First Clinical Results of a New Generation of Ablative Solid-State Lasers.

In the early 2000s, solid-state lasers emerged as an alternative technology to excimer systems in refractive surgery. Despite some technological limits at the time, good clinical results could be achieved with solid-state laser systems. This prospective case series reports clinical outcomes of five eyes treated with a newly developed solid-state laser system (AquariuZ) in three patients.

Longitudinal Effects of Teriparatide or Zoledronic Acid on Bone Modeling- and Remodeling-Based Formation in the SHOTZ Study.

Previously, we reported on bone histomorphometry, biochemical markers, and bone mineral density distribution after 6 and 24 months of treatment with teriparatide (TPTD) or zoledronic acid (ZOL) in the SHOTZ study. The study included a 12-month primary study period, with treatment (TPTD 20 μg/d by subcutaneous injection or ZOL 5 mg/yr by intravenous infusion) randomized and double-blind until the month 6 biopsy (TPTD, n = 28; ZOL, n = 30 evaluable), then open-label, with an optional 12-month extension receiving the original treatment. A second biopsy (TPTD, n = 10; ZOL, n = 9) was collected from the contralateral side at month 24.

Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab: A Longitudinal Analysis From Baseline to 3 Months in the AVA Study.

There has been renewed interest of late in the role of modeling-based formation (MBF) during osteoporosis therapy. Here we describe early effects of an established anabolic (teriparatide) versus antiresorptive (denosumab) agent on remodeling-based formation (RBF), MBF, and overflow MBF (oMBF) in human transiliac bone biopsies. Postmenopausal women with osteoporosis received subcutaneous teriparatide (n = 33, 20 μg/d) or denosumab (n = 36, 60 mg once/6 months), open-label for 6 months at 7 US and Canadian sites.

Differential Effects of Teriparatide and Zoledronic Acid on Bone Mineralization Density Distribution at 6 and 24 Months in the SHOTZ Study.

The Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study assessed the progressive effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone remodeling and material properties in postmenopausal women with osteoporosis. Previously, we reported that biochemical and histomorphometric bone formation indices were significantly higher in patients receiving TPTD versus ZOL. Here we report bone mineralization density distribution (BMDD) results based on quantitative backscattered electron imaging (qBEI).

Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study.

We compared effects of teriparatide and denosumab on PTH, bone turnover markers, and bone histomorphometry in osteoporotic postmenopausal women. The findings were inconsistent with an early indirect anabolic effect of denosumab.

A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial.

Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 μg/day (s.c.

Characteristics of Latinas in Puerto Rico and the US mainland receiving teriparatide in the DANCE observational study.

Objective: The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study investigated the use of teriparatide in men and women with osteoporosis in the United States (US) and Puerto Rico (PR). In a sub-analysis, we evaluated whether the baseline characteristics of Latinas differed from those of white women in the study population and whether any patient attributes affected physicians' decisions to prescribe teriparatide.

Methods: We assessed 3 patient cohorts treated with teriparatide 20 microg once daily for up to 24 months: 1) PR Latinas, 2) US Latinas, and 3) white women on the US mainland (white women).

Assessing the Effects of Teriparatide Treatment on Bone Mineral Density, Bone Microarchitecture, and Bone Strength.

Background: To gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.

Methods: In this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.

The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study: 2-year nonvertebral fragility fracture results.

Unlabelled: This observational study evaluated the occurrence of nonvertebral fragility fractures (NVFX) in over 4,000 men and women with osteoporosis treated with teriparatide (TPTD). The incidence of new NVFX decreased for patients receiving TPTD treatment for greater than 6 months. No new significant safety findings were observed in this large trial.

Skeletal histomorphometry in subjects on teriparatide or zoledronic acid therapy (SHOTZ) study: a randomized controlled trial.

Context: Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling.

Objective: We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL).

Design: This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study.

Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis.

Purpose: Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 μg/day subcutaneous) who had (99m)Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy).

Methods: Women were injected with 600 MBq (99m)Tc-MDP, and diagnostic bone scan images were assessed at 3.

Gender differences for initiating teriparatide therapy: baseline data from the Direct Assessment of Nonvertebral Fracture in the Community Experience (DANCE) study.

Unlabelled: The prospective, observational Direct Assessment of Nonvertebral Fracture in the Community Experience (DANCE) study shows that, among patients with risk factors for osteoporosis, women are more likely to be screened and to receive appropriate treatment than men. There needs to be greater awareness that osteoporosis affects both men and women.

Introduction: The prospective, observational DANCE study evaluated teriparatide use in the mainland USA and Puerto Rico in patients with osteoporosis in a community setting.

Dynamic equilibrium between calcineurin and kinase activities regulates the phosphorylation state and localization of the nuclear factor of activated T-cells.

The nuclear factor of activated T-cells (NFATp) is a phosphorylated transcription factor that resides in the cytoplasm of unactivated T-cells. T-cell activation results in the activation of the phosphatase calcineurin (CaN), which leads to the dephosphorylation and subsequent nuclear localization of NFATp. We have investigated the role of kinases in the phosphorylation state and subcellular localization of NFATp.

