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Biomedical subjects

E Ishimura

Publications and source records attributed to E Ishimura.

At least 55 records · Page 3Linked to original sources

Intrarenal hemodynamic abnormalities in diabetic nephropathy measured by duplex Doppler sonography.

Intrarenal hemodynamics were studied by duplex Doppler sonography in 112 inpatients with type II diabetes mellitus (DM; 65 males, 47 females, 58 +/- 13 years old). The resistive index (RI) and pulsatility index (PI) of the interlobar arteries were calculated. The patients were divided into four groups: group I consisted of patients with urinary albumin excretion (UAE) < 20 micrograms/min (N = 42), group II with 20 < or = UAE < 200 (N = 28), group III with UAE > or = 200 (N = 25), and group IV with serum creatinine > or = 1.5 mg/dl (N = 17). Both RI and PI values in groups II, III, and IV were significantly higher than those in the controls (age- and sex-matched healthy persons, N = 37; P < 0.001), and those in group IV were significantly higher than those in groups I, II, and III (P < 0.0001). Multiple regression analysis revealed that RI values in DM patients were significantly affected by creatinine clearance, age, and duration of diabetes (R2 = 0.554, P < 0.0001). When intima-medial thickness (IMT) of the femoral and carotid arteries were measured by B-mode ultrasonography, RI values were significantly correlated with both the femoral and carotid arterial IMT. These results demonstrate that intrarenal hemodynamic abnormalities are present in type II DM patients with nephropathy, and that intrarenal hemodynamics are affected by decreased glomerular function and also probably by advanced arteriosclerosis.

Aged↗

History of vitamin D treatment of renal osteodystrophy.

Vitamin D treatment was tried when renal osteodystrophy was first recognized in the early 20th century, using vitamin D2, D3, or dihydrotachysterol. Large doses of vitamin D2 or D3 (150,000-500,000 IU) were prescribed by monitoring serum calcium, phosphate, and alkaline phosphatase. After the discovery of 1,25-dihydroxycholecalciferol, this compound or 1 alpha-hydroxycholecalciferol was applied to the treatment of renal osteodystrophy. In a preclinical study, especially of 1 alpha-hydroxycholecalciferol, nephritogenoside nephritis was the most responsive condition. These active vitamin D preparations are now widely used in patients with chronic renal failure under hemodialysis. Other active vitamin D compounds, such as hexafluoro-1,25-dihydroxycholecalciferol and 22-oxacalcitriol, are also under investigation.

Animals↗

Relationship between gastric emptying and an alpha-glucosidase inhibitor effect on postprandial hyperglycemia in NIDDM patients.

OBJECTIVE: The purpose of the study was to examine the relationship between gastric emptying and the efficacy of an alpha-glucosidase inhibitor in NIDDM patients. RESEARCH DESIGN AND METHODS: Sixteen NIDDM patients (4 patients treated with diet therapy alone and 12 receiving a sulfonylurea) were given 0.6 mg of voglibose daily for 4 weeks. The efficacy of voglibose was assessed by measurement of HbA1c, fasting plasma glucose, and 45- and 120-min postprandial plasma glucose (PPG) and serum insulin concentrations before and after the 4 weeks of voglibose therapy. Gastric emptying was evaluated using the proportional cumulative area under the absorption curve (% AUC) of plasma acetaminophen concentration at 60 min after ingestion of a liquid test meal containing 20 mg/kg of acetaminophen. These measurements were also taken before and after the therapy. RESULTS: The change in the 45-min PPG levels from the fasting state correlated significantly with the % AUC of the plasma acetaminophen concentrations (r = 0.625, P = 0.0096) before the voglibose administrations. The mean 45-min and 2-h PPG levels were reduced significantly after 4 weeks of voglibose (P < 0.05 and P < 0.01, respectively). Two-hour postprandial serum insulin concentrations were also significantly reduced at the end of the treatment period (P < 0.05). The changes in the PPG levels between pre- and posttreatment periods correlated significantly with the % AUC of the plasma acetaminophen concentrations before the treatment period (r = 0.499, P = 0.0490; r = 0.713, P = 0.0019, respectively). There was no significant difference in the plasma acetaminophen concentrations between pre- and posttreatment periods. CONCLUSIONS: The rate of gastric emptying affects the efficacy of voglibose therapy in NIDDM patients. Voglibose did not however alter the rate of gastric emptying.

