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L M Demers

Publications and source records attributed to L M Demers.

At least 19 recordsLinked to original sources
PubMed2004

Acute effects of moderate intensity resistance exercise on bone cell activity.

Resistance exercise has positive effects on bone mass, but little is known about the mechanisms by which this occurs. The purpose of this study was to determine if a single bout of moderate intensity resistance exercise alters biochemical markers of bone cell activity. Indices of bone turnover were measured in nine healthy, untrained men (21.9 +/- 1.2 yrs old), before and following a single 45 minute session of resistance exercise, and during a control trial. A cross-over design was used so that all participants performed both trials in random order. Blood samples were collected immediately before, immediately after, and at 1, 8, 24, and 48 hours post exercise and analyzed for bone-specific alkaline phosphatase (BAP), type I collagen propeptide (PICP), and type I collagen N-telopeptide (sNTX). Urine from the second morning void was collected over four days (day before, day of, and two days following exercise) and analyzed for type I collagen N-telopeptide (uNTX). Exercise resulted in a significant increase (p < 0.05) in the ratio of biochemical markers of bone formation to bone resorption eight hours post exercise, largely due to a decrease in sNTX. Markers return to baseline within 24 hrs. These data suggest that moderate intensity resistance training acutely reduces bone resorption, leading to a favorable change in overall bone turnover, for at least 8 hours post exercise in untrained young men. Further work is needed to determine if long-term benefits to bone strength follow with persistent training.

Adult↗
PubMed2004

Baseline serum NTx levels are prognostic in metastatic breast cancer patients with bone-only metastasis.

BACKGROUND: There is significant heterogeneity in survival of patients with metastatic breast cancer who have bone-only metastasis. We studied the correlation of serum N-telopeptide (NTx), a marker of bone resorption, and its correlation with clinical outcomes in patients with metastatic breast cancer with bone-only or bone plus soft tissue metastasis. PATIENTS AND METHODS: Serum was taken from 250 metastatic breast cancer patients with bone-only or bone plus soft tissue metastasis who participated in two similar randomized studies of second-line hormone therapy. An enzyme-linked immunosorbent assay specific for NTx of type I bone collagen was used to detect serum levels. RESULTS: Sixty patients (24%) had elevated serum NTx levels, using the mean + 2 standard deviations (26 nanomoles Bone Collagen Equivalents per liter) of healthy women as a cut-off. The median duration of clinical benefit was significantly shorter in the group with elevated serum NTx levels compared with the group that had normal serum NTx levels (P=0.0004). Time to progression (TTP) was also significantly shorter in the patients with elevated serum NTx at 139 days compared with 220 days (P=0.0006). Median survival was also significantly shorter in patients with elevated baseline serum NTx levels at 663 days compared with 941 days (P<0.0001). CONCLUSION: In this study, breast cancer patients with bone-only or bone plus soft tissue metastasis and elevated serum NTx levels have a shorter duration of clinical benefit, TTP and overall survival.

Adult↗
PubMed2002

Direct patterning of modified oligonucleotides on metals and insulators by dip-pen nanolithography.

The use of direct-write dip-pen nanolithography (DPN) to generate covalently anchored, nanoscale patterns of oligonucleotides on both metallic and insulating substrates is described. Modification of DNA with hexanethiol groups allowed patterning on gold, and oligonucleotides bearing 5'-terminal acrylamide groups could be patterned on derivatized silica. Feature sizes ranging from many micrometers to less than 100 nanometers were achieved, and the resulting patterns exhibited the sequence-specific binding properties of the DNA from which they were composed. The patterns can be used to direct the assembly of individual oligonucleotide-modified particles on a surface, and the deposition of multiple DNA sequences in a single array is demonstrated.

Adsorption↗
PubMed2001

The potential role of estrogen in aromatase regulation in the breast.

