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Biomedical subjects

J McLaughlin

Publications and source records attributed to J McLaughlin.

At least 19 recordsLinked to original sources
PubMed2006

Human microvascular endothelial cellular interaction with atomic N-doped DLC compared with Si-doped DLC thin films.

This article reports results of endothelial cell interaction with atom beam source N-doped a-C:H (diamond-like carbon, DLC) as it compares with that of Si-doped DLC thin films. The RF plasma source exhibits up to 40% N-dissociation and N-atomic fluxes of approximately 0.85 x 10(18) atoms/s, which ensures better atomic nitrogen incorporation. Two different types of nitrogen species (with and without the use of sweep plates to remove charged ions) were employed for nitrogen doping. The number of attached endothelial cells is highest on Si-DLC, followed by the N-DLC (where the sweep plates were used to remove ions), the N-DLC (without the use of sweep plates), undoped DLC, and finally the uncoated sample. The contact angle values for these films suggest that water contact angle is higher in the atomic nitrogen neutral films and Si-DLC films compared to the ionized-nitrogen specie doped films and undoped DLC thin films, suggesting that the more hydrophobic films, semiconducting films, and film with relieved stress have better interaction with human microvascular endothelial cells. It seems evident that N-doping increases the Raman I(D)/I(G) ratios, whereas N-neutral doping decreases it slightly and Si-doping decreases it even further. In this study, lower Raman I(D)/I(G) ratios are associated with increased sp(3)/sp(2) ratio, an increased H concentration, photoluminescence intensity, and a higher endothelial cellular adhesion. These investigations could be relevant to biocompatibility assessment of nanostructured biomaterials and tissue engineering.

Cell Adhesion↗
PubMed2005

Validation and clinical application of molecular methods for the identification of molds in tissue.

BACKGROUND: Invasive fungal infections due to less-common molds are an increasing problem, and accurate diagnosis is difficult. METHODS: We used our previously established molecular method, which allows species identification of molds in histological tissue sections, to test sequential specimens from 56 patients with invasive fungal infections who were treated at our institution from 1982 to 2000. RESULTS: The validity of the method was demonstrated with the establishment of a molecular diagnosis in 52 cases (93%). Confirmation of the causative organism was made in all cases in which a mold had been cultured from the tissue specimen. Less-common molds were identified in 7% of cases and appear to be an increasing problem. CONCLUSIONS: Our previously established method has proven to be of value in determining the incidence of invasive infection caused by less-common molds. Institutions should continue to pursue diagnosis of invasive fungal infections by means of tissue culture and microbiologic analysis.

Aspergillosis↗
PubMed2005

Exploring diagnostic processes: social science perspectives.

This review explores social science analyses of diagnosis of childhood neurological disabilities. The paper moves through three sections, which capture the historical and conceptual trends within the literature. The first focuses on work identifying the need to communicate effectively with parents when giving a diagnosis, the second explores the role parents can play as "partners" or contributors to diagnosis, and the final section goes further in exploring the social complexity of diagnoses in order to examine the embedded nature of social practices, power relations and hierarchies, and institutions in the diagnosis encounter.

Child↗
PubMed2004

The MTT assays of bovine retinal pericytes and human microvascular endothelial cells on DLC and Si-DLC-coated TCPS.

MTT (Tetrazolium)-assay suggests that diamond-like carbon (DLC) and silicon-doped DLC (Si-DLC) films obtained under appropriate deposition parameters are not toxic to bovine retinal pericytes, and human microvascular endothelial cells (HMEC). The observed frequency distributions of the optical density (OD) values indicative of cell viability are near Gaussian-normal distribution. One-way ANOVA indicates that at 0.05 levels the population means are not significantly different for the coated and control samples. The observed OD values depend on the cell line (cell growth/metabolic rate), possibly cell cycle stage, the deposition parameters-bias voltage, ion energy, pressure, argon precleaning, and the dopant. For colored thin films like DLC with room temperature photoconductivity and photoelectric effects, it is important to account for the OD contribution from the coating itself. MTT assay, not surprisingly, seems not to be highly sensitive to interfacial cellular interaction resulting from the change in the film's nanostructure, because the tetrazolium metabolism is mainly intracellular and not interfacial. The thin films were synthesized by 13.56 MHz RF-PECVD using argon and acetylene as source gases, with tetramethylsilane (TMS) vapor introduced for silicon doping. This study could be relevant to biomedical application of the films in the eye, peri-vascular, vascular compartments, and for cell-tissue engineering.

