection of apoE. Cholesterol in very low density lipoproteins (VLDLs) and intermediate density lipoproteins fell rapidly during the first 2 hr after injection, followed by a reduction in the low density lipoprotein cholesterol level. Changes in apolipoprotein B levels in each lipoprotein fraction were very similar to those of cholesterol. Plasma apoE levels 3 min after injection were elevated 3-fold to 22.8 +/- 6.3 mg/dl and returned to initial levels 8 hr after injection. The rate of removal of intravenously injected 125I-labeled VLDL that had been incubated with apoE was 3-fold higher than that of unmodified VLDL. From these results, we conclude that the injected apoE is incorporated into VLDLs and that VLDL particles carrying more apoE are removed from the blood more rapidly, resulting in reduced formation of low density lipoprotein and lowered cholesterol levels.

Animals↗

Forskolin potentiates myocardial reactive hyperaemia in the open chest dog: the contribution of adenylate cyclase.

Forskolin, a diterpene, directly stimulates adenylate cyclase and also potentiates receptor mediated stimulation of this enzyme by many stimulatory agonists. We exploited the potentiating effect of forskolin to test the hypothesis that activation of adenylate cyclase contributes to myocardial reactive hyperaemia, especially by release of adenosine at the time of brief coronary occlusions. In 10 open chest dogs, intracoronary forskolin infusions which produced plasma concentrations between 0.22 and 0.34 mumol.litre-1 slightly increased coronary blood flow and had no effect on haemodynamics or myocardial metabolism. Under these conditions, though peak reactive hyperaemic flow rates were not affected, forskolin infusions reversibly potentiated repayments of flow debt by 28, 25 and 27% following coronary occlusions of 15 s, 20 s and 30 s, respectively (p less than 0.05). In another seven dogs, after observations of the effects of forskolin (0.16-0.26 mumol), 10 mumol of 8-phenyltheophylline, a potent adenosine antagonist, was infused simultaneously with forskolin into the coronary arteries. Forskolin increased debt repayments by about 23-27% following 15 s, 20 s and 30 s occlusions, but with simultaneous 8-phenyltheophylline, forskolin induced increments in the debt repayments were reduced significantly (p less than 0.05). These results indicate that adenylate cyclase contributes to myocardial reactive hyperaemia, and adenosine has a significant role as metabolic regulator of reactive hyperaemia through activation of adenylate cyclase.

Adenosine↗

Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation.

Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.

Animals↗

IgG subclasses of anti-A and anti-B antibodies bound to the cord red cells in ABO incompatible pregnancies.

IgG subclasses were determined in 138 A or B infants weighing over 2,500g, born to O mothers. Direct antiglobulin test (DAT) was positive in 43 infants and negative in 95 with anti-A and/or anti-B antibodies detected by heat elution test. In 59 out of 131 infants without ABO hemolytic disease (ABO-HDN), no IgG subclass was detectable. In the 72 others, IgG1 was found in 29/72, IgG2 in 63/72, and IgG3 was not detected. In 7 infants with ABO-HDN, DAT was positive in 4 and negative in 3. In conclusion, in DAT-positive infants without HDN, IgG1 or IgG2 may be bound to erythrocytes, but the amount of IgG1 is too small to cause hemolysis. In DAT-positive ABO-HDN the amount of IgG1 is sufficient to cause hemolysis. In DAT-negative ABO-HDN, IgG3 is responsible for hemolysis, even though undetectable by DAT.

ABO Blood-Group System↗

Morning and evening adrenocortical responses to ACTH stimulation in endogenously depressed patients: a preliminary report.

Adrenocortical stimulation with ACTH both in the morning (M-test) and in the evening (E-test) and the dexamethasone suppression test were carried out in patients suffering from endogenous depression (DEP) and normal controls (NOR). A greater cortisol release in DEP was recognized than in NOR in the M-test, an earlier peak response of DEP was shown in the M-test than in the E-test, and a lack of association between hypersecretion of cortisol during depression and cortisol output after ACTH administration was noted. These findings, together with the results of DST, suggest that excessive activity of the hypothalamic-pituitary-adrenal (HPA) axis in depression may result, partly, from adrenocortical hyperresponsiveness.

Adrenocorticotropic Hormone↗

Actin is associated with the formation of the cell wall in reverting protoplasts of the fission yeast Schizosaccharomyces pombe.

To clarify the involvement of actin in the formation of the yeast cell wall, reverting protoplasts of Schizosaccharomyces pombe were used as a simple model system. Actin of reverting protoplasts was labeled with rhodamine-conjugated phalloidin and observed by conventional fluorescence microscopy and laser scanning confocal microscopy. A close spatial as well as temporal relationship between actin and cell wall formation was observed in protoplast reversion. That is, the site of actin 'dots' in the reverting protoplasts coincided with the site of new wall formation and the timing of rearrangement of actin coincided with the initiation of cell wall formation and with the timing of cell wall expansion. Treatment of reverting protoplasts with cytochalasin D (CD) further clarified the close relationship between actin and cell wall organization. The effect of CD was dose dependent. A high dose of CD caused the absence of actin as well as the complete inhibition of cell wall formation. A low dose of CD caused weakly stained unlocalized actin, which induced grossly aberrant cell wall deposition as well as substantial changes in the morphology of the reverting protoplasts. These results demonstrated that actin is associated with initiation of cell wall formation, the proper deposition of cell wall materials, and maintaining the normal morphology of reverting protoplasts. Scanning electron microscopy revealed the presence of a fibrillar net structure on the surface of non-treated control reverting protoplasts. However, the absence of a fibrillar network on the surface of reverting protoplasts was observed in the presence of a high concentration of CD. Lack of localization of microfibrils as well as poor development of the fibrillar network were also observed in the presence of a low concentration of CD. Recovery experiments confirmed the close relationship between actin and cell wall formation.

