Biomedical subjects

L Meyn

Publications and source records attributed to L Meyn.

7 recordsLinked to original sources

PubMed2004

Safety and efficacy evaluations for vaginal and rectal use of BufferGel in the macaque model.

BACKGROUND: The nonhuman primate model allows for safety and efficacy testing of topical microbicide products. GOAL: The goal of this study was to evaluate the safety and efficacy of vaginal and rectal applications of BufferGel (ReProtect, Inc.). STUDY DESIGN: The safety of repeated product applications was evaluated by microflora, pH, vaginal colposcopy, and rectal lavage. To test efficacy in preventing chlamydia, infection was documented by culture and nucleic acid amplification tests. RESULTS: Repeated vaginal or rectal applications of BufferGel were not associated with significant changes in microflora. BufferGel use had a transient acidifying effect on vaginal and rectal pH. Colposcopic observations remained relatively normal in all test animals. A slightly increased incidence of epithelial desquamation was noted after rectal product use compared with the control group. BufferGel did not prevent cervical or rectal chlamydial infection. CONCLUSION: BufferGel has an acceptable safety profile after repeated vaginal and rectal use, but does not prevent chlamydial infection in the macaque models.

Acrylic Resins↗

PubMed2001

Neuron-specific expression of therapeutic proteins: evaluation of different cellular promoters in recombinant adenoviral vectors.

In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in the context of adenoviral vectors. Both the synapsin 1 gene and the tubulin alpha1 gene promoters were strictly neuron specific in cocultures of primary neurons with their essential feeder cells. The neuron-specific enolase gene promoter exhibited only weak activity in cultured hippocampal neurons and was not neuron specific in preparations of cerebellar granule cells. By attaining virtually 100% transduction efficiency we were able to generate "quasi-transgenic" primary neuron cultures using both differentiated and completely undifferentiated hippocampal neurons. In a functional assay, we used the synapsin promoter to evaluate the effect of Bcl-X(L) overexpression on potassium-withdrawal-induced apoptosis of cerebellar granule neurons. We found nearly complete inhibition of caspase-9 and -3 activation and apoptosis, indicating a major role for mitochondrial pathways in this paradigm of neuronal cell death. The excellent suitability of the synapsin promoter as a strong panneuronal promoter was further demonstrated by its restricted neuronal activity in various brain regions of adult rats in vivo.

Adenoviridae↗

PubMed2001

Accuracy of serum beta-human chorionic gonadotropin cutoff values at 42 and 49 days' gestation.

OBJECTIVE: The accuracy of serum beta-human chorionic gonadotropin levels as cutoff values for estimating gestational age was studied. MATERIAL AND METHODS: A database was created using information from previously performed research studies, which allowed entry of women both less than and greater than 49 days' gestation, involving medical abortion. Serum beta-human chorionic gonadotropin determinations and vaginal ultrasonography were performed in all studies before treatment. A total of 574 women had data available for analysis. A receiver operating characteristic curve was created to evaluate the predictive value of potential beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation. RESULTS: Appropriate serum beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation were 23,745 mIU/mL (sensitivity, 96%; specificity, 91%; positive predictive value, 68%; negative predictive value, 99%) and 71,160 mIU/mL (sensitivity, 95%; specificity, 62%; positive predictive value, 76%; negative predictive value, 91%), respectively. Under 42 days' gestation, the serum beta-human chorionic gonadotropin-time relationship appears to be linear, with a greater diversity of individual values after 42 days. CONCLUSION: Serum beta-human chorionic gonadotropin values can be used with reasonable accuracy to screen for a gestational age up to 49 days' gestation.

Abortion, Therapeutic↗

PubMed2000

Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases.

Endoproteolysis of beta-amyloid precursor protein (betaAPP) and Notch requires conserved aspartate residues in presenilins 1 and 2 (PS1 and PS2). Although PS1 and PS2 have therefore been proposed to be aspartyl proteases, no homology to other aspartyl proteases has been found. Here we identify homology between the presenilin active site and polytopic aspartyl proteases of bacterial origin, thus supporting the hypothesis that presenilins are novel aspartyl proteases.

Amyloid beta-Peptides↗

PubMed2000

Predicting cesarean delivery with decision tree models.