Aromatase is expressed in both normal and malignant breast tissues. Aromatase activity in the breast varies over a wide range. Our previous studies have demonstrated that in situ aromatization contributes to the estrogen content of breast tumors to a major extent. Consequently, alterations of aromatase activity could serve as a major determinant of tissue estradiol content. However, the mechanisms and extent of aromatase regulation in breast tissues have not been fully established. We have observed an inverse correlation between tumor aromatase activity and estrogen content in nude mice bearing xenografts of MCF-7 cells transfected with the aromatase gene. To investigate the potential role of estrogen in aromatase regulation in the breast, studies were carried out in an in vitro model. In this model, MCF-7 cells were cultured long term in estrogen-deprived medium and called by the acronym, LTED cells. We found that long-term estrogen deprivation enhanced aromatase activity by 3-4-fold when compared to the wild-type MCF-7 cells. Re-exposure of LTED cells to estrogen reduced aromatase activity to the levels of the wild-type MCF-7 cells. We also measured aromatase activity in 101 frozen breast carcinoma specimens and compared tumor aromatase activities in pre-menopausal patients versus post-menopausal patients and in post-menopausal patients with or without hormone replacement therapy (HRT). Although statistically not significant, there was a trend paralleling that observed in the in vitro studies. Aromatase activity was higher in breast cancer tissues from the patients with lower circulating estrogen levels. Our data suggest that estrogen may be involved in the regulation of aromatase activity in breast tissues.

Animals↗
PubMed2001

Bioavailable testosterone as a correlate of cognition, psychological status, quality of life, and sexual function in aging males: implications for testosterone replacement therapy.

Andropause is a syndrome described in aging males, is composed of a constellation of physical, sexual, and emotional symptoms, and is thought to be related to declining concentrations of serum testosterone. Numerous studies of testosterone replacement therapy in elderly hypogonadal males have documented the physical benefits of such treatment, but have failed to assess cognition, psychological functioning, and quality of life. Male outpatients greater or equal to 55 years of age completed cognitive, psychological, sexual, and quality of life assessments. A serum sample was provided for bioavailable testosterone assay. The associations between bioavailable testosterone concentrations and neuropsychological testing were assessed using Spearman rank correlation. Overall, bioavailable testosterone was not an important determinant of cognitive, psychological, or sexual functioning or of quality of life. The implications for future studies involving testosterone replacement therapy are discussed.

Aged↗
PubMed2001

Bone markers in the management of metastatic bone disease.

Newer markers of bone formation and bone resorption are now available. Alone these new markers do not appear to be useful to diagnose metastatic bone disease. Several markers appear to be of prognostic importance and correlate with the extent of tumour in the skeleton. Serial monitoring of bone markers may be useful to monitor the efficacy of bisphosphonate and/or systemic therapy of both lytic and blastic bone metastases.

Biomarkers↗
PubMed2000

A fluorescence-based method for determining the surface coverage and hybridization efficiency of thiol-capped oligonucleotides bound to gold thin films and nanoparticles.

Using a fluorescence-based method, we have determined the number of thiol-derivatized single-stranded oligonucleotides bound to gold nanoparticles and their extent of hybridization with complementary oligonucleotides in solution. Oligonucleotide surface coverages of hexanethiol 12-mer oligonucleotides on gold nanoparticles (34 +/- 1 pmol/cm2) were significantly higher than on planar gold thin films (18 +/- 3 pmol/cm2), while the percentage of hybridizable strands on the gold nanoparticles (1.3 +/- 0.3 pmol/cm2, 4%) was lower than for gold thin films (6 +/- 2 pmol/cm2, 33%). A gradual increase in electrolyte concentration over the course of oligonucleotide deposition significantly increases surface coverage and consequently particle stability. In addition, oligonucleotide spacer sequences improve the hybridization efficiency of oligonucleotide-modified nanoparticles from approximately 4 to 44%. The surface coverage of recognition strands can be tailored using coadsorbed diluent oligonucleotides. This provides a means of indirectly controlling the average number of hybridized strands per nanoparticle. The work presented here has important implications with regard to understanding interactions between modified oligonucleotides and metal nanoparticles, as well as optimizing the sensitivity of gold nanoparticle-based oligonucleotide detection methods.

Gold↗
PubMed2000

Biochemical markers and skeletal metastases.

