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Biomedical subjects

K Shima

Publications and source records attributed to K Shima.

At least 289 records · Page 16Linked to original sources

The relative value of glycated albumin, hemoglobin A1c and fructosamine when screening for diabetes mellitus.

We compared the usefulness of three glycated serum proteins, glycated albumin (GA), glycated hemoglobin (HBA1c) and fructosamine (FA), for diabetic screening purposes. We measured these indices in 302 adults, most of whom underwent yearly physical examinations. We measured GA and HbA1c with high precision using high-performance liquid chromatography (interassay coefficients of variation 4.9 and 4.0%, respectively) and FA using commercial reagents (interassay coefficient of variation 1.65%). All the individuals underwent a 75-g oral glucose tolerance test, which revealed significant correlations between the values of the three glycated proteins and the four plasma glucose concentrations measured as well as the sum of these glucose concentrations, sigma BS (GA, r = 0.80; HbA1c, r = 0.80; FA, r = 0.65). On the basis of the test, 130 of the subjects were classified as normal (N), 123 as borderline and 49 as having diabetes mellitus (D) according to the criteria of the Japan Diabetes Society. Of the 123 borderline cases, 26 showed impaired glucose tolerance (IGT) according to the WHO criteria. The normal group values of GA, HbA1c and FA were 17.8 +/- 0.17% (mean +/- SEM), 5.02 +/- 0.03%, and 2.55 +/- 0.02 mM/l, respectively. Borderline and IGT subjects had significantly more GA and HbA1c than normal but not more FA (P less than 0.01). We divided the subjects into 10 groups on the basis of their sigma BS values; those with values higher than 671 +/- 4.7 mg/dl had significantly more GA and HbA1c than normal, while those with values higher than 1068 +/- 40.9 mg/dl (the most extreme cases) had significantly more FA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lens protein glycation and the subsequent degree of opacity in streptozotocin-diabetic rats.

We measured how much glycated protein there was in rat eye lenses with different degrees of cataract, using an antibody against glucitol-lysine. Streptozotocin-diabetic (STZ) rats were in some cases treated with insulin (STZ + INS); control rats were normal. We graded the cataracts from 0 (transparent) to 3 (entirely opaque). STZ rats had significantly more grade 3 cataracts, and STZ + INS rats more grade 1 cataracts, than other groups. Grade 3 lenses had significantly more glycated protein than those of grade 0 (10.8 +/- 2.7 vs. 1.0 +/- 0.4 nmol/mg protein), grades 1 and 2 being intermediate. Glycosylated hemoglobin levels correlated similarly with severity of cataract. These data are consistent with the greater incidence of cataract among diabetics than among non-diabetics, and suggest that lens protein glycation contributes to the development of cataract.

Animals↗

Inhibitory action of gliclazide on platelet functions.

Gliclazide (GC), an oral hypoglycemic agent, inhibits platelet functions, but its effective concentration is reported to be much higher in vitro than in vivo. To determine why, we compared its inhibitory effect measured by impedance aggregometry using citrated whole blood with that measured by turbidometry using platelet-rich plasma. In addition, to see how GC inhibits platelet functions, we examined its effects on arachidonic acid metabolism in platelets in an in vitro system. Impedance aggregometry was found to be more sensitive than turbidometry for detecting the inhibition of platelet aggregation, and revealed significant inhibition at 1 x 10(-4) M GC. GC reduced the amount of prostaglandin I2 (PGI2) needed to inhibit ADP-induced platelet aggregation and the adhesiveness of platelets to a rabbit vessel wall after their preincubation with 1 x 10(-3) M GC for 10 min. GC (1 x 10(-4) -1 x 10(-2) M) had no effect on platelet cyclo-oxygenase activity. GC inhibited thromboxane A2 (TXA2)-induced platelet aggregation, but had no effect on the aggregation triggered by addition of mixtures of arachidonic acid (AA) and inhibitors of key enzymes regulating various steps of AA metabolism in platelets. GC had no significant effect on PGI2-stimulated cyclic AMP (cAMP) production in platelets. These results show that the difference in the effective concentrations of GC reported to modulate platelet functions in vivo and in vitro is partly due to differences in the methods used to evaluate its effect: turbidometry evaluates platelet aggregability, but not other platelet functions modulated by GC in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

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↗

Slow fluctuations of single unit activities of hippocampal and thalamic neurons in cats. I. Relation to natural sleep and alert states.

Spontaneous unit discharges during the natural sleep-wakefulness cycle in two different neuronal groups, the hippocampal pyramidal cells and thalamic ventrobasal neurons, have been analyzed. The results show that both neurons fire with white-noise-like fluctuations during the slow-wave sleep, and with slow fluctuations with power spectral densities inversely proportional to the frequency in the frequency range of 0.02-1.0 Hz, during the paradoxical sleep. This confirms that the characteristics of fluctuations in neuronal activities of the mesencephalic reticular formation observed in our previous study are more general phenomena in the cat's brain. Partly similar behavior of spectral densities is also observed during the alert state. These observations are quantitatively confirmed by the statistical time series analysis of the spike density processes of spontaneous activities.

