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Biomedical subjects

A Lynn

Publications and source records attributed to A Lynn.

At least 19 recordsLinked to original sources
PubMed2004

Chronic physical exercise reduces anxiety-like behavior in rats.

While many individuals with anxiety disorders receive drug therapy, many do not respond or adversely respond to drugs. An alternative treatment, exercise, has been shown to relieve negative feelings and induce positive shifts in mood. The purpose of this study was to establish an animal model to specifically test the effects of chronic physical exercise on anxiety-related behaviors. Thirty-two male Sprague Dawley rats were divided into two groups: runners (R) and nonrunners (NR). Runners ran on a treadmill for 45 minutes a day, five days a week, for ten weeks at a moderate intensity. Nonrunners remained in their cages in the treadmill room during the running period and were handled for an equal amount of time. After ten weeks of training, two behavioral tests were administered including the elevated plus maze and open field tests. Results comparing R and NR showed higher responses by R in percent open arm time and center square time during the elevated plus maze test, as well as in number of entries into the center, number of rears, and lower fecal boli count during the open field test, p < 0.05. In addition, there were no differences in total activity levels between groups as indicated by similar closed arm entries in the elevated plus maze test and total lines crossed in the open field test. These results indicate that treadmill training reduces anxiety-like behaviors in two animal tests of anxiety, without a significant change in total activity levels. These data are in support of treadmill training as a model to test the anxiolytic effects of exercise.

Animals↗
PubMed2004

Cytological studies of meiotic recombination in human males.

We combined immunostaining and fluorescence in situ hybridization (FISH) methodology to directly examine meiotic exchanges in over 2,000 pachytene stage spermatocytes from 25 individuals. Our results indicate that, on average, there are about 50 exchanges per cell and that, with the exception of the acrocentric chromosomes, all chromosome arms harbor at least one exchange. We also identified significant among-individual variation in the mean number of exchanges, with an approximate 20% difference between individuals with "low" and those with "high" exchange frequencies.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Radiological stenting provides effective palliation in malignant central venous obstruction.

Malignant superior vena caval obstruction (SVCO) due to lung cancer carries a poor prognosis and response to palliative radiotherapy is variable. Eighteen patients presenting with the appearance of malignant SVCO (thirteen due to primary bronchial tumours) in a four year period from June 1995 to July 1999 underwent venography with a view to placement of an expanding metal stent under radiological control. Fourteen patients were male and four female with a mean age at presentation of 65 years (range 44-84 years). At venography only three patients had isolated SVC stenosis, fivealso had brachiocephalic, internal jugular or subclavian vein stenoses and one had an isolated right brachiocephalic stenosis. Venography demonstrated thrombus in eight of the remaining patients, seven in association with stenosis. In one patient stenosis of the SVC was thought to be due to radiation fibrosis as no mass was visible. All underwent Seldinger catheterization of the great veins via a right femoral puncture with deployment of the stent over a guide wire. Balloon angioplasty was performed prior to stent placement in eight patients. The eight patients with thrombus underwent thrombolysis using rt-PA (recombinant tissue-type plasminogen activator) with subsequent stent placement in seven. Radiological relief of obstruction with abolition of collateral flow was observed in all cases. One patient required further stenting for recurrent obstruction after 160 days of palliation. The median duration of palliation after stenting was 87 days. No procedure-related morbidity was observed. Thrombolysis was of value in patients with occlusive thrombus, either in isolation or complicating a malignant stricture, where radiotherapy may not have been effective. Radiological stenting is a safe technique which offers rapid palliation of SVCO.

Adult↗
PubMed2001

Biochemical, biophysical, and functional characterization of bacterially expressed and refolded receptor binding domain of Plasmodium vivax duffy-binding protein.

Invasion of erythrocytes by malaria parasites is mediated by specific molecular interactions. Plasmodium vivax is completely dependent on interaction with the Duffy blood group antigen to invade human erythrocytes. The P. vivax Duffy-binding protein, which binds the Duffy antigen during invasion, belongs to a family of erythrocyte-binding proteins that also includes Plasmodium falciparum sialic acid binding protein and Plasmodium knowlesi Duffy binding protein. The receptor binding domains of these proteins lie in a conserved, N-terminal, cysteine-rich region, region II, found in each of these proteins. Here, we have expressed P. vivax region II (PvRII), the P. vivax Duffy binding domain, in Escherichia coli. Recombinant PvRII is incorrectly folded and accumulates in inclusion bodies. We have developed methods to refold and purify recombinant PvRII in its functional conformation. Biochemical, biophysical, and functional characterization confirms that recombinant PvRII is pure, homogeneous, and functionally active in that it binds Duffy-positive human erythrocytes with specificity. Refolded PvRII is highly immunogenic and elicits high titer antibodies that can inhibit binding of P. vivax Duffy-binding protein to erythrocytes, providing support for its development as a vaccine candidate for P. vivax malaria. Development of methods to produce functionally active recombinant PvRII is an important step for structural studies as well as vaccine development.