Direct demonstration of NFATp dephosphorylation and nuclear localization in activated HT-2 cells using a specific NFATp polyclonal antibody.

Nuclear factor of activated T cells (NFAT) regulates transcription of a number of cytokine genes, and NFAT DNA binding activity is stimulated following T cell activation. Several lines of evidence have suggested that NFAT is a substrate for calcineurin, a serine/threonine phosphatase. Using a polyclonal antibody to murine NFATp, Western blot analysis of various mouse tissues demonstrated that the 110-130-kDa NFATp protein was highly expressed in thymus and spleen.

A soluble binding assay for measuring 3H-FK506 binding to the hsp56 immunophilin.

Heat shock protein 56 (hsp56) was previously identified as an immunophilin based on its ability to specifically bind to FK506-Affi-Gel 10. In this report, we have quantitated human Jurkat T cell hsp56 binding to 3H-FK506, as well as to the immunosuppressant rapamycin. Binding was measured utilizing immunoadsorbed hsp56, and, in addition, we demonstrate that 3H-FK506 binds to hsp56 in solution.

Tissue distribution and cellular localization of hsp56, an FK506-binding protein. Characterization using a highly specific polyclonal antibody.

Heat shock protein 56 (hsp56) has been shown to be involved in two cellular pathways, as an immunophilin for FK506 and as a component of steroid receptor complexes. To help define its role in these cellular pathways, we have developed UPJ56, a polyclonal antibody raised against hsp56 purified from Jurkat cells. In Western blot experiments, hsp56 was highly expressed in rat thymus, liver, and spleen, with low levels in lung and muscle.

Alpha-thrombin stimulates nuclear diglyceride levels and differential nuclear localization of protein kinase C isozymes in IIC9 cells.

The mechanism by which an agonist, binding to a cell surface receptor, exerts an effect on events in the nucleus is not known. We have previously shown (Leach, K. L.

FKBP-12 is not an inhibitor of protein kinase C.

It was recently noted that the amino acid sequence of FK506 binding protein (FKBP-12) is nearly identical to that of an endogenous inhibitor of protein kinase C, PKCI-2. To follow up on this observation, we have tested the hypothesis that FKBP-12 is an inhibitor of PKC. The kinase activity of rat brain protein kinase C (PKC) was not inhibited by the presence of up to 700 micrograms recombinant human FKBP-12 per ml, in either the presence or absence of FK506.

The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13.

Extracts from human Jurkat cells or from calf thymus contain a 60-kDa protein that is bound to immobilized FK506. As expected, the NH2-terminal sequences of the 60-kDa protein from these two species were found to be nearly the same. We were surprised to discover, however, that the sequence of the human protein was identical to that of Hsp56, a heat shock protein of unknown function that has been shown to be a component of several steroid receptor complexes.

Dissociation of protein kinase C activation and sn-1,2-diacylglycerol formation. Comparison of phosphatidylinositol- and phosphatidylcholine-derived diglycerides in alpha-thrombin-stimulated fibroblasts.

Diacylglycerols (DAGs) derived from phosphatidylcholine (PC) hydrolysis have been shown to activate protein kinase C (PKC) in vitro, but it is not known whether this event occurs in response to DAGs generated via agonist-induced PC hydrolysis in intact cells. In this report we have addressed this question directly, using alpha-thrombin stimulation of IIC9 fibroblasts. PKC activation in intact cells was assessed in two ways, by measuring: 1) PKC membrane association as determined by kinase activity and Western blot analysis and 2) the phosphorylation of an endogenous PKC substrate, an 80-kDa protein.

Increased PKA and PKC activities accompany neuronal differentiation of NT2/D1 cells.

After retinoic acid treatment, a large percentage of cells of the human embryonal carcinoma cell line NT2/D1 differentiate into neuronal cells. We demonstrate here that the differentiated cells, but not the undifferentiated cells, contain high levels of neurofilament mRNA. We have also measured mRNA, protein, and activity levels of two kinases, cAMP-dependent protein kinase (PKA) and protein kinase C (PKC), in order to explore the role of protein kinases in the establishment of the differentiated state.

Type 3 protein kinase C localization to the nuclear envelope of phorbol ester-treated NIH 3T3 cells.

We have examined the immunocytochemical localization of protein kinase C (PKC) in NIH 3T3 cells using mAbs that recognize Type 3 PKC. In control cells, the immunofluorescent staining was similar with mAbs directed to either the catalytic or the regulatory domain of PKC. Type 3 PKC localized in a diffuse cytoplasmic pattern, while the nuclei were apparently unstained.

In vitro synthesis and processing of components of the Ascaris suum pyruvate dehydrogenase complex.

Poly(A)+ RNA was isolated from Ascaris suum body wall muscle and translated in a cell-free rabbit reticulocyte lysate system. Specific antisera and immunoglobulins against the alpha-pyruvate dehydrogenase and dihydrolipoyl transacetylase components of ascarid pyruvate dehydrogenase complex were used to immunoprecipitate individual radiolabelled polypeptides from the in vitro translation mixtures. Both polypeptides appeared to be synthesized as preproteins about 1.