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Biomedical subjects

Y Tahara

Publications and source records attributed to Y Tahara.

At least 91 records · Page 5Linked to original sources

Effects of very-low-calorie diet weight reduction on glucose tolerance, insulin secretion, and insulin resistance in obese non-insulin-dependent diabetics.

We put 12 obese subjects on a very-low-calorie diet (VLCD) and observed how their weight loss affected their glucose tolerance. Seven had non-insulin-dependent diabetes and five did not. They consumed 1000 kcal/day for at least 1 week, then 420 kcal/day for 4 weeks, and 1000 kcal/day thereafter. VLCD improved glucose tolerance and insulin response to a glucose load in the diabetics and did not affect these parameters in the non-diabetics. It did not change insulin responsiveness to intravenous glucagon in either group. Both groups showed improved insulin resistance, as measured by an insulin suppression test. Regression analysis showed that insulin resistance correlates well with obesity and glycemic control. Weight reduction did not change hepatic insulin extraction. Thus, the improvement in glucose tolerance by some of the diabetics seems to have arisen from improvements in their insulin resistance and insulin response to a glucose load. Insulin resistance improved because of weight reduction and subsequent improvements in glycemic control.

Adult↗

Tubular dysfunction in the early stage of diabetic nephropathy.

Renal tubular function was investigated in 98 non-insulin-dependent and 18 insulin-dependent diabetics under conditions of standard glycemic control. Mean urinary excretion of lysozyme, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) in both Albustix-negative and positive patients were significantly elevated above the control range. The increased excretion of lysozyme, beta 2-microglobulin and NAG was found in 21, 55 and 62% of the normoalbuminuric patients, and in 40, 57 and 74% of the microalbuminuric patients, respectively. Besides the parameters cited above, urinary acid-soluble glycoprotein (ASP) was measured to assess its potential as an indicator of early renal dysfunction. Mean urinary ASP excretion was also elevated in both Albustix-negative and positive patients. The albumin/ASP ratio increased as nephropathy advanced. Such a mode of excretion was similar to those of low-molecular-weight proteins (lysozyme and beta 2-microglobulin). The results of multiple regression analysis showed that serum creatinine most highly correlated with the excretion of the urinary proteins except for NAG.

Acetylglucosaminidase↗

Radioimmunoassay of glycated serum protein using monoclonal antibody to glucitollysine and coomassie-brilliant-blue-coated polystyrene beads.

A radioimmunoassay for glycated serum protein (GSP) was developed using monoclonal antibody to glucitollysine and polystyrene beads coated with Coomassie-Brilliant-Blue (CBB) as adsorbent for serum protein. The monoclonal antibody was raised by immunizing BALB/c mice with reduced glycated LDL and fusing their spleen cells with mouse myeloma cells. CBB-coated polystyrene beads were introduced to absorb a constant amount of serum protein. The protein adsorbed on the CBB-coated beads was reduced by NaHB4, and after treatment with radiolabeled antibody, the radioactivity of each bead was counted with an automatic gamma-counter. The standard glycated protein used was reduced glycated human serum albumin, in which 8 of 59 lysine residues were glycated. The intra- and interassay coefficients of variation of GSP were 4.8-6.5% and 1.6-6.0%, respectively. The GSP level of diabetic patients was significantly higher than that of normal controls (1.97 +/- 1.23 vs. 0.47 +/- 0.21 nmol/mg-protein; mean +/- SD, p less than 0.001). The GSP levels of patients with insulin-dependent and non-insulin-dependent diabetes mellitus were 3.03 +/- 1.05 and 1.51 +/- 1.00 nmol/mg-protein, respectively. A good correlation was found between the levels of GSP and hemoglobin A1c (HbA1c) (r = 0.85, p less than 0.001). In patients admitted to the hospital for diabetes education and glycemic control, the GSP level decreased 43 +/- 12% with the decrease in the fasting plasma glucose level (39 +/- 13%) and the mean daily plasma glucose level (MPG, 47 +/- 15%) in a four week period after admission, whereas the HbA1c level decreased only 13 +/- 6% during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthetic isoprenoid photoaffinity labeling of P-glycoprotein specific to multidrug-resistant cells.