Amino Acid Sequence↗
PubMed2001

Metacognitive remediation in adult ADHD. Treating executive function deficits via executive functions.

The neuropathology underlying ADHD most consistently points to dysfunction in corticostriatal pathways--leading to inactivation, or insufficient engagement, of frontal and prefrontal lobes. By implication there may be functional disconnection between the anterior and posterior higher cortical regions, instead of a fixed dysfunction in either one. Given this premise, reconnection of these systems via cognitive interventions constitutes a logical remedial approach in the treatment of ADHD, which this paper introduces. In particular, a hybrid model is developed which proposes integration of existing psychodynamic, cognitive, and neuropsychological interventions. An organizing theme is expansion of metacognitive understanding through these procedures, powerfully exemplified via use of metaphor in clinical vignettes.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Generation of retroviral packaging and producer cell lines for large-scale vector production and clinical application: improved safety and high titer.

For many applications, human clinical therapies using retroviral vectors still require many technological improvements in key areas of vector design and production. These improvements include higher unprocessed manufacturing titers, complement-resistant vectors, and minimized potential to generate replication-competent retrovirus (RCR). To address these issues, we have developed a panel of human packaging cell lines (PCLs) with reduced homology between retroviral vector and packaging components. These reduced-homology PCLs allowed for the use of a novel high multiplicity of transduction ("high m.o. t.") method to introduce multiple copies of provector within vector-producing cell lines (VPCLs), resulting in high-titer vector without the generation of RCR. In a distinct approach to increase vector yields, we integrated manufacturing parameters into screening strategies and clone selection for large-scale vector production. Collectively, these improvements have resulted in the development of diverse VPCLs with unprocessed titers exceeding 2 x 10(7) CFU/ml. Using this technology, human Factor VIII VPCLs yielding titers as high as 2 x 10(8) CFU/ml unprocessed supernatant were generated. These cell lines produce complement-resistant vector particles (N. J. DePolo et al., J. Virol. 73: 6708-6714, 1999) and provide the basis for an ongoing Factor VIII gene therapy clinical trial.

Base Sequence↗
PubMed2000

Patterns of meiotic recombination on the long arm of human chromosome 21.

In this study we quantify the features of meiotic recombination on the long arm of human chromosome 21. We constructed a 67. 3-centimorgan (cM) high-resolution, comprehensive, and accurate genetic linkage map of chromosome 21q using 187 highly polymorphic markers covering almost the entire long arm; 46 loci, consisting of mutually recombining marker sets, were ordered with greater than 1000:1 odds and with average interlocus distance of 1.46 cM. These markers were used to accurately identify all exchanges in 186 female and 160 male meioses and to show (1) significant excess of recombination in female versus male meioses, (2) an overall decline in female:male recombination between the centromere and the telomere, (3) greater positive chiasma interference in male than in female meioses, and (4) lack of correlation between exchange frequency and parental age. By comparing the genetic map with the 21q sequence map, we show a general trend of increasing male, but near-constant female, recombination versus physical distance across 21q, explaining the gender-specific recombination effect. The recombination rate varies considerably between genders across 21q but is the greatest (eightfold) in the pericentromeric region, with a rate of approximately 250 kb/cM in females and approximately 2125 kb/cM in males. We used information on the locations of all exchanges to construct an empirical map function that confirms the statistical findings of positive interference. These analyses reveal that occurrence of recombination on 21q is not only gender-specific but also region-specific and that recombination suppression at the centromere is not universal. We also find evidence that male exchange location is highly correlated with gene density.

Adolescent↗
PubMed1999

Heme binding and polymerization by Plasmodium falciparum histidine rich protein II: influence of pH on activity and conformation.

The histidine rich protein II (HRPII) from Plasmodium falciparum has been implicated as a heme polymerase which detoxifies free heme by its polymerization to inactive hemozoin. Histidine-iron center coordination is the dominant mechanism of interaction between the amino acid and heme. The protein also contains aspartate allowing for ionic/coordination interactions between the carboxylate side chain and the heme metal center. The pH profile of heme binding and polymerization shows the possibility of these two types of binding sites being differentiated by pH. Circular dichroism studies of the protein show that pH and heme binding cause a change in conformation above pH 6 implying the involvement of His-His+ transitions. Heme binding at pHs above 6 perturbs HRPII conformation, causing an increase in helicity.

Animals↗
PubMed1998

Two sequence-ready contigs spanning the two copies of a 200-kb duplication on human 21q: partial sequence and polymorphisms.