Animals↗
PubMed2004

Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations.

Protein kinase inhibitors can be effective in treating selected cancers, but most suppress several kinases. Imatinib mesylate has been useful in the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia and B cell acute lymphoblastic leukemia through the inhibition of BCR-ABL tyrosine kinase activity. Imatinib mesylate has also been shown to inhibit KIT, ARG, and platelet-derived growth factor receptors alpha and beta, and potentially other tyrosine kinases. We have produced a mutant allele of BCR-ABL (T315A) that is uniquely inhibitable by the small molecule 4-amino-1-tert-butyl-3-(1-naphthyl)pyrazolo[3,4-d]pyrimidine and used it to demonstrate that sole suppression of BCR-ABL activity was insufficient to eliminate BCR-ABL(+) KIT(+)-expressing immature murine myeloid leukemic cells. In contrast, imatinib mesylate effectively eliminated BCR-ABL(+) KIT(+)-expressing leukemic cells. In the cellular context of mature myeloid cells and Pro/Pre B cells that do not express KIT, monospecific BCR-ABL inhibition was quantitatively as effective as imatinib mesylate in suppressing cell growth and inducing apoptosis. These results suggest that the therapeutic effectiveness of small molecule drugs such as imatinib mesylate could be due to the inhibitor's ability to suppress protein kinases in addition to the dominant target.

Apoptosis↗
PubMed2004

Wearable and implantable monitoring systems: 10 years experience at University of Ulster.

Over the past 10 years or more, NIBEC and, more recently, Sensor Technology and Devices Ltd have been at the forefront of developments in sensor-related technologies which underpin a wide range of monitoring systems presently commercialised by leading multinationals. Systems developed/ commercialised include astronaut-monitoring arrays, cardiac mapping harnesses, ECG electrodes, Telemedicine systems and implant sensor arrays. This paper presents the main developments in this area and discusses outstanding issues for future research.

Astronauts↗
PubMed2003

Muscarinic receptor antagonism in the basolateral amygdala blocks acquisition of cocaine-stimulus association in a model of relapse to cocaine-seeking behavior in rats.

Recent evidence has demonstrated a critical role for the basolateral amygdala complex in the reinstatement of extinguished drug-seeking behavior produced by drug-paired cues. In the current study, we utilized a model of the acquisition and expression of cocaine-stimulus associative pairing in order to study the role of cholinergic input to the basolateral amygdala in mediating conditioned-cued reinstatement. Male, Sprague-Dawley rats were first trained daily to self-administer i.v. cocaine on a fixed ratio 1 schedule of reinforcement. The muscarinic acetylcholine receptor antagonist, scopolamine, was directly infused into the basolateral amygdala prior to: a) classically conditioned pairing of a tone+light stimulus with cocaine infusions (acquisition), or b) testing of conditioned-cued reinstatement following a period of withdrawal from cocaine and extinction of cocaine-paired lever responding. Infusion of scopolamine just prior to the classical conditioning trial produced a dose-dependent disruption of cocaine-seeking behavior maintained by cocaine-paired cues during the reinstatement test. In contrast, infusion of scopolamine prior to the reinstatement test had no effect on conditioned-cued reinstatement of cocaine-seeking behavior. These results indicate a crucial role for cholinergic innervation of muscarinic acetylcholine receptors in the basolateral amygdala during the formation, but not the expression, of stimulus-reward associations that mediate cue-induced cocaine-seeking behavior.

Amygdala↗
PubMed2003

Associations between genetic polymorphisms of Phase I and II metabolizing enzymes, p53 and susceptibility to esophageal adenocarcinoma.

