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Y Mimura

Publications and source records attributed to Y Mimura.

At least 19 recordsLinked to original sources
PubMed1999

Long-term administration of adrenocorticotropin modulates the expression of IGF-I and TGF-beta 1 mRNAs in the rat adrenal cortex.

The effects of long-term adrenocorticotropin (ACTH) therapy on the expression of IGF-I and TGF-beta 1 on rat adrenal cortex was investigated. ACTH (0.1 mg/kg/day) or saline as control was injected intraperitoneally in 5-week-old Wistar rats every day for 4 weeks. ACTH significantly increased adrenal weight (P < 0.05) and serum corticosterone (P < 0.05). Competitive RT-PCR analysis on the adrenocortical mRNA showed increased IGF-I (P < 0.01) at 4 weeks of ACTH and increased TGF-beta 1 (P < 0.01) at 1 week of ACTH compared the control group. ACTH also significantly increased proliferating cell nuclear antigen mRNA level (P < 0.01), at 4 weeks of treatment, which correlated with IGF-I level (P < 0.01), but correlated negatively with ACTH-stimulated TGF-beta 1 level (P < 0.05). There was a weak correlation between IGF-I and serum corticosterone (P < 0.05), and between TGF-beta 1 mRNA levels and serum corticosterone concentration (P < 0.05). Histologically, ACTH induced hypertrophy in the zona fasciculata cells and increased the clear cells containing lipid deposits. Immunohistochemistry showed that IGF-I peptide was mainly expressed in the periphery of the zona fasciculata at 4 weeks of ACTH therapy, while the same therapy caused a slight increase in TGF-beta 1 expression in the same area. Our results show that an increase in adrenocortical growth resulting from ACTH treatment is associated with an increase in IGF-I mRNA expression but only a transient increase in TGF-beta 1 mRNA expression.

Adrenal Cortex↗
PubMed1999

Changes in endotoxin-binding proteins during major elective surgery: important role for soluble CD14 in regulation of biological activity of systemic endotoxin.

Assessment of circulating endotoxin during the perioperative period, which is only demonstrated by the Limulus amebocyte lysate (LAL) test, may be modulated by several endotoxin-binding proteins. Endotoxin-neutralizing capacity (ENC) and the plasma levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein, and bactericidal/permeability-increasing protein (BPI) were determined in 40 patients 6 h prior to skin incision for major abdominal surgery. The bioactivity of plasma endotoxin was tested by the polymyxin B-inhibited stimulatory activity of the plasma samples on healthy monocytes as measured by the release of tumor necrosis factor alpha. Plasma endotoxin levels in almost all patients increased from 0.05 +/- 0.01 to 0.23 +/- 0.03 experimental units (EU) per ml (P < 0.001); more specifically, 17 of 40 samples showed endotoxin levels of greater than 0.2 EU per ml and corresponding reductions in ENC. Soluble CD14 plasma levels were decreased from 5. 6 +/- 0.3 to 4.6 +/- 0.3 microg per ml (P < 0.05). ENC was strongly correlated with the sCD14 plasma concentration throughout the period of observation. The addition of sCD14-neutralizing monoclonal anti-sCD14 antibodies reduced ENC both pre- and postoperatively. No correlation could be established between ENC and the plasma levels of BPI, high-density lipoproteins, or low-density lipoproteins determined by measuring the concentrations of apoprotein A and apoprotein B. Biologically active endotoxin was found in only 6 of 17 samples with endotoxin levels greater than 0.2 EU per ml in the LAL test. These samples could be characterized by their perioperative loss of at least 35% of their sCD14. No change in sCD14 was detected in the remaining 11 samples. The perioperative loss of ENC is partly caused by the loss of sCD14 resulting from its consumption by endotoxin reaching the bloodstream. This study demonstrated the role of sCD14 on the bioactivity of circulating endotoxin in a human model of endotoxemia after major abdominal surgery.

Abdomen↗
PubMed1999

Treatment with a Ca(2+) channel blocker, barnidipine, reduces platelet-derived growth factor B-chain mRNA in glomeruli of spontaneously hypertensive rats.