Physical mapping across a duplication can be a tour de force if the region is larger than the size of a bacterial clone. This was the case of the 170- to 275-kb duplication present on the long arm of chromosome 21 in normal human at 21q11.1 (proximal region) and at 21q22.1 (distal region), which we described previously. We have constructed sequence-ready contigs of the two copies of the duplication of which all the clones are genuine representatives of one copy or the other. This required the identification of four duplicon polymorphisms that are copy-specific and nonallelic variations in the sequence of the STSs. Thirteen STSs were mapped inside the duplicated region and 5 outside but close to the boundaries. Among these STSs 10 were end clones from YACs, PACs, or cosmids, and the average interval between two markers in the duplicated region was 16 kb. Eight PACs and cosmids showing minimal overlaps were selected in both copies of the duplication. Comparative sequence analysis along the duplication showed three single-basepair changes between the two copies over 659 bp sequenced (4 STSs), suggesting that the duplication is recent (less than 4 mya). Two CpG islands were located in the duplication, but no genes were identified after a 36-kb cosmid from the proximal copy of the duplication was sequenced. The homology of this chromosome 21 duplicated region with the pericentromeric regions of chromosomes 13, 2, and 18 suggests that the mechanism involved is probably similar to pericentromeric-directed mechanisms described in interchromosomal duplications.

Cell Line↗
PubMed1998

Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery.

UNLABELLED: We analyzed morphine clearance values in infants receiving the drug by continuous i.v. infusion for analgesia after surgery, because we found lower steady-state morphine concentrations than we expected from our previous studies. Infants received morphine after a loading dose of 0.05 mg/kg and continuous infusion calculated to reach a steady-state concentration of 20 ng/mL. Blood was sampled twice on Postoperative Day 1 at times separated by at least 2 h, and morphine and morphine-6-glucuronide (M-6-G) concentrations were determined by high-performance liquid chromatography. Clearance of morphine was calculated as infusion rate divided by the steady-state morphine concentration. Morphine given to 26 infants by continuous i.v. infusion after major noncardiac surgery has rapidly increasing clearance values, from a median value of 9.2 mL x min(-1) x kg(-1) in infants 1-7 days old, 25.3 in infants 31-90 days old, and 31.0 in infants 91-180 days old to 48.9 in infants 180-380 days old. Adult clearance values are reached by 1 mo of age, more quickly than in infants of the same age previously studied who received morphine after cardiac surgeries. M-6-G was measured in all infants. The ratio of M-6-G to morphine concentrations was 1.9-2.1 in these infants, which is lower than ratios reported in older infants or adults by others, but higher than those reported in newborns. Infants with normal cardiovascular systems undergoing surgery clear morphine more efficiently than infants of the same age undergoing cardiac surgery. IMPLICATIONS: Morphine removal from the body is slow in newborns but increases to reach adult values in the first months of life. Calculating the clearance of morphine from blood samples drawn during continuous i.v. infusions after surgery shows that this maturation occurs more quickly in infants undergoing noncardiac surgery (by 1-3 mo of age) than in those receiving morphine after cardiac surgery (by 6-12 mo of age).

Age Factors↗
PubMed1998

A study of the prevalence of Helicobacter pylori infection and other markers of upper gastrointestinal tract disease in patients with rosacea.

OBJECTIVE: Recent reports have suggested that patients with rosacea, a chronic inflammatory skin disorder of unknown etiology, have an increased prevalence of Helicobacter pylori infection. However, no causal relation has been identified. This study was designed to determine the prevalence of H. pylori infection and upper gastrointestinal symptoms in rosacea patients and in subjects without chronic skin disorders. METHODS: Forty-five patients with rosacea and 43 healthy subjects underwent serological testing for H. pylori infection. Demographics, gastrointestinal symptoms, and medication use were recorded using a structured questionnaire. RESULTS: There was no significant difference in the seroprevalence of H. pylori infection between rosacea patients and healthy subjects (26.7% vs 34.9%; p = 0.40). Significantly more patients with rosacea complained of indigestion (66.7% vs 32.6%; p = 0.001) and used antacids (60% vs 32.6; p = 0.01). There was no significant difference in the prevalence of H. pylori infection between symptomatic and asymptomatic rosacea patients, or in those using antacids. There were no differences in the frequency of heartburn, history of peptic ulcer disease, family history of peptic ulcer disease, use of H2-receptor antagonists, or use of nonsteroidal antiinflammatory drugs. CONCLUSIONS: Patients with rosacea have similar rates of H. pylori infection as healthy subjects. Rosacea patients complain significantly more frequently of "indigestion" and use more antacids unrelated to H. pylori infection.

