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Biomedical subjects

O Sakai

Publications and source records attributed to O Sakai.

At least 145 records · Page 8Linked to original sources

Vascular endothelial dysfunction in patients on regular dialysis treatment.

Circulating plasma immunoreactive thrombomodulin (i-TM) reflects the injury of vascular endothelium, and desmopressin stimulates tissue plasminogen activator (tPA) release from endothelium. Therefore, in order to estimate the damage of vascular endothelium in patients on regular dialysis treatment (RDT), we studied 1) basal plasma levels of i-TM and 2) a capability to release tPA by desmopressin. The basal plasma i-TM levels of the patients (n = 23) were significantly higher than those of the normal controls (p < 0.001). The basal plasma tPA levels of the patients (n = 8) were significantly lower than those of the controls (p < 0.05). The maximum increments of tPA from the basal levels by desmopressin in the patients were significantly reduced compared to those of the controls (p < 0.001). There was a significant inverse correlation in those cases between the maximum increments of tPA and the basal plasma levels of i-TM (p < 0.05, r = -0.75). The results actually suggested that there is a vascular endothelial damage in patients on RDT.

Adult↗

Anti-hypertensive effect of low Na connection (120 mEq/l) solution for CAPD patients.

In patients undergoing continuous ambulatory peritoneal dialysis (CAPD), transperitoneal sodium (Na) flux plays a crucial role in the control of blood pressure (BP), as it determines the net Na balance of the patient. However, with the conventional solution, Na removal into the effluent greatly depends on the drained ultrafiltration (UF) volume, and this can hinder the success of adequate Na removal in some patients. Therefore, we developed a low Na concentration solution to increase Na removal through diffusion force, and studied the clinical effect of this solution in patients with Na overload. The composition of the low Na solution is as follows: Na: 120 mEq/l, Ca: 3.5 mEq/l, Mg: 0.5 mEq/l, Cl: 84 mEq/l, lactate: 40 mEq/l, glucose (G) and osmolality: 1.36% (322 mOsm/l) and 2.27% (372 mOsm/l), vol: 2 l. Nine patients (age: 43 +/- 2 yr, oral Na intake: 3.4 +/- 0.3 g/day, mean arterial pressure: 123 +/- 6 mmHg, drained UF volume: 918 +/- 187 ml/day; mean +/- SEM) were studied. Compared to the conventional solution (Na: 132 mEq/l), Na removal using the low Na solution (4 h dwell) was increased from -7.8 +/- 8.7 to -2.3 +/- 5.7 mEq in 1.36% G solution, and from 25.3 +/- 3.1 to 35.4 +/- 4.7 mEq (p < 0.05) in 2.26% G solution. Patients were switched from the conventional solution to the low Na solution, exchanging four times daily for up to 4 weeks. Two patients discontinued low Na solution before the study ended, due to overhydration and hyponatremia, the remaining seven cases showed no adverse symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Pathogenesis and therapy of IgA nephropathy].

IgA nephropathy (IgAN) is the most common chronic glomerulonephritis of unknown cause. Two factors are important in the pathogenesis of IgAN; one is IgA immune complex (IgA-IC) formation and the other is IgA-IC deposition to mesangium. For the formation of IgA-IC, antibody of IgA class, T-cells which help the generation of IgA antibody, and antigen are necessary. The serum IgA level in patients with IgAN is elevated probably due not only to the activation of B-cell but also to the hyperactivity of alpha beta chain positive T-cells. Analysis of the immunoglobulin gene of IgAN patients indicated that the genetic polymorphism could be correlated with the production of IgA antibody. The gamma delta chain positive T-cell may play some role for the formation of IgA-IC. Food, bacteria, viral proteins are reported to be the antigens of IgA-IC. Regarding to IgA-IC deposition, cytokines from T-cells and the molecular weight of IgA-IC are also indispensable factors. Clinically, long-term prognosis of IgAN are not unanimously the same. Approximately 15% patients progress to renal failure over a period of 10 years, and 25% to renal failure within 20 years. Roughly, patients can be classified into three groups in view of clinical course. First group maintains stable renal function for more than 20 years, second exhibits progressive course in more than 20 years and third progresses more rapidly than the second. Although the exact mechanism(s) governing the fate of renal function in IgAN is unclear, non-immunological factors, such as intraglomerular hypertension, are presumed to participate in its progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene.

