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Biomedical subjects

M Fukagawa

Publications and source records attributed to M Fukagawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

[PTH assay: new and future].

Bone disease is one of the main complications in chronic dialysis patients, adynamic bone disease has become a major problem. It has been suggested that higher (parathyroid hormone) PTH is needed to maintain normal bone turnover in uremia. Thus, target PTH level has been recently set at 150 - 200 pg/ml by intact PTH assay. Nevertheless, even the intact PTH assay has several critical problems. Since PTH molecule is unstable, intact PTH assay may not evaluate the actual activity of circulating PTH. On the other hand, due to the recognition site of the antibody, conventional intact PTH assay may detect 7-84 PTH in addition to 1-84 PTH. Furthermore recent data suggest that 7-84 PTH fragments inhibits the action of 1-84 PTH. Thus, conventional intact PTH assay may overestimate the actual activity of circulating PTH molecules in uremic patients. Whole PTH assay, which detects only 1-84 PTH may be a better method for the evaluation of actual PTH activity. Target range of PTH in uremic patients should be set by deliberately considering these problems in near future.

English Abstract↗
PubMed2000

Is aplastic osteodystrophy a disease of malnutrition?

Adynamic bone disease is emerging as a major type of renal osteodystrophy in chronic dialysis patients. Relative hypoparathyroidism is one of the important abnormalities underlying this disease. Recently, several reports have suggested that hypoparathyroidism reflects, at least in part, a state of malnutrition and contributes to the poor prognosis of patients on hemodialysis and chronic ambulatory peritoneal dialysis. Such a risk of survival may result not only from the malnutritional state, but also from unknown mechanisms resulting from parathyroid hormone (PTH) deficiency, or from other abnormalities that suppress PTH secretion. Another major abnormality underlying adynamic bone disease is the skeletal resistance to PTH in patients with uremia. Owing to the recent research on bone turnover at the molecular level, several new mechanisms for this abnormality have been elucidated. Correction of this 'skeletal resistance to PTH' will lead to the optimal management of parathyroid function and bone turnover in the future.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed2000

Fact-finding survey of actual garbage discharged from dormitory and its biological anaerobic-aerobic treatment.

The objective of this study is to find a possibility of complete treatment of garbage and resource recovery (production of methane from available utility of carbon resource in garbage) by biological treatment process. As the first step, a fact-finding survey of actual garbage discharged from the dormitory of the Ube National College of Technology (equivalent to 300 population) was carried out. Second, the combined biological anaerobic-aerobic treatment, i.e. combination of upflow anaerobic sludge blanket (UASB) process and aerobic membrane bioreactor (AMB) process, was applied to the garbage treatment. The applicability and efficiency of this system were investigated in this study. The survey results showed that the composition and quantity of garbage from a student dormitory changed slightly during a week due to the change of the menu, however, they remained almost unchanged during the entire experimental period. The experimental results showed high biodegradability of the garbage, and demonstrated its suitability for methane production. The soluble nitrogen removal was high: over 97%. No excess sludge was wasted from the system. A high treatment efficiency of simultaneous organic carbon and nitrogen was obtained. The possibility of complete treatment of garbage with this process has been positively demonstrated by this study.

Bacteria, Aerobic↗
PubMed1999

Prognosis of parathyroid function after successful percutaneous ethanol injection therapy guided by color Doppler flow mapping in chronic dialysis patients.

Selective percutaneous ethanol injection therapy (PEIT) of the parathyroid glands has been shown to be effective in chronic dialysis patients with severe secondary hyperparathyroidism. In this study, we examined whether it was possible to maintain parathyroid function within target range (intact parathyroid hormone [iPTH], 160 to 360 pg/mL) in the long term after successful destruction of hyperplastic tissue. PEIT was performed in 46 patients resistant to calcitriol pulse therapy, and all glands larger than 5 mm in diameter were destroyed by ethanol, guided by power Doppler flow mapping. Serum iPTH levels decreased from 633.3 +/- 359.9 to 226.3 +/- 204.7 pg/mL at 3 weeks and were maintained at 289.9 +/- 222.4 pg/mL at 1 year after PEIT. Total alkaline phosphatase activity decreased from 384.9 +/- 160.1 to 234.0 +/- 110.5 IU/L at 1 year after PEIT. In 19 patients, iPTH levels decreased into relative hypoparathyroidism (iPTH < 160 pg/mL) at 3 weeks after PEIT; however, they recovered at 1 year after PEIT (191.1 +/- 29.6 pg/mL). Parathyroid function was maintained within target range in 80.4% of the patients at 1 year after PEIT with appropriate medical therapy. Surgical parathyroidectomy was not required in any patient. Conversely, in eight other patients with recurrent hyperparathyroidism after subtotal parathyroidectomy, iPTH levels recovered in only 50% of the patients at 1 year after PEIT. Thus, destruction of hyperplastic tissue should be optimized in such patients. Recurrent nerve palsy was observed in only one patient, but was reversible. In conclusion, selective PEIT guided by color Doppler flow mapping is an effective and safe adjunct to medical therapy with a low risk for hypoparathyroidism.

Administration, Cutaneous↗
PubMed1999

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis.

UNLABELLED: 22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.

Animals↗
PubMed1999

Medical and surgical aspects of parathyroidectomy.

A more logical approach to the management of the chronic dialysis patient with parathyroid hyperplasia has become possible thanks to recent progress in cellular and molecular analysis of surgically removed parathyroid glands and accumulation of clinical experience. When one or more parathyroid glands progress to the stage of nodular hyperplasia, it is usually difficult to control PTH secretion even by calcitriol pulse therapy. For such patients, we have developed two new therapeutic approaches, i.e., selective percutaneous ethanol injection therapy (PEIT) and direct calcitriol injection therapy, in combination with medical therapy. For optimal selection of therapeutic modalities it is indispensable to evaluate the degree and stage of parathyroid hyperplasia. For successful management, prevention of nodular hyperplasia is the most important strategy.

