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A Tenenhouse

Publications and source records attributed to A Tenenhouse.

At least 37 records · Page 2Linked to original sources
PubMed2000

Association of a polymorphism in the TNFR2 gene with low bone mineral density.

Previous genetic linkage data suggested that a gene on chromosome 1p36.2-36.3 might be linked to low bone mineral density (BMD). Here, we examine the gene for tumor necrosis factor receptor 2 (TNFR2), a candidate gene within that interval, for association with low BMD in a group of 159 unrelated individuals. We assess two polymorphic sites within the gene, a microsatellite repeat within intron 4, and a three-nucleotide variation in the 3' untranslated region (UTR) of the gene. The latter has five alleles of which the rarest allele is associated with low spinal BMD Z score (p = 0.008). Lowest mean spinal BMD Z scores were observed for individuals having genotypes that were heterozygous for the rarest allele. No homozygotes for the rarest allele were observed. Preliminary analysis suggests that there is a difference in the genotype frequency distribution between the group with low BMD and a control group.

3' Untranslated Regions↗
PubMed1998

Biochemical markers of bone turnover. A look at laboratory tests that reflect bone status.

Chemicals in serum and urine can serve as markers for monitoring bone loss, bone reformation, and the effectiveness of therapy in patients with osteoporosis. Although not yet well recognized or readily available, tests for these markers may prove preferable to densitometry in some settings or for some patients. In the future, biochemical markers may provide important information on fracture risks as well.

Biomarkers↗
PubMed1997

Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis.

BACKGROUND AND METHODS: Osteoporosis is a recognized complication of corticosteroid therapy. Whether it can be prevented is not known. We conducted a 12-month, randomized, placebo-controlled study of intermittent etidronate (400 mg per day for 14 days) followed by calcium (500 mg per day for 76 days), given for four cycles, in 141 men and women (age, 19 to 87 years) who had recently begun high-dose corticosteroid therapy. The primary outcome measure was the difference in the change in the bone density of the lumbar spine between the groups from base line to week 52. Secondary measures included changes in the bone density of the femoral neck, trochanter, and radius and the rate of new vertebral fractures. RESULTS: The mean (+/-SE) bone density of the lumbar spine and trochanter in the etidronate group increased 0.61 +/- 0.54 and 1.46 +/- 0.67 percent, respectively, as compared with decreases of 3.23 +/- 0.60 and 2.74 +/- 0.66 percent, respectively, in the placebo group. The mean differences between the groups after one year were 3.72 +/- 0.88 percentage points for the lumbar spine (P = 0.02) and 4.14 +/- 0.94 percentage points for the trochanter (P = 0.02). The changes in the femoral neck and the radius were not significantly different between the groups. There was an 85 percent reduction in the proportion of postmenopausal woman with new vertebral fractures in the etidronate group as compared with the placebo group (1 of 31 patients vs. 7 of 32 patients, P = 0.05), and the etidronate-treated postmenopausal women also had significantly fewer vertebral fractures per patient (P = 0.04). CONCLUSIONS: Intermittent etidronate therapy prevents the loss of vertebral and trochanteric bone in corticosteroid-treated patients.

Adult↗
PubMed1996

Correlation of ultrasound velocity in the tibial cortex, calcaneal ultrasonography, and bone mineral densitometry of the spine and femur.

We compared the attributes of tibial cortex speed of sound (SOS) measurements with the SOS and broadband ultrasound attenuation (BUA) of the calcaneus, and bone mineral densities of the lumbar spine and femoral neck in a patient crossover study. The three instruments used in the crossover study were the LUNAR DPX and AchillesTM, and a newly introduced device for measuring tibial cortical SOS, the SoundScanTM 2000. Ultrasound precision determinations on the two instruments were performed with the same group of 10 volunteers, and the bone densitometry precision was derived from 22 patients who were assessed twice in a single visit, with repositioning between spine and hip scans. There were 220 female patients in the clinical study, 28 of whom had thoracic spine fractures, and all had measurements with the three instruments. Of the three instruments, the best precision, or lowest coefficient of variation and standardized coefficient of variation, was obtained with the SoundScanTM 2000; 0.20% and 1.39%, respectively. The tibial SOS correlated more poorly with the lumbar spine and femoral neck bone mineral densities (BMDs) than the calcaneal parameters in 220 patients. Tibial SOS measurements could not distinguish the group with spinal fracture from an age-matched control group to a P < 0.05 level, whereas the lumbar spine BMD and calcaneal BUA and stiffness showed a significant difference. We conclude that the SoundScanTM 2000 system measures propagation of sound in the tibial cortex with great precision, but its role in clinical practice is moot. Yet to be established by a long-term prospective study is its efficacy in predicting fracture risk and how well it reflects bone change in response to treatment of osteoporosis.

