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Biomedical subjects

Y Shigeta

Publications and source records attributed to Y Shigeta.

At least 109 records · Page 6Linked to original sources
PubMed1991

Impaired autophosphorylation of insulin receptors from abdominal skeletal muscles in nonobese subjects with NIDDM.

We studied both autophosphorylation and phosphotransferase activity of insulin receptors from abdominal skeletal muscles of nonobese subjects with non-insulin-dependent diabetes mellitus (NIDDM). Partially purified insulin receptors were labeled on their alpha-subunit with 125I-labeled insulin by chemical cross-linking and on their beta-subunit by autophosphorylation with 1000 microM ATP. Thereafter, phosphorylated insulin receptors were separated from total receptors with the anti-phosphotyrosine antibody. Thus, the percentage of phosphorylated receptors in total receptors revealed the autophosphorylation activity. Using this method, we studied the function of insulin receptors from muscle obtained by biopsy during surgery in 10 nonobese NIDDM and 8' control subjects. In diabetic subjects, insulin binding capacity from abdominal skeletal muscles was 69.4% of the control subjects. Furthermore, the percentage of phosphorylated insulin receptors stimulated by 8.3 nM insulin was significantly lower than the control subjects (mean +/- SD, 29.0 +/- 12.0 vs. 56.0 +/- 7.4%, P less than 0.01), and there was a significant inverse correlation between fasting plasma glucose levels and the percentage of phosphorylated receptors among diabetic subjects (r = 0.73, P less than 0.025). Moreover, the insulin-stimulated kinase activity toward a synthetic peptide (Glu80Tyr20) was also impaired in diabetic subjects (28.5% of control). In summary, this is the first demonstration that the autophosphorylation step of insulin receptors from abdominal skeletal muscles is impaired in nonobese NIDDM subjects.

Adenosine Triphosphate↗
PubMed1991

Effect of dietary protein restriction on proteinuria in non-insulin-dependent diabetic patients with nephropathy.

To determine the effectiveness of dietary protein restriction on proteinuria in patients with non-insulin dependent diabetes (NIDDM), 14 diabetic patients with overt nephropathy were placed on either a low protein diet (N = 7) or conventional protein diet (N = 7) for one month. After the study period, daily urinary protein excretion rates decreased significantly, from 3.2 +/- 0.4 to 1.9 +/- 0.4 g/day, and serum albumin levels increased from 3.3 +/- 0.2 to 3.7 +/- 0.5 g/dl only in the low protein diet group, without any significant changes in either serum creatinine levels or creatinine clearance. These findings suggest that dietary protein restriction has a beneficial role in the treatment of NIDDM patients with overt nephropathy.

Adult↗
PubMed1991

[Vertebral bone density and its correlation with various factors related to bone metabolism in alcoholics: a quantitative study by computed tomography].

We measured vertebral bone density of 59 male alcoholics (ALC) using quantitative computed tomography (QCT). Bone density of ALC was decreased measured on admission compared with age-matched healthy male controls (ALC: 144 +/- 42, CONTROLS: 173 +/- 34 mg/cm3, p less than 0.05). The bone density was not correlated with serum ALP, Ca, and Pi. Serum parathyroid hormone and calcitonin were also not correlated with the bone density in ALC. Serum 25-(OH)-D showed significant positive correlation with the bone density (p less than 0.01) and 1,25-(OH)2-D showed trend of positive correlation with the bone density (p less than 0.01) in ALC. Severity of liver diseases did not have any relation to the bone density in ALC. Although the decreased bone density was not improved at the second QCT examined about 10 weeks after first QCT without medication, patients administered 1 microgram of 1 alpha-(OH)-D3 daily showed a significant increase in the bone density (on admission: 152 +/- 37, 10 weeks later: 162 +/- 35 mg/cm3, p less than 0.02). Combination therapy of 1 alpha-(OH)-D3 and calcitonin did not increase the bone density. These results indicate that bone density was decreased in ALC and a decrease in serum vitamin D metabolites may cause a decrease in the bone density, although liver dysfunction does not have a role in it. These data also suggest that 1 alpha-(OH)-D3 is effective in an increase in the bone density in ALC with osteoporosis after abstinence.