Action Potentials↗

Slow fluctuations of single unit activities of hippocampal and thalamic neurons in cats. II. Role of serotonin on the stability of neuronal activities.

A series of experiments was carried out both in the hippocampal pyramidal and thalamic ventrobasal neurons to investigate the effect of serotonin level in the brain on slow fluctuations of neuronal discharges. Single neuronal activities were recorded in the following two pharmacologically treated states: (1) a 5-hydroxytryptamine depleted state by p-chlorophenylalanine administration (PCPA phase) and (2) a 5-methoxy-N,N-dimethyltryptamine administered state under the PCPA pretreatment (5-MeODMT phase). The slow fluctuations of neuronal activities in the frequency range of 0.02-1.0 Hz in both nuclei were prominent during the PCPA phase and were similar to those during the paradoxical sleep. In contrast, slow fluctuations were suppressed during the 5-MeODMT phase and neuronal activities during this phase were similar to those during slow wave sleep (SWS). The results show that serotonin in the brain definitely plays a role in stabilizing single neuronal activities.

Action Potentials↗

Localization of gonadotropin binding sites in human ovarian neoplasms.

The binding of human luteinizing hormone and human follicle-stimulating hormone to ovarian tumor biopsy specimens from 29 patients was analyzed. The binding sites for human luteinizing hormone were demonstrated in one tumor of epithelial origin (mucinous cystadenoma) and in one of sex cord-stromal origin (theca cell tumor). The binding sites for human follicle-stimulating hormone were found in three tumors of epithelial origin (serous cystadenoma and mucinous cystadenoma) and in two of sex cord-stromal origin (theca cell tumor and theca-granulosa cell tumor). The surface-binding autoradiographic study revealed that the binding sites for gonadotropins were localized in the stromal tissue. The results suggest that gonadotropic hormones may play a role in the growth and differentiation of a certain type of human ovarian neoplasms.

Adolescent↗

Activity of digital area neurons of the primary somatosensory cortex in relation to sensorially triggered and self-initiated digital movements of monkeys.

Single-cell activity was examined in digital areas of the primary somatosensory cortex (SI) of monkeys performing sensorially triggered and self-initiated digital movements with the aim of rigorously determining the relative timing of onset of the neuronal activity with respect to movement onset. The activity of prime mover muscles for execution of a key-press movement was recorded simultaneously with the neuronal activity; movement onset was defined as the onset of muscle activity. Neuronal receptive fields were also identified. The following findings emerged from this study: (1) Few neurons, if any, in the SI(areas 3b, 1, 2), including pyramidal tract neurons, were active prior to movement onset. (2) The movement-related activity of SI neurons was basically similar in cases of signal-triggered and self-initiated movement. (3) No neuron in the SI showed activity associated with ipsilateral digital movement. (4) A majority of movement-related neurons in the precentral motor cortex, in contrast, started their activity before movement onset. These findings suggest that SI neuronal activity participates little in providing information necessary for developing motor responses in the initial phase of simple digital movements.

Afferent Pathways↗

Dihydropyrimidines: novel calcium antagonists with potent and long-lasting vasodilative and antihypertensive activity.

The novel calcium antagonists 3-N-substituted-3,4-dihydropyrimidines 1 and 9 and 3-N-substituted-dihydro-pyrimidin-2(1H)-ones 8 were regioselectively synthesized in good yields. Compounds 1 [especially 1s [R1 = (CH2)2N(benzyl)(2-naphthylmethyl), R2 = i-Pr, X = 0-NO2] and 1t [R1 = (CH2)2N(benzyl)(3,4-dichlorobenzyl), R2 = i-Pr, X = 0-NO2]] exhibited not only more potent and longer lasting vasodilative action but also a hypotensive activity with slow onset as compared with dihydropyridines. Moreover, some dihydropyrimidines [1q [R1 = (CH2)2N(benzyl)(3-phenylpropyl), R2 = CH2(cyclopropyl), X = 0-NO2], 1s, and 1t] were weaker in blocking atrioventricular conduction in anesthetized open-chest dogs and less toxic than the dihydropyridines.

Animals↗

Identification of glucagon-like peptide-1(7-36) amide in rat brain.

Acid-urea extract of rat brain was examined by glucagon-like peptide-1 (GLP-1) specific radioimmunoassay. A single peak was observed which co-eluted with GLP-1(7-36)amide on gel filtration and anion exchange chromatography. In contrast, GLP-1(1-37) was not detected under our experimental conditions. The fact that GLP-1 (7-36)amide, but not GLP-1(1-37), was present in rat brain suggests that preproglucagon was processed in the brain in the same manner as in the intestine and not as in the pancreas.