Adult↗
PubMed1996

Vitamin D receptor genotype is not associated with bone mineral density in three ethnic/regional groups.

We report a cross-sectional study of 48 men, 56 premenopausal women, and 80 postmenopausal women who were of three ethnic/regional backgrounds: southern European (Greek, Italian), eastern European (Jewish, Polish, Hungarian), and western European (French, British). We determined bone mineral density (BMD) at four skeletal sites and assessed the vitamin D receptor (VDR) genotype by the Bsml restriction site polymorphism. Age and body mass index had significant effects on BMD by multiple regression analysis. In addition, ethnic/regional group had a significant effect on spinal BMD in premenopausal females (P = 0.014) and in males (P = 0.039). However, VDR genotype had no significant effect on BMD in any of the three study groups.

Bone Density↗
PubMed1996

Osteopenia in 37 members of seven families: analysis based on a model of dominant inheritance.

BACKGROUND: The genetic factors involved in determining bone mineral density (BMD) have not been fully elucidated. We have begun genetic linkage analysis of seven families in which many members are osteopenic, in order to identify chromosomal loci that are potentially involved in determining BMD. MATERIALS AND METHODS: Spine BMD was measured in 143 members of seven kindred with familial osteopenia. The absolute BMD values for the spine (L2-L4) were converted to the age-, gender-, and weight-adjusted Z scores, and this corrected value was used as the quantitative trait on which to base subsequent genetic analyses. Simulations of linkage were performed in order to determine the information content of the pedigree set, and actual linkage analysis was conducted using polymorphic markers either within or near three candidate loci: COL1A1, COL1A2, and vitamin D receptor (VDR). RESULTS: The distribution of the corrected Z scores was bimodal (p = 0.001) suggesting a monogenic mode of inheritance of the low BMD trait. Simulation of linkage analysis suggested that the family data set was sufficient to detect linkage under a single major gene model. Actual linkage analysis did not support linkage to the three candidate loci. In addition, the VDR genotype was not statistically associated with low bone density at the spine. CONCLUSIONS: Loci other than COL1A1, COL1A2 and VDR are very likely responsible for the low BMD trait observed in these families. These families are suitable for a genome-wide screen using microsatellite repeats in order to identify the loci that are involved in osteopenia.

Analysis of Variance↗
PubMed1995

A correlative study of ultrasound calcaneal and dual-energy X-ray absorptiometry bone measurements of the lumbar spine and femur in 1000 women.

The objectives of the study were firstly to determine the accuracy of ultrasound calcaneal measurements in the prediction of bone mineral density determinations with dual-energy X-ray absorptiometry (DXA) of the lumbar spine (LS), femoral neck (FN), and Ward's triangle (FW) in a mixed population of 1000 women, unsorted as to diagnosis, and secondly to determine the accuracy of the various site-specific measurements in predicting each other. Ultrasound measurements [stiffness, speed of sound (SOS) and broadband ultrasound attenuation (BUA)] were made with the Lunar Achilles device, and the bone mineral density (BMD) of the LS, FN and FW were determined with the Lunar DPX. The data were analyzed for correlation, sensitivity, specificity, and accuracy of various paired sites. The coefficients of correlation of the young adult t-scores in the total group between calcaneal stiffness and BMDs of the LS, FN, and FW varied between 0.53 and 0.60. Coefficients for LS versus FN and FW were 0.70 and 0.62, respectively. A comparison of SOS and BUA values obtained at the calcaneus with BMDs of the LS, FN and FW yielded correlation coefficients that varied from 0.54 to 0.56. The general accuracy of prediction of one site by another ranged from 64.2% to 74.4%, where normality was defined as a t-score > -2. It is concluded that no site can predict the status of another site with sufficiently high accuracy to be clinically useful. The role of ultrasound transmission in bone as a predictor of fracture risk is theoretically promising, but has yet to be proved by a long term prospective study.

Absorptiometry, Photon↗
PubMed1988

Vitamin D and parotid gland function in the rat.

