Evidence against a major genetic basis for combined breast and colorectal cancer susceptibility.
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Adult↗
Biomedical subjects
C Langman
Publications and source records attributed to C Langman.
Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos.
Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park). The nutritional composition of the diet for each species at each institution met probable dietary requirements. Blood samples were collected from each animal and analyzed for vitamin D metabolites 25(OH)D and 1,25(OH)(2)D, vitamin A (retinol, retinyl stearate, retinyl palmitate), vitamin E (alpha-tocopherol and gamma-tocopherol) and selected carotenoids. Family differences were found for 25(OH)D, retinol, retinyl stearate, retinyl palmitate and gamma-tocopherol. Species differences were found for all detectable measurements. Carotenoids were not detected in any species. The large number of animals contributing to these data, provides a substantial base for comparing the nutritional status of healthy animals and the differences among them.
Animals↗
A pilot study on the effects of exercise in patients with systemic lupus erythematosus.
OBJECTIVE: A pilot study was designed to assess the efficacy and safety of different exercise therapies on patient-reported fatigue and functional status. METHODS: Ten patients with systemic lupus erythematosus (SLE) were randomly placed in either an aerobic exercise group (group 1: n = 5) or a range of motion/muscle strengthening (ROM/MS) exercise group (group 2: n = 5). Outcome measures assessed at baseline and the end of the study were fatigue, functional status, disease activity, cardiovascular fitness, isometric strength, bone mineral density (BMD) of the lumbar spine and femoral neck, and parathyroid hormone and osteocalcin as representative bone biochemical markers for bone resorption and bone formation, respectively. RESULTS: Both aerobic and ROM/MS types of exercise were safe and did not worsen SLE disease activity. Patients in both exercise groups showed some improvement in fatigue, functional status, cardiovascular fitness, and muscle strength. Both groups showed increased bone turnover, but BMD was unchanged. Eighty percent of the patients met the compliance standard for the study. CONCLUSIONS: This pilot study shows the feasibility of exercise for SLE patients. The potential value of this approach shows promise in the routine management of these patients.
Activities of Daily Living↗
A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia.
Two heterozygous PTH/PTH-related peptide (PTHrP) receptor missense mutations were previously identified in patients with Jansen's metaphyseal chondrodysplasia (JMC), a rare form of short limb dwarfism associated with hypercalcemia and normal or undetectable levels of PTH and PTHrP. Both mutations, H223R and T410P, resulted in constitutive activation of the cAMP signaling pathway and provided a plausible explanation for the abnormalities in skeletal development and mineral ion homeostasis. In the present study we analyzed genomic DNA from four additional sporadic cases with JMC to search for novel activating mutations in the PTH/PTHrP receptor, to determine the frequency of the two previously identified missense mutations, H223R and T410P, and to determine whether different mutations present with different severity of the disease. The H223R mutation was identified in three novel JMC patients and is, therefore, to date the most frequent cause of JMC. In the fourth patient, a novel heterozygous missense mutation was found that changes isoleucine 458 in the receptor's seventh membrane-spanning region to arginine (I458R). In COS-7 cells expressing the human PTH/PTHrP receptor with the I458R mutation, basal cAMP accumulation was approximately 8 times higher than that in cells expressing the wild-type receptor despite impaired surface expression of the mutant receptor. Furthermore, the I458R mutant showed higher responsiveness to PTH than the wild-type receptor in its ability to activate both downstream effectors, adenylyl cyclase and phospholipase C. Like the H223R and the T410P mutants, the I458R mutant had no detectable effect on basal inositol phosphate accumulation. Overall, the patient with the I458R mutation exhibited clinical and biochemical abnormalities similar to those in patients with the previously identified H223R and T410P mutations.
Animals↗
Topical calcipotriene for morphea/linear scleroderma.