The primary structure of human xanthine dehydrogenase (hXDH) was determined by cloning and sequence analysis of the cDNAs encoding the enzyme. The nucleotide (nt) sequence has an open reading frame of 3999 nt encoding a protein of 1333 amino acids (aa) with a calculated M(r) of 146,604. The deduced aa sequence of hXDH is homologous to the previously reported rat XDH (rXDH) and Drosophila melanogaster XDH sequences with identities of 90.2 and 52.0%, respectively. The aa residues involved in both the reversible and the irreversible conversion from the dehydrogenase type to the oxidase type of rXDH are completely conserved between the rat and the human enzymes. This implies that the molecular mechanisms of the conversion of hXDH from dehydrogenase to oxidase are common to those of the well-characterized rXDH. Five sequence variations were detected in the isolated cDNA clones. Spot blot hybridization using flow-sorted human chromosome revealed that the hXDH-encoding gene (hXDH) was located on chromosome 2.

Amino Acid Sequence↗

F-actin network may regulate a Cl- channel in renal proximal tubule cells.

A variety of mechanisms have been proposed for the regulation of ion channel molecules. As integral membrane proteins, ion channels may interact with the cytoskeleton. Regulation of channels by the actin network may therefore be important. In the present study we used cytochalasin D and exogenous actin to test this possibility. The Cl- channel of the apical membrane of renal proximal epithelium was detected in its active state after prolonged depolarization. Within 6 sec after its addition, cytochalasin D (0.05 microgram/ml) significantly decreased the number of open channels and mean open probability (NPo) of the Cl- channel. Colchicine (1 mM), which affects microtubules, did not influence channel activation. Cytochalasin D is known to not only disrupt the F-actin network but to inhibit polymerization of F-actin as well. The latter effect is also produced by DNaseI. Cytochalasin D, but not DNaseI, inactivated Cl- channels in cell-free membrane patches, suggesting that cytochalasin D inactivated the channel by disrupting the actin network. Cytochalasin D appeared to specifically affect the channel, as opposed to membrane permeability, since only the activated whole-cell Cl- currents were altered by cytochalasin D. Addition of actin polymer, but not actin monomer, reactivated the cytochalasin-D-depressed channel. Thus, repair of the disrupted F-actin network with actin polymer apparently restored the activity and number of open Cl- channels. We therefore conclude that the F-actin network interacts with and possibly regulates the Cl- channel of renal proximal tubule epithelia.

Actins↗

Mechanisms of calcium transport across the basolateral membrane of the rabbit cortical thick ascending limb of Henle's loop.

Although net Ca2+ absorption takes place in the thick ascending limb of Henle's loop, detailed mechanisms are unknown. Because it has been reported that the Ca2+ entry step across the luminal membrane is mediated by Ca2+ channels inserted by stimulation with parathyroid hormone, we studied the mechanism of Ca2+ transport across the basolateral membrane of rabbit cortical thick ascending limb (CTAL) perfused in vitro by using microscopic fluorometry of cytosolic Ca2+ ([Ca2+]i) with fura-2. The resting [Ca2+]i in this segment was 49.8 +/- 4.5 nmol/l. Neither Na+ removal from the bathing solution nor addition of ouabain (0.1 mmol/l) to the bath increased [Ca2+]i, indicating that a Na+/Ca2+ exchanger in the basolateral membrane may not contribute in any major way to [Ca2+]i of CTAL. To confirm our technical accuracy, similar protocols were conducted in the connecting tubule, where the existence of a Na+/Ca2+ exchanger has been reported. In this segment, Na+ removal from the bath increased cell Ca2+ from 148.6 +/- 6.4 nmol/l to 647.6 +/- 132.0 nmol/l, confirming the documented fact. [Ca2+]i in the CTAL was markedly increased when 1 mmol/l NaCN was added to the bath in the absence of glucose. Calmodulin inhibitors (trifluoperazine or W-7) increased [Ca2+]i. When the bath pH was made alkaline, [Ca2+]i was also increased. This response was abolished when Ca2+ was eliminated from the bath, indicating that the Ca2+ entry across the basolateral membrane is dependent on bath pH. Increase in [Ca2+]i induced by an alkaline bath was inhibited by increased the bath K+ from 5 nmol/l to 50 mmol/l, suggesting that the Ca2+ entry system is voltage-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of Sairei-to on gentamicin nephrotoxicity in rats.