1. We previously reported that parotid gland secretion is decreased in rats deprived of vitamin D (Glijer, Peterfy & Tenenhouse, 1985). In the present study we examine whether this effect is a direct result of the absence of vitamin D or due to the secondary systemic effects of vitamin D deficiency. 2. Offspring of rats maintained on a calcium-supplemented (1.2%), vitamin-D-deficient diet were weaned onto the same diet and examined after 8 weeks. Using this method it was possible to maintain serum calcium and parathyroid hormone concentrations within normal limits. Serum 25-hydroxyvitamin D (25(OH)D3) was not detectable, but 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations were normal. 3. Pilocarpine-stimulated flow of parotid saliva was reduced 57% in vitamin-D-deprived animals, but amylase secretion was unchanged. Treatment with vitamin D3 returned flow rates to normal. 4. The concentration of calcium in parotid saliva was normal in vitamin-D-deprived rats, although total parotid calcium output was reduced 57%. 5. Pilocarpine-stimulated salivary flow from submandibular gland, a tissue which does not possess 1,25(OH)2D3 receptors, was normal in vitamin-D-deprived rats. 6. Heart rate and arterial blood pressure changes in response to I.V. pilocarpine administration were identical in normal and vitamin-D-deficient rats. 7. Auriculotemporal nerve-stimulated flow of parotid saliva was also reduced by 50% and administration of vitamin D3 to these rats corrected this abnormality. 8. It is concluded that fluid and electrolyte secretion from parotid gland is directly dependent on vitamin D; abnormal parotid gland function seen in vitamin-D-deficient rats is not due to secondary hypocalcaemia or hyperparathyroidism, nor can it be explained by haemodynamic changes evoked during systemic administration of pilocarpine. We further conclude that the metabolite of vitamin D responsible for this effect is not 1,25(OH)2D3.

Animals↗
PubMed1988

Parathyroid hormone desensitization in renal membranes of vitamin D-deficient rats is associated with a postreceptor defect.

We examined the characteristics of PTH resistance in vitamin D-deficient rats employing renal membranes in vitro. Homologous desensitization was characterized by diminished PTH-stimulated adenylate cyclase activity and was associated with a reduction in PTH-binding capacity, but not affinity. Heterologous desensitization was also seen, as manifested by decreased calcitonin (CT)-stimulated adenylate cyclase activity with normal CT receptor binding. The reduced capacity of the nonhormonal effectors NaF and guanylylimidodiphosphate to stimulate adenylate cyclase indicated a postreceptor defect at the level of the guanyl nucleotide-binding protein (G protein), whereas a normal forskolin response was consistent with a fully functional catalytic component. The G protein deficiency was confirmed by demonstrating that the addition of extracts of vitamin D-sufficient membranes to preparations of vitamin D-deficient membranes restored the normal responses to NaF and guanylylimidodiphosphate. In addition, cholera toxin- and pertussis toxin-catalyzed labeling of vitamin D-deficient renal membranes with [32P]NAD revealed a decrease in both the stimulatory and inhibitory binding proteins. Experiments with testicular membranes in vitro indicated that the adenylate cyclase abnormality was absent in tissue lacking PTH receptors. The results suggest that a major contribution to PTH resistance in vitamin D-deficient animals is a postreceptor defect at the level of the G proteins and that this defect is manifest only in tissue expressing the PTH receptor.

Adenosine Diphosphate Ribose↗
PubMed1985

The effect of vitamin D deficiency on secretion of saliva by rat parotid gland in vivo.

The role of vitamin D in parotid gland function was investigated by measuring the composition and rate of production of parotid saliva in response to pilocarpine injection in vitamin-D-deficient and replete rats in vivo. Rats fed a vitamin-D-free diet from weaning (G1) were studied after 8 weeks of diet at which time they had a decreased rate of growth, were hyperparathyroid and hypocalcaemic but still had detectable serum 1,25-dihydroxycholecalciferol (1,25(OH)2D3). Rats which were the offspring of vitamin-D-deficient mothers and which were maintained on a vitamin-D-free diet from weaning (G2) had a decreased rate of growth from birth, were hypocalcaemic and hyperparathyroid and at no time had any detectable serum 1,25(OH)2D3. In response to pilocarpine, the volume of parotid saliva produced by G1 animals was no different from the controls (G1 animals receiving supplemental vitamin D) whereas that produced by G2 animals was reduced more than 65%. The total amount of amylase secreted was unchanged in either group of experimental animals so that the concentration of amylase in the parotid saliva from G2 animals was increased. The concentration of calcium in parotid saliva changed in parallel with the changes in serum calcium in G1 and G2 animals. It is concluded that the primary source of parotid saliva calcium is the extracellular fluid and not zymogen granules and the transepithelial transport of this calcium is independent of vitamin D; the secretion of electrolytes and water, which in the parotid gland require extracellular calcium, is dependent on vitamin D. It is proposed that the vitamin is necessary for the synthesis of a protein(s) which is essential for the utilization of extracellular calcium in this secretion process.

