Amino-terminal and midmolecule parathyroid hormone-related protein, phosphatidylcholine, and type II cell proliferation in silica-injured lung.

Acute silica lung injury is marked by alveolar phospholipidosis and type II cell proliferation. Parathyroid hormone-related protein (PTHrP) 1-34 could have a regulatory role in this process because it stimulates phosphatidylcholine secretion and inhibits type II cell growth. Other regions of the PTHrP molecule may have biological activity and can also exert pulmonary effects.

Identification of a novel glucocorticoid receptor mutation in budesonide-resistant human bronchial epithelial cells.

We developed a molecular genetic model to investigate glucocorticoid receptor (GR) signaling in human bronchial epithelial cells in response to the therapeutic steroid budesonide. Based on a genetic selection scheme using the human Chago K1 cell line and integrated copies of a glucocorticoid-responsive herpes simplex virus thymidine kinase gene and a green fluorescent protein gene, we isolated five Chago K1 variants that grew in media containing budesonide and ganciclovir. Three spontaneous budesonide-resistant subclones were found to express low levels of GR, whereas two mutants isolated from ethylmethane sulfonate-treated cultures contained normal levels of GR protein.

Hypohidrotic ectodermal dysplasia: prenatal diagnosis by three-dimensional ultrasonography.

Ectodermal dysplasia is the term used to describe a group of rare congenital anomalies characterized by abnormal development of 1 or several ectoderm-derived tissues. At least 154 different types, divided into 11 clinical subgroups, have been recognized. Among them, the hypohidrotic type is the most common form, with an incidence of 1 per 10,000 to 1 per 100,000 live births.

Intravital imaging of the kidney using multiparameter multiphoton microscopy.

Intravital optical microscopy provides a powerful means of studying the cell biology in the most physiologically relevant setting. The ability of multiphoton microscopy to collect optical sections deep into biological tissues has opened up the field of intravital microscopy to high-resolution studies of multiple organs. Presented here are examples of how two-photon microscopy can be applied to intravital studies of kidney physiology and the study of disease processes.

Proapoptotic effects of parathyroid hormone-related protein in type II pneumocytes.

Parathyroid hormone-related protein (PTHrP) promotes or suppresses apoptosis in various settings depending on cell type and context. PTHrP 1-34 and PTHrP 67-86 are type II cell growth factors with effects on pneumocyte growth and surfactant secretion. This study investigated the effects of 24 h pretreatment with these two peptides on rat type II cell apoptosis after 0.

Injury of the renal microvascular endothelium alters barrier function after ischemia.

The role of renal microvascular endothelial cell injury in the pathophysiology of ischemic acute renal failure (ARF) remains largely unknown. No consistent morphological alterations have been ascribed to the endothelium of the renal microvasculature as a result of ischemia-reperfusion injury. Therefore, the purpose of this study was to examine biochemical markers of endothelial injury and morphological changes in the renal microvascular endothelium in a rodent model of ischemic ARF.

A novel method to determine specificity and sensitivity of the TUNEL reaction in the quantitation of apoptosis.

Apoptosis is an important mode of cell death under both physiological and pathophysiological conditions. Numerous techniques are available for the study and quantitation of apoptosis in cell culture, but only few are useful when applied to complex tissues. Among these, the terminal transferase-mediated dUTP nick end-labeling (TUNEL) assay remains the most widely used technique.

ADF/cofilin mediates actin cytoskeletal alterations in LLC-PK cells during ATP depletion.

Ischemic injury induces actin cytoskeleton disruption and aggregation, but mechanisms affecting these changes remain unclear. To determine the role of actin-depolymerizing factor (ADF)/ cofilin participation in ischemic-induced actin cytoskeletal breakdown, we utilized porcine kidney cultured cells, LLC-PK(A4.8), and adenovirus containing wild-type (wt), constitutively active, and inactive Xenopus ADF/cofilin linked to green fluorescence protein [XAC(wt)-GFP] in an ATP depletion model.

Epilepsy-induced changes in signaling systems of human and rat postsynaptic densities.