BACKGROUND: Morphea and linear scleroderma are characterized by erythema, induration, telangiectasia, and dyspigmentation. There is no universally effective treatment. Oral calcitriol has been beneficial in the treatment of localized and extensive morphea/scleroderma, but the use of topical calcipotriene has not been reported. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of topical calcipotriene 0.005% ointment in the treatment of localized scleroderma. METHODS: In a 3-month open-label study, 12 patients aged 12 to 38 years with biopsy-documented active morphea or linear scleroderma applied calcipotriene ointment under occlusion twice daily to plaques for 3 months. The condition of each patient had previously failed to respond to potent topical corticosteroids and, for some patients, systemic medications. Efficacy was assessed at baseline, 1 month, and 3 months. Levels of serum ionized calcium, intact parathyroid hormone, and 1,25-dihydroxyvitamin D and of random urinary calcium excretion were measured. RESULTS: During the 3-month trial, the condition of all 12 patients showed statistically significant improvement in all studied features. No adverse effects were reported or detected through laboratory monitoring of mineral metabolism. CONCLUSION: Topical calcipotriene 0.005% ointment may be an effective treatment for localized scleroderma, but double-blind placebo controlled studies are needed for confirmation.
Administration, Topical↗
Five osteocalcin assays compared: tracer specificity, fragment interference, and calibration.
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Antibody Specificity↗
Alterations in composition and function of surfactant associated with torpor in Sminthopsis crassicaudata.
Cold profoundly influences lung compliance in homeothermic mammals. Much of this effect has traditionally been attributed to the inactivation of the surfactant system. However, many mammals undergo large fluctuations in body temperature (heterothermic mammals). Here, the surfactant lipid composition and lung compliance of warm-active dunnarts (Sminthopsis crassicaudata) and the homeothermic mouse (Mus musculus) [body temperature (Tb) = 35-37 degrees C] were compared with those of dunnarts killed after 1,4 or 8 h of torpor (Tb < 20 degrees C). Lung compliance was measured before and after the removal of surfactant, and tissue compliance was determined by inflating the lung with saline. Relative to total phospholipid (PL), mouse surfactant contained proportionately less phosphatidylinositol but more cholesterol (Chol) and phosphatidylglycerol than that of the dunnart. Lung compliance was lower in dunnarts than in mice, consistent with an allometric effect. Surfactant levels, including total PL, Chol, and disaturated phospholipid (DSP) increased during torpor. The relative proportions of Chol and DSP increased after 4 and 8 h, respectively. In marked contrast to previous studies on the behavior of isolated lungs from homeothermic mammals, in our study the lung compliance of dunnarts remained unchanged throughout torpor. Tissue compliance decreased at 1 and 4 h of torpor, but this decrease was abolished by 8 h. It appears that the surfactant of the dunnarts counteracted the negative effect of tissue compliance at 1 and 4 h, an effect not present in homeothermic mammals. However, because lung compliance was maintained at 1 h of torpor in the absence of a compositional change in surfactant lipids, the changes in lipid composition observed at 4 and 8 h of torpor are thought to relate to functions of surfactant other than that of maintaining lung compliance.
Animals↗
Childhood uremic bone disease.
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Chronic Kidney Disease-Mineral and Bone Disorder↗
Chronic DOCA treatment increases Ca absorption: role of hypercalciuria and vitamin D.
To examine the effects of mineralocorticoidism on calcium (Ca) absorption and to define the mechanism, rats received a high-salt diet and injections of vehicle or deoxycorticosterone acetate (DOCA). Net (44.2 vs. 31.4 mg/day) and percent Ca absorption (28.1 vs. 20.1%) was increased after 5 days of DOCA. This was associated with increased duodenal 45Ca uptake. Thus despite the hypercalciuria, Ca balance was similar. Although the hypercalciuria persisted chronically, the gut effects were sustained, which maintained normal ionized Ca, bone Ca, and Ca balance. Urinary cyclic adenosine monophosphate was elevated by DOCA. Compared with appropriate controls, neither DOCA alone nor polydipsia (elicited by dextrose) produced similar magnitudes of hypercalciuria as DOCA plus high-salt diet. These maneuvers also failed to increase Ca absorption. Neutralization of the metabolic alkalosis neither attenuated the DOCA-induced hypercalciuria nor abolished the Ca hyperabsorption. In vitamin D-deprived rats, the hypercalciuria but not the intestinal effects of DOCA were reproduced. Serum 1,25-dihydroxyvitamin D3 levels were increased during chronic DOCA treatment (224 vs. 139 pg/ml). These data best fit the hypothesis that increased Ca absorption is secondary to the calciuric effects of DOCA and high-salt diet and is mediated via the increased parathyroid hormone and 1,25-dihydroxyvitamin D3 activities.
