Biomedical subjects

Y L Chan

Publications and source records attributed to Y L Chan.

At least 181 records · Page 10Linked to original sources

PubMed1986

The effect of 1,25 dihydroxycholecalciferol on parathyroid hormone secretion by monolayer cultures of bovine parathyroid cells.

Controversy exists over a direct effect of 1,25(OH)2D3 on PTH secretion. To investigate the possibility that the suppressive effect of 1,25(OH)2D3 on PTH secretion may be demonstrable in 1,25(OH)2D3-depleted tissue and/or after prolonged periods of exposure to 1,25(OH)2D3, primary monolayer cultures of bovine parathyroid cells were established in 1:1 DMEM/Ham's F-12 media supplemented with 2% calf serum but not 1,25(OH)2D3. Ionized calcium was maintained at 1.0 mM. Experiments were performed on 4-day-old culture cells. PTH concentration was measured using both a mid-region/carboxyl and an amino-terminal PTH antisera. 1,25(OH)2D3 at a concentration of 0.1 ng/ml suppressed PTH secretion by 32 +/- 7% after 48 hours. High calcium concentration (2.0 mM) suppressed PTH secretion by 37 +/- 10% and this effect was not additive over that of 1,25(OH)2D3. PTH secretion rate recovered fully 48 hours after normalization of the external calcium concentration but not after the removal of 1,25(OH)2D3. It is concluded that 1,25(OH)2D3 directly suppresses PTH secretion by monolayer culture of bovine parathyroid cells.

Animals↗

PubMed1986

The effects of discontinuation of aluminum exposure on aluminum-induced osteomalacia.

Studies in patients on dialysis have shown that aluminum (Al) accumulation in bone plays a major role in the pathogenesis of osteomalacia. It has been suggested that deferoxamine (DFO) may be beneficial in the treatment of aluminum-induced osteomalacia. The present studies were performed in four groups of uremic rats to determine if DFO and/or discontinuation of Al administration have an effect on bone histomorphometry and blood chemistries. The groups were: 1) uremic control 2) aluminum (0.75 to 1.0 mg/rat i.p., five times a week for twelve weeks): 3) aluminum + DFO, after twelve weeks Al was discontinued and the rats received DFO (75 mg/rat two times a week for nine weeks); 4) aluminum + time, after twelve weeks Al was discontinued and the rats were sacrificed after nine weeks. High levels of Al in serum and bone and low levels of PTH were seen in rats receiving Al. Bone histology revealed Al at the mineralization front, abnormal tetracycline uptake, and an increase in osteoid. DFO treatment did not significantly change the level of Al in bone, however both DFO treatment and discontinuation of Al reversed towards normal the above described lesions. In conclusion, these studies suggest that DFO and/or discontinuation of Al administration to rats with approximately 30% of renal function greatly improve aluminum-induced osteomalacia.

Aluminum↗

PubMed1986

Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure.

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PTH] secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79 +/- 0.09 mg/dl and gradually increased up to 5.30 +/- 0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64 +/- 7.7 to 118 +/- 21 pg/ml. Serum 1,25(OH)2D3 decreased from 25.4 +/- 3.8 to 12.2 +/- 3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8 +/- 3.5 to a maximum of 69.6 +/- 4.4 pg/ml. In the second group the levels of serum 1,25(OH)2D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3. In summary, the dogs at no time developed hypocalcemia; however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.

Amino Acid Sequence↗

PubMed1986

Beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease: effect of propranolol.

This study was designed to investigate beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease (ESRD). Plasma potassium was measured over a period of 3 months in 20 patients with ESRD who were receiving the nonselective beta-blocker propranolol (n = 10) or not (n = 10). Both groups were virtually anuric and had a comparable plasma BUN, plasma bicarbonate, and red cell Na-K-ATPase activity. Plasma potassium measured before dialysis was higher in propranolol users than in nonusers (5.6 +/- 0.2 and 4.6 +/- 0.1 mEq/l, p less than 0.005). To examine beta-adrenergic-mediated internal potassium disposal more directly, epinephrine and epinephrine plus propranolol were acutely administered to another group of patients with ESRD and to normal subjects. Epinephrine resulted in a similar fall in plasma potassium in both groups (0.69 +/- 0.20 and 0.63 +/- 0.07 mEq/l, respectively), thereby suggesting unimpaired beta-adrenergic-mediated extrarenal potassium handling in patients with ESRD. In patients, however, the response to epinephrine was heterogeneous. In 4 of the 10 patients studied, epinephrine infusion did not result in a decrement in plasma potassium suggesting impaired beta-adrenergic responsiveness and thus blunting of this mechanism of extrarenal potassium disposal. In the remaining 6 patients, epinephrine infusion resulted in a fall in plasma potassium which was greater than that observed in normal subjects (1.13 +/- 0.14 and 0.63 +/- 0.07 mEq/l, respectively, p less than 0.01). In the presence of propranolol, the infusion of epinephrine did not result in a decrement in plasma potassium in these 6 patients or in the 6 normal subjects (0.04 +/- 0.07 and -0.02 +/- 0.06 mEq/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1986

An unusual laryngeal foreign body in an infant.

