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Biomedical subjects

T Yamanouchi

Publications and source records attributed to T Yamanouchi.

At least 19 recordsLinked to original sources

Perfusion and mechanical analysis with technetium-99m 2-methoxy-isobutyl-isonitrile in a case of dilated cardiomyopathy.

With technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-MIBI), regional wall thickening in a patient with dilated cardiomyopathy was analyzed by the first component Fourier method. The regional wall thickening was compared with thallium-201 and 99mTc-MIBI SPECT imaging. Thallium-201 SPECT images showed mildly reduced perfusion in the posterior wall and redistribution in the septum, whereas 99mTc-MIBI images showed heterogeneous accumulation around the left ventricular circumference. By means of phase analysis, diffusely decreased wall thickening and discontinuity of percent wall thickening in neighboring segments were observed throughout the left ventricle. Regional wall motion and wall thickening correlated roughly. However, discrepancies between the mechanical function and myocardial perfusion, and discrepancies in regional myocardial perfusion between thallium-201 and 99mTc-MIBI were observed.

Aged

Estimation of plasma glucose fluctuation with a combination test of hemoglobin A1c and 1,5-anhydroglucitol.

We investigated the effect of plasma glucose fluctuation on hemoglobin A1c (HbA1c) and plasma 1,5-anhydroglucitol (AG) levels, especially in insulin-dependent diabetes mellitus (IDDM). Plasma AG is a new marker that provides sensitive and analytical information on glycemic control. The basic mechanisms underlying both the reduction and recovery of the plasma AG level, ie, the excretion into urine with glucosuria and the amount supplied to the body, were presumed to be similar in IDDM and non-insulin-dependent diabetes mellitus (NIDDM) patients. The correlation coefficient for mean plasma glucose and AG was -.591, and it was .578 for mean plasma glucose and HbA1c in IDDM patients. In NIDDM, the correlation between mean plasma glucose and AG was -.869, and between mean plasma glucose and HbA1c, .875. The plasma AG levels in the IDDM group showed a lower range than in the NIDDM group, even with similar HbA1c levels. All the cases showing lower plasma AG levels among those with similar HbA1c levels manifested greater fluctuation of plasma glucose and a larger amount of urinary glucose. The lower AG level in IDDM patients was reversible to the level in NIDDM patients when the greater fluctuation of plasma glucose was corrected. Thus, it was suggested that because urinary glucose excretion is intermittently high in IDDM patients, plasma AG is frequently low, even though the mean plasma glucose and HbA1c levels suggest good control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body.

The origin and disposal of 1,5-anhydro-D-glucitol (AG), one of the main polyols found in the human body, was studied in normal subjects and diabetic patients. AG was detected in various kinds of foods. The mean AG supplement through foods was estimated to be approximately 4.38 mg/day, which was compatible with that calculated in a food analysis (average 0.22 mg AG/100 kcal in Japanese foods) on eight healthy subjects. The mean AG excretion in urine was approximately 4.76 mg/day in these subjects. Excretion into stools was negligible. From observations on the patients without oral supplement of AG, 0.4 mg of daily de novo synthesis of AG was strongly suggested. It was also implied that urinary AG excretion occurred soon after food ingestion and that its amount was closely correlated with daily supplement through foods. Thus the fundamental kinetics of AG were recognized as follows: 1) AG in the body originates mainly from foods and is well absorbed in the intestine, 2) AG is little degraded and metabolized in the body, and 3) an equilibrium exists between oral supplement plus a small but steady amount of de novo synthesis and excretion in urine.

Adult

Properties of agents that effectively entrap liquid lipids.

A droplet of an oil-in-water emulsion of methyl linoleate in a saccharide or protein solution that contained with a surfactant, a stabilizer, or both was dehydrated by drying equipment for a single droplet that resembled a spray drier. The lipid exposed on the surface of dehydated samples was extracted and measured by gas chromatography. Gum arabic or gelatin without additives resulted in little lipid being exposed; they were good entrapping agents. Little lipid was exposed with a pullulan solution containing lecithin, sugar ester, carboxymethylcellulose, or sodium caseinate but much was exposed with a maltodextrin solution containing any of the surfactants tested. When both the surfactant lecithin and the stabilizer xanthan gum were added to the emulsion prepared in a maltodextrin solution, lipid was not detected. The results suggested that effective entrapping agents of liquid lipids cause much emulsification, stabilize the emulsion (that is, they cause the continuous phase to be very viscous), and create a dehydrated matrix of fine, dense network layers.