We investigated the effect of barnidipine hydrochloride, a Ca(2+) channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-beta(1) in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR. The glomerular level of TGF-beta(1) mRNA expression was not affected by the treatment. Treatment with barnidipine significantly reduced the excretion of urinary protein. Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR.

Animals↗
PubMed1999

Antioxidant effect of zinc on acute renal failure induced by ischemia-reperfusion injury in rats.

Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury.

Acute Kidney Injury↗
PubMed1999

Giant insulinoma in a patient with multiple endocrine neoplasia-type I: a case report.

We report a case of giant cystic insulinoma constituting part of multiple endocrine neoplasia (MEN) type I. A 29-year-old Japanese man presented with a history of recurrent hypoglycemic attacks. Endocrine examination showed hyperinsulinemia discordant with hypoglycemia, and a giant cystic insulinoma (11 x 10 cm) located in the pancreatic tail was detected radiologically. Hyperprolactinemia due to pituitary adenoma and hyperparathyroidism due to parathyroid hyperplasia were also present. The insulinoma, prolactinoma and hyperplastic parathyroid gland were surgically removed. Fluorescent microsatellite analysis detected loss of heterozygosity (LOH) in chromosome 11q13 in DNA samples from all resected tissues but not from white blood cells. This is a rare case of MEN type I because of the giant cystic insulinoma and the evidence of common LOH detected in all MEN type I tissues.

Adult↗
PubMed1998

Effect of continuous infusion of vasopressin on glomerular growth response in spontaneously hypertensive rats.

Vasopressin (VP) is thought to play an important role in the pressor and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the H-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease.

Animals↗
PubMed1998

Evidence of intra- and extracellular modifications of monoclonal IgG polypeptide chains generating charge heterogeneity.

The heavy and light chains of IgG monoclonal antibodies (mAbs) can be shown to be heterogeneous, with respect to isoelectric points, when analyzed by two-dimensional electrophoresis (2-DE). The molecular basis for this charge heterogeneity has not been clearly defined but it has been suggested that it could be due, in part, to differences in glycosylation. To investigate this possibility we have compared the 2-DE pattern of glycosylated and aglycosylated forms of the mouse IgG1 mAb (1B7-11), produced in vitro in the presence and absence of tunicamycin. Charge heterogeneity was shown not to be a consequence of glycosylation status. Intracellular and secreted IgG mAbs were also analyzed to investigate the time course of change in charge properties of the heavy and light chains. The charge heterogeneity was found to be generated intracellularly, and alterations in charge properties could be induced during incubation under physiological conditions. Semilogarithmic plots of the density of the principal heavy and light chain spots against incubation time showed linear relationships, suggesting that the charge shifts result from a first-order reaction. The semilogarithmic plot for the light chain correlated well with the time after IgG synthesis. These results suggest that the charge heterogeneity of an IgG mAb is due to intra- and extracellular modifications of the polypeptide chains which reflect "aging" of antibody molecules.

Animals↗
PubMed1998

Parathyroid hormone activity increases during endotoxemia in conscious rats.