A case is presented of laryngeal impaction in an infant by a cervical vertebra of a toad. Symptoms were mild initially but became progressive later with secondary laryngeal edema. Early diagnosis was not made, which resulted in considerable difficulty in management. Computerized tomography (CT) scan was found to be useful in identifying the foreign body and thereby facilitating management. CT is recommended for suspected foreign bodies in the air and food passages where more conventional methods fail to make a diagnosis.

Animals↗

PubMed1985

The effect of metabolic acidosis on vitamin D metabolites and bone histology in uremic rats.

Biochemical data and skeletal histomorphometric measurements are presented for normal rats and for two groups of rats rendered uremic by partial nephrectomy. In one of these groups chronic acidosis was induced by the oral administration of hydrochloric acid. Uremic animals had higher urine calcium excretion rates and lower serum concentrations of vitamin D metabolites than normal rats. Chronic acid loading of uremic rats resulted in hypercalcemia, elevated serum parathyroid hormone concentrations, and a significant loss of trabecular bone in addition to the above changes. greater osteoclast densities and higher resorption surfaces wee seen in the uremic acidotic animals than in the other two groups. The acidotic uremic state induced more potent changes in calcium metabolism and bone structure than uremia alone.

Acidosis↗

PubMed1985

Some problems associated with adenylate cyclase bioassays for parathyroid hormone.

A renal adenylate cyclase system was assessed for its suitability in the performance of parathyroid hormone (PTH) bioassays. Membrane preparations from 1 week old chicks were found to be more sensitive to PTH than material from humans, dogs or rats. Because of the presence of non-specific inhibitors and stimulators of adenylate cyclase in human serum, each serum sample was assayed in the presence and in the absence of a specific PTH inhibitor and the difference was used to calculate PTH activity. Calcium, an inhibitor of adenylate cyclase, was either removed from serum samples by pretreatment with Chelex resin or chelated during assay by means of EGTA. Human and bovine PTH (1-34) stimulated adenylate cyclase in this system to the same extent. The lower limit of detectability was 19.5 pg/ml (final concentration). The intra-assay coefficient of variation at a final concentration of 45 pg/ml was 18%. The index of precision was 0.08 +/- 0.04 (n = 7). When synthetic human PTH (1-34) was infused into three normal volunteers, the mean biological half-life of this material was found to be 3.2 min. PTH-like bioactivity could be routinely detected in sera from normal rats, while such activity was significantly decreased in rats subjected to thyroparathyroidectomy.

Adenylyl Cyclases↗

PubMed1985

An adenylate cyclase bioassay for parathyroid hormone: some clinical experiences.

An adenylate cyclase bioassay for parathyroid hormone (PTH) was evaluated in peripheral sera of ten normal subjects, 15 patients with various types of hypoparathyroidism, nine patients with malignancy-associated hypercalcaemia and 60 patients with primary or secondary hyperparathyroidism. The lower limit of detectability was 150 pg/ml in terms of synthetic human PTH (1-34). PTH-like bioactivity was not detected in normal subjects, in patients with surgical hypoparathyroidism, in patients with idiopathic hypoparathyroidism or in patients with malignancy-associated hypercalcaemia. Serum from one untreated pseudohypoparathyroid patient consistently contained PTH-like bioactivity. Bioactivity was detected in sera from 50% of patients with primary or secondary hyperparathyroidism. In two patients with secondary hyperparathyroidism calcium infusions suppressed this activity within 5 min. Both in primary and in secondary hyperparathyroidism there was a significant positive correlation between levels of PTH-like bioactivity, PTH immunoreactivity and the histological severity of the disease.

Adenylyl Cyclases↗

PubMed1985

Dialysis osteodystrophy. A study involving 94 patients.