The effect of Sairei-to, an oriental traditional medicine, against gentamicin nephrotoxicity was examined in gentamicin nephrotoxicity rat models. Gentamicin nephrotoxicity was induced by s.c. injection of gentamicin (100 mg/kg/day, for 3 days) in male Sprague-Dawley rats. Renal functions of two rat groups were compared, one eating rat chow containing 2.5% Sairei-to, the other eating normal rat chow. Sairei-to administration reduced the increase of urinary N-acetyl-beta-D-glucosaminidase (NAG) and protein excretion, and decreased creatinine clearance induced by gentamicin. Gentamicin increased renal cortical malondialdehyde (MDA) concentration in normal diet group but not in the Sairei-to diet group. The renal cortical gentamicin concentration was not different between the two groups. In conclusion, Sairei-to shows reno-protective action against gentamicin nephrotoxicity, possibly through its anti-oxidant action.

Acetylglucosaminidase↗

Morphologic variations of dense deposit disease: light and electron microscopic, immunohistochemical and clinical findings in 10 patients.

Twenty-one renal biopsy specimens obtained from 10 patients with dense deposit disease (DDD) were investigated using light microscopy, electron microscopy and immunohistochemistry. The patients included four females and six males aged 6 to 35 years (mean 16.1 years). A morphological diagnosis of DDD was made following the ultrastructural detection of continuous intramembranous dense deposits (CIMDD) in some capillary loops of at least one of the series of the repeated biopsies from each patient. With light microscopy, six patients showed membranoproliferative glomerulonephritis (MPGN). The other four patients showed diffuse proliferative glomerulonephritis (DPGN) with acute lesions showing intraglomerular neutrophilic infiltration, hump formation and endothelial swelling in three and minor glomerular abnormalities in one. Follow-up biopsies were obtained in six patients. Two patients progressed from DPGN to MPGN within 7 months, whereas three patients with MPGN showed morphologic improvement that featured increased capillary patency and regional disappearance of dense deposits along with the reduction of proteinuria. Dense deposit disease did not always feature typical amorphous and osmiophilic CIMDD spreading across the whole width of the lamina densa. This classical ultrastructural manifestation was mainly found in the patients with histologic non-MPGN and a linear peripheral pattern of complement component (C3) deposition. The MPGN patients with a granular peripheral pattern of C3 deposition also had CIMDD, but also additionally featured less dense subepithelial deposits superimposed on the CIMDD to produce an appearance simulating membranous transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Treatment of severe pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) and Candida krusei with granulocyte colony-stimulating factor (G-CSF): a case report].

A 24-year-old male with chronic renal failure on Continuous Ambulatory Peritoneal Dialysis (CAPD) complained of cough and dyspnea. Chest X-ray film showed a pneumonia shadow and MRSA and Candida krusei were detected in the sputum. Pneumonia improved with vancomycin and fluconazole. Treatment with methylprednisolone was needed for retinodialysis. After this treatment, pneumonia deteriorated. Pneumonia did not improve with vancomycin and anti-fungal agents. This severe pneumonia was improved with a combination therapy of vancomycin, miconazole and G-CSF. A combination therapy of antibiotics and G-CSF is considered to be effective for severe pneumonia.

Adult↗

A case of pheochromocytoma of the urinary bladder in a long-term hemodialysis patient.