Our previous studies showed that the phosphaturic effect of parathyroid hormone (PTH) is blunted during acute-phase endotoxemia in anesthetized rats. However, the possibility that the antiphosphaturia was secondary to hyponatriuresis due to endotoxin (Et)-induced acute renal failure could not be ruled out. The objective of this study was to evaluate phosphate (Pi) excretion during early- and late-phase endotoxemia in conscious rats fed by total parenteral nutrition. Male Wistar rats weighing 270 g were used. Urine samples were taken to determine the Pi excretion rate for 12 h just after Et (E. coli B055) challenge (early-phase endotoxemia), and for 12 h after a 36-h recovery period following Et challenge (late-phase endotoxemia). Rats given isovolumetric saline instead of Et served as controls. Et injection reduced endogenous creatinine clearance markedly (0.88 +/- 0.12 ml/min, P < 0.0001, n = 7) and caused hyponatriuresis (0.80 +/- 0.19 microliters/min, P < 0.001) compared with saline injection (1.78 +/- 0.10 ml/min and 3.12 +/- 0.39 microliters/min, respectively, n = 8) during the early phase. Greater phosphaturia and hypocalciuria were observed simultaneously during early- (Pi excretion = 4.18 +/- 1.38 micrograms/min, P < 0.05; calcium excretion = 0.70 +/- 0.14 micrograms/min, P < 0.05) and late-phase (4.76 +/- 1.72 micrograms/min, P < 0.05; 0.60 +/- 0.18 micrograms/min, P < 0.05, respectively) endotoxemia (n = 8) in comparison with the respective control values (1.61 +/- 0.39 and 1.40 +/- 0.21 micrograms/min, early; 0.34 +/- 0.14 and 1.97 +/- 0.55 micrograms/min, late, n = 6). Et adminidstration resulted in a significantly increased plasma PTH concentration during the late phase (34.7 +/- 7.0 pg/ml, P < 0.05) compared with saline administration (15.4 +/- 2.4 pg/ml). In conclusion, these data suggest that the hyperphosphaturia during endotoxemia lasting longer than 12 h is attributable to elevated PTH secretion.

Animals↗
PubMed1998

Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in dahl salt-sensitive rats.

To elucidate the contribution of the renin-angiontensin system (RAS) to glomerular injury in salt-sensitive hypertension, we investigated the chronic effects of the angiotensin I-converting enzyme inhibitor cilazapril and the angiotensin II type 1-receptor antagonist (AT1a) TCV-116 in Dahl-Iwai rats. Dahl salt-sensitive (S) rats receiving 8% salt diet for 6 wk were simultaneously treated with cilazapril (n = 6), TCV-116 (n = 6), or saline (n = 14). The 8% salt diet markedly increased systolic blood pressure (SBP), urinary protein, and N-acetyl-beta-glucosaminidase (NAG) excretion compared with 0.3% salt-treated S (n = 6) or salt-resistant (n = 6) rats. Although neither cilazapril nor TCV-116 reduced the elevated SBP, TCV-116 significantly lowered urinary protein and NAG excretion. Histologically, 8% salt treatment in S rats induced progressive sclerotic and proliferative glomerular changes, which were ameliorated by both drugs. TCV-116 increased the glomerular diameter. Immunofluorescence demonstrated the increased level of type III collagen in the mesangium of 8% salt-treated S rats, which was completely reversed by TCV-116. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that 8% salt treatment significantly increased the levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor B-chain and that TCV-116 significantly reduced the levels of PCNA and transforming growth factor-beta1 (TGF-beta1). Thus, although the chronic RAS-inhibition in salt-sensitive hypertension exerted a histologically renoprotective effect by both ways without lowering blood pressure, the RAS inhibition due to AT1a had more beneficial advantages of reducing proteinuria and attenuating the levels of glomerular TGF-beta1 and extracellular matrix.

Acetylglucosaminidase↗
PubMed1998

Inappropriate elevation of intact PTH in the presence of normocalcemia after successful surgery for primary hyperparathyroidism.

We describe here a patient with primary hyperparathyroidism who had high serum intact PTH levels for over 16 months after parathyroidectomy without signs of recurrence or persistence of the disease. The patient was a 48-year-old female who appeared well nourished (body mass index, 23.7). She was received subtotal gastrectomy as treatment for a duodenal ulcer at 44 years and 5 months old and had reached menopaused at 46 years of age. Hypercalcemia and a high serum intact PTH level were pointed out three months before admission to our institute. A bone densitometric study revealed that the bone mass of the lumbar spine was extremely reduced (0.636 g/cm2, Z score, -2.17) preoperatively and had not increased 29.5 months after parathyroidal adenomectomy (0.656 g/cm2, Z score, -1.97). Hyperparathyroidism, menopause and gastrectomy may have together contributed to the reduced bone mass. The postoperative persistently increased PTH levels in our patient suggest that the remaining parathyroid glands could have been altered during hypercalcemia, causing an increase in the set-point of PTH secretion by serum calcium or a decrease in the renal responsiveness to PTH during the disease.

