7qter deletion with normal Hageman factor.
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Biomedical subjects
Publications and source records attributed to H Kawashima.
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Defined nephron segments were microdissected from the kidney of vitamin D-deficient rats, normal rats, and normal rats treated with 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3]. Tubule segments were incubated with 3H]labeled 25-hydroxyvitamin D3 and the rates of production of 3H]labeled 1 alpha, 25-(OH)2D3 and 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] were determined. Nephron segments tested include the glomerulus, proximal convoluted tubules (PCT), proximal straight tubules (PST), medullary and cortical thick ascending limbs of Henle's loop, distal tubules, and collecting tubules. Production of 1 alpha, 25-(OH)2D3 was detected only in PCT of vitamin D-deficient rats (mean +/- SEM, 0.70 +/- 0.05 fmol/mm per hr); the value decreased to 0.11 +/- 0.05 after parathyroidectomy. By contrast, significant 24,25-(OH)2D3 production occurred in PCT of normal rats (0.23 +/- 0.05 fmol/mm per hr). After administration of 1 alpha, 25-(OH)2D3 to normal rats, the rate of production of 24,25-(OH)2D3 in PCT increased to 0.64 +/- 0.06 fmol/mm per hr and also became apparent in PST (1.07 +/- 0.21). The rates of production of 1 alpha, 25-(OH)2D3 and 24,25-(OH)2D3 in these nephron segments were linear with tubule length over a wide range of lengths per incubation and with the incubation time. The results define the localization of 25-hydroxyvitamin D3 1 alpha-hydroxylase and 24-hydroxylase along the rat nephron: PCT is capable of producing both 1 alpha, 25-(OH)2D3 and 24,25-(OH)2D3 and PST can produce 24,25-(OH)2D3. the use of defined nephron segments may be useful for study of the distribution and regulation of 25-hydroxyvitamin D3 hydroxylases in the kidney.
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In summary, it is demonstrated, for the first time, that there is a marked reduction of bone mass in ob/ob mice and this was restored by the treatment with 1 alpha-OH-D3. The effect of the sterol was accompanied by the improvement of hyperglycemia, hyperinsulinemia, and fat tissue responsibility to hormones. Thus, it is of interest to study obesity in terms of calcium homeostasis.
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Clinical, cytogenetic, and immunological data of a 5-year-old Japanese girl with Bloom's syndrome are described. Growth deficiency, photosensitivity, and a very mild facial telangiectatic erythema were present. Cytological studies revealed chromosomal aberrations and the characteristic high frequency in sister chromatid exchanges. Immunological studies showed that the serum levels of IgM and IgA, but not IgG, were abnormally low as compared to the age-matched control values and that the generation of cytoplasmic immunoglobulin-producing cells in the peripheral blood lymphocytes, which was evaluated in the in vitro pokeweed mitogen-stimulated cultures, was markedly reduced.
Extracellular mitogen preparations from NY5 and S84 strains of streptococci induced different responses among rabbit, guinea pig, and mouse lymphocytes. Evidence of T-cell mitogenicity is presented.
Enzyme immunoassay for cortisol was developed using beta-galactosidase as an enzyme label and m-maleimidobenzoyl derivatives of cortisol, i.e. cortisol-21-m-maleimidobenzoate (CT-MB) and cortisol-21-hemisuccinate conjugated with m-maleimidobenzoic acid through p-phenylenediamine linkage (CHS-MB), as the haptens coupled to sulfhydryl groups of the enzyme. This enzyme-coupling procedure was highly efficient; over 90% of the enzyme was labeled while full enzyme activity was retained. CHS-MB-beta-galactosidase conjugate showed high immunoreactivity to antibody produced against cortisol-21-hemisuccinate-bovine serum albumin but showed poor displacement with the added cortisol. CT-MB-beta-galactosidase conjugate, however, showed not only a high immunoreactivity to the antibody but also displaced well with cortisol, showing maximum sensitivity of 1 microgram/dl with a 20-microliter sample size. Modification around the linkage of cortisol derivative resulted in high sensitivity to cortisol. Cross-reactions to cortisol-21-acetate, cortisone, and corticosterone were 150%, 10%, and 7%, respectively. The accuracy, precision and correlation with RIA of this method were satisfactory for clinical application.
Interaction of calcium regulating hormone, active form of vitamin D3, and aspirin (ASA) was studied in rats. One alpha-hydroxyvitamin D3 (1 alpha-OH-D3) produced a hypercalcemia in parathyroidectomized, thyroparathyroidectomized and thyroparathyroidectomized nephrectomized rats. The effect of 1 alpha-OH-D3 was inhibited by treatment with 200, 50 and 20 mg/kg p.o. of ASA. ASA did not stimulate the gut absorption of calcium in vitamin D deficient rats. These data suggest that ASA acts by inhibiting 1 alpha OH-D3 induced bone resorption. This is the first report demonstrating the inhibitory effect of ASA on bone resorption as induced by 1 alpha-OH-D3, although partial inhibition of bone resorption in vitro has been reported.
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A model of experimental renal osteodystrophy was established in the rats with chronic renal failure induced by partial nephrectomy and therapeutic effects of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) were studied. Male Wistar rats weighing 180 g were 5/6 nephrectomized and fed a normal diet (Ca and P : 1%) for 6 months. After the surgery, serum creatinine levels increased 60% and thereafter continued to rise gradually with their growth for 4 to 5 months, followed by rapid increase. The serum phosphorus levels were also elevated concomitantly and the serum calcium concentrations were normal. Marked bone resorption accompanied with hypertrophy of parathyroid glands was observed by histological examinations (Tetrachrome-Fuchsin stain, contact microradiography and H-E stain). The bone resorption seemed to be due to secondary hyperparathyroidism. Treatment with 0.25 micrograms/kg/day p.o. of 1 alpha-OH-D3 for 10 days in the uremic state resulted in remarkable new bone formation which was confirmed by histological examinations. These results clearly demonstrated that the reduction of nephron mass play a critical clue of renal osteodystrophy and 1 alpha-OH-D3 appears to have a good potential for clinical use in patients with renal failure and metabolic bone diseases.