Actins↗

Coronary flow reserve and oxygen metabolism of the right ventricle.

The flow reserve of the right coronary artery (RCA) and myocardial oxygen extraction are important tractors in any investigation of the mechanisms of impaired right ventricular function. The present study induced brief coronary occlusions and examined the effect on right coronary blood flow in normal dogs, and the effect on myocardial oxygen metabolism in dogs with right ventricular hypertrophy (RVH). Right coronary flow reserve, represented by occlusion duration causing a half maximum dilatation (T1/2), was greater in the RCA than in the left anterior descending coronary artery of normal dogs; 11.4 +/- 2.3 sec vs 5.9 +/- 1.4 sec. Myocardial oxygen extraction ratio (EO2) of the right ventricle (RV), 51.3 +/- 1.6%, was significantly (p less than 0.05) lower than the index of the left ventricle (LV), 60.6 +/- 1.0%, and the extraction of the RV increased significantly in association with an increase of myocardial oxygen demand. In dogs with RVH caused by chronic banding of the pulmonary artery, this dominant oxygen reserve was lost: the EO2 of the hypertrophied RV was high compared with the EO2 of the normal RV (57.3 +/- 3.4% vs 51.3 +/- 1.6%, p less than 0.05), and no further increase in EO2 was observed in the hypertrophied RV in response to the elevation of the myocardial oxygen requirement. Oxygen usage per 100g of the RV for a certain level of overall RV work, rate-pressure product, was significantly (p less than 0.02) lower in the hypertrophied RV (0.00054 mlO2/beat.mmHg) than in the normal RV (0.0012 mlO2/beat.mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Cardiovascular effects of beraprost sodium (TRK-100), a prostacyclin analogue in the dog].

Effect of prostacyclin analogue, beraprost sodium (Sodium (+/-)-(1R*, 2R*, 3aS*, 8bS*)-2, 3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen+ ++-6- ynyl]-1H-cyclopenta-[b]benzofuran-5-butyrate, TRK-100), on the cardiovascular system of the anesthetized dog was investigated. TRK-100 was injected intra-arterially and intravenously to study the vasodilating effect of the drug by a magnetic flow meter. Intra-arterial injection of TRK-100 augmented blood flow of vertebral, coronary, renal, supramesenteric, hepatic and femoral artery at a dose range of 0.0003 to 3,000 micrograms/bed. The threshold doses of TRK-100 and PGI2 in the mesenteric artery were 0.003 micrograms and 0.0003 micrograms, respectively, and the same values were obtained in the splenic artery. Those were slightly lower than those of other arteries. Intravenous injection of TRK-100 augmented mesenteric and renal arterial flow to 193 +/- 30% and 118 +/- 4%, respectively. In this system augmentation of mesenteric and renal arterial flow was 179 +/- 19% and 135 +/- 1%, respectively, while vertebral, carotid, and femoral arterial flow decreased, respectively, to 71.4 +/- 2.1%, 80.0 +/- 9.4% and 61.4 +/- 5.6% by TRK-100 and 70.6 +/- 5.6%, 79.5 +/- 6.9% and 67.1 +/- 4.7% by PGI2. Inhibitory effects on heart functions such as cardiac output, left ventricular pressure, LV dP/dt, oxygen consumption, and cardiac work were seen. The effect was similar to PGI2. Coronary vascular resistance, total peripheral resistance and systemic blood pressure were also decreased by TRK-100 and PGI2.

Anesthesia↗

Analysis of submandibular gland sialograms in Sjögren's syndrome.

We report here the sialographic appearances of the submandibular gland in both primary and secondary Sjögren's syndrome (SS). In order to compare these with those of the parotid gland, we defined new criteria for the staging for SS based on the degree of depiction of the peripheral ducts. In 24 out of 74 cases the submandibular sialogram showed more advanced, destructive disease compared with the parotid. This study suggests that although SS involves the parotid gland first, it progresses in the submandibular gland more rapidly.

Adult↗

Symptomatic Rathke's cleft cyst simulating arachnoid cyst--case report.

A case of symptomatic Rathke's cleft cyst simulating an arachnoid cyst is presented. Although computed tomography and magnetic resonance imaging showed that the cyst content was identical to cerebrospinal fluid, there was faint contrast enhancement in part of the wall. Histological observation suggested that the somewhat vascular connective tissue associated with nests of pituitary cells might have contributed to the enhancement. This type of Rathke's cleft cyst requires further clinical and neuroradiological studies.

Arachnoid↗