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Biomedical subjects

S Koshikawa

Publications and source records attributed to S Koshikawa.

At least 37 records · Page 2Linked to original sources

Recent progress in management of secondary hyperparathyroidism of chronic renal failure.

Recent progress in cellular and molecular biology has had a great impact on our understanding of parathyroid hormone-vitamin D physiology and of the pathogenesis of secondary hyperparathyroidism in chronic renal failure and made possible the development of new therapeutic approaches for management of bone disease in dialysis patients. Management of parathyroid hyperplasia by calcitriol pulse therapy is one example. Suppression of parathyroid hyperfunction by other vitamin D analogues was also proposed, and some of these analogues are now under clinical trial. Further, percutaneous ethanol injection into hyperplastic parathyroid glands under ultrasonographic guidance has become the choice practical procedure under certain clinical settings and can be an effective alternate to surgical parathyroidectomy. In this article, we review selected and pertinent progress in the pathogenesis and management of secondary hyperparathyroidism and parathyroid hyperplasia, major causes of morbidity in chronic dialysis patients, emphasizing the important contributions made by laboratory research and critical clinical observations.

Animals↗

Primary glomerulonephritis with predominant mesangial immunoglobulin G deposits--a distinct entity?

Six cases of primary glomerulonephritis with predominant IgG deposits in the mesangium are described on the basis of a review of renal-biopsy-proven 1,116 cases with primary glomerulonephritis between 1977 and 1990. All patients were female (6-52 years old). Six patients appeared with microscopic hematuria: 3 with episodes of gross hematuria and 3 with mild proteinuria, but none with the nephrotic syndrome. Renal function was normal except for 1 case (52 years old) complicated with hypertension. Serum levels of immunoglobulins and complements were almost normal. Morphologically minor or focal/segmental glomerular alterations were observed. Immunofluorescence showed that pure mesangial IgG deposition was characterized in all cases, whereas no IgA nor IgM was found in any of them. Mesangial deposition of C3 and C1q was observed in 4 and 3 cases, respectively. Electron microscopy revealed dense deposits within the mesangial area in all cases. The clinical course was benign, and the complication with systemic diseases like a rheumatic disease was not observed. This primary glomerulonephritis is an entity characterized by low incidence in Japan, mild abnormalities in urinalysis, minor glomerular alterations with predominant mesangial IgG deposits and a relative benign course.

Adolescent↗

Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding.

107 hemodialysis patients at high risk for intradialytic bleeding due to previous surgery or active bleeding from other sites were treated with nafamostat mesilate (FUT-175; FUT) as hemodialysis anticoagulant for 2 weeks. In contrast to heparin. FUT prolonged clotting times only in the extracorporeal circuit. Clotting times were not prolonged even at the conclusion of the treatment, and bleeding from the puncture site after removal of the needle was shorter than with heparin. The exacerbation of bleeding by hemodialysis was noted in only 21 out of 573 hemodialysis procedures (3.7%), and 134 of 145 hemodialysis procedures (92.4%) with active bleeding were successfully completed without increasing the bleeding. Adverse effects of FUT were noted in only 6 cases (5.6%) or 1.2% of HD procedures. These results indicate that FUT is a very useful anticoagulant for HD, especially in patients with high risk of bleeding.

Aged↗

The distribution of 3H-labeled endotoxin in the kidney of liver cirrhotic rats.

Although the etiology and pathogenesis of progressive renal failure is largely unknown, endotoxin is supposed to be one of the contributory factors. However, the distribution of endotoxin in liver cirrhosis has not been clarified. Therefore we studied the distribution of 3H-labeled endotoxin in the kidney in rats with CCl4-induced liver injury. Daily inhalations of CCl4 on rats for 6 and 10 weeks produced liver fibrosis (LF group, N = 5) and cirrhosis (LC group, N = 5), respectively. At 6 or 10 weeks, animals were sacrificed 24 hours after an intravenous injection of endotoxin labeled with 3H at the galactose moiety (12,000 cpm/1 g body weight). In the liver, 3H-labeled endotoxin was taken up mainly by Kupffer cells as determined by autoradiography. Compared to control rats, in rats of the LC or LF group the measured amount of 3H-labeled endotoxin per gram kidney or ml blood increased, while that of the liver was significantly decreased. A positive correlation of the amount of 3H-labeled endotoxin per weight or volume respectively was shown between kidney and blood, but not between lung or spleen and blood. These results suggest that overflow of endotoxin due to decreased inactivation in the liver causes endotoxemia in liver injury and that the resulting endotoxemia may directly affect the kidney. The resulting endotoxin-induced vasoconstriction may be a contributory factor for the progressive renal failure frequently observed in liver cirrhosis.

Animals↗

Endotoxin-induced acute tubular necrosis in cirrhotic rats.