Chemical Phenomena

New fluorescent probes E3810 and methoxy E3810 for determining distributions of the apical membrane and the acidic compartment of gastric acid secreting cells.

Substituted benzimidazoles such as omeprazole, E3810 and methoxy E3810 were inhibitors of gastric H+, K(+)-ATPase which is rich in the apical membrane of gastric parietal or oxyntic cells at the secreting state. The acid-activated compounds of omeprazole and methoxy E3810, which have methoxy group at the 5-position in the benzimidazole ring, are fluorescent (excitation wavelength = 370 nm; emission wavelength = 560 nm). The fluorescence disappeared when the activated compounds reacted with the ATPase or glutathione. Using this fluorescence property, the distribution of the intracellular acidic canalicular space in isolated single parietal cells was determined. On the other hand, irradiation with ultraviolet light (335 nm) of the acid-activated compound of E3810 which had been reacted with sulfhydryl group of the ATPase or glutathione resulted in a formation of a fluorescent compound (emission = 470 nm). Using this second fluorescence property, we determined the distribution of the apical membrane of the intracellular canaliculus of isolated single mammalian parietal cells and also the location of the apical membrane on the external surface of newt oxyntic cells.

2-Pyridinylmethylsulfinylbenzimidazoles

A pilot clinical trial of a new oral hypoglycemic agent, CS-045, in patients with non-insulin dependent diabetes mellitus.

CS-045, (+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramkethylchroman-2- ylmethoxy)benzyl]-2,4-thiazolidinedione, lowers plasma glucose in several animal models of non-insulin dependent diabetes mellitus (NIDDM) presumably by increasing insulin sensitivity. Little adverse effect was found in a phase 1 study on healthy male subjects. In order to test its efficacy in lowering plasma glucose in NIDDM in man, a pilot multi-center clinical trial of CS-045 was carried out in 146 patients with NIDDM whose glycemic control was inadequate (FPG greater than 140 mg/dl) on diet and/or other oral hypoglycemic agents. CS-045 was given orally in a daily dose of 200 mg or 400 mg for 12 weeks in addition to the previous treatment. The mean fasting plasma glucose (FPG) and fructosamine began to decrease within 2 weeks and the mean HbA1c within 8 weeks. After 12 weeks, the FPG fell from 192 +/- 41 to 155 +/- 45 mg/dl (P less than 0.01), fructosamine from 3.7 +/- 0.6 to 3.3 +/- 0.6 (P less than 0.01), and HbA1c from 8.9 +/- 1.5 to 8.1 +/- 1.5% (P less than 0.01). The drug was effective in 39% of patients in that FPG fell by more than 20% of the initial value. This rate of efficacy was the same when CS-045 was given alone or together with other oral hypoglycemic agents. The drug was more effective in a dosage of 400 mg than with 200 mg (the rate of efficacy 46% vs 25%) and more effective in obese patients than in lean patients (46% vs 25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers

Comparison of 1,5-anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus.

To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.

Biomarkers

[HPRT deficiency].

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Base Sequence

Monoclonal antibodies specific to a Ca2(+)-bound form of lipocortin I distinguish its Ca2(+)-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2.

Lipocortin I, a Ca2(+)-and phospholipid-binding protein without EF-hand structures, has many biological effects in vitro. Its actual role in vivo, however is unknown. We obtained and characterized five monoclonal antibodies to lipocortin I. Two of these monoclonal antibodies (L2 and L4-MAbs) reacted with the Ca(+)-bound form of lipocortin I, but not with the Ca2(+)-free form, both in vivo and in vitro. Lipocortin I required greater than or equal to 10 microM-Ca2+ to bind the two antibodies, and this Ca2+ requirement was not affected by phosphatidylserine. L2-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I and inhibited its binding to Escherichia coli membranes and to phosphatidylserine in vitro. L4-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I, but did not affect its binding to E. coli membranes or to phosphatidylserine. These findings indicated that the inhibition of phospholipase A2 by lipocortin I was not simply due to removal or capping of the substrates in E. coli membranes. Furthermore, an immunofluorescence study using L2-MAb showed the actual existence of Ca2(+)-bound form of lipocortin I in vivo.

Annexins

Mechanism for acute reduction of 1,5-anhydroglucitol in rats treated with diabetogenic agents.

