Search PubMed⌕ Search

Biomedical subjects

O Sakai

Publications and source records attributed to O Sakai.

At least 73 records · Page 4Linked to original sources
PubMed1996

Angiotensin I converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus.

A total of 168 patients with non-insulin dependent diabetes (NIDDM) followed over 10 years were recruited in this study. The patients were divided into two groups: Group 1 patients had a stable renal function (N = 96) and Group 2 had a declining renal function (N = 72). Group 1 included those whose serum creatinine was normal five years ago but had increased to > or = 2 mg/dl or those who has reached end-stage renal failure (requiring dialysis) by the time of study. All patients were genotyped for the insertion/deletion (I/D) polymorphism of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg) gene and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1) gene. The genotype frequency distributions of M235T Atg and the A116C AT1 gene polymorphisms were not different between Group 1 versus Group 2. While the frequency of the ACE DD genotype in Group 1 (7.3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds ratio, 4.56; 95% confidence interval, 1.80 approximately 11.56, P < 0.001). Among all 168 patients studied, the renal survival rate was significantly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabetes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decrease in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressive deterioration of renal function. Moreover, the DD genotype appears to increase the mortality once dialysis is initiated.

Albuminuria↗
PubMed1996

Jak3 expression in glomerular epithelia of IgA nephropathy (IgA-N) patients.

Jak3 is a member of the Janus kinase family which plays an important role in cytokine signal transduction. Jak3 associates the gamma(c) chain of receptors for IL-2, IL-4, IL-7, IL-9 and IL-15, and is essential for the signal transduction of these cytokines. We have isolated Jak3 kinase from renal mesangial cells and demonstrated the constitutive expression of Jak3 in glomeruli in vivo. To investigate the physiological and pathological role of Jak3 in glomeruli, we prepared anti-Jak3 antibody and analysed the localization of Jak3 in glomeruli of renal biopsy samples from various nephritis patients and normal subjects. Among 61 nephritis patients and four normal subjects investigated in the present study, Jak3 was selectively localized to glomerular epithelia of IgA-N patients (14/34 cases) and focal glomerulosclerosis patients (1/5 cases), but not detected in minimal changes (n = 6), membranous glomerulonephropathy (n = 7), crescentic glomerulonephritis (n = 4), lupus nephritis patients (n = 5), and normal subjects (n = 4). The intense immunoreactivity for Jak3 is significantly associated with the decrease in creatinine clearance (81.5 +/- 10.4 ml/min versus 104.3 +/- 29.6 ml/min; P < 0.05, Student's t-test) and the increase in level of serum creatinine (1.13 +/- 0.33 mg/dl versus 0.75 +/- 0.23 mg/dl; P < 0.01, Student's t-test) in IgA-N patients. Furthermore, gamma(c) chain was concomitantly expressed with Jak3 in glomerular epithelia in vivo and in vitro, suggesting that signal transduction via gamma(c)-Jak3 cascade may be involved in the pathogenesis of glomerular injury of IgA-N. Taken together with the recent findings that IL-4-secreting T lymphocytes in affected glomeruli injure glomerular epithelium, the responsiveness of glomerular epithelium for IL-4 may be pathologically enhanced in IgA-N.

Animals↗
PubMed1996

Macrophage-colony stimulating factor (M-CSF) enhances proteinuria and recruitment of macrophages into the glomerulus in experimental murine nephritis.

In this study, we examined the effects of macrophage-colony stimulating factor (M-CSF) on glomerular macrophages in lipopolysaccharide (LPS)-induced murine nephritis. Mice injected intraperitoneally with either M-CSF plus LPS, LPS alone, M-CSF alone or saline every day for 8 days were examined for the degree of urine albumin excretion and lymphocyte-function associated antigen-1-positive (LFA-1+) cells in peripheral blood as well as renal pathology. From our results, LPS or M-CSF combined with LPS emphasized the degree of proteinuria, glomerular deposition of immunoglobulins and mesangial proliferation, associated with accumulation of macrophages in the glomeruli. However, in immunohistological examination of kidneys from these nephritic mice, neither intercellular adhesion molecule-1 (ICAM-1), which may play an important role in the recruitment of macrophages into glomeruli, M-CSF receptor nor the number of LFA-1+ cells in peripheral blood was enhanced by M-CSF. On the other hand, M-CSF alone induced neither proteinuria nor any pathological changes and did not increase the number of glomerular Mac-1+ cells above that in saline-treated controls. These results indicate that M-CSF does not directly cause glomerulonephritis but might participate in accelerating the glomerular inflammatory process by stimulating a potent chemoattractant to recruit monocytes-macrophages into the glomeruli.