BACKGROUND: Skeletal metastases are common occurrences in patients with malignancies such as breast and prostate carcinoma, but they are difficult to diagnose nonradiologically, and treatment is difficult to follow clinically. Recent developments suggest that biochemical markers of bone remodeling, such as the bone collagen breakdown product N-telopeptide and the bone formation marker known as bone specific alkaline phosphatase, hold great promise as clinical tools for the management of patients with metastatic bone disease. METHODS: Serum levels of the bone formation marker known as bone specific alkaline phosphatase (BAP), along with serum levels of the bone collagen breakdown product carboxyterminal telopeptide of Type I collagen (ICTP) and urine levels of pyridinoline (PYD), deoxypridinoline (DPD), and N-telopeptide (NTx), were measured in a large cohort of patients with newly diagnosed or progressive cancer of the breast, prostate, lung, and other sites. Bone marker levels were correlated with the presence or absence of bone scan-documented metastases; metastatic disease extension in terms of the number of skeletal sites involved; and the type of lesion, whether blastic or lytic. Sites examined included the pelvis, spine, skull, ribs, and long bones. RESULTS: All of the bone markers examined, including BAP and NTx, were abnormally elevated in a high proportion of patients with confirmed metastases to bone. Urine NTx levels and bone specific alkaline phosphatase were significantly correlated with the number of skeletal sites involved, and a significant correlation between marker level and extent of skeletal involvement was also observed. In addition, both markers were higher in patients with a blastic disease presentation than in patients with osteolytic lesions. CONCLUSIONS: Biochemical markers of bone resorption and bone formation are abnormally raised in the blood and urine of patients with metastatic bone disease. Markers of bone collagen breakdown, such as N-telopeptide, as well as markers of osteoblast function, such as bone specific alkaline phosphatase, appear to be of use in assessing and managing patients with malignancies that metastasize to bone. In this study, both NTx and BAP showed a significant correlation with both the presence of bone metastases and the extent of skeletal involvement. Biochemical markers of bone remodeling can also be used to guide decision making regarding the treatment of metastatic bone disease and to determine the effectiveness of therapy for patients with cancer to bone whose broad-based symptoms make it difficult to discern true response to therapy.

Alkaline Phosphatase↗
PubMed2000

Impairment of NF-kappaB activation and modulation of gene expression by calpastatin.

To address the involvement of the calpain system in both basal and silica-induced nuclear factor (NF)-kappaB activation, several human bronchial epithelial cell lines were established in which an intracellular inhibitor of calpain, calpastatin, was stably expressed. Reduced basal and silica-induced inhibitor (IkappaBalpha) degradation and NF-kappaB activation were observed in cells stably overexpressing calpastatin. In addition, the cells in which calpain was constitutively inhibited by the overexpression of calpastatin exhibited a notable morphological change. Whereas empty vector-transfected cells displayed a morphology indistinguishable from that of parental cells, cells overexpressing calpastatin exhibited a mosaic morphological change with reduced formation of lamella 30 min after the cells were seeded. Genefilter microarray experiments, in which 3,965 human genes can be evaluated for their expression at the same time, showed that calpastatin downregulated genes encoding several membrane-associated proteins or nuclear proteins and upregulated genes of collagen alpha2, DAZ, and mitochondrial capsule selenoprotein. These results suggest that, in addition to their proteolytic activities on cytoskeletal proteins and other cellular regulatory proteins, calpain-calpastatin systems can also affect the expression levels of genes encoding structural or regulatory proteins.

Adrenergic beta-Agonists↗
PubMed2000

Rapid maturation of the reproductive axis during perimenarche independent of body composition.

The development of the reproductive axis is thought to be a gradual process, but our understanding of the complex endocrine changes that accompany the transition from premenarche to reproductive life in women has been hampered by the paucity of longitudinal studies. We studied 112 premenarchal Caucasian females at 6-month intervals over 4 yr and obtained a detailed reproductive and dietary history. We quantified reproductive hormones in 24-h urine collections as a measure of daily output and measured body composition biometrically and with the use of dual energy x-ray absortiometry scans. The percent body fat did not change appreciably in the study period (range, 21-24%) and was unrelated to menarche. Sex steroid and gonadotropin levels changed exponentially in the year approaching menarche. FSH levels peaked at menarche and then progressively declined thereafter. Estradiol output increased rapidly in the year approaching menarche and then plateaued thereafter. The frequency of menstrual bleeding increased rapidly and plateaued at 1 yr postmenarche. At 1 yr, 65% of these adolescent women had established a pattern of 10 or more menstrual episodes/yr, and by 3 yr postmenarche this figure exceeded 90%. There were no significant changes in dietary intake of protein, carbohydrate, or fat in the same period. Menarche occurs as a result of rapid maturation of the reproductive axis and heralds the reestablishment of a negative sex steroid feedback loop that parallels the adult threshold. These events appear to develop independent of changes in body composition and diet, but may reflect the improved nutrition and socioeconomic status of the late 20th century.

Adipose Tissue↗
PubMed1999

Involvement of 5'-flanking kappaB-like sites within bcl-x gene in silica-induced Bcl-x expression.