The synthetic isoprenoid N-solanesyl-N,N'-bis(3,4-dimethoxy-benzyl)ethylenediamine (SDB) is known to reverse drug resistance in human multidrug-resistant KB cells. SDB inhibits the photolabeling of P-glycoprotein with the vinblastine analog N-(pazido-(3-(125)l)salicyl)-N'-beta-aminoethylvindesine. We synthesized photoactive radioactive SDB and used it to photoaffinity label membrane vesicles from human KB cells and their multidrug-resistant subline KB-C2 cells. A 150 to 170 kDa protein in membrane vesicles from KB-C2 cells was specifically labeled by the photoanalog of SDB. The labeled band was not detectable in parenteral drug-sensitive cells. The photolabeled 150 to 170 kDa protein was immunoprecipitated with a monoclonal antibody (C219) specific to P-glycoprotein. P-glycoprotein labeling was inhibited by anticancer agents, vinblastine, vincristine, actinomycin D, and daunomycin, with half-maximal inhibition at 2.0, 2.3, 18, and 23 microM, respectively. Only 33 and 18% of the labeling was inhibited by 100 microM Adriamycin and colchicine, respectively. The labeling was also inhibited by agents that reverse multidrug resistance, such as verapamil, reserpine, cepharanthine, and SDB. The existence of other molecules that specifically bind to 125l-SDB-photoanalog was suggested in both KB and KB-C2 membrane vesicles. The fact that we could identify the synthetic isoprenoid acceptor in membrane vesicles from multidrug-resistant cells confirms that P-glycoprotein plays a role in the multidrug resistance phenotype and provides an explanation for the fact that SDB circumvents multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Epidemiological study on socio-psychological factors to affect the change in life style].

A cohort with the general population of 5698 was established to clarify the association between individual life style and health. This study investigated the association between life style and socio-psychological factors by means of a cross-sectional study of 1005 males aged 30 to 59 years. The health practice index consisted of 5 health practices, 1) smoking 2) drinking 3) physical activity 4) Quetelet's index, and 5) sleep. The subjects were divided into two groups, group I (aged 30 to 44 years) and group II (aged 45 to 59 years). Path analysis was used to clarify the relationship between various socio-psychological factors relating to the health practice index. In group I, the health locus of control and perceived daily life stress were directly related to the health practice index. In group II, the only health locus of control was directly related to the health practice index. It was found that the social support network formed the basis of these two factors. These results suggested that it is very important to consider individual socio-psychological factors when promoting good health practice.

Adult↗

Primary hypothyroidism in an adult patient with protein-calorie malnutrition: a study of its mechanism and the effect of amino acid deficiency.

A man with diabetes mellitus, chronic hepatitis, chronic pancreatitis, and blind loop syndrome but without any previous thyroid disease developed three episodes of transient primary hypothyroidism associated with protein-calorie malnutrition (PCM). Clinical examinations suggested that this primary hypothyroidism was not caused by chronic thyroiditis, iodine deficiency, or iodine excess. Since the three times association of primary hypothyroidism with PCM suggested the possibility that the primary hypothyroidism was caused by PCM, we have tried to clarify its mechanism. For this purpose we have investigated the change of thyroid functions during protein-calorie repletion and the effect of amino acid deficiency. Total parenteral nutrition with full supplementation of amino acids resulted in a rapid increase in serum thyroxine (T4), triiodothyronine (T3), free T4, and reverse T3, and subsequently, a rapid decrease in TSH in several days after the nutrition was begun. When amino acid solution was changed to that depleted of phenylalanine and tyrosine after the restoration of thyroid functions, serum T4 and T3 showed a gradual decrease, but serum free T4 and TSH remained within normal range. However, resupplementation of phenylalanine and tyrosine after 8 weeks of depletion gave a rapid increase in serum T4, T3, free T4, and reverse T3. These results suggested that the primary hypothyroidism was caused by an impaired T4 production and that the deficiency of amino acids in PCM partly contributed to the impairment of T4 production.

