A comparison of muscle activation and knee mechanics during gait between patients with non-traumatic and post-traumatic knee osteoarthritis.

Objective: The objective was to compare muscle activation and knee mechanics during gait between participants with non-traumatic knee osteoarthritis (OA), post-traumatic knee OA, and healthy adults.

Design: Participants with non-traumatic knee OA (n = 22), post-traumatic knee OA (n = 19), and healthy adults (n = 22) completed gait trials for this observational, cross-sectional study. Post-traumatic OA group had a history of traumatic anterior cruciate ligament (ACL) rupture.

Interobserver variability of carotid Doppler peak velocity measurements among technologists in an ICAVL-accredited vascular laboratory.

Objective: This study was designed to investigate interobserver variability in the measurement of internal carotid artery (ICA) peak systolic velocity (PSV). We hypothesize that the reproducibility of repeated duplex scanning parameters, in the hands of very experienced vascular technologists in a laboratory accredited by the Intersocietal Commission for Accreditation of Vascular Laboratories, would be excellent.

Methods: Thirty-one patients underwent carotid duplex scanning by three vascular technologists using the same duplex scanning system.

Pamidronate prevents the development of skeletal metastasis in nude mice transplanted with human breast cancer cells by reducing tumor burden within bone.

Pamidronate is used routinely in the treatment of established bone metastasis. However, pamidronate has not yet been assessed in the prevention of osteolytic bone metastasis and its precise mechanism of action in this disorder remains to be established. In the present study, pamidronate or vehicle alone was administered subcutaneously to nude mice either simultaneously or as post intracardiac injection of the human breast cancer MDA-MB-231 cells.

The female sexual pain disorders: genital pain or sexual dysfunction?

Vaginismus and dyspareunia have been typically classified as sexual dysfunctions. In practice and research, this conceptualization has led to a focus on sexual and interpersonal issues after biological causes were excluded. Although this approach has been very useful, it has not led to significant theoretical or therapeutic progress in the last 20 years.

Brain somatostatin receptors are up-regulated in somatostatin-deficient mice.

The peptide somatostatin (SST) is widely synthesized in the brain and periphery and acts through a family of five receptors (SSTR1-5) to exert numerous effects. A gene product related to SST, cortistatin (CST), also interacts with SSTR1-5. Here we have investigated the regulation of SSTR1-5 and of CST in SST knockout (SSTKO) mice.

Mechanisms which mediate the antiapoptotic effects of angiopoietin-1 on endothelial cells.

The main objective of this study was to identify molecular mechanisms through which angiopoietin-1 (Ang-1), a ligand for Tie-2 receptors, influences endothelial cell apoptosis. Human umbilical vein endothelial cells were cultured in a medium enriched with 2% fetal bovine serum (FBS) and growth supplements. Apoptosis was induced over 24 h by reducing FBS to 0.

Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D.

The calcium-sensing receptor (CASR), expressed in parathyroid chief cells, thyroid C-cells, and cells of the kidney tubule, is essential for maintenance of calcium homeostasis. Here we show parathyroid, thyroid, and kidney CASR mRNA levels increased 2-fold at 15 h after intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in rats. Human thyroid C-cell (TT) and kidney proximal tubule cell (HKC) CASR gene transcription increased approximately 2-fold at 8 and 12 h after 1,25(OH)2D3 treatment.

Lessons learned: Outcomes and methodology of a coping skills intervention trial comparing individual and group formats for patients with cancer.

Objective: Nucare, a short-term psychoeducational coping skills training intervention was evaluated in a randomized controlled clinical trial (RCT) of 225 newly diagnosed breast and colon cancer patients.

Method: Measures of psychosocial distress, well being and optimism were evaluated every four months during a one-year period. Patients were randomized to one of four arms: Nucare presented in an individual basis; Nucare presented in a group format; a non-directive supportive group; and a no-intervention control.