Acetaminophen↗

Gastric myoelectrical activity in patients with diabetes. Role of glucose control and autonomic nerve function.

OBJECTIVE: Gastric myoelectrical activity was studied in diabetic patients using electrogastrography (EGG) to elucidate the relationship between glucose control, diabetic autonomic neuropathy (AN), and gastrointestinal motility. RESEARCH DESIGN AND METHODS: Cutaneous EGG was recorded during 1 h of fasting and 1 h after the ingestion of a standard meal in 57 diabetic patients and 10 healthy subjects. EGG was measured in 12 diabetic patients after glycemic control for 4 weeks. Diabetic patients were also studied with respect to the presence of gastrointestinal symptoms and AN. RESULTS: The percentage of dominant electrical frequency (DF) in normal range (the percentage ratio between the power at 2.4-3.6 cycles/min [cpm] and at 1-10 cpm) was significantly lower in patients with AN than in either the control subjects or the patients without AN (P < 0.01). The dominant frequency instability coefficient (DFIC) was significantly higher in patients with and without AN than in the control subjects (P < 0.01). The postprandial-to-fasting power ratio (PR) was the lowest in patients with AN (P < 0.01). Multiple regression analysis revealed that HbA1c levels were independently associated with the DFIC (R2 = 0.099, P = 0.0170) and that AN and HbA1c levels were independently associated with the PR (R2 = 0.378, P < 0.0001) in diabetic patients. The percentage of normal DF increased and the DFIC decreased significantly after glycemic control in 12 diabetic patients (P = 0.0409; P = 0.0096, respectively). CONCLUSIONS: There appears to be an association between improvement in gastric myoelectrical activity and autonomic nerve function. Abnormalities of gastric myoelectrical activity may be partly ameliorated via the improvement of autonomic nerve function, which accompanies glycemic control.

Adult↗

A case of membranous glomerulonephritis associated with gastric cancer.

We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.

Glomerulonephritis, Membranous↗

Idiopathic portal hypertension associated with high serum titer of autoantibodies and liver dysfunction.

Idiopathic portal hypertension (IPH) is a condition marked by unexplained portal hypertension. Although a number of immunological abnormalities occur in patients with IPH, liver function is usually normal. We experienced an unusual case of IPH in a 49-year-old woman, who had pronounced splenomegaly. Laboratory data revealed pancytopenia, hypergammaglobulinemia, and liver dysfunction. Antinuclear antibodies were positive, with high titer at 1280 dilutions of sera. LE cell phenomena were also positive. Histological examination of biopsied liver showed only mild changes, but portal venous pressure was markedly elevated, at 38 cm H2O. This case was thus characterized by both a high serum titer of autoantibodies and liver dysfunction.

Autoantibodies↗

Serum type III, IV collagens and TIMP in patients with type II diabetes mellitus.

We investigated serum levels of type III procollagen aminopeptide (CIII), 7S type IV collagen (CIV), and tissue inhibitor of metalloproteinase (TIMP) in 33 patients with type II diabetes mellitus (DM) without uremia (serum creatinine less than 1.5 mg/dl). The patients were divided into three groups based on measurement of the urinary albumin excretion (UAE) index obtained during two morning outpatient clinic visits: non-proteinuric patients (n = 11), UAE index less than 2.26 mg/mmol Cr; patients with microalbuminuria (n = 15), UAE index of 2.26 - 22.6 mg/mmol Cr; and patients with proteinuria (n = 7), UAE index more than 22.6 mg/mmol Cr. Serum levels of CIV and TIMP in patients with microalbuminuria and proteinuria were significantly higher than non-proteinuric patients (ANOVA, p <0.05). Serum levels of CIII in patients with proteinuria were significantly higher than those in non-proteinuric patients (p < 0.05). There was a significant positive correlation between CIV and TIMP (r = 0.502, p < 0.003), but no correlation was observed between CIII and TIMP. These results demonstrated that serum CIII and CIV increases as diabetic nephropathy progresses in terms of increasing proteinuria in type II DM patients, suggesting feasibility and usefulness of measuring serum CIV and CIII in assessing diabetic nephropathy. The increase in TIMP may be, at least in part, a possible cause for the increase in serum CIV in type II DM patients.