The mechanism for acute reduction of plasma 1,5-anhydroglucitol (AG) in experimental diabetic rats was studied. Acute AG decrease was induced not only by diabetogenic agents, such as streptozotocin (STZ) and alloxan, but also by phloridzin, which caused glucosuria but not hyperglycemia. A similar reduction also occurred in hyperglycemia induced by glucose injection. The AG reduction induced by STZ was completely abolished by bilateral nephrectomy or by euglycemia with insulin treatment. The decrease of plasma AG was well correlated with the degree of urinary excretion of AG, which in turn reflected the degree of urinary glucose excretion, irrespective of the kind of agent causing the glucosuria. Under conditions of continuous glucose infusion, AG concentration decreased not only in plasma but also in various tissues and organs. The amount of AG lost was estimated to be almost equal to that excreted into urine during the period of infusion. These observations suggest that the degree of reduction of plasma AG depends simply on the urinary excretion of glucose, and it was assumed that the urinary excretion of 0.5 mg AG corresponds to the urinary excretion of 100 mg glucose during a short period after the onset of glucosuria.

Alloxan

Neural crest origin of clear cell sarcoma of tendons and aponeuroses. Ultrastructural and enzyme cytochemical study of human and nude mouse-transplanted tumours.

In order to clarify the histogenesis of clear cell sarcoma of tendons and aponeuroses (CCS), two cases of human and one nude mouse-transplanted CCS line were studied using an ultrastructural and enzyme cytochemical approach. Most of the tumour cells obtained from the primary and transplanted CCS demonstrated melanosomes in various stages of development within the cytoplasm, whereas no melanosomes could be identified in the metastatic CCS. However, cholinesterase and tyrosinase activities could be demonstrated not only in the melanotic primary and transplanted CCS but also in the amelanotic metastatic CCS. The results therefore support the hypothesis that CCS is a soft tissue tumour derived from the neural crest.

Animals

[A case of pneumococcal arthritis in a patient with gout].

A 62 year-old man had suffered from gout and mild renal insufficiency since he was 40 years old. He was admitted to our hospital complicated by a productive cough, high fever and a right swollen knee joint. The chest radiographs demonstrated a left upper lobe infiltration shadow. Streptococci pneumoniae were found in the sputum, arterial blood and synovial fluid of the right knee joint, suggesting a severe pneumonia followed by pneumococcal septicemia which led to purulent arthritis. He was treated with cefamandole (CMD) and penicillin G (PC-G) for one week, but the chest X-ray findings were not improved. After treatment with cefbuperazone (CBPZ) and latamoxef (LMOX), his fever and other symptoms gradually resolved. Streptococcus pneumoniae is an uncommon organism of septic arthritis. Pneumococcal arthritis in a patient without immunodeficiency such as this case is very rare, and has not been reported in Japan.

Arthritis, Infectious

Plasma 1,5-anhydro-D-glucitol as new clinical marker of glycemic control in NIDDM patients.

To elucidate the value of using plasma 1,5-anhydro-D-glucitol (AG) as a marker of glycemic control in diabetic patients, the relationship between the plasma concentration of AG and glucosuria was examined in 152 patients with non-insulin-dependent diabetes mellitus (NIDDM). After recovery from the deterioration of glycemic control in NIDDM patients had started, AG began to increase day by day. The recovery of plasma AG showed a constant linear increase curve when excellent glycemic control was attained. The ordinary daily recovery rate of plasma AG was estimated to be 0.3 microgram/ml, which was independent of body weight, sex, age, the difference in treatment, the duration of diabetes, or the level of plasma AG among NIDDM patients. This rate decreased according to the increase in urinary glucose. When we calculated the decrease rate of plasma AG (delta AG), assuming 0.3 microgram/day to be the maximum increase rate in a day, we found a high correlation between delta AG and urinary glucose at almost all AG levels except the normal range and observed that plasma AG (A) times urinary glucose (G) was relatively constant. The formula A x G = 16 is a simple equation for rough estimation of urinary glucose from the plasma AG concentration in a stable glycemic-controlled NIDDM patient, and we call it the A.G index. The plasma AG also correlated significantly with fasting plasma glucose (r = -.810) and glycosylated hemoglobin (r = -.856) in the same stable glycemic-controlled NIDDM patients. Based on these observations, we propose that plasma AG can serve as a new marker that may provide sensitive and analytical information about glycemic control.

Adult