In order to clarify the role of endotoxin in acute tubular necrosis in liver cirrhosis, lipopolysaccharide (LPS) was injected to rats with liver injury with exposure to carbon tetrachloride (CCl4) inhalation. Rats showed liver cirrhosis with ascites retention after 10 weeks' CCl4 treatment and liver fibrosis after 6 weeks' CCl4 treatment. Histopathological grading of kidney injuries after LPS treatment was more severe either in cirrhotic rats or in liver fibrotic rats than in normal rats. All cirrhotic rats had severe acute tubular necrosis after either dose of LPS, but only small necrotic foci of tubuli were seen in a few normal and liver fibrotic rats. The results indicate that endotoxin, which overflows due to disturbance of inactivation in the cirrhotic liver, may contribute to acute tubular necrosis. This effect of endotoxin is supposed to be a direct hemodynamic damage.

Animals↗

Role of uremic and endothelial factors in the development of beta 2-microglobulin amyloidosis.

To clarify the importance of uremic and endothelial factors in the development of beta 2-microglobulin (beta 2m) amyloidosis, in vitro evaluations were carried out using cultured synoviocytes and synovial tissues. Synoviocytes of patients with chronic renal failure were cultured with media containing uremic or normal serum. In cultures with uremic serum, greater proliferation of synoviocytes and stronger expression of CD68, beta 2m, interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) on synoviocytes were observed, compared with those containing normal serum. Uremic serum stimulated greater production of IL-1 beta and TNF alpha than normal serum (P < 0.05 for IL-1 beta, P < 0.01 for TNF alpha). Addition of supernatant of endothelial cell culture to medium containing uremic serum significantly accelerated production. After a three month culture of uremic synovial tissue, embedded in 3% type 1 collagen gel with uremic serum, beta 2m-positive 10 nm fibrils were recognized around the synoviocytes. In culture with uremic serum plus supernatant of endothelial cell culture, positive Congo red staining was noted. These findings indicate that uremic serum plays a significant role in the development of synovial beta 2m amyloidosis and that endothelial cell-derived factors contribute to the formation of beta 2m amyloid.

Amyloidosis↗

Antilymphocyte antibodies against CD4+CD45R+ subsets in patients with IgA nephropathy.

The authors analysed CD4+ subset populations and particularly subset killing in order to evaluate the presence of antilymphocyte antibody against CD4+ subsets in patients with IgA nephropathy (IgA N). This study was performed in 45 patients with IgA N, 30 patients with other forms of glomerulonephritis and 30 healthy controls. CD4+, CD4+CD45R- and CD4+CD45R+ cells in the peripheral blood were counted by a flow cytometric analysis, and those cell killings were analysed by microcytotoxic assays. The percentage of circulating CD4+CD45R+ cells was significantly decreased in IgA N, and the percentage of CD4+CD45R+ cell killing was significantly elevated in IgA N compared with other groups. There was a significant negative correlation between the percentage of CD4+CD45R+ cells present in IgA N patients' peripheral blood lymphocytes and the killing CD4+CD45R+ cells by the same patients' serum. Both a depletion of CD4+CD45R+ cells in peripheral blood lymphocytes and an elevation of CD4+CD45R+ cell killing correlated with the grade of mesangial proliferation in patients with IgA N. However, there were no correlations in other clinicopathological indices. These results suggest that low levels of antilymphocyte antibodies against CD4+CD45R+ cells were present in patients with IgA N, who showed a depletion of CD4+CD45R+ cells in the peripheral blood. These antibodies were strongly associated with the elimination of CD4+CD45R+ cells and the proliferation of glomerular mesangial cells in patients with IgA N.

Adolescent↗

Nafamostat as anti-coagulant for membrane plasmapheresis in high bleeding risk patients.

Nafamostat mesilate (NM), an ultrashort-acting multi-enzymatic inhibitor, is a useful anti-coagulant in high bleeding risk patients needing hemodialysis. We applied NM as a membrane plasmapheresis (MP) anti-coagulant in patients with high bleeding risk. Eleven patients, the majority with hepatic failure and active hemorrhagic foci or severe bleeding diathesis, could be treated with MP 22 times under anti-coagulation by 20-40 mg/h/NM by continuous infusion without any trouble. Celite-activated coagulation time (CCT) at the plasma separator inlet and outlet was adequately prolonged during MP, but CCT in systemic blood showed no prolongation throughout the procedure, because NM was rapidly inactivated. There was no observable blood coagulation in the extracorporeal circuit including the plasma separator. No adverse reaction or exacerbation of hemorrhage was noted throughout the MP. NM thus appears to be a useful and safe anti-coagulant not only for hemodialysis but also for MP in high bleeding risk patients.

Adolescent↗

[Clinical aspects of acid-base disorders].

