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Biomedical subjects

C Barrett

Publications and source records attributed to C Barrett.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of point-of-collection screening of drugs of abuse in oral fluid with a laboratory-based urine screen.

Oral fluid is becoming increasingly useful for the detection of drugs, since it is a non-invasive specimen to collect and, because collection is directly observed, it is difficult to adulterate. A point-of-collection (POCT) oral fluid drug analysis kit has been developed for use in many drug testing situations. This paper summarizes the results of field evaluations of the ORALscreen System for screening of drugs in oral fluid. The ORALscreen System consists of an oral fluid collection device and a test device containing a lateral flow membrane immunoassay system. Paired samples (oral fluid and urine) were collected from drug users and the results from the ORALscreen POCT system were compared to urine screening results conducted in a licensed laboratory. The results demonstrate that the ORALscreen System has excellent percent agreement with the laboratory-based urine screening test results for the detection of cocaine and opiates through 2.5-3 days following drug use, respectively. Tetrahydrocannabinol (THC) was detected by ORALscreen on the day of use and 1 day after use. Good correlation between urine and oral fluid screening results was observed for the methamphetamine positive samples; however, the number of days following drug use was not determined.

Clinical Laboratory Techniques↗
PubMed2001

What is the value added by human intervention in protein structure prediction?

This article presents results of blind predictions submitted to the CASP4 protein structure prediction experiment. We made two sets of predictions: one using the fully automated SAM-T99 server and one using the improved SAM-T2K method with human intervention. Both methods use iterative hidden Markov model-based methods for constructing protein family profiles, using only sequence information. Although the SAM-T99 method is purely sequence based, the SAM-T2K method uses the predicted secondary structure of the target sequence and the known secondary structure of the templates to improve fold recognition and alignment. In this article, we try to determine what aspects of the SAM-T2K method were responsible for its significantly better performance in the CASP4 experiment in the hopes of producing a better automatic prediction server. The use of secondary structure prediction seems to be the most valuable single improvement, though the combined total of various human interventions is probably at least as important.

Adenosine Triphosphatases↗
PubMed2001

Panic disorder.

In this article, the authors review the most recent advances in the pharmacotherapy, psychotherapy, and combined therapy for panic disorder. The authors focus on peer-reviewed data and on pragmatic clinical approaches that may help patients suffering from panic disorder.

Anti-Anxiety Agents↗
PubMed2001

Expression patterns of the netrin receptor UNC5H1 among developing motor neurons in the embryonic rat hindbrain.

The axon guidance molecule netrin-1 has been implicated in the midline repulsion of developing cranial motor axons. We have examined expression patterns of the netrin receptors UNC5H1 and DCC in embryonic rat hindbrains, in combination with labelling of developing motor neurons. We found that UNC5H1 expression colocalised with a number of cranial motor neuron subpopulations from embryonic day 11 (E11) to E14, while DCC was expressed by motor neurons at E12.

Animals↗
PubMed2001

Estimation of sex from the talus in prehistoric Native Americans.

We present both a multivariate discriminant analysis and a univariate procedure to estimate sex from measures of the talus (length, width and height). Both methods are comparable in accuracy (about 85%), but the univariate procedure ispreferred due to its simplicity.

Adult↗
PubMed2000

Lamivudine without HBIg for prevention of graft reinfection by hepatitis B: long-term follow-up.

BACKGROUND: This open, multicenter study was conducted to evaluate the efficacy and safety of lamivudine prophylaxis given to chronic hepatitis B virus-(HBV) infected patients before and after orthotopic liver transplantation (OLT). We now present long-term data that follow our previous short-term report. METHODS: Twenty-three patients were treated with lamivudine (100 mg orally, daily); 13 (57%), were serum HBV DNA positive (Abbott Genostics, Abbott Laboratories, Chicago, IL) at study entry. Patients received lamivudine for at least 4 weeks before OLT, and for up to 50 months (median 25 months) after OLT. RESULTS: Of the 23 treated patients, 17 survived to undergo OLT. Eleven patients (65%) survived up to 4 years (median 36 months) after OLT. One of the survivors stopped lamivudine because of a possible adverse reaction 9 months post-OLT, and prophylaxis with HBV immune globulin was then established. Ten survivors continue lamivudine. Eight long-term survivors have normal liver function without evidence of HBV reinfection. Of the 17 transplanted patients, 6 died. Four patients died (3 days to 5 months post-OLT) without evidence of graft reinfection. Two further patients died at 19 and 23 months post-OLT from graft failure. Both patients had YMDD variant detected at 12 months post-OLT. Two other patients with YMDD-variant HBV remain alive on lamivudine, 9 and 15 months after development of the variant. CONCLUSIONS: Lamivudine, given before and after OLT, prevents significant graft reinfection for the majority of treated patients. The study has also shown that lamivudine is extremely well tolerated by liver failure patients and for a prolonged period after transplantation.