OBJECTIVE: The purpose of this study was to determine whether decision tree-based methods can be used to predict cesarean delivery. STUDY DESIGN: This was a historical cohort study of women delivered of live-born singleton neonates in 1995 through 1997 (22,157). The frequency of cesarean delivery was 17%; 78 variables were used for analysis. Decision tree rule-based methods and logistic regression models were each applied to the same 50% of the sample to develop the predictive training models and these models were tested on the remaining 50%. RESULTS: Decision tree receiver operating characteristic curve areas were as follows: nulliparous, 0.82; parous, 0.93. Logistic receiver operating characteristic curve areas were as follows: nulliparous, 0.86; parous, 0.93. Decision tree methods and logistic regression methods used similar predictive variables; however, logistic methods required more variables and yielded less intelligible models. Among the 6 decision tree building methods tested, the strict minimum message length criterion yielded decision trees that were small yet accurate. Risk factor variables were identified in 676 nulliparous cesarean deliveries (69%) and 419 parous cesarean deliveries (47.6%). CONCLUSION: Decision tree models can be used to predict cesarean delivery. Models built with strict minimum message length decision trees have the following attributes: Their performance is comparable to that of logistic regression; they are small enough to be intelligible to physicians; they reveal causal dependencies among variables not detected by logistic regression; they can handle missing values more easily than can logistic methods; they predict cesarean deliveries that lack a categorized risk factor variable.

Adolescent↗

PubMed1997

Cellular expression and proteolytic processing of presenilin proteins is developmentally regulated during neuronal differentiation.

We have determined the expression of the Alzheimer's disease-associated proteins presenilin-1 and presenilin-2 in primary cultures of rat hippocampal neurons. Neurons highly express presenilin-1 and presenilin-2, whereas both proteins were not detected in astrocytes. Further, we have analyzed the subcellular localization and expression in rat hippocampal neurons during development. Although presenilin proteins were localized predominantly to the endoplasmic reticulum in nonneuronal cells transfected with presenilin cDNAs, in neurons, presenilin proteins were also found in compartments not staining with antibodies to grp78(BiP). Presenilin-1 and presenilin-2 were predominantly detected in vesicular structures within the somatodendritic compartment with much less expression in axons. Polarized distribution of presenilin-1 and presenilin-2 differs slightly, with more presenilin-2 expressed in axons compared with presenilin-1. Presenilin expression was found to be developmentally regulated. Presenilin expression strongly increased during neuronal differentiation until full morphological polarization and then declined. No full-length presenilin-1 or presenilin-2 could be detected within cell lysates. At early developmental stages the expected approximately 34-kDa N-terminal proteolytic fragment of presenilin-1 and the approximately 38-kDa fragment of presenilin-2 were detected. Later during differentiation we predominantly detected a approximately 38-kDa fragment for presenilin-1 and a approximately 42-kDa fragment for presenilin-2. By epitope mapping, we show that these slower migrating peptides represent N-terminal proteolytic fragments, cleaved C-terminal to the conventional site of processing. It is noteworthy that both presenilin-1 and presenilin-2 undergo alternative proteolytic cleavage at the same stage of neuronal differentiation. Regulation of presenilin expression and proteolytic processing might have implications for the pathological as well as the biological function of presenilins during aging in the human brain.

Animals↗

PubMed1994

Semliki Forest virus as a tool for protein expression in cultured rat hippocampal neurons.

We use the Semliki Forest Virus (SFV) as a tool for protein expression in primary cultures of rat hippocampal neurons. These cells develop in vitro into polarized neurons that can be infected with recombinant SFV with an efficiency of 60 - 80%. SFV-driven protein expression is detectable within 3-4 hours postinfection, at which time the newly-synthesized proteins are mainly present in the cell soma. By 6 to 8 hours postinfection foreign proteins are detectable in the neurites. Protein expression can continue for up to 48 hours. However, after 8 - 10 hours infected neurons start to suffer from cytopathic effects as evidenced by a change in morphology and detachment from the coverslip. The infection does not seem to affect the polarized distribution of proteins. Upon overexpression of rab8, a somatodendritic distribution is observed, similar to that of the endogenous protein. Therefore, the SFV expression system is suitable for short-term expression of proteins and can be used successfully to study the polarized distribution of heterologous proteins expressed in cultured hippocampal neurons.

Animals↗