Syndecan-3: a cell-surface heparan sulfate proteoglycan important for chondrocyte proliferation and function during limb skeletogenesis.

Syndecans are single-pass integral membrane components that serve as co-receptors for growth factors and cytokines and can elicit signal transduction via their cytoplasmic tails. We review here previous studies from our groups on syndecan-3 biology and function in the growth plates of developing long bones in chick and mouse embryos. Gain- and loss-of-function data indicate that syndecan-3 has important roles in restricting mitotic activity to the proliferative zone of growth plate and may do so in close cooperation and interaction with the signaling molecule Indian hedgehog (IHH).

DARPP-32 genomic fragments drive Cre expression in postnatal striatum.

To direct Cre-mediated recombination to differentiated medium-size spiny neurons (MSNs) of the striatum, we generated transgenic mice that express Cre recombinase under the regulation of DARPP-32 genomic fragments. In this reported line, recombination of an R26R reporter allele occurred postnatally in the majority of medium-size spiny neurons of the dorsal and ventral striatum (caudate nucleus and nucleus accumbens/olfactory tubercle), as well as in the piriform cortex and choroid plexus. Although regulatory fragments were selected to target MSNs, low levels of Cre-recombinase expression, as detected by beta-galactosidase activity from the R26R reporter gene, were also apparent in widely dispersed areas or cells of the forebrain and hindbrain.

Retinoid signaling regulates CTGF expression in hypertrophic chondrocytes with differential involvement of MAP kinases.

Unlabelled: Retinoids are important for growth plate chondrocyte maturation, but their downstream effectors remain unclear. Recently, CTGF (CCN2) was found to regulate chondrocyte function, particularly in the hypertrophic zone. The goal of the study was to determine whether CTGF is a retinoid signaling effector molecule, how it is regulated, and how it acts.

The distribution of cocaine in mice differs by age and strain.

Few studies have examined the influence of the age and the strain of mouse on the pharmacokinetics of psychostimulants, or the role of pharmacokinetics in age-related differences in drug responses. The present study compared concentrations of cocaine, and its metabolite, benzoylecgonine (BZE), in the blood and brain of early (P35) and later (P42) periadolescent and adult (P63) CD-1 and C57BL/6 male mice 15 min after acute intraperitoneal injection of cocaine (20 mg/kg). Brain levels of cocaine and BZE after seven daily cocaine injections in CD-1 and C57BL/6 mice beginning on P35 and on P63 were also measured.

Influence of serum cholesterol on atherogenesis and intimal hyperplasia after angioplasty: inhibition by amlodipine.

The objectives of the present study were to determine whether serum hypercholesterolemia (HC) promotes the development of spontaneous and angioplasty-induced lesions and whether amlodipine inhibits these lesions and cellular processes underlying their genesis. Rabbits were fed normal, 0.5%, or 2% cholesterol diets for 9 wk, which resulted in the development of increasing HC.

Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet.

Background: Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function.

Methods And Results: We examined the effects of cholesterol feeding (0.5%) on cardiac function in rabbits.

The physiology of lipoproteins.

The seminal studies of Brown and Goldstein (Science 1986;232:34-47) coupled with the findings of the Framingham study revolutionized our understanding of the metabolic basis for vascular disease. These studies led to the widespread use of the coronary risk lipid profile, which uses the total cholesterol/high-density lipoprotein (HDL) ratio (or low-density lipoprotein [LDL]/HDL ratio) in predicting risk for vascular disease and as a tool for therapeutic management of patients at risk for vascular disease. However, although these methods are predictive of coronary artery disease (CAD) in general, it is also well known that the extent of occlusive disease and CAD varies greatly between individuals with similar cholesterol and HDL lipid profiles.

Idiopathic Parkinson's disease(s) may follow subclinical episodes of perivenous demyelination.

Three case studies of postvaccinal parkinsonism (PVP) demonstrated signs and symptoms identical to conventional diagnostic standards of idiopathic Parkinson's disease (PD). PVP is a sub-type of acute disseminated encephalomyelitis (ADE) that also includes postinfectious parkinsonism (PIP) and postinfectious encephalomyelitis (PIE). All ADE has a unitary pathology consisting of monophasic perivenous inflammation followed by demyelination compared with PD in which Lewy bodies are present in only 75% of studies.

