Alpha V integrin prolongs collagenase production through Jun activation binding protein 1.

Robust expression of alphav integrin and matrix metalloproteinase 1 (MMP1) plays an important role in cancer metastasis and wound healing. A patient with an abnormal scar that appeared stretched and thinned out was found to have fibroblasts that overexpressed alphav integrin; therefore, a relationship between alphav integrin expression and MMP1 production was sought. A yeast 2 hybrid screen revealed alphav integrin interacts with jun activation binding domain-1 (JAB1).

Amantadine therapy for chronic hepatitis C: a dose escalation study.

Objectives: Amantadine reduces liver transaminase levels in some patients with chronic hepatitis C at doses of 200 mg daily and may improve the sustained virological response (SVR) when given with interferon and ribavirin. The primary purpose of the present investigation was to study the safety and toxicity of higher doses of amantadine in subjects who previously failed or were intolerant to interferon. The secondary aim was to test the efficacy of higher dose of amantadine against hepatitis C.

Thyroid disease: pathophysiology and diagnosis.

The thyroid is a butterfly-shaped gland that is located in the front of the neck just above the trachea; it weighs approximately 15 g to 20 g in the adult human. The thyroid produces and releases into the circulation at least two potent hormones, thyroxine (T4) and triiodothyronine (T3), that influence basal metabolic processes or enhance oxygen consumption in nearly all body tissues. Thyroid hormones also influence linear growth; brain function, including intelligence and memory; neural development; dentition; and bone development.

Metastatic breast cancer: overview of treatment.

Patients with metastatic breast cancer have a median survival of 2 to 3 years. Twenty percent of the patients who present with bone-only metastasis will be alive at 5 years from diagnosis. Current therapies are aimed at improving the quality of life, symptom control, and prolongation of survival.

Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome.

Objective: To assess neuropathology in individuals with restless legs syndrome (RLS).

Methods: A standard neuropathologic evaluation was performed on seven brains from individuals who had been diagnosed with RLS. The substantia nigra was examined in greater detail for iron staining and with immunohistochemistry for tyrosine hydroxylase and proteins involved in iron management.

Functions of insulin and insulin receptor signaling in retina: possible implications for diabetic retinopathy.

Insulin action regulates the metabolic functions of the classically insulin-responsive tissues: liver, adipose, and skeletal muscle. Evidence also suggests that insulin acts on neural tissue and can modulate neural metabolism, synapse activity, and feeding behaviors. Insulin receptors are expressed on both the vasculature and neurons of the retina, but their functions are not completely defined.

17beta-estradiol activates ICI 182,780-sensitive estrogen receptors and cyclic GMP-dependent thioredoxin expression for neuroprotection.

Clinical studies suggest that estrogen may improve cognition in Alzheimer's patients. Basic experiments demonstrate that 17beta-estradiol protects against neurodegeneration in both cell and animal models. In the present study, a human SH-SY5Y cell model was used to investigate molecular mechanisms underlying the receptor-mediated neuroprotection of physiological concentrations of 17beta-estradiol.

Opioid growth factor inhibits intimal hyperplasia in balloon-injured rat carotid artery.

Objective: The endogenous opioid [Met(5)]-enkephalin (opioid growth factor [OGF]) is a tonically active, receptor-mediated inhibitory growth peptide in developing and adult vasculature. This study was designed to determine the role of OGF in neointimal hyperplasia.

Methods: The carotid artery in adult male Sprague-Dawley rats was denuded with balloon catheterization.

Brain iron uptake and homeostatic mechanisms: an overview.

Timely and adequate iron acquisition by the brain is essential to normal neurological function. Despite the numerous cognitive and neurological impairments that are associated with disruptions in brain iron acquisition, including both too much and too little iron, the mechanism and regulation of the mechanisms by which the brain acquires iron are poorly understood. In this article, we review the current state of knowledge regarding expression of iron transport proteins in the brain, brain iron uptake and discuss why a model for brain iron uptake must take into consideration the potentially competing influences on the endothelial cell between the status of iron in the brain versus the systemic iron status.

Ferritin binding in the developing mouse brain follows a pattern similar to myelination and is unaffected by the jimpy mutation.

We have previously provided evidence that ferritin binds selectively to white matter tracts in adult mouse and human brains. In cell culture experiments, ferritin binding is specifically localized to oligodendrocytes. The goal of the present study is to test the hypothesis that the developmental pattern for ferritin binding will coincide with the onset and progression of myelination.

Overexpression of integrin alphav promotes human osteosarcoma cell populated collagen lattice contraction and cell migration.

Cells attach and interact with the extracellular matrix (ECM) through heterodimeric alphabeta integrin receptors. Specifically, the promiscuous alphavbeta3 integrin and the alpha2beta1 integrin receptors engage numerous matrix components to influence cell adhesion, cell motility, and matrix organization. However, the role of alphav integrin mediating cell-collagen interactions is not clear.

Is hemochromatosis a risk factor for Alzheimer's disease?

Excess iron accumulation in the brain is a consistent observation in Alzheimer's Disease. Iron affects amyloid precursor protein (AbetaPP) processing and promotes deposition of Abeta. Iron is also among the most potent biological toxins because of its ability to react with oxygen to form reactive oxygen species.