Aged↗

Biodistribution of N-isopropyl-p-iodoamphetamine in mice.

Biodistribution of N-isopropyl-p-iodoamphetamine (IMP) was evaluated in mice. After synthesis of IMP and exchange labeling with radioactive iodine, IMP was injected intravenously in male ddY mice. Activity in the brain reached 8.0 (%dose/g), at 10 min after injection and it was almost constant till 120 min. Activities in the lung and heart were high just after injection, decreased rapidly and was almost constant from 30 to 120 min. Activity in the liver increased slowly compared with other organs, and reached peak level at 60 min. In autoradiography, almost the same activity in the spinal cord as the brain was observed. Uptake and excretion of IMP were shown in kidneys and stomach, which may be the main route of the excretion of IMP and their metabolites. We concluded IMP showed good uptake in the central nervous system.

Amphetamines↗

Correlation between minimal secretory capacity of pancreatic beta-cells and stability of diabetic control.

The significance of the minimal secretory capacity of pancreatic beta-cells for the stability of the plasma glucose level was studied in 20 patients with insulin-dependent diabetes mellitus. Changes in plasma concentrations of major counterregulatory hormones in response to hypoglycemia were also investigated in these patients to clarify their contribution to diabetic brittleness. beta-Cell function was evaluated on the basis of elevation of plasma C-peptide immunoreactivity (CPR) during the intravenous glucagon test with a highly sensitive assay for plasma CPR that could detect as little as 0.03 ng/ml. After stimulation with glucagon, a significant increase in plasma CPR was observed in 10 of the patients whose beta-cell function had been evaluated as completely depleted by a conventional assay for plasma CPR. A clear inverse correlation was found between the secretory capacity of pancreatic beta-cells measured in this way and the degree of glycemic instability (r = -.74, P less than .01). Infusion of insulin at a rate of 0.15 U.kg-1.h-1 for 60 min caused a continuous decrease in the plasma glucose level, resulting in neuroglycopenia in 7 of the 10 CPR nonresponders but only 2 of the CPR responders. During insulin-induced hypoglycemia, plasma glucagon immunoreactivity did not increase in the CPR nonresponders but increased significantly in the CPR responders. A positive correlation was found between the minimal residual beta-cell capacity and the responsiveness of alpha-cells to hypoglycemia (r = .65, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Discrepancy of fasting plasma glucagon levels measured by different glucagon antisera.

To investigate the possible discrepancy between immunoreactive glucagon (IRG) levels measured by two glucagon-specific antisera, OAL-123 and 30K, fasting plasma IRG levels were measured in 30 diabetics (DM group), 56 patients with impaired glucose tolerance (IGT group) and 96 normal subjects (normal group). The fasting plasma IRG measured by OAL-123 (OAL-IRG) in DM, IGT and normal groups were 121 +/- 53, 125 +/- 43 and 119 +/- 57 pg/ml, whereas the fasting plasma IRG measured by 30K (30K-IRG) were 109 +/- 92, 92 +/- 44 and 91 +/- 68 pg/ml, respectively. There was no significant difference in the distribution of the fasting IRG levels among DM, IGT and normal groups. Although there was a statistically significant correlation between OAL- and 30K-IRG, their correlation coefficient was as small as 0.29, and 31 of 182 cases showed a large discrepancy exceeding 100 pg/ml between the two IRG values. The OAL- and 30K-IRG measured again six months later did not show a significant change, where the first and second IRG levels showed a good correlation (0.72 and 0.83 for OAL- and 30K-IRG, both p less than 0.001). The gel chromatography of the 14 plasma with fasting OAL-IRG higher than 200 pg/ml showed that the main contributor to the fasting IRG was the component of big plasma glucagon (BPG). These data suggest that there is a significant discrepancy in the fasting plasma IRG levels measured by the different glucagon antisera and that the discrepancy is caused by the different immunoreactivity of BPG to the different glucagon antisera.