Adenoma↗
PubMed1998

Hypocalcemia due to spontaneous infarction of parathyroid adenoma and osteomalacia in a patient with primary hyperparathyroidism.

A 49 year-old Japanese woman had subjected enlargement of a cervical tumor, and also suffered two bone fractures in 2 years. The cervical tumor had enlarged further in the month prior to admission, becoming warm and tender. Endocrinological examination revealed that the serum intact PTH concentration was remarkably high at 400 pg/mL despite the low serum calcium concentration, and that the serum vitamin Ds concentration was decreased. Bone roentgenograms revealed severe osteolytic changes compatible with osteitis fibrosa cystica and a pathologic fracture of the humerus. Under a diagnosis of primary hyperparathyroidism, parathyroidectomy was performed, followed by fixation surgery for the pathologic fracture. Histologically, the cervical tumor was a parathyroid chief-cell adenoma with massive necrosis, and the bone pathology by iliac bone biopsy revealed the existence of osteomalacia. She was treated with calcium, vitamins D and K2 and calcitonin after the surgery. This case is a rare condition manifesting hypocalcemia with catastrophic osteoporosis under the coexistence of spontaneous infarction of parathyroid adenoma with osteomalacia, suggesting that the clinical features of hyperparathyroidism are modified by both the autoparathyroidiectomy and the existence of osteomalacia due to vitamin D deficiency.

Adenoma↗
PubMed1998

Atrial natriuretic peptide has no potential to protect against endotoxin-induced acute renal failure in the absence of renal nerves.

Atrial natriuretic peptide (ANP) has been shown to have the potential to restore renal function after ischemic injury, an underlying component of endotoxin (Et)-induced acute renal failure, and is known to counteract renal sympathetic nerve activity in renal function. We have recently found that renal denervation restores the Et-induced renal dysfunction. The purpose of this study was to examine effects of ANP infusion on the Et-induced acute renal failure in the absence of renal nerves. Ten to 14 days after bilateral renal denervation (DNX), Wistar rats (250 to 300 g body wt) were used in the acute experiment. Rats with intact renal nerves (INN) served as controls. Following control clearance measurements, rats were intravenously injected with 4 mg/kg Et (Escherichia coli, 055: B5). During endotoxemia, rats were infused with 10 microg/kg/h ANP or saline vehicle. Et injection reduced the glomerular filtration rate (GFR) significantly in saline-infused INN and DNX rats. ANP infusion restored the greatly reduced GFR to the pre-endotoxemia level in DNX rats but not in INN rats. There was significant difference between the ANP- and saline-infused DNX rats in the percentage change relative to the basal GFR value during the ANP infusion period. ANP infusion did not improve the hyponatriuresis and oliguria after Et administration, which is independent of renal nerves. In conclusion, ANP infusion has a minor reno-protective effect in rats with Et-induced acute renal failure in the absence of the renal nerves.

Acute Kidney Injury↗
PubMed1998

Cushing's syndrome due to unilateral adrenocortical hyperplasia.

A 49-year-old woman with Cushing's syndrome due to unilateral adrenal hyperplasia is presented. She had developed obesity and menopause for 2 years, but no hypertension or hypertrichosis was observed. Although plasma adrenocorticotropin and serum cortisol levels were within normal ranges, the circadian rhythm has completely disappeared. Free thyroxine and triiodothyronine levels were decreased. Adrenocorticotropin did not respond to corticotropin-releasing hormone, and urinary excretion of 17-hydroxycorticosteroids was not suppressed by dexamethasone. Abdominal computed tomography and 131I-Adosterol scintigraphy demonstrated a unilateral functioning mass in the left adrenal gland. The resected left adrenal mass was pathologically diagnosed as the rare condition of adrenocortical nodular hyperplasia.

17-Hydroxycorticosteroids↗
PubMed1998

Renal AT1 receptor: autoradiographic localization and quantification in rat.