An acceptor splice site mutation in the calcium-sensing receptor (CASR) gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

We studied family members of a large kindred expressing both familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) and found, by PCR amplification of the extracellular calcium-sensing receptor (CASR) gene exons and flanking intronic sequences, that FHH individuals were heterozygous for a g to t substitution in the last nucleotide of intron 2 (IVS2-1G>T). Defects in messenger RNA splicing were investigated by illegitimate transcription of the CASR gene in lymphoblastoid cells from an FHH affected individual, as well as by transfection of a CASR minigene harboring this mutation into HEK293 cells. The mutation resulted predominantly in exon III skipping causing a shift in exon IV reading frame and introduction of a premature stop codon leading to a predicted truncated protein of 153 amino acids.

A randomized comparison of group cognitive--behavioral therapy, surface electromyographic biofeedback, and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis.

This study compared group cognitive-behavioral therapy (12-week trial), surface electromyographic biofeedback (12-week trial), and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis. Subjects were 78 women randomly assigned to one of three treatment conditions and assessed at pretreatment, posttreatment and 6-month follow-up via gynecological examinations, structured interviews and standard questionnaires pertaining to pain (Pain Rating Index and Sensory scale of the McGill Pain Questionnaire, vestibular pain index, pain during intercourse), sexual function (Sexual History Form, frequency of intercourse, Information subscale of the Derogatis Sexual Functioning Inventory), and psychological adjustment (Brief Symptom Inventory). As compared with pretreatment, study completers of all treatment groups reported statistically significant reductions on pain measures at posttreatment and 6-month follow-up, although the vestibulectomy group was significantly more successful than the two other groups.

Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity.

Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear.

Extracellular calcium-sensing receptor is expressed in rat hepatocytes. coupling to intracellular calcium mobilization and stimulation of bile flow.

Liver cells respond to changes in Ca(2+)(o). The hepatic functions affected include bile secretion, metabolic activity, liver regeneration, and the response to xenobiotics. In the present study, we demonstrate the presence, in the liver, of the extracellular calcium-sensing receptor (CASR), described previously in the parathyroid and thyroid glands and kidney.

The vitamin D analogue EB 1089 prevents skeletal metastasis and prolongs survival time in nude mice transplanted with human breast cancer cells.

1,25-Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, its calcemic effect in vivo limits its therapeutic applications. Here, we report the efficacy of EB 1089, a low calcemic analogue of vitamin D, on the development of osteolytic bone metastases after intracardiac injection of the human breast cancer cell line MDA-MB-231 in nude mice.

A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo.

Urokinase plasminogen activator (uPA) plays an important role in the progression of several malignancies including breast cancer. We have identified a noncompetitive antagonist of the uPA-uPAR interaction derived from a nonreceptor binding region of uPA (amino acids 136-143). This 8-mer capped peptide (A6) inhibited breast cancer cell invasion and endothelial cell migration in a dose-dependent manner in vitro without altering cell doubling time.

Synthetic inhibitor of matrix metalloproteases decreases tumor growth and metastases in a syngeneic model of rat prostate cancer in vivo.

Members of the matrix metalloprotease (MMP) family are implicated in the progression of several malignancies including prostate cancer due to their ability to break down extracellular matrix (ECM) components. In this study, we have evaluated the ability of a synthetic MMP inhibitor (A-177430) to block tumor growth and metastases in a syngeneic model of rat prostate cancer. In an in vitro substrate assay, A-177430 exhibited nanomolar potency (IC(50) 2-6 nM) against the enzymatic activity of several MMPs.

Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers.

The existence of receptor dimers has been proposed for several G protein-coupled receptors. However, the question of whether G protein-coupled receptor dimers are necessary for activating or modulating normal receptor function is unclear. We address this question with somatostatin receptors (SSTRs) of which there are five distinct subtypes.

Regulation of acidification and apoptosis by SHP-1 and Bcl-2.

Recruitment of the SH2 domain containing cytoplasmic protein-tyrosine phosphatase SHP-1 to the membrane by somatostatin (SST) is an early event in its antiproliferative signaling that induces intracellular acidification-dependent apoptosis in breast cancer cells. Fas ligation also induces acidification-dependent apoptosis in a manner requiring the presence of SHP-1 at the membrane. Moreover, we have recently reported that SHP-1 is required not only for acidification, but also for apoptotic events that follow acidification (Thangaraju, M.