Adult↗

Angiotensin converting enzyme gene polymorphism and renal artery resistance in patients with insulin dependent diabetes mellitus.

The present study was carried out to elucidate whether renal hemodynamic changes are associated with angiotensin converting enzyme (ACE) gene polymorphism in patients with insulin dependent diabetes mellitus (IDDM). We studied 32 Japanese patients with IDDM (aged 15 +/- 3 years in mean +/- SD) without renal failure or retinopathy. Renal hemodynamics were examined by duplex Doppler sonography and arterial resistance index was calculated. ACE genotypes were determined by polymerase chain reaction amplification. Resistance index (RI) of arcuate arteries in IDDM patients with DD genotype was significantly elevated, being 0.64 +/- 0.04, 0.66 +/- 0.05, and 0.71 +/- 0.05 for II, ID and DD genotype groups, respectively (II vs. DD, p < 0.02). In patients with DD genotype with normoalbuminuria (n = 27), it was also significantly elevated in DD genotype patients (II vs. DD, p < 0.02). In addition, multiple regression analysis with a forward elimination procedure showed that only the ACE genotype was associated with RI of arcuate arteries (R2 = 0.24, p < 0.01) among the parameters of sex, age, IDDM duration, body mass index, HbA1c, plasma glucose levels, serum levels of total cholesterol and creatinine, urinary albumin excretion index, mean blood pressure and ACE genotype. The present study demonstrated that renal arterial resistance is elevated in IDDM patients with DD genotype. ACE gene polymorphism which could be linked to intrarenal circulatory disturbance may be associated with the initiation and progression of diabetic nephropathy.

Adolescent↗

Effect of insulin on urinary phosphate excretion in type II diabetes mellitus with or without renal insufficiency.

We investigated the effect of insulin on urinary excretion of phosphate in type II diabetes mellitus (DM) with respect to the absence or presence of renal insufficiency. A euglycemic-hyperinsulinemic clamp was performed in 37 type II DM patients. Subjects were divided into two groups: group A consisted of patients with serum creatinine levels less than 1.5 mg/dL (n = 22), and group B consisted of patients with serum creatinine levels of 1.5 mg/dL or greater (n = 15). Blood and urine samples were collected at the beginning and end of the clamp, and urinary excretion of phosphate was evaluated by calculating fractional excretion (FE-P). Tissue sensitivity to insulin in the whole body was expressed as the glucose infusion rate (M value) and that divided by steady-state plasma insulin levels (M/I ratio) during the last 30 minutes of the clamp. FE-P in group A patients significantly decreased during the clamp (from 9.46 +/- 0.67% before the clamp to 7.12 +/- 0.73% after the clamp, P < .004), whereas FE-P in group B patients did not change significantly during the clamp. The percent decrease of FE-P (decrease of FE-P during the clamp divided by FE-P before the clamp) in group A patients was significantly higher than in group B patients (22.5 +/- 7.0% and 2.5 +/- 5.1 %, respectively, P < .04). In all 37 patients, the percent decrease of FE-P was negatively correlated with blood urea nitrogen ([BUN] r = -.36, P < .05), serum creatinine (r = -.34, P < .05), and serum beta2-microglobulin (r = -.44, P < .01) and positively correlated with creatinine clearance (r = .570, P < .004), but it was not correlated with the M value or M/I ratio. These results showed that the kidneys of diabetic patients with renal insufficiency are insulin-insensitive in terms of phosphate transport, and the insulin insensitivity is related to the glomerular filtration rate but not to systemic insulin insensitivity. The percent decrease of FE-P on clamp study could be useful for assessing the insulin insensitivity of the kidney, which probably occurs primarily in the renal tubules.