The objectives of this exploratory case-control study were to evaluate whether genetic polymorphisms of selected Phase I and II metabolizing enzymes are associated with the risk of developing primary esophageal adenocarcinoma, and to investigate potential associations between genotypes and p53 tumor suppressor gene alterations. Cases comprised 45 patients with surgically resected esophageal adenocarcinomas, defined according to strict clinico-pathologic criteria. PCR-based assays (RFLP/SSCP) were used to genotype cytochrome P450 (CYP) 1A1 [MspI; Ile:Val], microsomal epoxide hydroxylase (mEH) (fast and slow alleles), and glutathione S-transferase (GST) T1, M1 and P1. Healthy controls (n=45) from the same geographic region were matched for age, gender and smoking history. For GSTP1, the Ile/Val (a/b) and Val/Val (b/b) variants were seen at increased frequency in cases compared to controls (49% versus 27% and 15% versus 9%, respectively), although these differences achieved only borderline statistical significance (P=0.09). For mEH (exon 3), the presence of the Tyr polymorphism (slow allele) was reduced in cases (42%) compared to controls (53%; P=0.05). Predicted high mEH activity was seen more frequently in cases than controls (OR, 2.2; 95% CI, 0.7-7.3). Polymorphism frequencies for GSTT1, GSTM1, and CYP1A1 were not statistically different between cases and controls. Cases with the GSTT1 null genotype had tumors with altered p53 more frequently than did cases with the common form of GSTT1 (25 versus 6%, respectively; P=0.08). We conclude that polymorphisms of GSTP1 and mEH may be implicated in individual susceptibility to esophageal adenocarcinoma, possibly as a result of increased Phase I activation (mEH) and impaired Phase II detoxification (GSTP1). GSTT1 may also play a role in esophageal tumorigenesis through a pathway that involves abnormalities in the p53 tumor suppressor gene.

Adenocarcinoma↗
PubMed2003

Piezoelectric sensor determination of arterial pulse wave velocity.

Arterial pulse wave velocity (APWV) is a measure of the elasticity (or stiffness) of peripheral arterial blood vessels. The pulse referred to here will be the pressure pulse as opposed to the flow pulse measured by ultrasound Doppler. The pressure pulse velocity varies over the range from about 12 m s(-1) to 15 m s(-1) in stiff peripheral arteries, whereas in normal arteries it has a velocity in the range of 7 to 9 m s(-1). The aim of this project was the development of a fast and easy to use system for the determination of peripheral arterial pulse wave velocity. The principle of the PWV measurement is based on simultaneous measurement of two pulse waves at two different positions, such as the radial artery at the wrist and the brachial artery just above the elbow. By determining the pulse transit time between these points and the distance measured between the two locations, pulse wave velocity may then be calculated. The pressure pulse detection is done by using two piezoelectric sensors which generate a measurable voltage at the output contacts if they are mechanically deformed. The deformation produced voltage is first amplified and filtered and then digitalized with a data acquisition card. The analysis of the data obtained from the sensors includes a filtering process, the calculation of the PWV with three different methods--foot-to-foot, cross-correlation and peak-to-peak-and the determination of the arterial pulse rate. Extensive measurements with human test subjects were carried out to optimize the techniques of data acquisition and analysis. For example, it was found that the best procedure was to hold the sensors in place using elastic straps alone. The data analysis was upgraded with an additional software module, which deletes, in effect, outriders or invalid measurements. With the optimized system, a series involving eight test subjects ranging in age from 22 to 32 years was completed (all normotensive). The arterial pulse wave velocities determined covered a range from 6 m s(-1) to 12 m s(-1), with an average standard deviation of less than 2.5 m s(-1) for individual results. These are slightly higher, but close to published APWV data. The results showed that reproducible results can be obtained with the existing PWV acquirement and analysis system.

Arteries↗
PubMed2003

Development of molecular methods for the identification of aspergillus and emerging moulds in paraffin wax embedded tissue sections.