Adult↗
PubMed1991

[A case of spinal cord sarcoidosis with interesting MRI findings].

A case of spinal cord sarcoidosis was reported with special reference to MRI findings. A 15-year-old man was admitted to our hospital because of gait disturbance for last six months. Neurological examination on admission showed spastic paraparesis and posterior column signs. MRI of the cervical spinal cord revealed diffuse swelling and low intensity signal in T1-weighted sequences, diffuse high intensity signal in T2-weighted, and multiple micro-nodular lesion in Gd-DTPA enhanced T1-weighted. At first multiple sclerosis was suspected, although the data of cerebrospinal fluid was not suggestive. Four weeks after admission general fatigue, fever, cough, and headache appeared and the neurological symptoms got worse. Chest film and CT revealed diffuse small nodular shadows in the lung field. Abdominal ultrasonography and CT showed hepatosplenomegaly. The general condition became worse in spite of antibiotic and antituberculotic drug therapy, but remitted spontaneously in four weeks. MRI findings also exacerbated and improved during the same period, being compatible with neurological manifestations. The diagnosis of sarcoidosis was made by transbronchial lung biopsy which revealed sarcoid granuloma. Multiple small nodules on Gd-DTPA enhanced T1-weighted MRI had not been reported in patient with spinal cord sarcoidosis.

Adolescent↗
PubMed1991

[Hypoglycemic coma].

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Administration, Oral↗
PubMed1991

[Metabolic and mitogenic effects of insulin-like growth factor I on rat glomerular mesangial cells cultured under high concentration of glucose].

Recent studies indicate the important roles of mesangial cell dysfunction and insulin-like growth factor I (IGF-I) in the development of diabetic nephropathy. In order to know whether hyperglycemia could alter IGF-I action on mesangial cells, we examined mitogenic and metabolic effects of IGF-I on mesangial cells. Mesangial cells revealed to express considerable numbers of receptors specific to IGF-I will relatively small numbers of insulin receptors. The uptake of [3H]-2-deoxy-glucose, [3H]-aminoisobutyric acid (AIB), or [3H]-thymidine into mesangial cells was stimulated by IGF-I at physiological concentrations. Under high concentrations of glucose (55 mM), the stimulation of thymidine uptake by IGF-I was significantly suppressed from 5863 +/- 549 (at 11 mM glucose) to 1731 +/- 146 DPM/100 micrograms/prot. On the contrary, AIB incorporation by IGF-I was significantly enhanced in the cells cultured under high concentration of glucose, as 2.03 +/- 0.03n mol/mg protein/15 min at 55 mM glucose vs 0.59 +/- 0.01 at 11 mM glucose. In conclusion; 1) IGF-I had metabolic and mitogenic effects on rat mesangial cells at physiological concentrations. 2) under excess glucose conditions, mitogenic action of IGF-I on rat mesangial cells was suppressed, while amino acid incorporation was enhanced. These results suggest that modulation of IGF-I effects on mesangial cell by glucose could be associated with mesangial cell dysfunction in diabetes.

Aminoisobutyric Acids↗
PubMed1990

Apolipoprotein B-48 analysis by high-performance liquid chromatography in VLDL: a sensitive and rapid method.