The development is reported of a pheochromocytoma of the urinary bladder in a 33-year-old patient with systemic lupus erythematosus who had undergone long-term hemodialysis. A hypertensive episode followed by defecation was demonstrated by the monitoring of blood pressure with a portable automated sphygmomanometer without elevation of plasma catecholamines. The tumor was surgically removed and normalization of the patient's blood pressure followed. Thus, monitoring of blood pressure for 24 h proved useful for the diagnosis of pheochromocytoma and, in particular, of paroxysmal hypertension.

Adult↗

Glomerular growth in the remnant kidney after a contralateral nephrectomy.

A unilateral nephrectomy enhances growth or weight gain in the remaining kidney, although it is not known whether the mechanism involves the division of glomerular cells. We have isolated glomeruli from the remnant kidney at different time intervals after a nephrectomy and measured the percentage of cells in the G1, G2 + M and S phases by flow cytometry. All the steady-state glomerular cells remained in G1 phase, while a significant percentage had progressed into the S phase by 4 h after the uninephrectomy. The rise in the number of cells in the S phase gradually decreased to control values by 48 h, during which time the number of cells in both G1 and G2 + M phases increased concomitantly. Neither DNA nor RNA content per glomeruli was altered by 4 and 24 h after uninephrectomy. The data suggest an early division of the glomerular cells in the remnant kidney after a contralateral nephrectomy.

Animals↗

Lactic dehydrogenase anomaly in a patient with chronic renal failure.

A 67-year-old man with chronic renal failure (CRF) was defined to have lactic dehydrogenase (LDH)-immunoglobulin A (IgA) complex, the so-called "LDH anomaly", in his serum and pleural effusion. He was found to have a pleural effusion on the right side during maintenance dialysis at a satellite hospital. A LDH-IgA complex was detected in the serum and pleural effusion by the method of current electrophoresis. The immunoglobulin class was found to be IgA (K) by counter immunoelectrophoresis. LDH anomaly is extremely rare in patients with CRF; the clinical significance of this substance in serum and pleural effusion remains unclarified.

Aged↗

Suppression of secondary hyperparathyroidism in chronic dialysis patients by single oral weekly dose of 1,25-dihydroxycholecalciferol.

Eleven hemodialysis patients who developed refractory secondary hyperparathyroidism, despite conventional vitamin D therapy, were treated with large oral doses of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. Therapeutic regimen was a single oral dose of up to 8.0 micrograms administered once weekly following hemodialysis. A maximum serum level of 1,25(OH)2D occurred four hours after the 8.0 micrograms dose. A positive correlation (Y = 84.3X-22.1: P < 0.01) was found between the maximal serum 1,25(OH)2D concentration (Cmax) and the dose of 1,25(OH)2D3 when plotted on a logarithmic scale. Forty-eight hours after the administration of the 8.0 micrograms dose, the parathyroid hormone (PTH) level and the alkaline phosphatase activity (ALP) were markedly decreased without evidence of hypercalcemia. A significant inverse relationship was found between the Cmax of 1,25(OH)2D and the percent change in the PTH level measured after 48 hours, either with carboxy-terminal (C-PTH) or the highly sensitive mid-portion assay (HS-PTH). From these results, the level of serum 1,25(OH)2D required to blunt the rise in serum PTH was 168 pg/ml and 203 pg/ml, respectively; these serum levels were achieved by the oral administration of doses of 6.0-8.0 micrograms or higher. There were no adverse effects of treatment. Following this study, one patient was continuously treated with 8.0 micrograms of 1,25(OH)2D3 orally once a week for 18 months. There was a therapeutic effect (as evidenced by PTH suppression, ALP suppression and the disappearance of subjective complaints) without the development of severe hypercalcemia or hyperphosphatemia. This treatment may help to prevent or treat secondary hyperparathyroidism in patients receiving long-term dialysis.

Administration, Oral↗

CT visualization of the major pulmonary fissures: value of 25 degrees cranially tilted axial scans.