Acid-base disorders are frequently recognized in a wide variety of clinical settings such as severe systemic hospitalized patients. The principal object is to assessment of acid-base equilibrium and to obtain an appropriate guide to therapy. The approach is centered to a systemic analysis of blood gas evaluation. To establish this complex matter is followed. Is an acid-base disorder present? Is the disorder a simple or a mixed abnormality? What is the primary cause? These evaluations should be obtained by accurate history taking, physical examination, and routine laboratory tests. In addition, the supporting analysises such as anion gap (AG) calculation, urine AG assessment, urine chloride concentration and so on are also useful for correct diagnosis. In view of the complexty and difficult expression of acid-base disorders, it is desirable that clinicians must have full knowledges of systemic approach to the blood gas analysis and its evaluation.

Acid-Base Imbalance↗

Aggravation of minimal change nephrotic syndrome by administration of human albumin.

Human albumin infusions are frequently administered to patients with nephrotic syndrome. We reviewed the clinical course of 27 patients with minimal change nephrotic syndrome (MCNS) in which 16 patients were treated with human albumin (group A) and 11 were not (group B). The percent of body weight gain, serum total protein, serum albumin, urine protein excretion and renal function were equivalent in both groups as was the initial dose of corticosteroid and amount of dietary protein intake. The period from the start of corticosteroid therapy to complete remission for group A (73.4 +/- 19.2 days, mean +/- SEM) was significantly longer than that for group B (17.1 +/- 3.6), (p less than 0.05). 10 patients of group B (10/11 = 90.9%) showed complete remission within 20 days from the start of corticosteroid therapy, but more than 20 days were needed for 9 cases (9/16 = 56.3%) of group A. Moreover, significant correlations were observed between the period required for remission and the duration of albumin administration (p less than 0.01) or the total volume of albumin infused (p less than 0.01). Proportion of relapsers within 2 years after discharge was also higher in group A (68.8%) than in group B (9.1%), (p less than 0.01). In conclusion, administration of albumin may delay the response to corticosteroid therapy and induce more frequent relapses after remission, possibly due to more severe glomerular epithelial changes induced by albumin infusion in addition to preexisting glomerular epithelial changes from the MCNS.

Adult↗

[Changes of urinary human epidermal growth factor excretion in 16 patients with acute renal failure].

In order to evaluate the clinical significance of urinary human epidermal growth factor (hEGF) in patients with acute renal failure (ARF), urinary hEGF levels were determined by radioimmunoassay, and were corrected for creatinine (creat.) concentrations in 16 patients with ARF and 12 healthy controls. The urinary hEGF levels significantly decreased in patients with ARF in acute phase compared with normal control subjects (0.98 +/- 0.20 vs 13.74 +/- 1.18 ng/mg creat. p less than 0.01), and it subsequently increased during recovery phase (6.10 +/- 0.73 ng/mg creat. p less than 0.01 vs acute phase). A significant correlation between the urinary hEGF levels and creatinine clearance (r = 0.712, p less than 0.001) and an inverse correlation between urinary hEGF levels and fractional excretion of sodium (r = -0.406, p less than 0.05) was demonstrated. The remarkable decrease of urinary hEGF excretion preceded the increase of urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase levels. Our data suggests that urinary hEGF originates from renal tissues in humans and measurement of urinary hEGF is useful for diagnosing renal damage and recovery of renal tissues from severe tubular injury.

Acetylglucosaminidase↗

Three-dimensional ultrastructure of anionic sites of the glomerular basement membrane by a quick-freezing and deep-etching method using a cationic tracer.

The ultrastructure of anionic sites in the lamina rara externa (LRE) of rat glomerular basement membrane (GBM) was studied in three dimensions by a quick-freezing and deep-etching method using polyethyleneimine (PEI) as a cationic tracer. Results were compared with those obtained with conventional ultrathin sections examined by transmission electron microscopy. Examination with the quick-freezing and deep-etching method was done without (group 1) or with (group 2) contrasting/fixation with a phosphotungstic acid and glutaraldehyde mixture and post-fixation with osmium tetroxide, which were necessary for visualization of PEI particles by conventional ultrathin sections. Using the quick-freezing and deep-etching method without following contrasting/fixation and post-fixation (group 1), many PEI particles were observed to decorate around fibrils, which radiated perpendicularly from the lamina densa to connect with the podocyte cell membrane. The arrangement of PEI particles was not as regular as that previously reported using conventional ultrathin sections. In contrast, the tissue that was studied with quick-freezing and deep-etching followed by contrasting/fixation and post-fixation (group 2) showed a shrunken appearance. The arrangement of PEI particles was regular (about 20 particles/1000 nm of LRE) as that previously observed using conventional ultrathin sections. However, the number of PEI particles on the LRE was markedly decreased and interruption of decorated fibrils was prominent, as compared with group 1. Ultrastructural examination using conventional ultrathin sections with contrasting/fixation and post-fixation (group 3) demonstrated PEI particles on the LRE in reasonable amounts (18-21 particles/1000 nm of LRE) with fairly regular interspacing (45-65 nm) as reported previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