Dynamic skeletal histomorphometry was performed in 94 unselected patients receiving maintenance dialysis for chronic renal failure. An attempt was made to correlate the results with the clinical, biochemical and radiological findings. Skeletal histology was abnormal in each case. Hyperparathyroidism was present as the only abnormality in 18 patients and osteomalacia in 26; 50 patients showed both abnormalities. Osteomalacia, in contrast to hyperparathyroidism, increased in prevalence and severity with the duration of dialysis and with bone aluminum content. The majority of patients had histological osteosclerosis. It was impossible to predict either the nature or the severity of the histological lesions on the basis of symptoms and physical signs or on the basis of most biochemical parameters (including serum concentrations of three vitamin D metabolites). Serum alkaline phosphatase values and serum immunoreactive parathyroid hormone (iPTH) concentrations were positively correlated with the severity of histological hyperparathyroidism. Subperiosteal erosions of the phalanges were associated with severe histological hyperparathyroidism in each case but this radiological sign was absent in 66% of patients with histological hyperparathyroidism. Radiological osteosclerosis was associated with severe histological osteomalacia in each case, but this radiological sign was absent in 87% of patients with histological osteomalacia. No other radiological sign proved a reliable guide to the underlying skeletal histology. In the majority of dialysis patients, a skeletal biopsy is required for an accurate diagnosis of the nature and severity of azotemic osteodystrophy.

Adolescent↗

PubMed1985

The compartmentalization and metabolism of aluminum in uremic rats.

Aluminum levels in bone are significantly higher and those in the liver are significantly lower in uremic rats than in control rats receiving similar amounts of parenterally administered aluminum. We evaluated the possibility that the hyperparathyroidism present in uremia might affect aluminum metabolism and toxicity. Uremia was induced by establishing the remnant kidney and hypoparathyroidism was induced by selective parathyroidectomy. Aluminum loading was accomplished by intraperitoneal aluminum injection. Bone aluminum concentration in the uremic group was 113 +/- 16 mg/kg, compared with 80 +/- 7 mg/kg in the uremic parathyroidectomy group and 55 +/- 9 mg/kg in controls (p less than 0.001 between all groups) and 52 +/- 16 mg/kg in parathyroidectomy controls. When parathyroidectomy was performed after the uremic animals were already loaded with aluminum, bone aluminum levels did not change, suggesting that the parathyroidectomy prevented some of the excess bone aluminum levels in uremia by decreasing bone uptake of aluminum rather than enhancing mobilization of bone aluminum. The only other effect the parathyroidectomy procedure had on tissue aluminum was to slightly decrease brain aluminum levels in uremic animals and kidney aluminum levels in control rats. Uremic rats with parathyroidectomy were found to have a significantly greater trabecular bone osteoid area than uremic rats (45.9% +/- 9.7% and 13.4% +/- 10.6%). We conclude that parathyroidectomy, especially in the uremic state, has a major influence on the compartmentalization of aluminum in bone and intensifies aluminum-induced osteomalacia.

Aluminum↗

PubMed1984

The nucleotide sequence of a rat 18 S ribosomal ribonucleic acid gene and a proposal for the secondary structure of 18 S ribosomal ribonucleic acid.

The nucleotide sequence of a rat 18 S rRNA gene was determined. The 18 S rRNA encoded in the gene contains 1874 nucleotides, and the molecular weight estimated from the sequence is 6.09 X 10(5). The sequences of rat and Xenopus laevis 18 S rRNAs are very similar; the only differences of consequence are the insertions between nucleotides 197 and 206 and between 258 and 279 of the rat nucleic acid of sequences rich in guanine and cytosine. A proposal is presented for the secondary structure of rat 18 S rRNA based on a comparison with the sequences of 17 other small ribosomal subunit RNAs. While the primary sequences of rat and eubacterial RNAs are different, the deduced secondary structures are remarkably similar.

Animals↗

PubMed1984

Vitamin D conversion by sarcoid lymph node homogenate.

Recent studies suggest that hypercalcemia of sarcoidosis is due to high blood concentrations of calcitriol and that this compound may be synthesized at an extra-renal site. We report that sarcoid lymph node homogenate metabolized calcifediol to a substance indistinguishable from calcitriol, whereas six nonsarcoid lymph nodes failed to produce this compound.

Calcifediol↗

PubMed1983

The structure of rat 28S ribosomal ribonucleic acid inferred from the sequence of nucleotides in a gene.

The nucleotide sequence of a rat 28S rRNA gene was determined. The 28S rRNA encoded in the gene contains 4718 nucleotides and the molecular weight estimated from the sequence is 1.53 x 10(6). The guanine and cytosine content is 67%. The sequence of rat 28S rRNA diverges appreciably from that of Saccharomyces carlsbergensis 26S rRNA (about 50% identity), but more closely approximates that of Xenopus laevis 28S rRNA (about 75% identity). Rat 28S rRNA is larger than the analogous nucleic acids from yeast (3393 nucleotides) and X, laevis (4110 nucleotides) ribosomes. The additional bases are inserted in specific regions and tend to be rich in guanine and cytosine. 5.8S rRNA can interact with 28S rRNA by extensive hydrogen bonding at two sites near the 5' end of the latter.

Animals↗

PubMed1983

The sequence of the nucleotides at the alpha-sarcin cleavage site in rat 28 S ribosomal ribonucleic acid.