To elucidate the precise localization of angiotensin II (Ang II) type 1 (AT1) receptors in the kidney, we utilized in vitro macro- and micro-autoradiography (ARG) of [3H]-Ang II bindings to the Wistar rat kidney in the presence of L-158,809, a specific non-peptide AT1 receptor antagonist. Besides, we estimated the density of renal AT1 receptors using the quantification of macro-ARG. The density of [3H]-Ang II binding to renal tissue was concentration-dependent in both renal cortex and medulla. Although the addition with 500 nM arginine vasopressin and 500 nM atrial natriuretic peptide had no effect on [3H]-Ang II, the total binding of [3H] Ang II completely displaced by the addition with 500 nM unlabeled Ang II or L-158,809. Macro-ARG revealed that the amount of both Ang II and AT1 receptors in the renal medulla greatly exceeded those in the renal cortex. In the medulla, the density of these receptors was not localized on the outer medulla but was confirmed mainly to the inner medulla, especially to the inner zone and longitudinal bands. Since the density and localization of AT1 receptors was consistent with that of total Ang II receptors, it appears that AT1 receptors comprise most of the Ang II receptors in the kidney. Micro-ARG revealed that Ang II receptors were mainly located in the glomerulus and proximal tubules of the renal cortex, as well as on the circumferences of vessels and the vasa recta of the renal medulla. The present study established a method for ARG of AT1 receptors in the kidney as well as a method for quantifying the macro-ARG.

Angiotensin I↗
PubMed1998

Renal AT1 receptor: computerized quantification in spontaneously hypertensive rats and DOCA-salt rats.

To assess the involvement of angiotensin II (Ang II) in the regulation of blood pressure, we investigated the alterations of renal Ang II type 1 (AT1) receptors in two different models of hypertension; i.e., in spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using the method for quantification of in vitro macro-autoradiography (ARG). In the SHR model, although the number of cortical AT1 receptors equaled that of Wistar Kyoto (WKY) rats at 4 and 12 weeks of age, the number of medullary AT1 receptors in the 4-week-old SHR animals was significantly lower than that in age-matched WKY rats, and increased by 12 weeks of age. The renal AT1 receptor number in DOCA-salt hypertensive rats was significantly higher than that in control rats. The amount of these receptors also increased with age in both DOCA-salt hypertensive rats and control rats. These findings indicate that the development of medullary AT1 receptors in early stages of hypertension in the SHR model differs from that in WKY rats or DOCA-salt hypertensive rats. This suggests that renal AT1 receptors may contribute to the hypertension seen in the SHR group. The renal AT1 receptors appear to be up-regulated in early stages of DOCA-salt-induced hypertension as well.

Age Factors↗
PubMed1997

Effects of OPC-21268, a vasopressin V1-receptor antagonist, on expression of growth factors from glomeruli in spontaneously hypertensive rats.

To assess the chronic in vivo effects of OPC-21268, a vasopressin-V1 receptor antagonist, on renal injury, we investigated the mRNA expressions of platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta1 and proliferating cell nuclear antigen (PCNA) in the glomeruli of spontaneously hypertensive rats (SHR) treated with OPC-21268 for 3 weeks. SHR aged 10 weeks were given 2% NaCl in drinking water for 3 weeks. The OPC group was fed a 0.5% OPC-21268-containing diet for 3 weeks and the control group was given a normal diet. There were no significant changes in the time course of systolic blood pressure, heart rate, urine volume, or urinary sodium, protein and N-acetyl-beta-glucosaminidase (NAG) excretion between the two groups. Serum electrolytes, protein and creatinine levels also did not differ between the groups. The mRNA expressions of PDGF B-chain, TGF-beta1 and PCNA in the glomerulus were examined using reverse transcriptase-polymerase chain reaction (RT-PCR) methods. The mRNA expressions of PDGF B-chain and PCNA among these were significantly suppressed in the OPC group. No significant differences in renal histology including the organ weights were found between the two groups; however, the glomerular size tended to be enlarged in the OPC group. These findings suggest that chronic V1-receptor blockade directly inhibits the glomerular proliferative injury of salt-loaded SHR at the established hypertension stage.

Acetylglucosaminidase↗