Apolipoprotein (apo) B subspecies were separated by high-performance liquid chromatography (HPLC) to analyze Apo B-48 contents in very-low-density lipoproteins (VLDL) more easily. Apo B-100 and B-48 were eluted through two connected column of Shim-pack Diol-300 at a retention time of 24 min and 32.3 min, respectively. The molecular masses estimated by this method were approximately 600 kDa in apo B-100, 220 kDa in apo B-48. % apo B-48 in total apo B (% B-48) determined by measuring peak area of HPLC-separated apo B in a healthy subject was 76% in chylomicrons, 13% in fasting VLDL, and 20% in 2 h-postprandial VLDL. No peak of apo B-48 was detected in LDL. Recovery of Apo B determined by re-chromatography of HPLC-separated sample was 91 +/- 4.0% and 95 +/- 3.6% in Apo B-100 and apo B-48, respectively. 125I-labeled apo B in VLDL were also analyzed by both HPLC and SDS-PAGE. Percent radioactivity of apo B-48 fraction in the total apo B determined by the HPLC (17.3%) was similar to the value obtained through the measurement of radioactivity separated by the SDS-PAGE (17.6%). Coefficient of variation in % B-48 determined by the peak area was 2.5%. Percent B-48 determined by the HPLC method was significantly correlated with % B-48 by SDS-PAGE, but 6-8 times higher, which might be accounted for in part by the reported difference of chromogenicity between apo B-100 and apo B-48. % B-48 in VLDL separated from fasting plasma were 17.1 +/- 5.6% in 14 healthy subjects, and positively related to VLDL triglyceride and cholesterol concentrations. Apo B isoprotein analysis by the HPLC method is reliable and easy to perform for studying apo B metabolism in triglyceride-rich lipoproteins in physiological as well as pathological conditions.

Adult↗
PubMed1990

The ligand binding characteristics of a kinase-defective A/K1018 human insulin receptor expressed in Rat 1 fibroblasts.

Expression of the cDNA encoding a human insulin receptor with replacement of alanine for lysine at residue 1018 in the ATP binding domain of the beta subunit results in a receptor that is not only kinase-defective, but also biologically inactive. Interestingly, this mutated receptor shows a decreased insulin binding affinity when expressed at high level. We, therefore, studied the binding property of this mutant receptor expressed in Rat 1 fibroblasts. The association rate (Ka) of insulin to the mutant receptor was comparable to normal, but the dissociation rate (Kd) was twice as fast. Furthermore, the Kd of the mutant receptor was also more sensitive to changes in pH, accelerating more rapidly with pH changes than did the Kd of normal receptors. Despite this difference, the mutant receptor still exhibited negative cooperativity. These results indicate that the loss of tyrosine kinase activity of the beta subunit of the insulin receptor leads to alteration of the ligand binding affinity of the alpha subunit.

Animals↗
PubMed1990

Transfection of cDNA with G----T point mutation at the cleavage site of insulin receptors to COS 7 cells.

To study whether the G----T point mutation of insulin proreceptors at the cleavage site which changed -Arg-Lys-Arg-Arg- to -Arg-Lys-Arg-Ser- caused unprocessed insulin receptors with decreased insulin binding affinity, we performed transfection of cDNA with the mutation in COS 7 cells and examined the expressed insulin receptors. After site-directed mutagenesis, an expression vector pGEM3SV was used to make a plasmid which contained full-length HIRcDNA behind SV40 early promoter. Transfection of normal HIR cDNA produced normal insulin receptors on the plasma membranes in COS 7 cells. However, transfection of cDNA with the mutation resulted in the presence of 210K proreceptors in the plasma membranes with decreased insulin binding ability (35% of normal). These results suggest that the mutation, not the defect of converting enzyme, was the cause for unprocessed insulin proreceptors in the patients with insulin resistance.

Amino Acid Sequence↗
PubMed1990

Spinal cord compression with paraplegia in xanthomatosis due to normocholesterolemic sitosterolemia.

A 48-year-old woman with a 30-year history of tendinous xanthomatosis developed paraplegia. The magnetic resonance image revealed extramedullary tumors. The analysis of her sera and tumors revealed increased amount of plant sterols, especially sitosterol, and the diagnosis of sitosterolemia was made. This is the first reported case of a patient with sitosterolemia who had the neurological complication of spinal cord compression due to extramedullary sitosterolemic xanthomas.

Cholesterol↗
PubMed1990

Glucose inhibits myo-inositol uptake and reduces myo-inositol content in cultured rat glomerular mesangial cells.

