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Biomedical subjects

Y Nishii

Publications and source records attributed to Y Nishii.

At least 19 recordsLinked to original sources
PubMed1997

Sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a kidney transplant recipient.

A case of sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a cadaver renal transplant recipient is reported in this article. The patient underwent a kidney transplant at the age of 43 and was treated with various immunosuppressive agents after surgery. Twelve months after the transplantation, multiple tumors were found in the liver, and the patient died 8 months later. Pathological examination at autopsy revealed renal cell carcinoma with a sarcomatoid component in the right native kidney and metastases to liver and bones. It is unusual for renal cell carcinoma to undergo sarcomatous transformation and to metastasize to the liver before reaching other organs. We speculate that immunosuppressants may have altered malignant cell proliferation, invasion, and the form of metastasis in this case.

Adult↗
PubMed1997

Elevation of serum creatine kinase during treatment with antithyroid drugs in patients with hyperthyroidism due to Graves disease. A novel side effect of antithyroid drugs.

We describe 4 patients with Graves disease who had abnormal increases of serum creatine kinase (CK) concentrations during treatment with antithyroid medications. Three of the patients experienced myalgia and muscle cramps. All of the patients manifested an increase in serum CK levels 1 to 3 months after the administration of antithyroid drugs. Thyrotropin concentrations and cardiac systolic time indexes during the elevation of serum CK concentrations were not consistent with hypothyroidism. The mechanisms are not obvious, but it is likely that the rapid decrease of thyroid hormones in tissues may temporarily cause hypothyroid states, resulting in alterations in CK concentrations. It is suggested that hasty correction of thyrotoxicosis should be avoided in susceptible patients, unless the thyrotoxic conditions are critical.

Adult↗
PubMed1997

Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element.

Peroxisome proliferators (e.g. clofibric acid) and thyroid hormone play an important role in the metabolism of lipids. These effectors display their action through their own nuclear receptors, peroxisome proliferator-activated receptor (PPAR) and thyroid hormone receptor (TR). PPAR and TR are ligand-dependent, DNA binding, trans-acting transcriptional factors belonging to the erbA-related nuclear receptor superfamily. The present study focused on the convergence of the effectors on the peroxisome proliferator response element (PPRE). Transcriptional activation induced by PPAR through a PPRE was significantly suppressed by cotransfection of TR in transient transfection assays. The inhibition, however, was not affected by adding 3,5,3'-triiodo-L-thyronine (T3). Furthermore, the inhibition was not observed in cells cotransfected with retinoic acid receptor or vitamin D3 receptor. The inhibitory action by TR was lost by introducing a mutation in the DNA binding domain of TR, indicating that competition for DNA binding is involved in the molecular basis of this functional interaction. Gel shift assays revealed that TRs, expressed in insect cells, specifically bound to the 32P-labeled PPRE as heterodimers with the retinoid X receptor (RXR). Both PPAR and TR bind to PPRE, although only PPAR mediates transcriptional activation via PPRE. TR.RXR heterodimers are potential competitors with PPAR.RXR for binding to PPREs. It is concluded that PPAR-mediated gene expression is negatively controlled by TR at the level of PPAR binding to PPRE. We report here the novel action of thyroid hormone receptor in controlling gene expression through PPREs.

Animals↗
PubMed1997

History of vitamin D treatment of renal osteodystrophy.

Vitamin D treatment was tried when renal osteodystrophy was first recognized in the early 20th century, using vitamin D2, D3, or dihydrotachysterol. Large doses of vitamin D2 or D3 (150,000-500,000 IU) were prescribed by monitoring serum calcium, phosphate, and alkaline phosphatase. After the discovery of 1,25-dihydroxycholecalciferol, this compound or 1 alpha-hydroxycholecalciferol was applied to the treatment of renal osteodystrophy. In a preclinical study, especially of 1 alpha-hydroxycholecalciferol, nephritogenoside nephritis was the most responsive condition. These active vitamin D preparations are now widely used in patients with chronic renal failure under hemodialysis. Other active vitamin D compounds, such as hexafluoro-1,25-dihydroxycholecalciferol and 22-oxacalcitriol, are also under investigation.

Animals↗
PubMed1996

Molecular cloning and expression of human caldecrin.

Earlier we reported the primary structure of serum calcium-decreasing factor (caldecrin) from rat pancreas, a protein which is considered to be a member of the elastase family. In this report, we describe the isolation of the two homologous cDNA clones encoding caldecrin from human pancreas, the structures of which are identical except for one base and the corresponding amino acid residue. These human caldecrin isoforms are composed of a signal peptide of 16 amino acids, a propeptide of 13 amino acids, and a mature form of 239 amino acids. Both recombinant caldecrins showed the same chymotrypsin-type protease activity and hypocalcemic activity. The hypocalcemic activity of both remained intact even after treatment with PMSF to abolish their protease activity. These results suggest that human caldecrin possesses hypocalcemic activity that has no connection with its protease activity.