Biopsy↗
PubMed2000

Expression of p300-truncated fragments results in the modulation of apoptosis in rat mesangial cells.

BACKGROUND: Mesangial cell proliferation, apoptosis, and matrix deposition have pivotal roles in the pathogenesis of renal diseases such as diabetic nephropathy and glomerulonephritis. The behavior of mesangial cells depends on the integration of intracellular signals elicited by hormones and cytokines. We hypothesized that p300 is primarily involved in the integration of signal transduction pathways in rat mesangial cells (RMCs) and that interference with p300 function will alter apoptotic signals. METHODS: We established an RMC cell line expressing the Tet-activator (tTA). RMC-tTA cells were transiently transfected with vectors coding for either the N-terminal third or the C-terminal third of p300. Expression was induced by the addition of doxycycline [Dox; 1 microg/mL; 5% fetal bovine serum (FBS)]. The percentage of apoptosis was determined using the TUNEL technique. Specific protein-protein interactions were determined by Western blot analysis of immunoprecipitated complexes. Cells were treated with 5% FBS or with H2O2 (500 micromol/L, 1 h) with and without Dox. RESULTS: The expression of p300-C resulted in increased susceptibility to low serum-induced (20.0 +/- 4.6 vs. 3.0 +/- 1.7%) and to H2O2-induced apoptosis (75.3 +/- 13.3 vs. 50.8 +/- 6.5%) compared with controls. Immunoprecipitation of p300-C showed an interaction with the transcription factor c-Fos, which was enhanced by H2O2 treatment. Expression of the p300-N resulted in a rescue (34.8 +/- 6. 4 vs. 50.8 +/- 6.5%) from H2O2-induced apoptosis compared with controls. P300-N was shown to form a complex with the transcription factor nuclear factor-kappaB (NF-kappaB). CONCLUSIONS: The data indicate that endogenous p300 is involved in apoptosis in mesangial cells. We propose that interference or enhancement of endogenous p300 function, by expression of exogenous fragments, can alter interactions with c-Fos or NF-kappaB and modulate signals during cellular stress.

Animals↗
PubMed2000

The globalization of nursing knowledge.

External influences placed upon nurses working in universities and in clinical practice require them to attract research funding, carry out research, generate new knowledge and publish in national and international journals. While there does not appear to be an agreed, unified body of nursing knowledge, critical and scholarly debate is essential to generate knowledge, but this is not an activity in which the majority of nurses can effectively participate. Nevertheless, nurses in the Western world are free to communicate their research, theories or ideas, essentially uncensored, to a vast invisible audience, and there is global dissemination through a vast array of literature and educational materials. This paper challenges nurses to examine the implications of globalization and suggests that the continuing debate on the nature of nursing knowledge should be updated to include consideration of both a change in philosophical stance and the far reaching effects of global dissemination of information.

Attitude of Health Personnel↗
PubMed2000

Diurnal and dietary-induced changes in cholesterol synthesis correlate with levels of mRNA for HMG-CoA reductase.

We determined the extent to which diurnal variation in cholesterol synthesis in liver is controlled by steady-state mRNA levels for the rate-limiting enzyme in the pathway, hydroxymethylglutaryl (HMG)-CoA reductase. Rats 30 days of age and maintained on a low-cholesterol diet since weaning were injected intraperitoneally with (3)H(2)O. The specific radioactivity of the whole-body water pool soon became constant, allowing for expression of values for incorporation of label into cholesterol as absolute rates of cholesterol synthesis. In liver, there was a peak of cholesterol synthesis from 8 pm to midnight, a 4-fold increase over synthesis rates from 8 am to noon. Increases in synthesis were quantitatively in lock step with increases in mRNA levels for HMG-CoA reductase occurring 4 h earlier. In a parallel experiment, rats received 1% cholesterol in the diet from weaning to 30 days of age. Basal levels of hepatic cholesterol synthesis were greatly diminished and there was little diurnal variation of cholesterol synthesis or of levels of mRNA for HMG-CoA reductase. Levels of mRNA for the low density lipoprotein receptor and scavenger receptor-B1 (putative high density lipoprotein receptor) showed little diurnal variation, regardless of diet. This suggests that diurnal variation of hepatic cholesterol synthesis is driven primarily by varying the steady-state mRNA levels for HMG-CoA reductase. Other tissues were also examined. Adrenal gland also showed a 4-fold diurnal increase in accumulation of recently synthesized cholesterol. In contrast to liver, however, there was little corresponding change in mRNA expression for HMG-CoA reductase. Much of this newly synthesized cholesterol may be of hepatic origin, imported into adrenal by SR-B1, whose mRNA was up-regulated 2-fold. In brain, there was no diurnal variation in either cholesterol synthesis or mRNA expression, and no influence of high- or low-cholesterol diets on synthesis rates or HMG-CoA reductase mRNA levels.