Animals↗

Alterations in fructosamine and glycated albumin levels during childhood.

Age-related changes in the blood concentrations of glycated proteins during childhood and adolescence were examined by measuring the blood fructosamine (FA), glycated albumin (GA), glucose levels and total serum protein levels in 611 healthy children (325 boys and 286 girls) aged 0-18 years old. These levels were compared with those of 130 healthy adults. GA was measured by a newly developed, highly precise method of high-performance liquid chromatography (inter-assay coefficient of variation, 4.9%). The FA values of all groups of up to 15 years old (grouped in two year age brackets) were significantly lower than those of adults. The mean serum concentrations of GA in infants up to four years old were also significantly lower than in adults. A slight but statistically significant positive correlation was found between age and values of FA (r = 0.36, P less than 0.001), but not of GA (r = 0.04). Levels of total serum proteins showed a positive correlation with those of FA (r = 0.47, P less than 0.001) but a weak correlation with those of GA (r = 0.29). These results suggest that age should be taken into account when the FA levels of children and the GA values of infants are evaluated.

Adolescent↗

Radioimmunoassay of human pancreatic amylase with monoclonal antibody.

A monoclonal antibody (E-21) was obtained that specifically binds to human pancreatic amylase and shows negligible cross-reaction with human salivary amylase. Using this antibody a radioimmunoassay was developed for pancreatic amylase in human serum. The assay was shown to be sensitive (detectable up to 7 mg/L), reproducible, and specific for pancreatic amylase. In normal subjects, the mean concentration of serum pancreatic amylase determined by this method was 36.3 mg/L with a 95% confidence range of 16.5 to 79.2 mg/L. A good correlation was observed between the concentrations of immunoreactive pancreatic amylase (IR-PA) and enzymatic activities in 20 serum samples (r = 0.97). The concentration of serum IR-PA was below the detectable limit in pancreatectomised patients, and was greatly increased in patients with acute pancreatitis; the latter was accompanied by parallel changes in total enzymic activity. In patients with mumps, the serum IR-PA level was within the normal range whereas the total enzymic activity was elevated.

Amylases↗

Insulin and glucagon secretion after pancreatectomies. Correlation of secretion and hormonal contents of remaining pancreas.

We studied whether insulin and glucagon secretory capacities change in relation to the corresponding hormonal contents in the pancreas remnant after pancreas resection. The following groups of dogs were used: sham operated (S-O), left pancreatectomized (L-Px), right pancreatectomized (R-Px), subtotal pancreatectomized (St-Px), and total pancreatectomized (T-Px). Endocrine functions were assessed by intravenous glucose tolerance test (IVGTT) and insulin tolerance test (ITT) in each dog under anesthesia before surgery and 1 wk after. In these five groups, the insulin secretory capacities, assessed as the integrated incremental secretion of immunoreactive insulin (sigma delta IRI) from the IVGTT, decreased to 95 +/- 11, 78 +/- 9, 48 +/- 8, 12 +/- 8, and -4 +/- 4% of the respective preoperative values, and these values were proportional to the percentage residual weight (100, 64 +/- 2, 35 +/- 2, 13 +/- 2, 0%) and IRI content (100, 59 +/- 4, 45 +/- 3, 10 +/- 2, 0%) of the pancreas remnant. After surgery, glucagon secretory capacity, the integrated incremental secretion of immunoreactive glucagon (sigma delta IRG) during the ITT, decreased significantly in the L-Px, St-Px, and T-Px groups but not in the R-Px group. The sigma delta IRG values as percentages of the preoperative values were 109 +/- 25, 46 +/- 11, 89 +/- 13, 19 +/- 11, and 3 +/- 3%, respectively, for the five groups. These values were proportional to the percentage residual IRG contents of the pancreas remnants (100, 48 +/- 6, 65 +/- 8, 12 +/- 2, 0%) rather than to the percentage residual pancreatic weights.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Changes in normal reference ranges for serum chemical analyses with ageing].

To get normal reference ranges for blood chemistry in elderly subjects, laboratory data on serum chemical analytes obtained from 1822 male and 1870 female outpatients were statistically analyzed with a non-parametric method with iterative truncation. Regarding the difference in the test data between male and female, the values for most analyses except for inorganic phosphorus and total protein were significantly higher in male than in female when an adult group including subjects of age ranging from 21 to 50 years was compared. The values for lactic dehydrogenase, albumin, sodium and calcium were higher in female of over 50 years of age than in their counterpart. When male and female were combined, the normal reference ranges for lactic dehydrogenase, alkaline phosphatase, uric acid, blood urea nitrogen, creatinine and potassium tended to be elevated while those for total protein, albumin and calcium to be declined with ageing. The values for total cholesterol and triglyceride reached a peak at a certain age. Total and direct bilirubin, sodium and chloride values were constant throughout whole age categories.

Adolescent↗

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↗