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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 199 records · Page 11Linked to original sources

Urinary excretion of aquaporin-2 water channel protein in human and rat.

Previous studies by the authors demonstrated that the response of urinary aquaporin-2 (AQP2) excretion to dDAVP (deamino-8-D-arginine vasopressin) infusion is an index of vasopressin action on the kidney (N Engl J Med 332: 1540-1545, 1995). In the study presented here, the characteristics of urinary excretion of AQP2 were examined further. An RIA suitable for AQP2 in the urine was established. Relatively high concentrations of detergent and bovine serum albumin in the RIA buffer allowed analysis of urine samples with a wide range of concentrations and increased the sensitivity of the assay. AQP2 in the urine existed as a high molecular weight form of approximately 190 kD by HPLC analysis. The mean urinary AQP2 concentration corrected for creatinine in spot urine samples of healthy subjects who voided in the morning was 1081 +/- 699 fmol/mg creatinine (mean +/- SD, n = 208). The amount of daily excretion of AQP2 in the urine was the same in men and women. Urinary AQP2 content was not affected by age of the subjects and showed a positive correlation with urine osmolality. Finally, the fraction of AQP2 excreted in the urine compared with whole kidney content was determined in the rat. Approximately 3% of AQP2 in the kidney was excreted daily, and this fraction did not change when rats were dehydrated for 3 d. These data demonstrate the necessity of establishing well-designed protocols to use urinary AQP2 as a marker of AVP action.

Adult↗

Long-term, low-dose, cadmium-induced nephropathy with renal osteopathy in ovariectomized rats.

To establish an animal model of chronic cadmium nephropathy and osteopathy, we intraperitoneally administered 0.228 mg CdCl2 (Cd) or normal saline (NS) to 52 female Sprague-Dawley (S.D.) rats 3 times a week for 16 months following ovariectomy (OV) or sham surgery (Sham), dividing the animals into three experimental groups (OV-Cd, Sham-Cd and OV-NS). Two groups of male S.D. rats were also administered Cd or NS (22 animals; Male-Cd and Male-NS). Cd-administered rats gained significantly less body weight than NS rats after 16 months of experiments with no signs of emaciation. Serum creatinine levels and Cd contents in the kidney had significantly increased in the Cd-administered rats. OV-Cd rats showed significant decreases in PTH levels and increases in calcium contents in the kidney and other organs. Kidneys of Cd-administered rats showed atrophy, dilatation, and interstitial fibrosis of tubules. Sclerosis and collapse of the glomeruli were observed in the Cd groups with no proliferation in mesangial cells or matrix. The Haversian canal system of the Cd-administered rats disappeared and was replaced by a large quantity of degenerated, necrotic, and restorative tissues. Bone histomorphometric parameters showed that osteoid volume and osteoid surface had significantly increased in the Male-Cd group. In contrast, decreases in bone mass and increases in fibrous tissue were found to be more prominent in the OV-Cd group. Our results have demonstrated for the first time that long-term, low-dose CdCl2 administration to ovariectomized S.D. rats is capable of inducing irreversible nephropathy with osteopathy exhibiting pathological and bone histomorphometric characteristics that are very similar to those of Itai-Itai disease.

Animals↗

A left atrial myxoma complicated with acute myocardial infarction.

A 43-year-old female, admitted because of acute infero-posterior myocardial infarction, showed angiographic findings of 100% occlusion of left circumflex artery. Echocardiographic findings showed inferior hypokinesis, while a large left intraatrial tumor was also observed. The coronary angiography on the 17th hospital day showed complete reperfusion of the culprit lesion without stenosis. On the 21st hospital day, the removal operation of the tumor was performed. Pathological findings showed typical cardiac myxoma, and the etiology of the occlusion at the culprit vessel was presumed to be closely related to the existence of the left atrial tumor.

Adult↗

Hemolysis, elevated liver enzymes, and low platelets syndrome associated with primary anti-phospholipid antibody syndrome.

A 28-year-old woman with a history of a spontaneous abortion developed thrombocytopenia, Coombs-negative hemolytic anemia, and liver dysfunction at the sixteenth week of pregnancy. These findings were compatible with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome (hemolysis, elevated liver enzymes, and low platelet counts). Moreover, serum anti-phospholipid antibodies were positive, suggesting the association of anti-phospholipid antibody syndrome. An artificial abortion, anti-coagulation therapy, and plasma exchange were performed concomitantly with corticosteroid therapy. She responded to the therapy, a remission was obtained. Anti-phospholipid antibodies may play a role in the pathogenesis of HELLP syndrome.

Abortion, Induced↗

Effects of quinapril hydrochloride in patients with essential hypertension and impaired renal function.

