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Biomedical subjects

M Nagase

Publications and source records attributed to M Nagase.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adrenomedullin amidation enzyme activities in hypertensive patients.

Adrenomedullin (AM) is a potent vasodilating peptide secreted from the vasculature of various organs. It is biologically active when its C-terminus is amidated. Recently, an RIA method was developed for measurement of the active form of AM, or mature AM. We here employed this method to investigate the significance of amidation of AM in controlling cardiovascular function. Thirty-six patients under hemodialysis were recruited and divided into hypertensive (n = 25; 157/86 mmHg) and normotensive (n= 11; 116/66 mmHg) groups. Mature AM, immature AM and blood pressure were monitored during hemodialysis in all patients. There was a significant reduction in blood pressure during hemodialysis in both groups, although after hemodialysis blood pressure was still higher in hypertensives than in normotensives (139 +/-14.8/76 +/- 2.5 mmHg vs. 110 +/- 5.1/66.7 +/- 3.1 mmHg). Mature AM before hemodialysis were lower in hypertensives than normotensives and it decreased in both groups. Although mature AM decreased more in normotensives than in hypertensives (-27 +/- 8% vs. -17 +/- 5%), at the end point, its level was still higher in normotensives. The ratio of mature AM/immature AM decreased only in normotensives (-11.4 8.7%), whereas it remained stable in hypertensives (0.2 +/- 5.6%). Both groups showed similar changes in ANP, endothelin, catecholamines, cGMP, and NOx. The low level in mature AM level in hypertensives may have contributed to the higher blood pressure in this group. The attenuation of AM amidation in normotensives indicates that an unspecified amidative enzyme of AM was regulated in order to normalize blood pressure.

Adrenomedullin↗
PubMed2000

Crouzon syndrome with acanthosis nigricans: case report and mutational analysis.

OBJECTIVE: To describe the 22nd case of Crouzan syndrome with acanthosis nigricans, a hyperkeratotic skin disorder with hyperpigmentation. METHODS: DNA analysis and sequencing of the FGFR3 gene were performed. RESULTS: The 13-year-old Japanese boy described here also had dyspnea, facial palsy, sensorineural hearing loss, and skeletal and mental retardation. Examination of a skin biopsy specimen revealed the typical findings of acanthosis nigricans. Genetic analysis revealed the Ala391Glu mutation in one FGFR3 gene. CONCLUSIONS: Crouzon syndrome with acanthosis nigricans is a distinct clinical entity different from classic Crouzon syndrome.

Acanthosis Nigricans↗
PubMed2000

Catastrophic exacerbation of antiphospholipid syndrome after lung adenocarcinoma biopsy.

We describe a 60-year-old man with nephrotic syndrome due to a glomerular thrombotic microangiopathy caused by the antiphospholipid syndrome (APS) associated with a lung adenocarcinoma. Although no significant aggravation of APS was noted following renal biopsy, catastrophic exacerbation of APS occurred 3 days after a lung adenocarcinoma biopsy while warfarin and prednisolone were being administered. The patient died of multiple organ failure 37 days after the lung adenocarcinoma biopsy. This case emphasizes the need for great caution for catastrophic exacerbation of malignancy associated APS following biopsy of the underlying malignancy.

Adenocarcinoma↗
PubMed1999

Increased transforming growth factor-beta2 expression in the glomerular arteriole of the juxtaglomerular apparatus in a Bartter's-like syndrome.

Although transforming growth factor-beta (TGF-beta) has been shown to participate in regulating hormone synthesis and release, little is known about involvement of individual human TGF-beta isoforms, TGF-beta1, -beta2, and -beta3, in renin synthesis and release. We examined expression of these TGF-beta isoforms in a 50-year-old man with a Bartter's-like syndrome whose renal biopsy specimen showed hyperplasia of the juxtaglomerular apparatus (GA), mild mesangial hypercellularity, focal tubular atrophy, and interstitial fibrosis. Immunoreactivity for renin and marked expression of TGF-beta2 mRNA were noted in the glomerular arteriole of the JGA, whereas mRNA expression for TGF-beta1 was only slight and that for TGF-beta3 was still more faint. Expression of mRNAs for all 3 TGF-beta isoforms was increased in the fibrotic interstitium. This expression pattern suggests that TGF-beta2 may be involved in inducing renin synthesis and/or release in the glomerular arteriole of the JGA.