Purpose: To study seizure-induced changes in signaling proteins present in postsynaptic densities (PSDs) isolated from human epileptic neocortex and from rat cortex in which seizures were induced by injection of kainic acid.

Methods: We performed Western blot analysis of signaling proteins in PSDs isolated from cortical tissue.

Results: Seizures induce a strong upregulation of TrkB, the receptor for brain-derived neurotrophic factor (BDNF), whereas components of the N-methyl-d-aspartate (NMDA)-receptor complex are downregulated in both human and rat PSDs.

Tennessee Self-concept Scale scores of urban African-American women.

The Tennessee Self-concept Scale: Second Edition scores of 33 urban, African-American women were compared in a pretest-posttest design. The treatment was exposure to a 3-mo. literacy and social skills training program.

Nucleotide depletion increases trafficking of gentamicin to the Golgi complex in LLC-PK1 cells.

Having shown rapid trafficking of aminoglycosides to the Golgi complex in cell culture, we focused on the injurious interaction that occurs when gentamicin administration is preceded by renal ischemia. Using Texas red-labeled gentamicin as a tracer, we determined that 15 min of cellular nucleotide depletion did not significantly increase subsequent uptake. However, cells previously depleted of nucleotides accumulated significantly more Texas red-labeled gentamicin within a dispersed Golgi complex.

Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation.

Kinases of the Jak family (Jak1/2/3 and Tyk2) interact with the membrane proximal domain of different cytokine receptors and play a critical role in the activation of cytokine and growth factor signaling pathways. In this report we demonstrate that both the Box 1 and Box 2 motif collaborate in the association and activation of Jak1 by type I interferons. Mutational analysis of the beta chain of type I interferon receptor (IFNalphaRbetaL/IFNAR2) revealed that Box 1 plays a more significant role in activation than in the association with Jak1.

[Liver transplantation in adults: a caseload from Clínica Alemana de Santiago, Chile].

Background: The success of orthotopic liver transplantation (OLT) has resulted in its widespread use for different liver diseases.

Aim: To report our 8 years experience with adult OLT at Clinica Alemana de Santiago.

Patients And Methods: In all transplantations done at the center, we recorded patient's overall data and survival, postoperative medical and surgical complications and causes of death.

Functional studies of the kidney of living animals using multicolor two-photon microscopy.

Optical microscopy, when applied to living animals, provides a powerful means of studying cell biology in the most physiologically relevant setting. The ability of two-photon microscopy to collect optical sections deep into biological tissues has opened up the field of intravital microscopy to high-resolution studies of the brain, lens, skin, and tumors. Here we present examples of the way in which two-photon microscopy can be applied to intravital studies of kidney physiology.

Parathyroid hormone-related protein-(38-64) regulates lung cell proliferation after silica injury.

Inhalation of silica leads to acute lung injury and alveolar type II cell proliferation. Type II cell proliferation after hyperoxic lung injury is regulated, in part, by parathyroid hormone-related protein (PTHrP). In this study, we investigated lung PTHrP and its effects on epithelial proliferation after injury induced by silica.

[Treatments to quit smoking, available in Mexico].

Objective: To describe smoking cessation therapies available in Mexico.

Material And Methods: Literature review of meta-analysis, controlled clinical trials, and behavioral therapy studies.

Results: Smoking cessation pharmacotherapy interventions showed a good chance of success on average, expressed as the ratio of the active drug vs.

[Impact of mass communication media on an anti-smoking campaign].

Objective: To assess the impact of the mass media (MM) on smoking cessation process in Mexico.

Material And Methods: Between June 1998 and May 1999, the effects of an anti-smoking mass media campaign and alternative strategies were evaluated, by comparing the monthly sales average of all smoking-cessation aid products before and after marketing a new nicotine patch. Student's t paired and unpaired t tests were used to compare sales.

Endothelial injury and dysfunction in ischemic acute renal failure.