BACKGROUND/AIMS: Invasive infection with emerging moulds is increasing in incidence and reliable methods for speciating these organisms in tissue sections need to be developed. METHODS: Two methods for extracting fungal DNA from paraffin wax embedded tissue sections, based on the TaKaRa DEXPAT kit and QIAamp DNA mini kit, were optimised and compared. DNA was amplified by PCR using pan-fungal probes, and detected by Southern blot hybridisation using a high stringency method with a probe specific for Aspergillus fumigatus and A flavus. RESULTS: The method based on the TaKaRa DEXPAT kit, with additional steps using lyticase and ethanol precipitation, was superior. Less than 10 conidia were detectable using spiked samples and a positive result was obtained with 100% of clinical samples known to be culture positive for A fumigatus. Other moulds could be identified by using species specific probes or by sequencing PCR products. CONCLUSIONS: The method based on the TaKaRa DEXPAT kit could detect less than 10 conidia/sample. The method allowed accurate identification of A fumigatus and A flavus and other species could be identified using species specific probes or by DNA sequencing. These methods will provide a valuable diagnostic tool for both patient management and future antifungal and epidemiological studies.

Aspergillus↗
PubMed2002

Characterization of the neuronal changes in the medial prefrontal cortex during jaw movement and eyeblink Pavlovian conditioning in the rabbit.

Medial prefrontal (mPFC) single-unit activity was assessed in defensive (eyeblink, EB) and appetitive (jaw movement, JM) Pavlovian conditioning in the rabbit. Concomitant heart rate (HR) changes were also assessed. In a first experiment robust JM conditioned responses (CRs) were observed to a tone-water (CS+) contingency but not to tone-alone (CS-), indicating discriminative JM conditioning. However, the CS-evoked accelerative HR response was not discriminative. Nevertheless, several single-unit discharge patterns were evoked by both tone-water and tone-alone, many of which were uniquely associated with either the CS+ or CS-. In a second experiment, Three separate stimuli, consisting of tone followed by periorbital shock (tone-shock), water (tone-water), and white noise not followed by shock or water, were presented in the same paradigm. Discrimination of conditioned JM, EB and HR changes were observed, i.e. each of these behavioral responses were uniquely associated with the relevant CS presentation. Conditioned bradycardia was evoked by tone-water during the first training session, which changed to tachycardia with further training. However, conditioned bradycardia was evoked by tone-shock throughout training. Different subpopulations of mPFC cells were activated by the tone-shock and tone-water contingencies, but a small group of cells were activated by both.

Acoustic Stimulation↗
PubMed2001

A novel presenilin mutation (M233V) causing very early onset Alzheimer's disease with Lewy bodies.

Presenilin 1 mutations are the major cause of autosomal dominant Alzheimer's disease: here we identify a new missense mutation causing a methionine to valine change at codon 233. This codon is homologous to a pathogenic presenilin 2 mutation with the same base change (ATG to GTG) and amino acid change (M239V). This mutation causes disease with an exceptionally early onset age (approximately 30 years) in which pathological examination shows extensive Lewy bodies as well as plaques and tangles.

Adult↗
PubMed2001

Neuroprotective effects of an adenoviral vector expressing the glucose transporter: a detailed description of the mediating cellular events.

Considerable knowledge exists concerning the events mediating neuron death following a necrotic insult; prompted by this, there have now been successful attempts to use gene therapy approaches to protect neurons from such necrotic injury. In many such studies, however, it is not clear what sequence of cellular events connects the overexpression of the transgene with the enhanced survival. We do so, exploring the effects of overexpressing the Glut-1 glucose transporter with an adenoviral vector in hippocampal cultures challenged with the excitotoxin kainic acid (KA). Such overexpression enhanced glucose transport, attenuated the decline in ATP concentrations, decreased the release of excitatory amino acid neurotransmitters, and decreased the total free cytosolic calcium load. Commensurate with these salutary effects, neuronal survival was enhanced with this gene therapy intervention. Thus, the neuroprotective effects of this particular gene therapy occurs within the known framework of the mechanisms of necrotic neuronal injury.

Adenosine Triphosphate↗
PubMed2001

Cellular telephones and cancer--a nationwide cohort study in Denmark.