Arterioles↗
PubMed1999

Increased serum and urinary neopterin in nephrotic syndrome indicate cell-mediated immune dysfunction.

T-cell-mediated immune disturbances are likely but not certain to cause the nephrotic syndrome. Because neopterin (NP) production is closely related to activation of cell-mediated immunity, we addressed the question by measuring serum NP concentrations and urinary NP/creatinine (Cr) ratios, as well as by assessing interstitial lymphocyte and monocyte infiltration in the kidney and activation of the same cell types in peripheral blood. Finally, we observed whether urinary NP/Cr ratios in nephrotic syndrome are changed by steroid therapy. Seventy-four patients with primary glomerulonephritis were divided into 4 groups based on presence or absence of nephrotic syndrome and presence or absence of mesangial proliferation and expansion. Serum and urinary NP concentrations were measured chromatographically. Infiltrating cells in the kidney were identified by immunohistochemistry, and activation of peripheral blood cells was examined by fluorescent surface marker antibodies and flow cytometry. Irrespective of the pathohistology of glomeruli, nephrotic groups showed significantly higher urinary NP/Cr ratios and serum NP concentrations. Nephrotic groups also exhibited more activation of T cells in peripheral blood than did nonnephrotic groups or a healthy control group. Serum NP did not correlate with extent of interstitial renal infiltrates. Steroid therapy decreased urinary NP/Cr ratios in steroid-responsive patients, but not in steroid-resistant patients. Increased serum NP concentrations and urinary NP/Cr ratios may reflect disordered cell-mediated immunity in the nephrotic syndrome, irrespective of glomerular histology or interstitial cell infiltration.

Adult↗
PubMed1999

Increased levels of transforming growth factor-beta in HIV-associated nephropathy.

BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) is a renal disease of unknown pathogenesis. Recent evidence suggests that the fibrogenic cytokine transforming growth factor-beta (TGF-beta) might be involved. We hypothesized that overproduction of TGF-beta in the kidney might be involved in the pathogenesis of HIVAN. METHODS: The mRNA and protein expression of TGF-beta isoforms, TGF-beta 1, TGF-beta 2, and TGF beta 3, deposition of matrix proteins induced by TGF-beta, and levels of HIV Tat protein were studied in HIVAN. Controls included normal and diseased kidneys from HIV-positive and -negative patients. The ability of Tat to induce production of TGF-beta and matrix proteins was also studied in human mesangial cells. RESULTS: Normal kidneys, thin basement membrane nephropathy, and minimal change disease were negative for the three TGF-beta isoforms and Tat. In HIVAN, levels of TGF-beta isoforms and Tat were significantly increased, along with the expression of TGF-beta mRNA and deposition of matrix proteins stimulated by TGF-beta. Increased levels of TGF-beta isoforms, but not Tat, were also found in other glomerular diseases characterized by matrix accumulation. HIV infection, in the absence of HIVAN, was not associated with an increase in TGF-beta or Tat expression. Tat stimulated the expression and production of TGF-beta 1 and matrix proteins by human mesangial cells. CONCLUSIONS: Our findings suggest that overproduction of TGF-beta is involved in the pathogenesis of HIVAN.

AIDS-Associated Nephropathy↗
PubMed1999

Retrotransposons transcribed preferentially in proximal tubules of salt-hypertensive rats.