The short-term effects of administration of an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride (quinapril) (5-10 mg/day), for 12 weeks on blood pressure and renal function were evaluated in 8 patients (60.5 +/- 7.3 years old, mean +/- SD) with mild to moderate essential hypertension and mild impairment of renal function due to nephrosclerosis. Systolic blood pressure and diastolic blood pressure were significantly reduced from 163.0 +/- 4.0 to 132.3 +/- 17.6 mmHg (p < 0.01) and from 98.3 +/- 4.6 to 81.5 +/- 6.4 mmHg (p < 0.001), respectively, before to after treatment. Both renal plasma flow (RPF) and glomerular filtration rate (GFR) were significantly increased in all patients, from 203.9 +/- 33.3 to 245.4 +/- 36.7 ml/min/1.73 m2 (p < 0.01), and from 43.4 +/- 6.4 to 53.5 +/- 4.6 ml/min/1.73 m2 (p < 0.05), respectively. Short-term quinapril administration was beneficial to renal function in patients with essential hypertension and impaired renal function.

Aged↗

Solitary and multiple pyogenic liver abscesses: characteristics of the patients and efficacy of percutaneous drainage.

OBJECTIVES: Although percutaneous drainage has emerged as one of the first line of therapies for pyogenic liver abscesses, the presence of multiple abscesses may warrant surgical drainage, which remains controversial in the literature. We studied whether the multiplicity of the lesions influences the outcome of the treatment. METHODS: Ultrasonography-guided percutaneous drainage was carried out in 48 patients with pyogenic liver abscesses. The abscesses were solitary in 38 patients and multiple (two to seven lesions) in 10 patients. Clinical characteristics and the efficacy of the treatment were compared between these two groups. RESULTS: Biliary diseases and malignancies were more frequently observed in the solitary cases than multiple cases. A past history of surgery for cholelithiasis was seen exclusively in the multiple cases. E. coli was more frequently cultured from the abscesses in the multiple cases. Three of the multiple cases required more than a single catheter. All of the multiple cases and 36 of the 38 solitary cases were successfully treated. Two patients died of biliary peritonitis as a complication of the procedure, and three died of other underlining diseases. CONCLUSION: Ultrasonography-guided percutaneous drainage is effective even in patients with multiple pyogenic liver abscesses by adding catheters to obtain sufficient drainage.

Adult↗

Is the bone mass of hemodialysis patients genetically determined?

Polymorphism of the vitamin D receptor gene (VDR) has been linked to bone mineral density in twins, postmenopausal osteoporosis, and premenopausal woman. We examined the possibility that the bone mass in hemodialysis (HD) patients might be determined by VDR. The study consisted of 229 HD patients with a mean age of 53.3 years (range 21 to 83), who were dialyzed three times a week for an average of 8.65 (range 0.2 to 24) years. We determined their VDR using DNA of peripheral white blood cells by restriction enzyme BsmI and the polymerase chain reaction-restriction fragment length polymorphism method. Bone mineral content (BMC) was estimated at 1/3 of the radius using dual energy X-ray bone absorptiometry, and expressed in z-scores standardized by gender and age. Distributions of VDR in this hemodialysis population were BB (9.9%), Bb (13.1%), and bb (77.0%), showing no significant different from those in 105 healthy volunteers (BB, 7.6%; Bb, 13.3%; and bb, 79.0%). Multiple regression analysis revealed that gender, age, duration on HD, and serum osteocalcin are major determinants of BMC (r = 0.762, P < 0.001), while VDR and serum parathyroid hormone are not. In a subgroup with younger (< 65 years) patients dialyzed for less than 8.65 years, the z-score of BMC of patients with BB allele was less than those with Bb and bb allele (N = 77, P = 0.020). We conclude that vitamin D receptor polymorphism is not one of the main determinants of BMC of HD patients, though it might partially effect bone mass in a subgroup of younger HD patients with shorter HD histories. Further studies with longitudinal observation will be needed to confirm these possibilities.

Adult↗

Water channel AQP1, 3, and 4 in the human peritoneum and peritoneal dialysate.

To clarify the mechanism of water transport driven by osmotic gradient through "ultrasmall pores" in the peritoneum, we tried to identify water channels in the peritoneum and cells in the peritoneal dialysate. Peritoneum was surgically excised from uremic patients at the insertion or removal of a catheter. Sediment was collected from 2 L of peritoneal dialysate by centrifugation at 1500 rpm. RNA was extracted and amplified by reverse transcription-polymerase chain reaction (RT-PCR). Contamination of reticulocytes was tested by the presence of ankyrin mRNA. Peritoneal tissue expressed aquaporin (AQP) 1, 3, and 4 (AQP1 > 3 > 4). Sediment of dialysate expressed mRNA of AQP1 and AQP3 (AQP1 > AQP3). The sample did not express ankyrin mRNA, indicating that the AQP1 in the sediment did not originate from reticulocytes. These data indicate that aquaporins are present in the peritoneum and might participate in water transport. Further quantitative analysis of aquaporin messages in the dialysate might clarify the pathogenesis of water removal failure.