Animals↗
PubMed1999

Modulation of parathyroid cell function by calcium ion in health and uremia.

Extracellular calcium ion concentration is the major determinant of parathyroid hormone (PTH) secretion from parathyroid cells. In dialysis patients with secondary hyperparathyroidism, higher calcium concentration is needed to suppress PTH secretion as demonstrated by the PTH-calcium curve. Such abnormal sensitivity to extracellular calcium ion has been recently explained by the decrease in number of calcium-sensing receptors, especially on cells in nodular hyperplasia, which is the advanced type of parathyroid hyperplasia in uremia. Modulation of the sensitivity of parathyroid cells to calcium has become partly possible through the use of newly developed calcimimetics.

Calcium↗
PubMed1999

Cell biology of parathyroid hyperplasia in uremia.

Marked parathyroid hyperplasia of heterogeneous degrees is often seen in chronic dialysis patients with severe secondary hyperparathyroidism. In uremia, parathyroid cell proliferation is initially stimulated by decreased concentration of calcium ions and calcitriol and also by direct effect of phosphate accumulation, leading to diffuse hyperplasia of the parathyroid. Then, small nodules caused by monoclonal cell proliferation form within diffuse hyperplasia, which progress to form nodular hyperplasia. Cells in nodular hyperplasia have a lower density of calcitriol receptor and calcium-sensing receptor than diffuse hyperplasia and are thus more resistant to medical therapy, including calcitriol pulse therapy. One of these nodules may grow more vigorously than the others and may finally occupy a large part of the enlarged gland. Genetic mutations and rearrangements of these cells in nodular hyperplasia remain to be fully elucidated in the near future to establish an effective method for the prevention of parathyroid hyperplasia in uremia.

Calcitriol↗
PubMed1999

Time and memory efficient algorithm for extracting palindromic and repetitive subsequences in nucleic acid sequences.

Genomic science and structural biology meet in the relationship between the sequence and the structure of nucleic acids. The structure that supports each function is preserved in the process of evolution as specific sequences. Particularly, the same sequence which appears in a different place such as a palindromic or repetitive sequence has biophysical meaning: recognition site of dimers, forming stem-loops, and contributions to global structure of nucleic acids. Also, the genetic network, transduction pathway, and tissue specificity largely depend on these. Although the relationship between them can be found experimentally, there is increasing demand for automated analysis. Especially, it is desirable to extract the same character sequences of arbitrary length (especially, very long ones) which co-occur at an arbitrary separation. We propose an algorithm to identify the maximum match sequence at each position with a calculation cost of O(N log N) and memory space of O(N). Applying it to some sequences, we found unexpectedly large palindromes and repeats in DNA.

Algorithms↗
PubMed1998

Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the alphavbeta3 integrin receptor.

We have taken advantage of an enhancer trap event in a line of transgenic mice to identify a unique developmentally regulated endothelial cell locus (Del1). The protein encoded in this locus contains three EGF-like repeats homologous to those in Notch and related proteins, including an EGF-like repeat that contains an RGD motif, and two discoidin I-like domains. Del1 is shown to be a matrix protein and to promote adhesion of endothelial cells through interaction with the alphavbeta3 integrin receptor. Embryonic endothelial-like yolk sac cells expressing recombinant Del1 protein, or grown on an extracellular matrix containing Del1 protein, are inhibited from forming vascular-like structures. Expression of Del1 protein in the chick chorioallantoic membrane leads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the alphavbeta3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.

Amino Acid Sequence↗
PubMed1998

Anti-latent TGF-beta binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells.

Transforming growth factor-beta (TGF-beta) is usually secreted as a large latent complex associated with latent TGF-beta binding protein-1 (LTBP-1), which is known to bind to extracellular matrix (ECM) components. Although the LTBP-ECM interaction has been suggested to play a role in the activation and biological action of TGF-beta, the precise mechanism is still unclear. In glomerular hypertension mesangial cells are believed to perceive the increased cyclic strain and we have recently reported that cyclic mechanical stretch in vitro enhances the expression of ECM components via an autocrine/paracrine secretion of TGF-beta in cultured rat mesangial cells. Therefore, in this study we examined the role of LTBP-1 in the stretch-induced, TGF-beta-mediated ECM expression. Mesangial cells expressed mRNA for short and long forms of LTBP-1 (LTBP-1S and LTBP-1L, respectively). Mesangial cells were subjected to cyclic stretch to provide a maximal elongation of 20% at a rate of 60 cycles/min for 24 to 36 hours in the presence of polyclonal antibody raised against human LTBP-1 or synthetic oligopeptides corresponding to the N-terminal portions of human LTBP-1, which may work as competitive inhibitors against the LTBP-ECM association. Both anti-LTBP-1 antibody (Ab39) and synthetic oligopeptides inhibited the stretch-induced mRNA expression of type I collagen and fibronectin in a dose-dependent manner, but the inhibition by Ab39 or the oligopeptides was recovered by adding recombinant TGF-beta. Ab39 or the oligopeptides did not change the effect of exogenously added TGF-beta, such as growth-inhibition in mink lung epithelial cells. These results suggest that mesangial cells secrete TGF-beta as a large latent complex, and the LTBP-ECM interaction may be a pivotal step in TGF-beta action and ECM accumulation, providing a new therapeutic strategy against progression of glomerulosclerosis and other fibrotic diseases.

Amino Acid Sequence↗