Relationship of serum HER-2/neu and serum CA 15-3 in patients with metastatic breast cancer.

Background: Serum HER-2/neu antigen concentrations have been reported to correlate with increased tumor volume in patients with breast cancer. We measured serum CA 15-3, a surrogate marker of disease burden, and correlated serum CA 15-3 with serum HER-2/neu and analyzed the association of both markers with clinical outcomes.

Methods: Pretreatment serum samples from 566 patients were retrospectively analyzed from 2 phase III clinical trials of estrogen receptor-positive (ER(+)), ER(-)/progesterone receptor-positive, or ER status unknown metastatic breast cancer patients randomized in two similar studies to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole).

Self-selected women with polycystic ovary syndrome are reproductively and metabolically abnormal and undertreated.

Objective: To determine whether self-selected women with polycystic ovary syndrome (PCOS) are abnormal compared with a control population.

Design: Case-control.

Setting: Support group meeting organized and initiated by patients.

Polycystic ovary syndrome. Long term sequelae and management.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women and is defined by hyperandrogenic chronic anovulation with the exclusion of secondary causes, such as congenital adrenal hyperplasia or an androgen secreting tumor. PCOS women are uniquely insulin resistant. It is estimated that 5% of the female population is affected.

Polycystic ovary syndrome in adolescents.

Recent findings suggest substantial metabolic sequelae to polycystic ovary syndrome (PCOS), including risk of diabetes and cardiovascular disease. Primary treatment of the metabolic sequelae should be the focus of the clinician. The definition of PCOS has been expanded from a disorder that presents at menarche and ends at menopause to a disorder that may be present from birth to senescence.

Empathy and social-emotional factors in recovery from stroke.

There is growing interest in evaluating the social and emotional effects of stroke, with the aim of improving recovery and outcome. Recent investigations indicate that post-stroke depression and social impairment are cross-cultural consequences that affect between one-third and two-thirds of patients. These conditions appear to be undertreated, even though studies confirm measurable benefits of medical and caregiver education interventions.

Polycystic ovary syndrome: the new millenium.

Our understanding of Polycystic Ovary Syndrome (PCOS) has been hampered by varying diagnostic criteria, and ignorance of the etiology of the syndrome. PCOS women are uniquely insulin resistant and obesity aggravates this underlying predisposition to insulin resistance. Diagnostic criteria which focus on hyperandrogenism and/or menstrual irregularity are more likely to identify insulin resistant women, than such criteria as abnormal gonadotropin secretion or ovarian morphology.

Differences in alpha smooth muscle actin expression between fibroblasts derived from Dupuytren's nodules or cords.

Dupuytren's contracture is a fibrotic lesion of the palmar fascia that includes two distinct structures, the nodule and the cord. Histologically the Dupuytren's nodule has a high cell density with numerous myofibroblasts (alpha smooth muscle actin-expressing fibroblasts). The Dupuytren's cord has a rich connective tissue matrix containing a low density of elongated spindle-shaped fibroblasts.

Iron and iron management proteins in neurobiology.

The ability of the brain to store a readily bioavailable source of iron is essential for normal neurologic function because both iron deficiency and iron excess in the brain have serious neurologic consequences. The blood-brain barrier presents unique challenges to timely and adequate delivery of iron to the brain. The regional compartmentalization of neurologic function and a myriad of cell types provide additional challenges.

MR imaging and T2 mapping of femoral cartilage: in vivo determination of the magic angle effect.

Objective: The purpose of this study was to perform a quantitative evaluation of the effect of static magnetic field orientation on cartilage transverse (T2) relaxation time in the intact living joint and to determine the magnitude of the magic angle effect on in vivo femoral cartilage.

Materials And Methods: Quantitative T2 maps of the femoral-tibial joint were obtained in eight asymptomatic male volunteers using a 3-T magnet. Cartilage T2 profiles (T2 vs normalized distance from subchondral bone) were evaluated as a function of orientation of the radial zone of cartilage with the applied static magnetic field (B(0)).

Safety and efficacy of bisphosphonates beyond 24 months in cancer patients.

Purpose: Bisphosphonate therapy has decreased the risk of skeletal complications associated with osteolytic bone lesions in patients with breast cancer and multiple myeloma. The large prospective studies have used 21 to 24 months of treatment. We studied the safety and efficacy of bisphosphonates in a subset of patients who received therapy for more than 24 months.

Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions.

The capsid (CA) protein, the major structural component of retroviruses, forms a shell that encases the ribonucleoprotein complex in the virion core. The most conserved region of CA, approximately 20 amino acids of the major homology region (MHR), lies within the carboxy-terminal domain of the protein. Structural and sequence similarities among CA proteins of retroviruses and the CA-like proteins of hepatitis B virus and various retrotransposons suggest that the MHR is involved in an aspect of replication common to these reverse-transcribing elements.

Characterization of a novel brain-derived microglial cell line isolated from neonatal rat brain.

We observed highly aggressively proliferating immortalized (HAPI) cells growing in cultures that had been enriched for microglia. The cells were initially obtained from mixed glial cultures prepared from 3-day-old rat brains. HAPI cells are typically round with few or no processes when cultured in 10% serum containing medium.