Animals↗
PubMed1996

Sepsis associated with hematological malignancies: prophylaxis of Pseudomonas aeruginosa sepsis.

Underlying diseases, pathogenic bacteria, clinical background and outcome were studied during 91 febrile episodes complicated by sepsis in 55 patients with hematological malignancies, who had been admitted to our hospital (Jikei University Kashiwa Hospital) between January 1990 and December 1994. Particularly in patients with P. aeruginosa sepsis, we compared the prophylactic effect of ciprofloxacin (CPFX) alone with that of the combination of polymyxin B (PL-B) plus kanamycin (KM). The major underlying diseases were acute myelocytic leukemia and malignant lymphoma, followed by myelodysplastic syndrome, acute lymphocytic leukemia and chronic myelocytic leukemia. Nearly two-thirds of the pathogenic microorganisms isolated were gram-positive bacteria (including coagulase-negative staphylococci and Staphylococcus aureus); approximately one-quarter were gram-negative bacteria (such as Pseudomonas aeruginosa), and the remainder were fungi. These microorganisms usually induced sepsis when granulocyte counts were decreased. Sepsis was a direct cause of death in about 60% of the patients and P. aeruginosa sepsis had the worst outcome. Oral administration of CPFX was more effective than PL-B plus KM in preventing P. aeruginosa sepsis. The difference in effectiveness might depend on the absorption profile of the drugs.

Adolescent↗
PubMed1996

[Two cases of gram-positive sepsis successfully treated with vancomycin in combination with imipenem or cilastatin].

Against gram-positive sepsis, vancomycin (VCM) was administered in combination with imipenem or cilastatin (IPM/CS). Its excellent efficacy was confirmed in 2 cases, one affected with methicillin resistant Staphylococcus aureus and another with Gemella morbillorum. By calculating the FIC index according to a checkerboard technique, the in vitro synergistic effect was also demonstrated. At the present state multi-drug resistant gram-positive infections prevailed, the combination of VCM with IPM/CS can be expected as an effective measure for treating these diseases.

Adolescent↗
PubMed1996

Mizoribine reduces urinary protein excretion in rats given puromycin aminonucleoside.

Mizoribine (MZR), a purine nucleoside antibiotic, is an effective immunosuppressive agent that prevents rejection reactions after kidney transplantation in humans. The present study was performed to examine the effect of MZR on nephrosis produced in rats given puromycin aminonucleoside (PAN). Urinary protein excretion in rats injected with PAN and MZR (PAN + MZR rats) was shown to be reduced significantly in comparison with rats given only PAN (PAN rats). Although mild hypoproteinemia persisted during the experimental period in PAN + MZR rats, no loss of body weight or state of malnutrition was observed. The reduction of serum IgG and C3 was reversed by administration of MZR. Polyethyleinamine (PEI) staining of renal sections showed increased numbers of anionic sites in PAN + MZR rats in comparison with PAN rats, suggesting that MZR improved the permselectivity of the glomerular basement membrane (GBM). Moreover, the production of thromboxane B2 (TxB2) was significantly inhibited in PAN + MZR rats compared with PAN rats. No serious adverse effects of MZR were observed after a large dose of the agent. It is possible that restoration of the charge barrier of the GBM damaged by PAN, or reduction of TxB2 production by the glomeruli may underlie the reduction of protein excretion induced by administration of MZR.

Animals↗
PubMed1996

Significance of serum lipase in patients undergoing hemodialysis.