Ischemic acute renal failure is the most common cause of acute renal failure in hospitalized patients and has an average mortality rate of 50%. Although epithelial and vascular smooth muscle cell abnormalities have been clearly delineated in association with this condition, the extent of endothelial injury and dysfunction has been difficult to document, primarily for anatomic reasons. However, endothelial tight junction separation and endothelial cell detachment, blebbing, and necrosis have been observed after ischemia in other organs.

Development of a pharmacist-managed lipid clinic.

Objective: To describe the development of a pharmacist-managed lipid clinic within a primary care medical clinic and review its results after approximately 12 months of operation.

Methods: A pharmacist-managed lipid clinic was developed at Naval Medical Center San Diego. Administrative background, treatment algorithm development, operational issues, clinical activities, and barriers to the clinic are discussed.

Modulatory role of focal adhesion kinase in regulating human pulmonary arterial endothelial barrier function.

The adhesive force generated by the interaction of integrin receptors with extracellular matrix (ECM) at the focal adhesion complex may regulate endothelial cell shape, and thereby the endothelial barrier function. We studied the role of focal adhesion kinase (FAK) activated by integrin signalling in regulating cell shape using cultured human pulmonary artery endothelial cells. We used FAK antisense oligonucleotide (targeted to the 3'-untranslated region of FAK mRNA (5'-CTCTGGTTGATGGGATTG-3') to determine the role of FAK in the mechanism of thrombin-induced increase in endothelial permeability.

Voxx: a PC-based, near real-time volume rendering system for biological microscopy.

Confocal and two-photon fluorescence microscopy have advanced the exploration of complex, three-dimensional biological structures at submicron resolution. We have developed a voxel-based three-dimensional (3-D) imaging program (Voxx) capable of near real-time rendering that runs on inexpensive personal computers. This low-cost interactive 3-D imaging system provides a powerful tool for analyzing complex structures in cells and tissues and encourages a more thorough exploration of complex biological image data.

Characteristics of EYFP-actin and visualization of actin dynamics during ATP depletion and repletion.

Disruption of the actin cytoskeleton in proximal tubule cells is a key pathophysiological factor in acute renal failure. To investigate dynamic alterations of the actin cytoskeleton in live proximal tubule cells, LLC-PK(10) cells were transfected with an enhanced yellow fluorescence protein (EYFP)-actin construct, and a clone with stable EYFP-actin expression was established. Confluent live cells were studied by confocal microscopy under physiological conditions or during ATP depletion of up to 60 min.

Synergistic effects of tumor necrosis factor-alpha and thrombin in increasing endothelial permeability.

Because activation of the coagulation cascade and the generation of thrombin coexist with sepsis and the release of tumor necrosis factor (TNF)-alpha, we determined the effects of TNF-alpha on the mechanism of thrombin-induced increase in endothelial permeability. We assessed Ca(2+) signaling in human umbilical vein endothelial cells. In human umbilical vein endothelial cells exposed to TNF-alpha for 2 h, thrombin produced a rise in the intracellular Ca(2+) concentration ([Ca(2+)](i)) lasting up to 10 min.

Ca(2+) signalling and PKCalpha activate increased endothelial permeability by disassembly of VE-cadherin junctions.

1. The role of intracellular Ca(2+) mobilization in the mechanism of increased endothelial permeability was studied. Human umbilical vein endothelial cells (HUVECs) were exposed to thapsigargin or thrombin at concentrations that resulted in similar increases in intracellular Ca(2+) concentration ([Ca(2+)](i)).

Ischemic injury induces ADF relocalization to the apical domain of rat proximal tubule cells.

Breakdown of proximal tubule cell apical membrane microvilli is an early-occurring hallmark of ischemic acute renal failure. Intracellular mechanisms responsible for these apical membrane changes remain unknown, but it is known that actin cytoskeleton alterations play a critical role in this cellular process. Our laboratory previously demonstrated that ischemia-induced cell injury resulted in dephosphorylation and activation of the actin-binding protein, actin depolymerizing factor [(ADF); Schwartz, N, Hosford M, Sandoval RM, Wagner MC, Atkinson SJ, Bamburg J, and Molitoris BA.