The present study investigated the involvement of the transcription factor NF-kappaB in the expression of an anti-apoptotic gene, bcl-x, using a murine macrophage cell line and peritoneal macrophages from both wild type (p50(+/+)) and NF-kappaB p50 gene knockout (p50(-/-)) mice. Increased expression of Bcl-x protein was observed in native and silica-exposed p50(-/-) macrophages in which the NF-kappaB p65-containing complex was predominantly induced. Co-transfection experiment using a bcl-x promoter reporter construct and an expression vector for NF-kappaB p50 or p65 indicates that p65, but not p50, up-regulates the promoter activity of the bcl-x gene. DNA sequence analysis revealed that there are several kappaB-like sites within the 5'-flanking region of the bcl-x gene. Electrophoretic mobility shift assay suggested differences in binding of the NF-kappaB complexes to these putative NF-kappaB binding sites of the bcl-x gene.

Animals↗
PubMed1999

Vanadate induction of NF-kappaB involves IkappaB kinase beta and SAPK/ERK kinase 1 in macrophages.

The present studies investigated the signaling pathways of vanadate, a vanadium ion with +5 oxidation state, to activate NF-kappaB transcription factor, a pivotal regulator of inflammatory responses. Treatment of macrophages with vanadate results in the activation of both NF-kappaB and c-Jun N-terminal kinase (JNK). The activity of a recently identified cellular kinase, IkappaB kinase-beta (IKKbeta), was significantly elevated concomitant with the increased degradation of IkappaBalpha and enhanced NF-kappaB activity in cells exposed to vanadate. To determine whether the IKK pathway and JNK pathway are interconnected or bifurcate upon vanadate stimulation, cells were transfected with either a kinase inactive form of IKKbeta or a kinase inactive form of SAPK/ERK kinase 1 (SEK1). Inactive IKKbeta was able to block vanadate-induced degradation of IkappaBalpha, yet it was unable to influence the activation of JNK by vanadate. Conversely, blockage of JNK activation by transfection of a kinase-inactive form of SEK1 resulted in partially inhibition of vanadate-induced IkappaBalpha degradation. Both vanadate-induced degradation of IkappaBalpha and activation of JNK were potently inhibited by pretreatment of cells with N-acetylcysteine or dimercaprol. These results demonstrate that early activation of stress kinases or change of cellular redox states plays a key role in vanadate-induced activation of NF-kappaB and JNK.

Animals↗
PubMed1999

Effect of the potent aromatase inhibitor fadrozole hydrochloride (CGS 16949A) in postmenopausal women with breast carcinoma.

BACKGROUND: Fadrozole hydrochloride (CGS 16949A) is a highly potent, nonsteroidal aromatase inhibitor that significantly lowers estrogen levels in postmenopausal women and can be effective therapy for patients with advanced hormone-dependent breast carcinoma. Circulating estradiol, estrone, and estrone sulfate are reduced to undetectable levels within weeks of the initiation of therapy. Before this study, it was not known whether this decrease in serum estrogen levels results in altered parameters associated with cardiovascular disease. The authors examined the levels of several critical blood parameters that are important to cardiovascular risk for heart disease and thromboembolic disorders in patients treated with fadrozole. METHODS: Cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), antithrombin III, protein C, protein S, and fibrinogen were serially measured in 21 postmenopausal women with advanced breast carcinoma treated with various doses of fadrozole (1.8 mg/day, n=3; 2.0 mg/day, n=13; 4.0 mg/day, n=5) over 3-24 months (mean, 15.8 months). A repeated measure analysis of variance was applied to each cardiovascular variable to assess changes in the response over time. Analyses were performed separately for each dose group and were also pooled over the dose groups. RESULTS: There was no statistically significant change over time in lipid parameters, namely, total cholesterol (P=0.57), triglyceride (P=0.27), LDL (P=0.99), HDL (P=0.30), and VLDL (P=0.43), over the 24 months of therapy. There were also no significant changes in coagulation factors, namely, antithrombin III (P=0.41), protein C (P=0.49), or protein S (P=0.31), over the 24 months. However, an increase in fibrinogen that occurred over time did reach statistical significance (P=0.011). CONCLUSIONS: With the exception of acute phase reactant fibrinogen, this study did not identify an increase in parameters associated with cardiovascular disease in women treated with fadrozole, a potent aromatase inhibitor.

Aged↗