Amylases↗
PubMed1985

Regulation of renal vitamin D hydroxylase activity in vitamin D deficient rats.

The regulation of renal mitochondrial 1-hydroxylase activity in chronic vitamin D deficiency was studied in male rats. These rats were born of mothers who had been raised from weaning (21 days) on a vitamin D deficient diet and who had no detectable serum 1,25-dihydroxycholecalciferol (1,25-(OH)2D) at the time their offspring were weaned (28 days). In the pups, renal mitochondrial 1-hydroxylase activity was undetectable before the 3rd week of life even though the animals were severely hypocalcemic from birth. The 1-hydroxylase activity first became detectable at 26 days of age, rapidly reached a maximum at day 34, then decreased to become undetectable again by 65 days. Throughout this time serum calcium concentration was less than 5.0 mg/dL and serum parathyroid hormone (PTH) concentration, measured by a midmolecule radioimmunoassay, was two- to five-fold greater than that found in vitamin D replete rats. 1-Hydroxylase activity could be restored in the +65-day-old animals by administration of a single dose of 2.5 micrograms vitamin D3. Enzyme activity was detected within 24 h, was maximal at 72 h, and returned to undetectable levels by 96 h after administration of the vitamin. Serum 1,25-(OH)2D which was undetectable before administration of the vitamin D3, was 108 and 458 pg/mL at 16 and 40 h, respectively, after the injection. The serum concentration of this metabolite then decreased progressively to 80 pg/mL by 6 days. 24-Hydroxylase activity first became detectable 48 h after vitamin D administration, increased to a maximum at 96 h, and thereafter decreased to become undetectable by 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1984

Decarboxylation of L-dopa and 5-hydroxytryptophan in dispersed rat pancreas acinar cells.

Amino acid decarboxylation activity in dispersed rat pancreas acinar cells and fractions derived by differential centrifugation of homogenate of these cells was studied. The rate of decarboxylation was measured by determining the rate of production of the [3H]-amine from [3H]-amino acid or the rate of production of 14CO2 from the [14C]-carboxy-labelled amino acid. Only the hydroxylated amino acids L-dopa and 5-hydroxytryptophan are decarboxylated by intact dispersed pancreas acinar cells or cell homogenates at all pH values and amino acid concentrations tested. The decarboxylase activity is located exclusively in the cell cytosol. Each substrate competitively inhibits the decarboxylation of the other and the decarboxylation of each is inhibited by NSD-1055. The estimated Km and Vmax are, for L-dopa, 4.8 X 10(-5) M and 2.5 nmol/mg protein/min and for 5-hydroxytryptophan, 2.9 X 10(-5) M and 0.3 nmol/mg protein/min. The pH optimum for 5-hydroxytryptophan decarboxylation is from 7.0-8.5 while that for L-dopa is 7.0. It is concluded that pancreas acinar cells possess a single aromatic amino acid decarboxylase specific for the hydroxylated amino acids L-dopa and 5-hydroxytryptophan, and which is similar in all properties studied to the aromatic amino acid decarboxylase found in several other mammalian tissues.

Animals↗
PubMed1983

Uptake, storage and secretion of 5-hydroxytryptamine and its amino acid precursor by dispersed rat pancreas acinar cells.

Rat pancreas acinar cells contain 5-hydroxytryptamine (5-HT; 10.86 +/- 2.52 ng/i.u. amylase), all of which can be accounted for by the 5-HT recovered from the zymogen granule fraction of these cells (10.70 +/- 3.06 ng/i.u. amylase). When incubated with [14C]5-HT dispersed acinar cells take up the amine and concentrate it in zymogen granules. These cells will also take up [14C]5-HTP (5-hydroxytryptophan), decarboxylate it and store the [14C]5-HT so produced in zymogen granules. 5-HTP itself is not taken up by the granules. 5-HT is incorporated into zymogen granules early in their formation; no amine is accumulated by mature zymogen granules and the amine within the mature granule is not exchangeable with extragranular amine. When dispersed acinar cells pre-labelled with [14C]5-HT and [3H]leucine are stimulated with caerulein, there is a synchronous increase in amylase activity and secretion of [14C]5-HT and [3H]protein; the ratios of [3H]protein/[14C]5-HT in zymogen granules and in the secretory products are identical. Pancreas acinar cells take up L-DOPA, decarboxylate it and store the dopamine produced in zymogen granules but the dopamine is not retained by the granules (t1/2 approximately equal to 90 min) and dopamine secretion from cells exposed to caerulein could not be demonstrated. It is concluded that 5-HT is a normal component of rat pancreas acinar cell zymogen granule. The granular amine has a turnover rate similar to that of granular protein and is released when the cells are stimulated to secrete protein. All the 5-HT released from the cell originates in zymogen granules.