Amino Acid Sequence↗
PubMed1996

In vitro metabolism of the vitamin D analog, 22-oxacalcitriol, using cultured osteosarcoma, hepatoma, and keratinocyte cell lines.

Using four cultured cell models representing liver, keratinocyte, and osteoblast, we have demonstrated that the vitamin D analog, 22-oxacalcitriol is degraded into a variety of hydroxylated and side chain truncated metabolites. Four of these metabolic products have been rigorously identified by high pressure liquid chromatography, diode array spectrophotometry, and gas chromatography-mass spectrometry analysis as 24-hydroxylated and 26-hydroxylated derivatives as well as the cleaved molecules, hexanor-1alpha,20-dihydroxyvitamin D3 and hexanor-20-oxo-1alpha-hydroxyvitamin D3. Comparison with chemically synthesized standards has revealed the stereochemistry of the biological products. Although differences exist in the amounts of products formed with the different cell types, it is apparent that 22-oxacalcitriol is subject to metabolism by both vitamin D-inducible and noninducible enzymes. Time course studies suggest that the truncated 20-alcohol is derived from a side chain hydroxylated molecule via a hemiacetal intermediate and the 20-oxo derivative is likely formed from the 20-alcohol. Biological activity measurements of the metabolites identified in our studies are consistent with the view that these are catabolites and that the biological activity of 22-oxacalcitriol is due to the parent compound. These results are also consistent with recent findings of others that the biliary excretory form of 22-oxacalcitriol is a glucuronide ester of the truncated 20-alcohol.

Animals↗
PubMed1996

Effects of a synthetic vitamin D analog, ED-71, on bone dynamics and strength in cancellous and cortical bone in prednisolone-treated rats.

To determine the action of corticosteroid on bone metabolism and assess the effects of a synthetic vitamin D analog, ED-71, on them, 56 SD rats, 8 weeks of age, were assigned to seven groups of eight animals each. Group 1 was the basal control. Group 2 was the nontreated control. Groups 3-7 were given prednisolone at 30 mg/kg of body weight (BW) twice a week and concomitantly administered ED-71 with respective doses of 0, 0.0125, 0.025, 0.05, and 0.1 micrograms/kg of BW for 12 weeks. In group 3, urinary calcium (U-Ca) and deoxypyridinoline (U-Dpy) were significantly increased compared with group 2. In groups 4-7, U-Ca values were increased but U-Dpy values were dose-dependently decreased. Age-dependent increases in the parameter values of BMD, compressive strength, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) of the lumbar body were significantly suppressed in group 3 but dose-dependently increased in groups 4-7, and the values of group 7 exceeded those of group 2. The parameters of bone mineral density (BMD) and the bending strength of the femur in groups 4-7 were larger than the values in group 3 but did not reach the levels of group 2. The trabecular bone formation rate (BFR/BS) of the lumbar body measured by calcein labeling in group 3 was reduced when compared with group 2, but the values were not further decreased in groups 4-7. The perimeter ratios of double labels over single labels (dLS/sLS) greatly decreased by prednisolone, were dose-dependently increased to the level of the normal control by ED-71. Double-labeled perimeters and the dLS/sLS ratios were also increased in the periosteal envelope of the midfemur. These findings clearly demonstrate that prednisolone administration affects the age-related changes in bone metabolism, and ED-71 administration counteracts the effects by increasing intestinal calcium absorption, reducing bone resorption, and enhancing mineralization. The action of ED-71, however, seems to be less potent in the cortical bone.

Absorptiometry, Photon↗
PubMed1996

1,25-dihydroxyvitamin D3 and 22-oxacalcitriol prevent the decrease in vitamin D receptor content in the parathyroid glands of uremic rats.

Decreased content of the 1,25-dihydroxyvitamin D3 receptor (VDR) in parathyroid glands from patients and animals with chronic renal failure has been implicated in the pathogenesis of secondary hyperparathyroidism. In these studies, we examined the regulation of VDR by 1,25-dihydroxyvitamin D3 (1,25-D3) and 22-oxacalcitriol (OCT) in parathyroid glands of uremic rats. After eight weeks of renal failure, VDR content in parathyroid glands of uremic rats was decreased (400 +/- 42 vs. 729 +/- 47 fmol/mg protein in normal control rats, P < 0.05) and strongly correlated with serum 1,25-D3 levels (r = 0.829, P = 0.0001). Treatment with either 1,25-D3 or OCT prevented the decrease in VDR. We conclude that low serum 1,25-D3 levels, at least in part, account for the decrease in VDR content in parathyroid glands of uremic rats and that treatment with 1,25-D3 or OCT prevents this decrease ameliorating the development of secondary hyperparathyroidism.