Effects of glucose and amino acids on free ADP in betaHC9 insulin-secreting cells.

Stimulation of insulin release by glucose is widely thought to be coupled to a decrease in the activity of ATP-sensitive K+ channels (KATP channels) that is caused by a decreased concentration of free ADP. To date, most other investigators have reported only on total cellular ADP concentrations, even though only a small fraction of all ADP is free and only the free ADP affects KATP channels. We tested the hypothesis that amino acids elicit insulin release via a decrease in the activity of KATP channels owing to a decrease in the level of free ADP.

The abandoned radical hysterectomy: a Gynecologic Oncology Group Study.

Objective: The aim of this study was to evaluate the frequency with which intended radical hysterectomy for cervical cancer is abandoned and the outcomes for those patients.

Methods: A secondary evaluation of a prospective surgical pathological trial was performed. There were 1127 patients with Stage IB carcinoma of the cervix entered on Gynecologic Oncology Group Protocol No.

Luminometric assays of ATP, phosphocreatine, and creatine for estimation of free ADP and free AMP.

We present methods to measure ATP, phosphocreatine, and total creatine (the sum of creatine and phosphocreatine) in alkaline cell extracts. Knowledge of these parameters, together with the known equilibrium constants for the creatine kinase and adenylate kinase-catalyzed reactions, allows one to estimate the levels of free ADP and free AMP inside cells. The enzymatic assays for the above-mentioned metabolites all lead up to the production of ATP, which is measured luminometrically with the ATP-dependent oxidation of luciferin catalyzed by firefly luciferase.

Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.

Purpose: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities.

Methods: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix.

Correlation between herpes simplex virus type 1 rate of reactivation from latent infection and the number of infected neurons in trigeminal ganglia.

The presence of wild-type herpes simplex virus type 1 (HSV-1) and several latency associated transcript (LAT) region mutants within the trigeminal ganglia (TG) of latently infected mice was examined. A combination of methods including conventional in situ hybridization to detect viral LAT and an in situ DNA polymerase chain reaction (PCR) to detect viral DNA was used. These data show that, for all virus strains in which a comparison was possible, the population of neurons expressing detectable levels of LAT was approximately one-third the total number of viral DNA-containing cells.

Management issues for the neonatal patient.

Immediate management needs of the neonate are defined in terms of the physiology of maternal-fetal gas transport and the oxyradical hypothesis of cellular injury as it pertains to hypoemic-ischemic encephalopathy. Resuscitation, stabilization, and assessment needs are defined as related to outcome and factors of information systems. Psychosocial and legal issues are included as factors in neonatal management.

Erythropoietin response to blood loss in hemodialysis patients in blunted but preserved.

In anemic non-renal and hemodialysis (HD) patients, erythropoietin (EPO) levels vary > 10 fold at any hematocrit (Hct), suggesting marked variation in endogenous EPO production among individuals. We hypothesized that this intrinsic variation that reflects differences in bone marrow sensitivity to circulating EPO could account for the > 10 fold variability in recombinant human erythropoietin (rHuEPO) requirements of HD patients to correct their anemia, and could be evaluated by examining the response to blood loss and measurement of red blood cell (RBC) survival (tau). The renal response to blood loss was studied in normal patients (N = 14) and in non-rHuEPO treated HD (n = 12) patients by measuring the increase in EPO (delta EPO) above basal level.

Arthritis of the cervical spine.

Neck pain often occurs in the absence of neurologic findings, and the diagnostic dilemma of the clinician is to determine if there is a definable lesion. Radiographically, the cervical spine is commonly involved, especially in persons older than 50 years. Excluding soft-tissue inflammation and spasm, osteoarthritis is the most common rheumatic disease of the cervical spine.

Arthritis of the lumbar spine.

Many types of arthritis can disturb the normal lumbar anatomy. This review intentionally omits many endocrine, metabolic, and genetic disorders that ultimately lead to breakdown of cartilage. Osteoarthritis remains the most common cause of sustained back pain as well as one of the most compensable disabilities in the United States.