Alkalosis↗
Pathophysiology of spontaneous hypercalciuria in laboratory rats. Role of deranged vitamin D metabolism.
Recent data suggest a causal role of deranged 1,25(OH)2D metabolism in the syndrome of idiopathic hypercalciuria. To test this hypothesis, we evaluated if vitamin D availability and/or increased serum 1,25(OH)2D were critical for the expression of hypercalciuria in laboratory rats. Ca balance, serum 25OHD3, and 1,25(OH)2D3 were studied in D-deprived (-D) and D-repleted (+D) male progeny (p) born to normocalciuric (NC) and spontaneously hypercalciuric (SH) rats. 7 of the 14 pSH and 2 of 21 pNC had SH, which was defined as urinary Ca greater than two standard deviations above the mean of values for control animals on days 5 and 6 of a low Ca +D diet (1.19 vs. 0.58 mg/d, P less than 0.001). Fasting serum Ca and 25OHD3 were similar to control. Serum 1,25(OH)2D3 was elevated in these nine SH rats (232 vs. 145 pg/ml, P less than 0.005). However, during vitamin D deprivation, their Ca excretion was also increased (1.53 vs. 0.45 mg/d, P less than 0.001), despite comparably reduced serum 1,25(OH)2D3 (102 vs. 106 pg/ml) and undetectable serum 25OHD3. Net intestinal Ca absorption on a low Ca diet was comparable during D repletion (-0.75 vs. -0.82 mg/d) or D deprivation (-0.80 vs. -2.15 mg/d), excluding primary hyperabsorption as the mediator of the hypercalciuria. Mild hypophosphatemia was present in SH on +D (5.8 vs. 6.9 mg/dl, P less than 0.005) and -D diets (6.2 vs. 7.9 mg/dl, P less than 0.005), and was associated with higher rates of cyclic adenosine monophosphate excretion (32.8 vs. 26.9 and 48.5 vs. 41.0 nmol/mg of creatinine, respectively). Spontaneous hypercalciuria is therefore dissociable from increased Ca absorption, serum levels of 25OHD3, or 1,25(OH)2D3. The data are most compatible with the hypothesis of a renal Ca leak which stimulates parathyroid hormone activity and increases serum 1,25(OH)2D3, if provided adequate 25OHD3 as substrate.
Animals↗
Renal histopathological changes in a child with Laurence-Moon-Biedl syndrome.
This report describes a case of Laurence-Moon-Biedl syndrome identified in a 24-month-old boy. Significant renal involvement was present with right-sided vesicoureteral reflux, cystocele, urinary tract infections, and growth arrest of the right kidney. After the development of hypertension a left renal biopsy was performed to determine if bilateral renal disease was present. Histopathological and ultrastructural changes in the left kidney are described. These changes appear to be unrelated to pyelonephritis or hypertension and to be most consistent with the nephropathy of Laurence-Moon-Biedl syndrome.
Humans↗
Cardiovascular response to mental stress in normal adolescents with hypertensive parents. Hemodynamics and mental stress in adolescents.
The hemodynamic response to mental stress (mental arithmetic) was studied in adolscents with varying risk factors for essential hypertension (EH), One group (genetic) consisted of normotensive well adolescents who had at least one parentnt with EH. Another group (labile) consisted of adolescents with labile hypertension each of whom also had at least one pare with EH. The control population consisted of normotensive adolescents with a negative family history of EH. Subjects with labile hypertension demonstrated a sustained increase in systolic and diastolic pressure and heart rate during stress. This response was significantly different than the control population (P less than THE CONTROL POPULATION (P LESS THAN 0.001). The stress response of the normotensive genetic population was qualitatively similar to the group with labile hypertension and significantly different than the controls in diastolic pressure and heart rate (p less than 0.001, less than 0.02). Post-stress plasma catecholamines were higher in the labile hypertensive and genetic groups than in the control group. These findings demonstrate increased central nervous system mediated adrenergic activity and cardiovascular response in labile hypertension and also in some normotensive subjects with a genetic risk for hypertension.
Adolescent↗