Aged↗

Amyloid goiter: radiological study in a case presenting hypothyroidism.

We report herein a case of amyloid goiter associated with rheumatoid arthritis in which hypothyroidism was observed. A 52-year-old housewife who had suffeed from rheumatoid arthritis for 15 years was referred to our hospital because of general fatigue. On admission, a large goiter was observed. Laboratory data showed primary hypothyroidism. Renal biopsy and gastric mucosa biopsy showed amyloid deposition of AA-type. Thyroid biopsy showed massive amyloid involvement. Although the findings of iodine-123 scintigraphy, technetium-99m pertechnetate scintigraphy, computed tomography and magnetic resonance image studies were similar to those for goiter associated with chronic thyroiditis, tallium-201 chloride scintigraphy gave a differing result, demonstrating absent uptake at 3 hours in this case. Replacement therapy with levothyroxine relieved the symptoms. This case was unusual in that amyloid goiter presented clinically as hypothyroidism. Absence of tallium-201 chloride uptake at 3 hours may be a diagnostic specificity for amyloid goiter in differentiating its hypothyroidism from that caused by chronic thyroiditis.

Amyloid↗

Case of a parathyroidectomized patient observed longitudinally by ultrasonography. Relationship between the growth rates and 1,25-dihydroxyvitamin D3 receptor contents in the parathyroid glands.

Parathyroid glands enlarge gradually with the progression of secondary hyperparathyroidism. The significance of down-regulation of the 1,25-dihydroxyvitamin D receptor (VDR) in parathyroid glands has been emphasized. Here we report a case in whom the relationship between the growth rates of the parathyroid glands and their VDR content was examined. A 36-year-old man, who had been hemodialyzed for 8.8 years because of chronic renal failure due to chronic glomerulonephritis, developed severe secondary hyperparathyroidism. The first ultrasonographic examination of the parathyroid glands, performed 10 months before parathyroidectomy, revealed that the sizes of the right upper (RU) and left upper (LU) glands were 10 x 8 x 5 and 14 x 10 x 9 mm3, respectively, although the right lower (RL) and left lower (LL) glands were not detected. The second ultrasonographic examination performed 5 days before PTX revealed that the RU gland had enlarged up to 24 x 12 x 10 mm3, while the LU gland remained unchanged at 16 x 9 x 8 mm3. At this time, the sizes of the RL and LL glands were determined only in the longitudinal section to be 10 x 5 and 4 x 3 mm2, respectively. In the excised specimens, the sizes and weights of the RU and RL glands were 25 x 10 x 9 mm3 and 1,950 mg and 17 x 10 x 8 mm3 and 1,160 mg, respectively, while those of the LU and LL glands were 16 x 10 x 7 mm3 and 850 mg and 9 x 8 x 7 mm3 and 350 mg, respectively. Histopathologic study demonstrated that the RU and RL glands exhibited nodular hyperplasia, while the LU and LL glands exhibited diffuse hyperplasia. Using a ligand binding assay, the VDR content of the rapidly growing RU and RL glands were significantly reduced to 32.6 +/- 9.6 and 32.7 +/- 5.2 fmol/mg protein, respectively, as compared to that of the LU gland with no significant proliferating activity (111.8 +/- 0.8 fmol/mg protein). It is of great interest that the smallest LL gland, which showed some proliferating potential in spite of a histologic pattern of diffuse hyperplasia, has a VDR content of 41.0 +/- 2.6 fmol/mg protein. In summary, it was implied from this case that the VDR content in the parathyroid gland might reduce as the growth rate of the parathyroid gland increases and, furthermore, that the VDR content seems to depend to some degree on the histopathologic pattern rather than on gland weight.

Adult↗

Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells.

Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG-63 in a dose-dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3-induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose-dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3-induced increase in OC mRNA abundance in MG-63 cells, suggesting that the inhibition of the 1,25(OH)2D3-induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG-63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia.

Amino Acid Sequence↗

Heat-insoluble cryoglobulin in a patient with essential type I cryoglobulinemia and massive cryoglobulin-occlusive glomerulonephritis.

We report a case of type I essential cryoglobulinemia with massive cryoglobulin-occlusive glomerulonephritis, in which the clinical course and the physical characteristics of the cryoglobulin were unusual. Nine years before appearance of cryoglobulin, this 54-year-old man noted edema and purpura of the lower extremities. Renal biopsy performed 2 years later showed large amounts of amorphous, weakly eosinophilic, weakly periodic acid-Schiff (PAS)-positive materials occluding the glomerular capillaries. Immunostaining showed the material to be weakly immunoglobulin (Ig) G positive, and electron microscopy showed homogeneous, electron-dense deposits. Nephrotic syndrome and azotemia did not respond to steroid treatment, and dialysis was begun 5 years after the biopsy. A small amount of cryoglobulin was first detected 2 years later, 9 years after the onset of disease. The cryoglobulin had a white gelatinous appearance, was resistant to resuspension, and did not redissolve when rewarmed to 37 degrees C. Immunoelectrophoresis of the cryoglobulin, which partially dissolved at 54 degrees C, showed it to be composed of monoclonal IgG-kappa and a small amount of albumin. We consider that the unusual physical characteristics of the cryoglobulin in this case precipitated a massive cryoglobulin-occlusive glomerulonephritis, which progressed to end-stage renal failure in the absence of significant cryoglobulinemia during the initial onset of disease.

Cryoglobulinemia↗

Impaired vitamin D metabolism and response in spontaneously diabetic GK rats.

Several studies of diabetes mellitus patients have demonstrated abnormalities in calcium, phosphate and vitamin D metabolism. In an earlier study, the authors reported impaired renal processing of phosphate in spontaneously diabetic GK rats, an animal model of type II diabetes mellitus. In the present study, which represents an extension of the earlier study, vitamin D metabolism and response are examined in 20-week-old GK rats. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was found to be lower in GK rats than in Wistar rats. After intraperitoneal administration of 0.5 micrograms/kg 1,25-(OH)2D, serum calcium increased in GK rats, but not in Wistar rats, while serum phosphate remained unchanged in GK rats, but increased in Wistar rats. Although serum 1,25-(OH)2D rose abruptly in 3 h and decreased thereafter in both GK and Wistar rats, the decrease in serum 1,25-(OH)2D at 6 h was more marked in GK rats than in Wistar rats. Serum 24,25-dihydroxyvitamin D was consistently higher in GK rats than in Wistar rats. Northern blotting and dot blotting with use of a cDNA probe for the 24-hydroxylase gene showed an increased expression of the gene in the kidney of GK rats. These results demonstrate impaired vitamin D metabolism in GK rats. Increased activity of 24-hydroxylase, in addition to impaired phosphate metabolism, may play a role in impaired vitamin D metabolism in GK rats.

Animals↗

Presence of gene expression of vitamin D receptor and 24-hydroxylase in OK cells.

We investigated the gene expression of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) receptors (VDR) and 25-hydroxy-vitamin D3-24-hydroxylase (24-hydroxylase) in opossum kidney (OK) cells. Reverse transcription-polymerase chain reaction demonstrated the presence of VDR gene expression in OK cells. Northern hybridization, using rat VDR cDNA, also demonstrated a 4.4 kbp VDR mRNA expression which was affected by serum but not by 1,25(OH)2D3 and/or parathyroid hormone stimulation. Stimulation with 1,25(OH)2D3 induced 24-hydroxylase mRNA expression which peaked at 6 h. This study clearly demonstrates for the first time the presence of VDR and 24-hydroxylase gene expression in OK cells, suggesting that OK cells are a useful model for investigating the genetic action mechanisms of 1,25(OH)2D3.

Animals↗