Adrenal Glands↗
PubMed1999

Predicting protein structure using only sequence information.

This paper presents results of blind predictions submitted to the CASP3 protein structure prediction experiment. We made predictions using the SAM-T98 method, an iterative hidden Markov model-based method for constructing protein family profiles. The method is purely sequence-based, using no structural information, and yet was able to predict structures as well as all but five of the structure-based methods in CASP3.

Algorithms↗
PubMed1999

Calcium influx and activation of calpain I mediate acute reactive gliosis in injured spinal cord.

Buffering extracellular pH at the site of a spinal cord crush-injury may stimulate axonal regeneration in rats (1; Guth et al., Exp. Neurol. 88: 44-55, 1985). We demonstrated in cultured astrocytes that acidic pH initiates a rapid increase in immunoreactivity for GFAP (GFAP-IR), a hallmark of reactive gliosis (2; Oh et al., Glia 13: 319-322, 1995). We extended these studies by investigating the effects of certain treatments on reactive gliosis developing in situ in a rat spinal cord injury model. A significant reactive gliosis was observed within 2 days of cord lesion in untreated crush or vehicle-treated, crush control animals as evidenced by increased GFAP-IR and hypertrophy of astrocytes. By contrast, infusion of Pipes buffer (pH 7.4) into the lesion site significantly reduced this increase. The increased GFAP-IR appeared to be linked to Ca2+ influx since infusion of a blocker of L-type calcium channels, nifedipine, reduced the ensuing reactive gliosis significantly. While Ca2+ modulates many signaling pathways within cells, its effect on reactive gliosis appeared to result from an activation of calpain I. Calpain inhibitor I, a selective inhibitor of mu-calpain, also significantly reduced reactive gliosis. However, calpain inhibitor II, a close structural analog which blocks m-calpain, had no salutary effect. We suggest, therefore, that the initial reactive gliosis seen in vivo may result from the activation of a neutral, Ca2+-dependent protease, calpain I, through calcium influx.

Acute Disease↗
PubMed1999

Further clinical clarification of the muscle dysfunction in cervical headache.

The Headache Classification Committee of the International Headache Society listed impairments in cervical muscle function as criteria for headaches of cervical spine origin. Fifteen subjects with cervical headache and 15 controls were tested for the frequency of abnormal responses to passive stretching and abnormal muscle contraction. A new test of cranio-cervical flexion was used to assess the contraction of the deep neck flexors. Results indicated a trend towards a higher frequency of abnormal response to passive stretching of the muscles examined in the cervical headache group but only the upper trapezius proved significantly different to the control group. Deep neck flexor muscle contraction was significantly inferior in the cervical headache group. From the perspective of physical characterization of cervical headache, it appears that response from passive stretch of muscle may not be a strong criterion for cervical headache but deep neck flexor performance may have potential to identify musculoskeletal involvement in headache. The finding may also provide positive directions for conservative treatment of cervical headache.

Adult↗
PubMed1999

Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). The CAESAR Coordinating Committee.

The efficacy and safety of lamivudine in persons coinfected with human immunodeficiency virus (HIV) type 1 and hepatitis B virus (HBV) were examined in the CAESAR study, a randomized placebo-controlled trial assessing the addition of lamivudine (150 mg 2x/day) or lamivudine (150 mg 2x/day) plus loviride (100 mg 3x/day) to zidovudine-containing background antiretroviral treatment. Baseline hepatitis B surface antigen (HBsAg) results were available for 1790 study subjects, of whom 122 (6.8%) tested positive. Retrospective analyses for serial HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg) were performed on stored sera from 118 HBsAg-positive subjects. HBV DNA and HBeAg were present in 83% and 63%, respectively. At weeks 12 and 52, median log10 HBV DNA change was -2.0 and -2.7, respectively, in the lamivudine arms, compared with no reduction among placebo recipients (P<.001). A trend to lower alanine transferase level, and delayed progression of HIV-1 disease (relative hazard, 0.26; 95% confidence interval, 0.08-0.80) were also seen in the lamivudine arms, compared with the placebo group.