5-Hydroxytryptophan↗
PubMed1982

Vitamin D receptors in isolated rat parotid gland acinar cells.

Rat parotid gland was examined for the presence of 1 alpha, 25-dihydroxycholecalciferol receptors using sucrose density gradient ultracentrifugation techniques. [3H] DHCC bound specifically and with high affinity to a 3.2 S protein present in nuclear and cytosolic fractions of isolated parotid acinar cells. Values for the equilibrium dissociation constant and for the receptor concentration were determined to be approx. 0.1 nM, and 12 fmol/mg protein, respectively. In competitive inhibition experiments, the 3.2 S protein displayed 100-fold lower affinity for 25-hydroxycholecalciferol than for DHCC, and did not bind estradiol or methylprednisolone. These results suggest that rat parotid gland acinar cells contain classical DHCC receptors. A similar approach failed to provide evidence of DHCC receptors in isolated pancreas acinar cells, lacrimal gland or submandibular gland. It has been previously reported that vitamin D is essential for normal exocrine secretion from the rat parotid gland (Tenenhouse, A. and Afari, G. (1978) Biochim. Biophys. Acta 538, 631-634). The present findings suggest that this effect is the result of a direct action of DHCC on the parotid gland acinar cell. The absence of DHCC receptors in other exocrine cells suggests that tissue sensitivity to DHCC is not a general property of exocrine systems.

Animals↗
PubMed1982

The effects of theophylline and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724) on protein secretion from rat parotid gland.

1 The effects of two chemically distinct cyclic nucleotide phosphodiesterase (PDE) inhibitors on protein secretion from superfused rat parotid gland were studied.2 In the presence of 1.0 mM Ca(2+), Ro 20-1724 (10 muM), an imidazolidinone derivative, increased the secretory response to isoprenaline 100% and the isoprenaline-dependent accumulation of adenosine cyclic 3',5'-monophosphate (cyclic AMP) 300-400%. At this concentration Ro 20-1724 alone did not cause protein secretion, accumulation of cyclic AMP or significantly inhibit PDE activity in cell-free preparations from parotid gland.3 In the absence of added Ca(2+) and in the presence of 1.0 mM EGTA, Ro 20-1724 inhibited the secretory response to isoprenaline 65% while increasing isoprenaline-dependent cyclic AMP accumulation 200%.4 In the presence of Ca(2+), theophylline (10 mM) stimulated protein secretion but did not cause the accumulation of cyclic AMP. When combined with isoprenaline the rate of secretion was greater than the sum of the effects of the individual drugs but there was no effect of theophylline on the isoprenaline-dependent accumulation of cyclic AMP.5 Theophylline-stimulated protein secretion is increased by omitting Ca(2+) from the superfusion medium without any detectable change in cyclic AMP accumulation. Under these conditions Ro 20-1724 inhibits theophylline-stimulated protein secretion and the maximum rate of protein secretion in the presence of isoprenaline and theophylline is no greater than that seen with either agent alone.6 It is concluded that the theophylline effects do not result from inhibition of PDE. It is suggested that the primary action of both drugs on parotid gland acinar cells is to alter the distribution of intracellular Ca(2+). Ro 20-1724 may also inhibit Ca(2+)/calmodulin activated enzymes such as PDE.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1978

Protein secretion from parotid glands of vitamin D deficient and glucocorticoid-treated rats.

The rate of isoproterenol stimulated secretion of protein from parotid glands of vitamin D deficient rats and rats treated with methylprednisolone was increased compared to the secretory response of tissue from control rats. It is suggested that the increased secretory response is secondary to a decreased capacity of mitochondria from the tissue of these animals to take up and store Ca2+; i.e. the mitochondria are less efficient buffers of cytoplasmic Ca2+. Under these conditions any process, such as protein secretion, which requires an increased cytoplasmic Ca2+ concentration will operate more effectively.

Animals↗