The sequence of the 521 nucleotides at the 3' end of a rat 28 S rRNA gene was determined. The region encompasses the site of cleavage of 28 S rRNA by the cytotoxin alpha-sarcin. The toxin hydrolyzes a phosphodiester bond on the 3' side of a guanine residue 393 nucleotides from the 3' end. The alpha-sarcin domain is composed of a purine-rich sequence of 14 highly conserved nucleotides.

Animals↗

PubMed1983

Effect of aluminum on normal and uremic rats: tissue distribution, vitamin D metabolites, and quantitative bone histology.

The effects of intraperitoneal aluminum chloride (1.5 mg aluminum/kg/day for 9 weeks) were studied in normal and uremic rats. Parameters measured included tissue aluminum, serum vitamin D metabolites, and quantitative bone histology. Aluminum administration increased tissue concentrations of this metal in uremic and nonuremic animals. Bone aluminum concentrations were higher in uremic rats (121 +/- 27 mg/kg compared to 47 +/- 4), whereas liver values were higher in the nonuremic group (175 +/- 47 mg/kg compared to 100 +/- 36). Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were reduced in uremia, but aluminum was without apparent effect on any vitamin D metabolite. Aluminum, in the doses administered, caused no skeletal changes in nonuremic animals. Some uremic, non-aluminum-treated rats developed osteomalacia and marrow fibrosis. However, osteomalacia was more severe and the osteoclast count was higher in the uremic, aluminum-treated rats. In this group of animals the mineral apposition rate was reduced at the metaphyseal endosteum but increased at the periosteum, indicating different control mechanisms at the two sites.

Aluminum↗

PubMed1983

Vitamin D metabolism in nephrotic rats.

Vitamin D metabolites were measured in sera of normal, vitamin D deficient and nonazotemic nephrotic rats. The concentrations of all metabolites were reduced in nephrotic and vitamin D deficient animals although 1,25-dihydroxyvitamin D values remained relatively normal in the nephrotic group. Twenty-four hours after the intravenous injection of tritiated 25-hydroxycholecalciferol, approximately 34% of the injected radioactivity appeared in the urine of the nephrotic animals compared with 0.4% in the controls. In extracts from nephrotic sera subjected to high performance liquid chromatography, the percentage of radioactive counts comigrating with 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol was significantly increased. The various metabolites were present in urine in approximately the same ratios as in serum. Dynamic histomorphometry of tibial metaphyses showed no abnormality. Urinary losses of vitamin D metabolites constitute the major cause for low serum values in nephrotic rats. The apparent synthetic rates are not impaired.

24,25-Dihydroxyvitamin D 3↗

PubMed1983

The vascular lesions associated with skin necrosis in renal disease.

Three renal allograft recipients and one uraemic patient presented with skin necrosis. In all cases, the subcutaneous arteries and arterioles were narrowed or occluded by mural calcification with or without intimal fibrosis. A review of the literature shows that uraemic patients or allograft recipients with skin necrosis involving the trunk or thighs have a poor prognosis while recovery is common in patients with more peripheral lesions. The aetiology of the arterial lesions is unknown. Their relationship to renal disorders and/or hyperparathyroidism is uncertain and therapy remains unsatisfactory.

Adult↗

PubMed1983

Passive driving forces of proximal tubular fluid and bicarbonate transport: gradient dependence of H+ secretion.

The effect of oncotic pressure changes on fluid (Jv) and net bicarbonate transport (JHCO-3) and the transepithelial bicarbonate permeability (PHCO-3) were measured by an improved luminal and capillary microperfusion method that allows paired experiments on the same tubule. Rat proximal tubules were pump-perfused and Jv and [HCO-3] measured with [14C]inulin and a pH glass electrode. Raising peritubular protein (0-8-15 g/100 ml bovine serum albumin) stimulated Jv and HCO-3 reabsorption. The response to oncotic pressure changes was asymmetrical since changes of the luminal protein concentration had no significant effects. Whereas transepithelial solvent drag effects on HCO-3 must be minimal, peritubular protein most likely stimulates translocation of fluid and bicarbonate from intercellular spaces into peritubular capillaries. PHCO-3 was measured from HCO-3 net flux along a lumen-to-capillary-directed electrochemical potential gradient. In these experiments active H+ transport and Jv were minimized by 10(-4) M acetazolamide and luminal raffinose. PHCO-3 was 1.77 X 10(-5) cm X s-1 and was unaffected by increasing luminal flow rate from 10 to 45 nl X min-1. Since bicarbonate backflux is only a small fraction of physiological rates of JHCO-3, net transport alterations at varying [HCO-3] in the lumen must be due to changes in active HCO-3 (H+) transport. Thus, active H+ ion secretion across the luminal membrane of the proximal tubule is gradient dependent.

Acetazolamide↗