Acetamides↗
PubMed1998

Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods.

The sequences of related proteins can diverge beyond the point where their relationship can be recognised by pairwise sequence comparisons. In attempts to overcome this limitation, methods have been developed that use as a query, not a single sequence, but sets of related sequences or a representation of the characteristics shared by related sequences. Here we describe an assessment of three of these methods: the SAM-T98 implementation of a hidden Markov model procedure; PSI-BLAST; and the intermediate sequence search (ISS) procedure. We determined the extent to which these procedures can detect evolutionary relationships between the members of the sequence database PDBD40-J. This database, derived from the structural classification of proteins (SCOP), contains the sequences of proteins of known structure whose sequence identities with each other are 40% or less. The evolutionary relationships that exist between those that have low sequence identities were found by the examination of their structural details and, in many cases, their functional features. For nine false positive predictions out of a possible 432,680, i.e. at a false positive rate of about 1/50,000, SAM-T98 found 35% of the true homologous relationships in PDBD40-J, whilst PSI-BLAST found 30% and ISS found 25%. Overall, this is about twice the number of PDBD40-J relations that can be detected by the pairwise comparison procedures FASTA (17%) and GAP-BLAST (15%). For distantly related sequences in PDBD40-J, those pairs whose sequence identity is less than 30%, SAM-T98 and PSI-BLAST detect three times the number of relationships found by the pairwise methods.

Databases, Factual↗
PubMed1998

Azocarbazole Polymethacrylates as Single-Component Electrooptic Materials.

A series of amorphous azobenzene and carbazole-containing polymers was prepared, which incorporates both electrooptic activity and photoconductivity into a single multifunctional structural unit. The polymers were cast as thin films and were shown to be suitable for photoinducing birefringence reversibly with polarized light, as well as for the inscription of photorefractive diffraction gratings after electric field poling. Since the polymer series encompasses a range of spacer lengths (from 3 to 10 methylene groups) between the multifunctional side chains and the polymer backbone, these materials are suitable for study of the influence of chromophore mobility on these optical phenomena. The extent of orientational order which could be photoinduced in the films was found to decrease with increasing spacer length, as did the photoconductivity and the photorefractive two-beam optical coupling gain. In thin films of polymers with the highest glass transition temperature, a birefringence of 0.065 could be photoinduced, with a time constant of <0.8 s. A two-beam optical gain of 0.024 µm-1 was also demonstrated in films of the polymer with the highest glass transition temperature, although this gain was exceeded by absorption losses.

Journal Article↗
PubMed1998

Monocyte chemoattractant protein 1 is responsible for macrophage recruitment following injury to sciatic nerve.

Following injury to the peripheral nervous system, circulating monocytes/macrophages are recruited to the damaged tissue, where they play vital roles during both nerve degeneration and subsequent regeneration. Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C or beta-chemokine family, is a powerful leukocyte recruitment/activation factor that is relatively specific for monocytes/macrophages. Because these are the predominant leukocyte type recruited by injured nerve, we hypothesized that upregulation of MCP-1 expression is involved in recruitment of these cells. Indeed, assay of steady-state levels of MCP-1 mRNA in rat sciatic nerve during tellurium-induced primary demyelination indicated up-regulation of this chemokine with a peak after 3 days of tellurium exposure, preceding the peak of accumulation of phagocytic macrophages (assayed as lysozyme mRNA levels) by 6 days. Increasing levels of MCP-1 mRNA expression, induced by increasing levels of tellurium exposure, resulted in corresponding increases in subsequent recruitment of macrophages. In situ hybridization suggested that MCP-1 mRNA was localized in Schwann cells. No expression of MIP-2, which is a C-X-C or alpha-chemokine that is specific for recruitment of neutrophils, was detected, consistent with the lack of recruitment of significant numbers of these cells. In addition, we also investigated the response seen following nerve transection (axonal degeneration and secondary demyelination with no subsequent regeneration) and nerve crush (degeneration followed by regeneration). In these latter two nerve injury models, there was also a marked, early up-regulation of MCP-1 mRNA, with a time course that is compatible with a role for this chemokine in macrophage recruitment. We conclude that MCP-1 is involved in recruiting monocytes/macrophages to injured peripheral nerve and that the specificity of leukocyte types recruited results from specificity of chemokine production.

Animals↗