Although activation of polyol pathway has been proposed as one of the etiologic factors of diabetic complications, precise mechanism of the effect of polyol accumulation is still unclear. In order to test the hypothesis that there is an association of polyol pathway with myo-inositol metabolism, we measured myo-inositol content in cultured rat glomerular mesangial cells. By exposing the cells to high concentrations of glucose, intracellular myo-inositol content was reduced from 12.39 +/- 0.64 nmol/mg protein at 0 mmol/L glucose to 6.54 +/- 0.38 nmol/mg protein at 27.5 mmol/L glucose and 4.88 +/- 0.43 nmol/mg protein at 55 mmol/L glucose. This decrease of myo-inositol content was partially prevented by co-incubation with aldose reductase inhibitor, sorbinil. To examine further the mechanism of myo-inositol depletion, myo-inositol uptake by mesangial cells was studied. Major myo-inositol uptake process was sodium-dependent, saturable, and ouabain sensitive with Vmax of 171 pmol/mg protein/20 min and Km of 33 mumol/L. Sodium-dependent myo-inositol uptake was significantly inhibited by glucose in a dose-dependent manner only when glucose was present during uptake experiment, and kinetic analysis revealed the inhibition was competitive. Aldose reductase inhibition failed to prevent inhibitory effect of glucose on myo-inositol uptake. These data suggest that myo-inositol content of glomerular mesangial cells, which is reduced by high concentrations of glucose, is maintained by two processes: a glucose-sensitive but sorbitol-insensitive process, sodium-dependent myo-inositol uptake; and a sorbitol (aldose reductase) sensitive process, myo-Inositol depletion under high glucose condition may induce dysfunction of mesangial cells seen in diabetes.

Aldehyde Reductase↗
PubMed1990

Peripheral neuropathy associated with osteosarcoma in a Japanese monkey.

Peripheral neuropathy associated with osteosarcoma of the humerus was reported in a Japanese monkey (Macaca fuscata). The monkey developed osteosarcoma in the right humerus. Postmortem morphometric analyses on lower limb nerves revealed loss and size reduction of myelinated nerve fibers. Pathological findings including various demyelinative processes were found with electron microscopy. These findings were more predominant in the distal part than in the proximal part of the nerves, which is compatible with axonal degeneration of peripheral nerve fibers. This is the first case found in a monkey of dying-back neuropathy associated with malignancy, which is not infrequent in humans.

Animals↗
PubMed1990

Chronic immune thrombocytopenia in sarcoidosis.

We report a 69 year-old female with sarcoidosis who developed chronic thrombocytopenia, a rare complication of this disorder. Histologically normal bone marrow with increased number of megakaryocytes and high level of PAIgG strongly suggest the immune destruction of platelets as the cause of thrombocytopenia. In addition to thrombocytopenia, this case is also distinctive in its clinical manifestation. The patient developed several infrequent manifestations of sarcoidosis including complete AV block, uveitis, skin eruptions and middle lobe syndrome, but, did not have an intrathoracic adenopathy, the commonest manifestation of this disease.

Aged↗
PubMed1990

Increase in [3H]PN 200-110 binding to cardiac muscle membrane in streptozocin-induced diabetic rats.

Voltage-sensitive Ca2+ channels in cardiac left ventricular muscle membranes isolated from nondiabetic control and diabetic rats were measured with [3H]PN 200-110, a dihydropyridine derivative, as a ligand. The binding site (Bmax) of [3H]PN 200-110 in cardiac membranes isolated from streptozocin-induced diabetic (STZ-D) rats (128 +/- 10 fmol/mg protein) significantly (P less than 0.01) increased by 64% compared with that of control rats (78 +/- 4 fmol/mg protein) 10 wk after STZ administration without a significant change in Kd. However, the significant increase in Bmax of [3H]PN 200-110 binding in diabetic rats depended on the duration of diabetes such that the increase was not found until 6 wk after STZ injection. An 8-wk intensive insulin treatment, which was initiated 2 wk after STZ injection, normalized the increase in [3H]PN 200-110 binding in STZ-D rats to control levels (85 +/- 4 fmol/mg protein). Furthermore, [3H]PN 200-110 binding to control cardiac membranes was dose-dependently inhibited in the presence of verapamil, a phenylalkylamine Ca2+ antagonist, but that was not the case in cardiac membranes isolated from STZ-D rats. These results indicate that voltage-sensitive Ca2+ channels in cardiac muscle isolated from STZ-D rats are quantitatively and qualitatively altered, because the course of diabetes and the increase in the channels can be prevented by treatment with insulin.

Animals↗