Serum levels of lipase (Lp) during the end of the dialysis showed a significant increase after the administration of heparin in hemodialysis patients. However, serum Lp levels were not increased after the administration of the anti-coagulant nafamostat mesylate in hemodialysis patients. Serum levels of Lp were significantly correlated with serum levels of lipoprotein lipase (LPL), hepatic triglyceride lipase (H-TGL) and nonesterified fatty acid (NEFA) 20 min after the administration of heparin during maintenance hemodialysis. Lp activity did not appear with the NEFA ligand for determining the NEFA activity. Inhibitors of LPL and H-TGL reduced the measured Lp activity in vitro. The main mechanism of elevated measured serum Lp activity in hemodialysis patients was determined to be cross-reactivity with LPL or H-TGL. Furthermore, measurement of Lp may be a method for determining optimal coagulation time in patients with hemodialysis.

Adult↗
PubMed1996

Effect of cilazapril on hyperdipsia in hemodialyzed patients.

To investigate whether angiotensin-converting enzyme inhibitor (ACE-I) potentially alleviates hyperdipsia, the effect of cilazapril on dialysis-associated excessive thirst was studied by evaluating various dipsogenic parameters in patients undergoing chronic hemodialysis (HD) who manifest an excessive interdialysis body weight gain of more than 5%, and show simultaneous severe-to-moderate hyperdipsia. An initial single dose of 1 mg of cilazapril given at the end of the HD session produced a marked improvement in the interdialysis thirst scores and a simultaneous reduction in plasma angiotensin II (AII) concentration due to the inhibition of ACE activity. The interdialysis body weight gain in the cilazapril treatment period was significantly smaller than that in the nontreatment period. None of the other parameters including blood pressure, plasma osmolarity, and serum Na and K concentration were different in the treatment vs. the nontreatment period. The present data help to explain the potential pharmacological action of AII in the physiology of thirst and suggest that cilazapril may effectively alleviate dialysis-associated hyperdipsia at least on some occasions. The mechanism by which ACE-I exerts an antidipsogenic action may, in part, be accounted for by the reduction in plasma concentration of AII, as a result of the ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Hyperammonemia in a patient with short bowel syndrome and chronic renal failure.

A patient with short bowel syndrome (SBS) and renal failure developed a disturbance of consciousness with hyperammonemia. Abnormally low concentrations of ornithine, citrulline, and arginine were observed on the plasma aminogram. These results suggested that the activities of amino acid synthetase localized in the small intestinal flora were lost. The small intestine is required for arginine synthesis; thus, infusion limited to the essential amino acids to SBS patients will cause a deficiency of the urea cycle intermediates, ornithine, citrulline, and arginine and may lead to hyperammonemia. In addition, the renal insufficiency may have caused decreased excretion of ammonia. In this patient, supplemental arginine improved the symptoms.

Aged↗
PubMed1996

A case of nephrotic syndrome developing during postoperative gamma interferon therapy for renal cell carcinoma.

A 70-year-old man developed minimal-change nephrotic syndrome and acute interstitial nephritis while undergoing gamma interferon therapy following right nephrectomy for renal cell carcinoma. It appears that gamma interferon as well as renal cell carcinoma may have played a role as etiologic factors in this nephropathy. We report this extremely rare case of renal cell carcinoma complicated by minimal-change nephrotic syndrome and acute interstitial nephritis, and present a review of the literature.

Acute Disease↗
PubMed1996

Unexplained increase in serum corticosteroid-binding globulin levels in a patient with chronic thyroiditis, pituitary adenoma and empty sella.

Unexplained high serum corticosteroid-binding globulin (CBG) concentrations (mean +/- SD, 74.1 +/- 12.1 micrograms/dl; normal women, 32.5 +/- 5.6 micrograms/dl) were found in an unmarried women who was not pregnant or taking exogenous estrogens. She was also found to suffer from subclinical chronic thyroiditis, pituitary adenoma and empty sella. The increased serum CBG concentrations in this patient were not due to any of the factors known to increase CBG. Consistently high basal serum GH levels and unusual GH responses to GH-releasing factor (GRF) and L-dopa were also noted.

Adenoma↗
PubMed1996

A rare case of idiopathic hypoparathyroidism with varied neurological manifestations.