Animals↗
PubMed1996

Acromegaly associated with Chiari-I malformation and polycystic ovary syndrome.

We report a 19-year-old female case of acromegaly associated with Chiari-I malformation and polycystic ovary syndrome. She also had syringomyelia and thoracic scoliosis. Although the association of acromegaly and Chiari-I malformation was by chance, exaggerated secretion of growth hormone may have aggravated the scoliosis. The incidence of polycystic ovary in acromegalic patients remains to be elucidated. However, elevation of plasma insulin and insulin-like growth factor, that is usually observed in patients with acromegaly, could stimulate androgen production in the ovaries. The patient was successfully treated with transsphenoidal adenomectomy for pituitary tumor and correction surgery for thoracic scoliosis.

Acromegaly↗
PubMed1995

Molecular cloning and expression of serum calcium-decreasing factor (caldecrin).

We previously reported on the purification of a serum calcium-decreasing factor, referred to as caldecrin, from porcine pancreas, that is thought to be a serine protease (Tomomura, A., Fukushige, T., Noda, T., Noikura, T., and Saheki, T. (1992) FEBS Lett. 301, 277-281). In the present study, we purified caldecrin from rat pancreas and determined its primary structure by cDNA cloning. The predicted caldecrin protein is presumed to be synthesized as a preproenzyme of 268 amino acids with a signal peptide of 16 amino acids and an activation peptide of 13 amino acids, and is, with the exception of a central region, almost identical to the reported rat pancreatic elastase IV sequence. The caldecrin gene is selectively expressed in the pancreas, as judged by Northern blot analysis. After expression in BMT-10 cells, immunoreactive caldecrin was found in the culture supernatant, and it inhibited the parathyroid hormone-stimulated 45Ca release from cultured fetal long bones. Catalytic site mutants were synthesized in a baculovirus system, and recombinant mutants also decreased the serum calcium level of mice. These data implicate caldecrin, a protease closely related to elastase IV, in the regulation of blood calcium levels.

Amino Acid Sequence↗
PubMed1995

[An autopsy care of hemophagocytic syndrome associated with miliary tuberculosis].

A 56-year-old female with chronic renal failure secondary to diabetic glomerulosclerosis was hospitalized and had a fluminant clinical course with pancytopenia, abnormal liver function tests, and coagulopathy. Bone marrow aspirate findings were typical of reactive hemophagocytosis. The patient died after 21 days of hospitalization and autopsy findings showed disseminated miliary tuberculosis. To our knowledge, only eight cases of miliary tuberculosis with bone marrow hemophagocytosis have previously been described. The presence of reactive hemophagocytosis requires a prompt and thorough search for treatable infections.

Female↗
PubMed1995

Mouse primary osteoblasts express vitamin D3 25-hydroxylase mRNA and convert 1 alpha-hydroxyvitamin D3 into 1 alpha,25-dihydroxyvitamin D3.

We examined whether 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) is metabolized into 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) in bone. Northern blot analysis indicated that the expression of vitamin D3 25-hydroxylase mRNA was highest in the liver, followed by the duodenum, calvaria, lung, kidney, skin and long bone, and lowest in the spleen. Of the bone cell fractions isolated from fetal mouse calvaria by a sequential enzymatic digestion, fraction 3, which consisted of mostly osteoblastic cells, showed the highest expression of vitamin D3 25-hydroxylase mRNA. When either cultured bone cells of fraction 3 or mouse calvaria were incubated with [3H]-1 alpha (OH)D3, a radioactive peak which comigrated at the same position as authentic 1 alpha,25(OH)2D3 was found on an HPLC chromatogram. The radioactive fraction obtained from the conditioned media of fetal mouse calvaria was tentatively identified as 1 alpha,25(OH)2D3 by cochromatography with authentic 1 alpha,25(OH)2D3 on three different HPLC systems and a thermal isomerization analysis. These results indicate that 1 alpha(OH)D3 is hydroxylated at the 25-position in bones, resulting in the local synthesis of 1 alpha,25(OH)2D3 from 1 alpha(OH)D3 in the skeletal tissues.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1994

1 alpha-hydroxyvitamin D3 inhibits type II collagen-induced arthritis in rats.

The effects of 1 alpha-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 on Type II collagen-induced arthritis in rats, an experimental model of rheumatoid arthritis, were examined. Oral administration of 1 alpha-hydroxyvitamin D3 significantly suppressed the incidence of arthritis and inhibited hind paw swelling. The level of anti-Type II collagen antibodies was decreased in the 1 alpha-hydroxyvitamin D3 treated-group. In contrast, 24,25-dihydroxyvitamin D3, indomethacin, and gold had no effect on either the incidence of arthritis or the antibody levels. These findings demonstrate a beneficial effect of 1 alpha-hydroxyvitamin D3 on Type II collagen-induced arthritis in rats and indicate that it has an antirheumatic effect.