Ankyrins↗

Calcitonin gene-related peptide (CGRP) and hypertrophy of cardiomyocytes.

We studied whether calcitonin gene-related peptide (CGRP), a neuropeptide secreted from the sensory nervous supply to the myocardium, induces hypertrophy of cardiomyocytes in culture. CGRP increased the cell surface area of neonatal rat cardiomyocytes; the surface area of the cells was almost doubled by treatment with CGRP for 48 h. Furthermore, CGRP up-regulated mRNA expression for skeletal alpha-actin and atrial natriuretic peptides, which are genetic markers for cardiac hypertrophy. These results indicate that CGRP is a potent hypertrophic factor for cardiomyocytes.

Animals↗

Effect of training program based on anaerobic threshold in the early phase after acute myocardial infarction.

We devised a new physical training program on the basis of anaerobic threshold for rehabilitation in the early phase of acute myocardial infarction. Forty-four patients were divided into two groups, control and training. We measured the left ventricular ejection fraction using nuclear stethoscopy during the treadmill test and calculating radioactive cardiac output. In the training group, anaerobic threshold and exercise time to the anaerobic threshold point were significantly increased, and stroke volume at rest measured by the dye dilution method increased significantly. Radioactive cardiac output during exercise also increased after the exercise therapy. These results indicate that the rehabilitation program consisting of physical training based on the anaerobic threshold is effective.

Adult↗

Molecular cloning of endothelial, inducible nitric oxide synthase gene from rat aortic endothelial cell.

We have isolated and sequenced clones of an inducible nitric oxide synthase (iNOS) from cDNA library of interleukin-1 beta-treated rat aortic endothelial cells (EC) completely free from other cell types. The cloned cDNA contains an ORF consisting of 3441 bp, which encodes 1147 amino acid residues. The deduced amino acid sequence contains putative binding sites for NADPH, FMN, FAD, calmodulin and heme. By comparison with amino acid sequences of other isoforms, rat EC iNOS is very similar (92% similarity) to mouse macrophage iNOS. There are four AUUUA motifs, potentially responsible for the instability of the mRNA, in 3'non-coding region of rat EC iNOS cDNA. Transient transfection of cultured rat vascular smooth-muscle cells with a full-length rat EC iNOS cDNA/SR alpha 296 construct by electroporation resulted in massive NO production in proportion to the doses of cDNA used. Northern blot analysis using rat EC iNOS cDNA as a probe revealed that cycloheximide treatment led to a marked accumulation of iNOS mRNA in the presence and absence of interleukin-1 beta. No appreciable decay in the cycloheximide-induced iNOS mRNA accumulation was observed, suggesting that blockade of de novo protein synthesis stabilizes mRNA. These results demonstrate that rat EC iNOS is identical (or very similar) to macrophage iNOS, and suggest that the EC iNOS gene is also regulated at the post-transcriptional level.

Amino Acid Sequence↗

Identification of a new outwardly rectifying Cl- channel that belongs to a subfamily of the ClC Cl- channels.

A new outwardly rectifying Cl- channels (ORCC) that belongs to ClC Cl- channel family has been identified from rat kidney and designated as ClC-5. ClC-5 cDNA encodes a polypeptide of 746 amino acids, which is indicated by hydrophobicity analysis to have structural features that are common of the ClC family. However, the amino acid sequence was weakly homologous to those of other ClC Cl- channels except for ClC-3, which we recently identified as a Ca2+-sensitive ORCC. Northern blot analysis of rat tissues showed that ClC-5 mRNA was predominantly expressed in the kidney and colon. To characterize the functional properties of ClC-5 by whole cell patch-clamp technique, we established the stably transfected CHO-K1 cell line using intranuclear microinjection technique. The transfected cells induced outwardly rectifying and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive Cl- currents on whole cell configuration. Following the identification of two highly homologous ORCCs, ClC-3 and ClC-5, a new subfamily encoding ORCC has emerged in the ClC family. Furthermore, ClC-5 was almost identical to a partial sequence of human cDNA that is related to Dent's disease. The molecular structure and functional properties of ClC-5 will provide an important insight into ORCCs and the pathogenesis of Dent's disease.

Animals↗