BACKGROUND: The kidney is considered to play an important etiologic role in salt-sensitive hypertension. The aim of the present study was to isolate genes whose expression differs between the kidneys of salt-hypertensive and control rats using an mRNA differential display method. METHODS: Dahl salt-sensitive (DS) and control salt-resistant rats (DR) were fed a 0.3% or 8% NaCl diet. Renal RNA was amplified by RNA arbitrarily primed polymerase chain reaction (RAP-PCR) and compared among DR 0.3%, DR 8%, DS 0.3%, and DS 8%. Gene expression and localization were examined by Northern blotting, RNase protection assay, and in situ hybridization. Full-length nucleotide sequence was determined by screening a DS rat kidney cDNA library. RESULTS: We identified one differentially displayed clone, and its expression was greater in DS than DR, which was not affected by salt loading. The sequence was 90% homologous to the 3'-noncoding region of the nicotinic acetylcholine receptor alpha7 subunit gene. Its expression was kidney-specific, and was localized in the proximal tubules. The transcript level was markedly increased precedent to the development of hypertension. Its expression was also high in other salt-sensitive rats, and low in normotensive Sprague-Dawley and Wistar rats. The full-length cDNA contained elements homologous to the retroviral pol gene, a primer binding site sequence for reverse transcriptase, and long-terminal repeats. CONCLUSION: These results demonstrated that the newly identified transcripts (REPT1) belong to a novel retrotransposon family, which showed unique strain-, age-, tissue-, and cell type-specific expression pattern.

Animals↗
PubMed1999

A high-fat diet aggravates tubulointerstitial but not glomerular lesions in obese Zucker rats.

BACKGROUND: Despite a large body of evidence that manipulation of dietary fat alters glomerular lesions, reports regarding the effects of dietary fat on tubulointerstitial lesions are limited. Obese Zucker rats (OZR) spontaneously develop glomerular and tubulointerstitial lesions in association with hyperlipidemia. We sought to elucidate the effects of dietary fat on glomerular and tubulointerstitial lesions in OZR versus lean Zucker rats (LZR) and to assess the involvement of macrophages in the development of these lesions. METHODS: We fed LZR and OZR either a low- (1%) or high-fat (20%) diet. After 30 weeks of the specified diet, the creatinine clearance (Ccr) and renal histology as well as plasma lipid concentrations were examined. For morphological evaluation, glomerular sclerosis (GSI) and tubulointerstitial indices (TII) were each determined by a point-counting method. Infiltrating macrophages were stained immunohistochemically using an avidin-biotin complex technique. RESULTS: The high-fat diet increased the plasma low-density lipoprotein concentration in OZR. Both low- and high-fat OZR groups had higher GSI and TII than LZR receiving either diet. The high-fat diet aggravated TII but not GSI or Ccr in OZR; conversely, high fat intake worsened GSI and Ccr but not TII in LZR. Tubulointerstitial macrophages were most prominent in the high-fat OZR group, followed by the low-fat OZR group. Glomerular macrophages were similar in number in all groups. CONCLUSIONS: The manipulation of dietary fat has diverse effects on the kidney. A high-fat diet aggravated macrophage-mediated tubulointerstitial lesions in OZR, whereas in LZR, the diet induced glomerulosclerosis.

Albuminuria↗
PubMed1999

[A clinical study on treatment results of apicoectomy].

In this study, the treatment results of apicoectomy with orthograde filling were compared with those of apicoectomy with retrograde gutta-percha filling and retrograde sponge gold filling. The long-term follow-up results of the teeth treated by apicoectomy are presented, and the possible prognostic factors are discussed. The healing process of the apical bone cavity was analyzed with standard X-ray techniques and image analysis system. One hundred nineteen teeth were apicoectomized with orthograde filling, 196 teeth with retrograde gutta-percha root filling and 42 teeth with sponge gold filling. There was no significant correlation between the treatment results and the sex or age of the patients, kinds of teeth, preoperative radiolucent areas, the number of operations or histopathological diagnosis of apical lesion. The success rate of apicoectomy with orthograde filling or apicoectomy with retrograde gutta-percha root filling was significantly higher than that with retrograde sponge gold filling. The filling materials and the operation method were considered to be the most important factors for a successful outcome. Bone reconstruction was found to start from the periphery of the bone cavity and the bone defect became gradually reduced in a star-like pattern. At 4 months after operation, in the successful cases, the area of bone cavity decreased 46-64% compared with before operation, but in the unsuccessful cases, the area did not change or increased 75-120%. Thus at 4 months after operation, it is possible to determine whether or not apicoectomy is successful.

Adolescent↗
PubMed1999

[A case of an 86-year-old patient treated with thoracoscopic pericardiectomy of recurrent pericardial effusion].