Regulation of urokinase production by androgens in human prostate cancer cells: effect on tumor growth and metastases in vivo.

During the complex multistep process of tumor progression, prostate cancer is initiated as an androgen-sensitive, nonmetastatic cancer, followed by a gradual transition into a highly metastatic and androgen-insensitive variety that lacks the expression of functional androgen receptors (AR). Urokinase (uPA), a member of the serine protease family, has been implicated in the progression of various human malignancies, including prostate cancer. Although uPA production is regulated by various growth factors and cytokines, the role of sex steroids (androgens) in regulating uPA gene expression in prostate cancer is poorly understood.

Proparathyroid hormone processing by the proprotein convertase-7: comparison with furin and assessment of modulation of parathyroid convertase messenger ribonucleic acid levels by calcium and 1,25-dihydroxyvitamin D3.

We previously showed that the processing of proparathyroid hormone (proPTH) to PTH was accomplished most efficiently by furin (17). Colocalization studies demonstrated that furin is expressed in the parathyroid, whereas proprotein convertase (PC)1 and PC2 are not. Since that time, another member of the PC family, called PC7, has been identified.

Reversal of hypercalcemia with the vitamin D analogue EB1089 in a human model of squamous cancer.

EB1089, an analogue of 1,25 dihydroxyvitamin D with low calcemic activity is a potent inhibitor of parathyroid hormone-related peptide (PTHRP) production in vitro. The purpose of the present study was to determine whether EB1089 could reverse established hypercalcemia in BALB C nude mice implanted s.c.

Src-dependence and pertussis-toxin sensitivity of urokinase receptor-dependent chemotaxis and cytoskeleton reorganization in rat smooth muscle cells.

The catalytically inactive precursor of urokinase-type plasminogen activator (pro-u-PA) induced a chemotactic response in rat smooth muscle cells (RSMC) through binding to the membrane receptor of urokinase (u-PA receptor [u-PAR]). A soluble form of u-PAR activated by chymotrypsin cleavage as well as a peptide located between domain 1 and 2 of u-PAR reproduced the effect of pro-u-PA on cell migration. The chemotactic pro-u-PA effect correlates with a dramatic reorganization of actin cytoskeleton, of adhesion plaques, and with major cell shape changes in RSMC.

Interdependent regulation of intracellular acidification and SHP-1 in apoptosis.

The G protein-coupled receptor agonist somatostatin (SST)-induces apoptosis in MCF-7 human breast cancer cells. This is associated with induction of wild-type p53, Bax, and an acidic endonuclease. We have shown recently that its cytotoxic signaling is mediated via membrane-associated SHP-1 and is dependent on decrease in intracellular pH (pHi) to 6.

Over-production of parathyroid hormone-related peptide results in increased osteolytic skeletal metastasis by prostate cancer cells in vivo.

Prostate carcinoma is one of the most common malignancies affecting males, resulting in a high rate of morbidity and mortality. This hormone-dependent malignancy is characteristically associated with a high incidence of osteoblastic skeletal lesions. However, osteolytic lesions invariably accompany blastic ones.

C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest.

Ligand-activated somatostatin receptors (SSTRs) initiate cytotoxic or cytostatic antiproliferative signals. We have previously shown that cytotoxicity leading to apoptosis was signaled solely via human (h) SSTR subtype 3, whereas the other four hSSTR subtypes initiated a cytostatic response that led to growth inhibition. In the present study we characterized the antiproliferative signaling mediated by hSSTR subtypes 1, 2, 4, and 5 in CHO-K1 cells.

Effect of nucleoside analogue BCH-4556 on prostate cancer growth and metastases in vitro and in vivo.

Prostate carcinoma is a common malignancy among males that results in high morbidity and mortality. Here, we have evaluated the capacity of nucleoside analogue BCH-4556 [beta-L-(-)-dioxolane-cytidine] to control prostate cancer progression in our syngeneic model of rat prostate cancer using the rat prostate cancer cell line Dunning R3227 Mat Ly Lu. Different concentrations (50 microM-1 mM) of BCH-4556 resulted in a marked decrease and, eventually, a complete arrest of Mat Ly Lu cell growth in vitro.