OBJECTIVE: CT visualization of the major (oblique) pulmonary fissures is often hampered by partial volume effects of adjacent lung parenchyma. We attempted to improve visualization of the fissures by using 25 degrees cranially tilted axial scans. An initial in vitro study also was performed. MATERIALS AND METHODS: Both conventional and 25 degrees tilted axial CT scans were obtained in 40 adult patients. After scans with 2-mm collimation were obtained at 1 cm and 6 cm below the carina, the gantry was tilted 25 degrees cranially to be perpendicular to the plane of the major fissures, and scans with 2-, 5-, and 10-mm collimation were obtained at the same two levels. The appearance of the fissures was classified as linear opacity, band-like opacity, or avascular area for each lung at each level. RESULTS: On 2-mm conventional axial scans, the major fissures were seen as linear opacities in three to 23 patients (8-58%), as band-like opacities in 13-31 (32-78%), and as avascular areas in one to seven (2-18%). (Ranges indicate lowest and highest values when data for the two levels in the two lungs are grouped separately.) On 2-mm tilted scans, the ranges were 32-38 patients (80-95%), one to eight (2-20%), and zero to one (0-2%), respectively. The 2-mm tilted scans were significantly superior to the 2-mm conventional axial scans for showing the fissures (p < .01). Direct visualization as linear or band-like opacities was possible even on 10-mm tilted scans in 15-32 cases (38-80%). CONCLUSION: Our results show that visualization of the major fissure is improved when tilted CT scans rather than conventional axial scans are used.

Adult↗

Pravastatin administration to hyperlipidemia in patients with nephrotic syndrome.

We treated hyperlipidemia in patients with nephrotic syndrome (NS) using pravastatin for more than one year. There were 7 cases consisting of 3 with minimal change nephrotic syndrome (MCNS), 1 with focal glomerulosclerosis (FGS), 1 with proliferative glomerulonephritis (PGN), 2 with membranous glomerulonephritis (MGN) and 1 of unknown origin. Three cases consisted of frequent relapsers, and 4 were steroid-resistant. Six randomly selected age- and sex-matched nephrotic patients were used as controls. The daily excretion of proteinuria was not decreased after pravastatin treatment, but, the serum albumin rose from 3.1 +/- 1.1 to 3.4 +/- 1.0 mg/dl. The serum total cholesterol level was significantly reduced from 401 +/- 174 mg/dl to 331 +/- 103 mg/dl in spite of an absence of marked change in the control group. However, there were no significant changes in the triglyceride and lipoprotein levels. The atherogenic index was 7.1 +/- 3.7 before and 2.8 +/- 1.7 after pravastatin treatment, respectively. Improvement of renal function defined by delta decrement of renal function per year (0.08 +/- 0.06 vs. 0.12 +/- 0.26) was observed after the discontinuation of pravastatin administration in 3 out of 4 intractable cases. We conclude that pravastatin has a potent effect in reducing the serum level of total cholesterol, but not triglyceride in NS. Furthermore, pravastatin can induce renal dysfunction especially in patients with intractable nephrotic syndrome.

Adult↗

[Pure red cell aplasia complicated with polyarthritis, angitis, and acute renal failure].

A case of pure red cell aplasia (PRCA) with various complications polyarthritis, angitis, acute renal failure and DIC was successfully treated with steroid pulse therapy was described. A 55-year-old woman was hospitalized with a 9-month of intermittent but progressive joint pain, morning stiffness, general fatigue, and fever. Her initial laboratory evaluation revealed a hemoglobin of 4.4 g/dl and absence of reticulocyte. Her bone marrow aspirate showed no erythroblast which was compatible with a diagnosis of PRCA. Marked leukocytosis and thrombocytosis, positive antinuclear antigen, elevation of gammaglobulin and C-reactive protein and the presence of polyarthritis and angitis which was confirmed by renal angiography, indicated an underlying autoimmune disorders. Steroid pulse therapy was administered at 500 mg/day for 3 days, resulting in the complete response in both red cell aplasia and above findings. PRCA is known to be associated with systemic lupus erythematosus and rheumatoid arthritis very rarely, but this case did not fulfill the criteria of known collagen diseases, and there is no previous report representing PRCA with various complications such as polyarthritis, angitis and acute renal failure. This case may help us to understand more about the relationship between PRCA and autoimmune disorders.

Acute Kidney Injury↗