Adult↗
PubMed1998

Pain scores in infants: a modified infant pain scale versus visual analogue.

This study describes an observational system (modified infant pain scale, MIPS) with elements from a previously published observational scale and from assessments of video-recorded infant facial expressions. It was designed to allow rapid and repeated assessments of pain in infants after brief training by an observer without pediatric experience. Forty healthy term infants (17 +/- 7 weeks) undergoing elective surgery had simultaneous independent assessment of pain using two scales: a naive observer used the MIPS and an experienced pediatric nurse used a 10-cm unmarked horizontal visual analogue scale (VAS). This validation of the MIPS included its division during analysis into partial (P-MIPS, without data on sleep or vital signs) and total scores. Infants had a broad range of MIPS scores, and the two scales categorized infants as "comfortable" or "not comfortable" with a high degree of concordance. The MIPS was easily incorporated into an infant's physical examination. We recommend its use for two-point clinical pain assessment.

Female↗
PubMed1997

Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human chromosome 21q22.3.

To contribute to the development of the transcript map of human chromosome 21 and to the understanding of the pathogenesis of Down syndrome, we have used exon trapping to identify portions of genes from pools of HC21-specific cosmids. More than 550 potential exons have been isolated to date. One such trapped exon, hmc37a09 (GenBank Accession No. X88106), was identical to a region of a human EST, L12425 (GenBank Accession No. D31072). Its predicted amino acid sequence was homologous to the homeodomain region of homeobox-containing genes. Using the trapped sequence and the EST as probes to screen human fetal brain and kidney cDNA libraries, we have cloned the corresponding full-length cDNA. This novel gene encodes a homeodomain-containing polypeptide of 436 amino acids. The most closely related sequence is that of the mouse Meis1, a PBX-like homeobox gene. The homeodomain of the novel gene is closely related to those of the mammalian PBX family and the plant Knotted1 family (involved in plant development). This gene is named PKNOX1 by the Human Nomenclature Committee. By PCR amplification, hybridization, and genetic linkage analysis using a (GT)n polymorphism in the 3'UTR, we have precisely localized PKNOX1 to chromosome 21q22.3 between markers D21S212 and D21S25 on YAC350F7. PKNOX1 is expressed in many human tissues tested by Northern blot analysis. The involvement of the PKNOX1 gene in Down syndrome and/or monogenic disorders associated with dysfunction of this gene is presently unknown. Targeted disruption of the PKNOX1 homolog in mice will enhance our understanding of its biological function in normal mammalian development.

Amino Acid Sequence↗
PubMed1997

Antigen presentation in retroviral vector-mediated gene transfer in vivo.

We have examined mechanisms involved in gene transfer, protein expression, and antigen presentation after direct administration of retroviral vectors using a variety of antigen systems. We have identified transduced infiltrating cells at the injection site, and the majority of the infiltrating cells were of the monocyte/macrophage lineage. We found that the splenic dendritic cell fraction contained proviral DNA, expressed antigenic proteins, and was able to present antigens efficiently to the immune system. Furthermore, the dendritic cell fractions from retroviral vector-immunized mice were able to prime naive T cells in vitro, and adoptive transfer of in vitro-transduced dendritic cell fractions elicited antigen-specific cytotoxic T lymphocytes. These data suggest a role for dendritic cells in induction of immune responses elicited by retroviral vector-mediated gene transfer.

Adoptive Transfer↗
PubMed1997

Transthyretin amyloidosis: a new mutation associated with dementia.

Familial transthyretin (TTR) amyloidosis commonly presents with peripheral neuropathy and involvement of visceral organs. In contrast, signs of central nervous system (CNS) involvement are exceptional. We report that members of a kindred affected by a slowly progressive dementia, seizures, ataxia, hemiparesis, and decreased vision without neuropathy have TTR amyloid deposits in the leptomeninges, the brain parenchyma, and the eye. This condition, previously labeled oculoleptomeningeal amyloidosis, is linked to a mutation at codon 30 of TTR gene, resulting in the substitution of valine with glycine in this family, TTR amyloid deposits were present in the leptomeninges, especially the leptomeningeal vessels, and in the subependymal regions of the ventricular system where they disrupted the ependymal lining and resulted in amyloid-glial formations protruding into and narrowing the ventricular system. Hydrocephalus and atrophy and infarction of cerebral and cerebellar cortexes were also present. Review of the literature shows that amyloid deposition in the leptomeninges is not uncommon in TTR amyloidoses clinically characterized by peripheral neuropathy and lack of CNS signs. The present kindred, which presented exclusively with signs of CNS involvement, expands the phenotype of TTR amyloidosis and raises questions concerning the mechanisms determining phenotypic expression in TTR familial amyloidosis.

Amyloid Neuropathies↗