Blood Glucose↗

Failure of human insulin to influence endogenous basal insulin secretion in mild diabetics.

In evaluating the possibility of self-regulation of insulin secretion in man, human insulin may be more appropriate as an inhibitor to be considered than insulins from other species because the differences in the structure of the hormones might play some part in this conflicting proposal. The present study was carried out to examine whether human insulin per se can exert a feedback effect on the insulin secretion of B-cell in mild diabetics under physiologic condition. Fifteen mild diabetics were given a two-hour infusion of human insulin at a constant rate of 40 mU/m/min after a priming dose of 160 mU/m/min for the first two minutes. The plasma glucose in nine of these patients were maintained at their basal level of 92.8 +/- 3.7 mg/dL (Group A) with a glucose clamp technique (the coefficient of variation = 5.0 +/- 0.8% during the clamp), while that in the remaining six patients were intentionally altered, within physiologic range, from 114.5 +/- 8.4 mg/dL to 83.8 +/- 4.9 mg/dL (Group B). During insulin infusion the plasma immunoreactive insulin (IRI) level were well-maintained at about 50 microU/mL level in both groups, whereas the C-peptide reactivity (CPR) in group B decreased from 1.28 +/- 0.15 ng/mL to 0.59 +/- 0.14 ng/mL in parallel to the change of plasma glucose, in contrast to the relatively stable CPR level of 0.92 +/- 0.08 ng/mL in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Somatic antigens of Pseudomonas aeruginosa. The structure of O-specific polysaccharide chains of the lipopolysaccharides from P. aeruginosa O1 (Lányi), O3 (Habs), O13 and O14 (Wokatsch), and the serologically related strain NCTC 8505.

Lipopolysaccharides from Pseudomonas aeruginosa O1 (Lányi classification), O3 (Habs classification), O13 and O14 (Wokatsch classification), and strain NCTC 8505, which is also related to serogroup O3 (Habs), have structurally similar O-specific polysaccharide chains built up of tetrasaccharide repeating units involving L-rhamnose (Rha), 2-acetamido-2-deoxy-D-glucose (GlcNAc), 2-acetamido-2-deoxy-L-galacturonic acid (GalNAcA), and a di-N-acyl derivative of bacillosamine (BacN): 2,4-diacetamido-2,4,6-trideoxy-D-glucose or 2-acetamido-2,4,6-trideoxy-4-[(S)-3-hydroxybutyramido]-D-glucose. The latter derivative was obtained free by solvolysis with hydrogen fluoride of carboxyl-reduced Habs O3 polysaccharide, and was identified by 1H-nuclear magnetic resonance spectroscopy and by mass spectrometry of the corresponding methylated alditol. Habs O3, Lányi O1, and Wokatsch O14 polysaccharides contained O-acetyl groups. Solvolysis with hydrogen fluoride of the native Habs O3 polysaccharide resulted in selective cleavage of the glycosidic linkages of 6-deoxy sugars to give the trisaccharide fragment involving all three N-acylated amino sugars. Similar solvolysis of NCTC 8505 polysaccharide afforded a mixture of disaccharide and trisaccharide with N,N'-diacetylbacillosamine at the reducing end. Smith degradation of Habs O3 polysaccharide resulted in selective oxidation of rhamnose to give a glycoside of a trisaccharide with glyceraldehyde as the aglycone. Smith degradation of NCTC 8505 polysaccharide was complicated by the formation of the glycoside of a trisaccharide with an aglycone of unknown structure. A trisaccharide with rhamnose at the reducing end was also isolated after Smith degradation of the latter polysaccharide. Analysis of the composition and structure of all oligosaccharides obtained, and detailed examination of the 13C-nuclear magnetic resonance spectra of these oligosaccharides, and of both intact and modified polysaccharides, revealed the following structures of the repeating units. The structure for the NCTC 8505 polysaccharide differs from that proposed previously [Tahara, Y. and Wilkinson, S.G. (1983) Eur. J. Biochem. 134, 299-304] in the configurations assigned to the glycosidic linkages of rhamnose and bacillosamine. The results obtained show the P. aeruginosa strains studied to represent three different O-serotypes in a single O-serogroup (Formula: see text).