BACKGROUND: Use of cellular telephones is increasing exponentially and has become part of everyday life. Concerns about possible carcinogenic effects of radiofrequency signals have been raised, although they are based on limited scientific evidence. METHODS: A retrospective cohort study of cancer incidence was conducted in Denmark of all users of cellular telephones during the period from 1982 through 1995. Subscriber lists from the two Danish operating companies identified 420 095 cellular telephone users. Cancer incidence was determined by linkage with the Danish Cancer Registry. All statistical tests are two-sided. RESULTS: Overall, 3391 cancers were observed with 3825 expected, yielding a significantly decreased standardized incidence ratio (SIR) of 0.89 (95% confidence interval [CI] = 0.86 to 0.92). A substantial proportion of this decreased risk was attributed to deficits of lung cancer and other smoking-related cancers. No excesses were observed for cancers of the brain or nervous system (SIR = 0.95; 95% CI = 0.81 to 1.12) or of the salivary gland (SIR = 0.72; 95% CI = 0.29 to 1.49) or for leukemia (SIR = 0.97; 95% CI = 0.78-1.21), cancers of a priori interest. Risk for these cancers also did not vary by duration of cellular telephone use, time since first subscription, age at first subscription, or type of cellular telephone (analogue or digital). Analysis of brain and nervous system tumors showed no statistically significant SIRs for any subtype or anatomic location. CONCLUSIONS: The results of this investigation, the first nationwide cancer incidence study of cellular phone users, do not support the hypothesis of an association between use of these telephones and tumors of the brain or salivary gland, leukemia, or other cancers.

Adult↗
PubMed2001

A genetic epidemiological study of carcinoma of the fallopian tube.

OBJECTIVE: The goal of this work was to evaluate the importance of genetic factors in the etiology of fallopian tube cancer. METHODS: All pathologically confirmed cases of fallopian tube cancer diagnosed in Ontario from 1990 to 1998 were identified from the records of the Ontario Cancer Registry. Living patients were approached to provide information about their family history and to provide a blood sample for testing for mutations in BRCA1 and BRCA2. RESULTS: A modest increase in the risk of ovarian cancer (relative risk (RR) = 2.2; 95% confidence interval (CI) = 0.4, 6.3) and of early-onset breast cancer (RR = 2.4; 95% CI = 0.6, 6.1) was observed in the first-degree relatives of the fallopian cancer cases. Five of the forty-four cases were positive for a mutation in BRCA1 (11%) and two were positive for a BRCA2 mutation (5%). Five of eighteen women diagnosed at or before age 55 were positive (28%). Two of the seven mutation carriers had a strong family history of breast and ovarian cancer, and three carriers had a modest family history. Three of the forty-four cases were Jewish, and of these, two carried a founder mutation characteristic of this population. CONCLUSIONS: Fallopian tube carcinoma should be considered to be a clinical component of the hereditary breast-ovarian cancer syndrome, and may be associated with BRCA1 and BRCA2 mutations. Genetic evaluation should be offered to women who present with fallopian tube carcinoma. It is important to consider the risk of fallopian tube carcinoma when prophylactic oophorectomy is performed in high-risk women.

Adult↗
PubMed2001

Medial prefrontal lesions attenuate conditioned reflex facilitation but do not affect prepulse modification of the eyeblink reflex in rabbits.

Conditioned reflex facilitation occurs when the amplitude of the eyeblink (EB) unconditioned reflex (UR) is increased as a result of prior pavlovian conditioning. Prepulse modification of the EB reflex is produced by preceding the unconditioned stimulus (US) by a brief low-level neutral stimulus. This study examined both conditioned EB facilitation and prepulse modification in rabbits with either medial prefrontal (mPFC) lesions or sham lesions. Conditioned reflex facilitation was assessed by comparing EB UR amplitude prior to and after pavlovian EB conditioning. Animals that received CS/US paired presentations showed evidence of conditioned reflex facilitation, but animals with unpaired training did not. However, this increase in EB UR magnitude in the paired groups was smaller in animals with mPFC lesions, compared to those with sham lesions. In two subsequent experiments different groups of sham and lesion animals received an intense burst of white noise preceded by tones with different interstimulus interval durations to assess prepulse modification. Unlike conditioned facilitation, prepulse modification was unaffected by mPFC lesions.

Acoustic Stimulation↗