We performed thoracoscopic pericardiectomy to an 86-year-old patient with recurrent pericardial effusion of unknown origin. Etiology of pericardial effusion was established by this procedure. Postoperative course was uneventful. She was discharged within two weeks and has been well 8 months postoperatively. Thoracoscopic surgery is superior to thoracotomy in terms of less invasion and postoperative pain. Thoracoscopic surgery is replacing standard thoracotomy in the management of many thoracic diseases.

Aged↗
PubMed1999

[The experience of telemedicine transmitting CT image of ruptured thoracic aortic aneurysm on the Internet].

The report describes our experience in establishing CT image transmission of ruptured thoracic aortic aneurysm to Gifu university hospital on the Internet. In this emergent case CT image transmission to the cardiovascular surgent provided medical informations in detail, which is very useful to decide the operative method and to prepare the assist circulation devices for the operation before the patient get to the hospital by ambulance. The Internet may prove to be major vehicle for telemedicine, consulting the professionals located in remote clinical institute.

Aged↗
PubMed1999

[Marked hypernatremia in suprasellar germinoma lacking a sense of thirst].

We here report a 17-year-old high school boy having suprasellar germinoma who presented marked hypernatremia probably due to damages of both the osmoregulation and thirst centers. He was in good health until July, 1996, when he noticed slight general malaise and complained of dryness of the mouth, but without polyuria. He was found to have hypernatremia of mild degree (serum Na 151 mEq/l), but dropped out from the follow-up. In April, 1997, he was admitted to our hospital with complaints of general malaise and weakness of the upper and lower extremities. Serum Na was high at 202 mEq/l with a plasma osmolality of 390 mOsm/kg H2O. He completely lacked a sense of thirst and polydipsia/polyuria. Computed tomography and magnetic resonance imaging indicated a suprasellar tumor, possibly a germinoma. Hypernatremia was first treated with intravenous infusion of a half-normal saline solution, followed by immediate polyuria of 3 to 6 l/day. Subsequently, nasal administration of desamino-D-arginine vasopressin (DDAVP) induced stabilization of serum Na to a range between 140 and 160 mEq/l. The tumor disappeared following steroid pulse therapy and irradiation of 50 Gy to the brain. At the time of discharge, he and his family were instructed to record the urine volume, amount of water intake, body weight and amount of DDAVP used. The patient was instructed to drink water corresponding to the urine volume while maintaining the dose of DDAVP. One year after treatment, the water balance reverted to a positive direction, leading to a normal range of serum Na probably because of partial recovery of the osmoreceptors and/or trained drinking habit. This case illustrates the so-called adipsic hypernatremia which is attributed to partial osmoreceptor destruction by a suprasellar germinoma.

Adolescent↗
PubMed1998

Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene.

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a recently identified receptor for oxidized low-density lipoprotein, one of the major atherogenic substances. Although LOX-1 was reported to be expressed abundantly in endothelial cells, including atheromatous lesions, the regulation of LOX-1 gene has not yet been clarified. In the present study, we isolated the rat LOX-1 gene and investigated the regulation of gene expression. The rat LOX-1 gene was encoded by a single copy gene spanning over 19 kilobases and consisted of eight exons. Exon boundaries correlated well with the functional domain boundaries of the receptor protein. The promoter region contained putative TATA and CAAT boxes and multiple cis-elements such as NF-kappaB, AP-1 and AP-2 sites, and a shear stress response element. Northern blot analysis revealed that LOX-1 gene expression was up-regulated 9-fold by shear stress, 21-fold by lipopolysaccharide, and 4-fold by tumor necrosis factor-alpha, in cultured vascular endothelial cells. LOX-1 was also expressed in macrophages but not in vascular smooth muscle cells. These data provide important information for elucidating the molecular mechanisms of LOX-1 gene regulation and suggest a role for LOX-1 in the pathophysiology of atherosclerotic cardiovascular disease.

Animals↗
PubMed1998

Do obesity and non-insulin dependent diabetes mellitus aggravate exercise-induced microproteinuria?