A 47-year-old man was admitted for evaluation of unsteady gait, postural instability, and dysarthria. On admission, neurological examinations revealed cerebellar ataxia, extrapyramidal signs including parkinsonism and positive Trousseau's sign. Laboratory findings revealed severe hypocalcemia and hyperphosphatemia, and serum intact parathyroid hormone was not detectable. Brain computed tomography revealed severe calcification of basal ganglia and dentate nuclei. He was diagnosed as idiopathic hypoparathyroidism; treatment with 1 alpha (OH) vitamin D3 brought marked improvement of neurological manifestations. We report a rare case of idiopathic hypoparathyroidism presenting with extrapyramidal and cerebellar dysfunction with a review of literature.

Basal Ganglia↗
PubMed1996

47 XXY/46 XY mosaic Klinefelter's syndrome presenting with multiple endocrine abnormalities.

We report here a rare case of 47 XXY/46 XY mosaic Klinefelter's syndrome associated with multiple endocrine disorders. A 35-year-old male admitted for the evaluation of renal dysfunction and recurrent bone fractures was diagnosed as having Klinefelter's syndrome by endocrinological examinations and sex chromosome analysis. He has suffered from diabetes mellitus for more than ten years. The serum FSH and LH levels were high together with low free testosterone and estradiol levels. There was a discrepancy between basal serum GH and somatomedin-C levels. On admission, thyroid function revealed thyrotoxicosis with low radioactive iodine uptake and negative thyroid autoantibodies. During hospitalization, serum FT3 and FT4 levels were gradually decreased and serum TSH levels became elevated, leading to the diagnosis of subacute thyroiditis. Serum ACTH levels showed high basal levels with delayed, exaggerated responses to insulin-induced hypoglycemia. Rapid ACTH test (1-24ACTH 0.25 mg) showed low cortisol responses and many of the adrenocortical steroids in plasma and urine were low or low normal. Furthermore, bone mineral density (BMD) by DEXA showed marked osteoporosis. Possible mechanisms underlying these varied endocrine disorders remain to be elucidated.

Adult↗
PubMed1996

Williams syndrome associated with chronic renal failure and various endocrinological abnormalities.

A 31-year-old man who had been under regular hemodialysis for 6 months was diagnosed as Williams syndrome (WS) by fluorescence in situ hybridization (FISH) chromosomal analysis. The association of WS and chronic renal failure (CRF) is only rarely encountered. Endocrinological examinations revealed hypergonadotropic hypogonadism. Prolonged and exaggerated responses of adrenocorticotropin (ACTH) to insulin-induced hypoglycemia and corticotropin releasing hormone (CRH) were also noted. While most of the endocrinological abnormalities observed in this patient could be attributed to altered endocrine circumstances in CRF, some findings stand in contrast. Furthermore, the testicular biopsy specimen showed severe hypospermatogenesis. Endocrine disorders observed in this patient may be at least in part, responsible for various clinical features underlying WS.

Adult↗
PubMed1996

[Long-term renal prognosis in patients with lupus nephritis treated with pulse methylprednisolone].

To elucidate the long-term renal prognosis in patients with lupus nephritis treated with pulse methylprednisolone, the renal outcome and the risk factors associated with poor renal prognosis were studied in 14 female lupus nephritis patients treated with pulse methylprednisolone. The mean age when the pulse methylprednisolone was started was 28.1 years old and their renal pathology were 3 of WHO III, 10 of WHO IV and 1 of WHO V. Four of the patients fell into renal insufficiency at 5.7 (mean, 1.3 approximately 10) years after pulse methylprednisolone, however residual 10 patients kept their renal function for 11.5 (mean, 3.5 approximately 19.6) years observation. The deterioration of renal function significantly (p = 0.033) correlated with glomerular sclerosing index before pulse methylprednisolone, but did not correlate with sustained immunological activity, hypoproteinemia or hypertension. Because glomerular sclerosing index was thought to be one of the risk factors for poor renal prognosis, the indication for pulse methylprednisolone in lupus nephritis was the patients with low glomerular sclerosing index.

Adult↗