Acetylation↗

alpha-Dihydrodecaprenyl phosphate as a sugar carrier in the membrane of AH 70Btc hepatoma cells.

The effect of alpha-dihydrodecaprenyl phosphate, dolichyl phosphate and solanesyl phosphate on the lipid intermediate pathway for protein glycosylation was studied with crude membrane fraction prepared from AH 70Btc hepatoma cells. alpha-Dihydrodecaprenyl phosphate increased the incorporations of [14C]mannose from GDP-[14C]mannose into CHCl3-CH3OH (2:1, v/v) extract, oligosaccharide-lipid and proteins. The above and the other data showed that alpha-dihydrodecaprenyl phosphate may function as a mannose carrier in the lipid intermediate pathway.

Animals↗

Ontogeny of substance P-containing structures in the chicken retina: immunohistochemical analysis.

We examined the ontogeny of the system with substance P-like immunoreactivity (SPI) in the chicken retina by indirect immunofluorescence method. Amacrine cells containing SPI first appeared at embryonic day 7 (E7) in the peripheral portion of the retina. At E8, they had increased in number and now extended medially to the central portion. They continued to increase in number, reaching a maximum between E13-15. After the chicks hatched, the number of SPI cells was unchanged. SPI fibers first appeared at E8 in the periphery. SPI fibers were both at the ora serrata and in the inner plexiform layer (IPL), which were not abundant. After E8, they increased in number. The increase was particularly rapid in the IPL between E10 and E16 and at the ora serrata between E15 and E19. SPI fibers reached the maximum number immediately after hatching. After that, SPI fibers in the IPL were unchanged in number. Those at the ora serrata decreased slightly in number with age, though SPI fibers were still numerous in the chicken retina 2 weeks and 1 month after hatching. These results showed that development of SPI is different for subtypes of SPI cells and for different location. This heterogeneity in development may reflect the functional differences of substance P depending on cell type and fiber location.

Animals↗

Glucagon-degrading activity in acid-ethanol extract of rat submandibular gland.

To investigate whether immunoreactive glucagon really exists in salivary gland, the integrity of glucagon radioimmunoassay was tested in the acid-ethanol extract of rat submandibular gland. Though immunoreactive glucagon was apparently measured in acid-ethanol extract of rat submandibular gland, the extract contained a significant amount of intact glucagon-degrading activity. The apparent % bound in radioimmunoassay highly correlated with the degradation of [125I] glucagon during incubation. Gel filtration profiles of [125I] glucagon incubated with acid-ethanol extract were the same as those of [125I] glucagon damaged by submandibular acid-saline extract. These data suggest that the immunoreactive glucagon in acid-ethanol extract is, as in the case of acid-saline extract, an artifact due to degradation of [125I] glucagon during radioimmunoassay.

Animals↗

Interindividual variation in the absorption of glibenclamide in man.

To investigate the interindividual variation in the absorption of sulphonylureas and its relation to unexpected hypoglycaemia during therapy with these drugs, serum concentration profile of glibenclamide, as well as plasma glucose and insulin response after an oral intake of glibenclamide were studied in 17 patients with non-insulin-dependent diabetes mellitus. In 12 patients glibenclamide was rapidly absorbed, reaching a peak concentration of 138.0 +/- 15.8 ng/ml (mean +/- SEM) at about 2 h. However, in 5 patients the absorption of glibenclamide was delayed and reached a serum peak of 134.1 +/- 29.5 ng/ml at later than 4 h. This delayed absorption was reproducible. There were no significant differences in age, duration of diabetes, per cent of ideal body weight, fasting plasma glucose or HbA1C between the rapid absorption group and the delayed group. However, autonomic nerve function, assessed by coefficient of variation of R-R intervals, was significantly impaired in the latter group in comparison with the former. Plasma glucose and insulin response to glibenclamide was also delayed in the delayed absorption group.

Absorption↗