We evaluated the role of obesity in proteinuria by treadmill exercising of simple obese subjects and non-obese subjects with non-insulin dependent diabetes mellitus in whom the albumin excretion rate at rest was within normal range. Non-obese healthy volunteers were studied as the controls. The fractional renal clearances of four endogenous proteins, albumin, IgG, IgG4, and beta2-microglobulin were measured before, during, and after treadmill exercise in 17 simple obese and 15 non-obese diabetic subjects, and in 21 normal subjects. Exercise increased the fractional albumin clearance in all groups. In diabetic subjects, the fractional IgG4 clearance also increased: fractional beta2-microglobulin clearance increased in normal controls and in diabetics. In obese subjects, the fractional clearances of albumin, IgG, and IgG4 were similar to those in normal controls, but fractional beta2-microglobulin clearance was significantly lower. These results suggest that enhanced microalbuminuria in obese subjects is probably of glomerular origin. In normal subjects and diabetics, exercise-induced microproteinuria is probably of both glomerular and tubular origin. Defect in the charge-selective barrier of the glomerular capillary wall has been implicated in diabetics. Thus some additional factors relevant to obesity must be taken into account in the consideration of the mechanism of microalbuminuria in diabetics with obesity.

Adolescent↗
PubMed1998

Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1).

We report the identification of a unique repetitive sequence in the rat endothelial receptor for oxidized low-density lipoprotein (LOX-1) and unexpected blood-pressure-associated regulation of its expression, a new link between lipid metabolism and blood-pressure control. A rat aorta cDNA library was constructed and screened with a probe synthesized by degenerate PCR. Rat LOX-1 cDNA encoded a protein of 364 amino acids that showed approximately 60% similarity to its bovine and human counterparts. The protein consisted of intracellular N-terminal, transmembrane and extracellular lectin-like domains. Rat LOX-1 was unique in having three repeats of a 46-amino-acid motif between the transmembrane and lectin-like regions. Two isoforms of mRNA were found to be generated by alternative use of two polyadenylation signals in a tissue-specific manner. The 3'-untranslated region contained multiple A+U-rich elements for rapid degradation of mRNA. Northern-blot analysis revealed that LOX-1 mRNA was expressed predominantly in the lung. Quite unexpectedly, the expression was dramatically up-regulated in the aorta in hypertensive SHR-SP/Izm rats compared with very low levels in control WKY/Izm rats, suggesting a potential role for LOX-1 in the pathogenesis of hypertension as well as atherosclerosis.

Alternative Splicing↗
PubMed1998

T-2 toxin induces thymic apoptosis in vivo in mice.

A single intraperitoneal injection of T-2 toxin (0.35, 1.75, or 3.5 mg/kg body wt) induced time- and dose-dependent thymic atrophy in young female BALB/c mice. T-2 toxin (1.75 mg/kg) induced maximal atrophy by day 3 with complete recovery by day 7. Flow cytometric analysis showed that the CD4(+)CD8(+) double positive thymocyte population decreased markedly. Histopathological examination of the thymus indicated that the pattern of cell death in the thymocytes had a characteristic apoptotic morphology with cell shrinkage and nuclear condensation. The in vivo effects of T-2 toxin included the induction of DNA fragmentation of approximately 200 base pairs in ladder form and cell death in thymocytes. Furthermore, flow cytometric analysis of PI-stained thymocytes from animals dosed with T-2 toxin revealed the formation of apoptotic cells. Of nine kinds of trichothecene mycotoxins tested, T-2 toxin appeared to be the most potent agent to induce apoptosis in the thymus. We sought insight into the mechanism of T-2 toxin-induced apoptosis in vivo. Administration of the protein synthesis inhibitor, CHX (15 mg/kg ip), 5 min after T-2 toxin (1.75 mg/kg ip) inhibited the induction of apoptosis in thymocytes, suggesting that the de novo protein synthesis was necessary. By using adrenalectomized mice and anti-TNF-alpha antibody-injected mice, it was shown that neither endogenous glucocorticoid nor TNF-alpha appeared to be involved in the apoptotic process. Taken together, these findings suggest that T-2 toxin-induced thymic atrophy is associated with cell death through a mechanism of apoptosis.

Animals↗