Animals↗
PubMed1994

A novel synthetic vitamin D analogue, 2 beta-(3-hydroxypropoxy)1 alpha, 25-dihydroxyvitamin D3 (ED-71), increases bone mass by stimulating the bone formation in normal and ovariectomized rats.

We performed dosing experiments to evaluate the bone mass increasing action of a novel, synthetic vitamin D derivative, 2 beta-(3-hydroxypropoxy)-1 alpha,25(OH)2D3 (ED-71), in normal and estrogen-deficient rats. The first experiment consisted of 31 Sprague-Dawley rats, 28 weeks of age. The second experiment consisted of 44 animals who were ovariectomized (OVX) or sham operated at the age of 12 weeks. ED-71 was given twice a week for the duration of 12 weeks. At the end of the experiments, serum chemistries were examined and lumbar vertebrae were assessed histomorphometrically. Serum alkaline-phosphatase levels tended to decrease by ED-71 administration in the first experiment and their elevated values after ovariectomy were also depressed by ED-71 in the second experiment. Serum osteocalcin levels, however, increased by the agent. In the first experiment, cancellous bone volume (BV/TV) increased dose dependently. Bone formation rates (BFR/BS) also increased. In the second experiment, BV/TV significantly decreased by ovariectomy and it increased in ED-71-treated groups, but not in 1 alpha-(OH)D3-treated group. BFR/BS increased by ED-71. Activation frequency did not decrease by ED-71 in either experiment. These data clearly demonstrated that ED-71 administration was capable of increasing the bone mass by stimulating bone formation in normal and estrogen-deficient rats.

Alkaline Phosphatase↗
PubMed1994

The binding properties, with blood proteins, and tissue distribution of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a noncalcemic analogue of 1 alpha, 25-dihydroxyvitamin D3, in rats.

The binding properties, with blood proteins, and tissue distribution of 22-oxa-1 alpha,25-dihydroxyvitamin (22-oxacalcitriol; OCT), a noncalcemic analogue of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], in rats were investigated. The binding affinity of OCT to plasma vitamin D binding protein (DBP) is extremely low and OCT mainly circulates in the blood as an intact form nonspecifically bound to lipoproteins especially to chylomicrons and low density lipoprotein (LDL). OCT intravenously injected into normal rats rats rapidly disappeared from the blood, and rapidly appeared in the bile as glucuronides of intact OCT and 1 alpha, 3 beta,20(S)-trihydroxy-9,10-secopregna-5,7,10(19)-triene (23,24,25,26, 27-pentanorOCT; pentanorOCT) as an OCT metabolite. When OCT or 1,25(OH)2D3 was injected into normal rats, significant amounts of OCT and 1,25(OH)2D3 were quickly detected in the thyroid and parathyroid glands, thymus, adrenals, liver, plasma, small intestine, kidneys, and calvaria. The detected amounts of OCT in the parathyroid glands, thymus, adrenals, liver, small intestine, and kidneys were significantly higher than the respective values for 1,25(OH)2D3 2 and/or 10 min after injection, while those of OCT in the plasma and calvaria were significantly lower than those of 1,25(OH)2D3. The in vivo rapid turn-over, nonspecific transportation, and incorporation of detectable amounts into the tissues are typical characteristics of OCT which may account for its specific activities.

Animals↗
PubMed1994

Response of hepatic proteins to 3,5,3'-tri-iodo-L-thyronine in diabetic rats.

In order to study whether peripheral action of thyroid hormones is altered in insulin deficiency and to elucidate the biological consequences of alteration of the cytosolic 3,5,3'-tri-iodo-L-thyronine (T3) binding protein (CTBP), we measured malic enzyme, T3-responsive nuclear n protein, CTBP and nuclear thyroid hormone receptor in the liver and kidney of streptozotocin (STZ)-induced diabetic rats that were treated with or without insulin and/or a receptor-saturating dose of T3. The following results were obtained. 1. Induction of malic enzyme by T3 was apparently diminished in diabetic rats. However, supplementary injection of insulin enabled previously given T3 to take effect in diabetic rats. 2. T3-responsiveness of other hepatic proteins (n protein and CTBP) was not altered by insulin in diabetic rats. 3. The level of n protein was increased by insulin in diabetic rats in vivo and in perfused rat liver, indicating that the hepatic n protein is a novel insulin-responsive protein. T3 and insulin increased the level of n protein non-synergistically in diabetic rat liver. 4. Hepatic nuclear receptor levels were not altered in diabetic rats. 5. Hepatic CTBP levels were decreased in diabetic rats. This was not due to the toxic effect of STZ. Low CTBP level was only partially increased by insulin after 30 days of diabetic period. Renal CTBP levels were not altered in diabetic rats with or without insulin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