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Biomedical subjects

P Lee

Publications and source records attributed to P Lee.

At least 91 records · Page 5Linked to original sources
PubMed2000

Movement sequencing in children with Tourette's syndrome and attention deficit hyperactivity disorder.

Little research has been conducted to examine sequential motor functioning of children with Tourette's syndrome (TS) and attention deficit hyperactivity disorder (ADHD). Movement sequencing performance for a group of 12 children with TS and 24 children with ADHD children (12 taking and 12 not taking stimulant medication) and matched control subjects was examined using a serial choice reaction time button-pressing procedure. Aspects of movement preparation and execution were measured for 10 sequential two-way choice points along a response board that extinguished the illuminated target buttons at certain specific times contingent on the previous button press or release. The level of advance information was systematically reduced to provide three levels of reduction of advance information, including no reduction, moderate reduction, and high reduction. Children with TS and ADHD (unmedicated) showed larger increases in down time, reflecting aspects of movement preparation, for the highest level of reduction of advance information than did their respective control groups. These deficits are suggestive of underlying frontostriatal dysfunction. Furthermore, the normalization of performance for children with ADHD taking stimulant medication assists in the confirmation of the validity of such a clinical diagnosis and seems to add to the clinical efficacy of this form of treatment, which has previously been associated with improvements for predominantly attentional and inhibitory symptoms of ADHD.

Analysis of Variance↗
PubMed2000

Genomic structure of the human p47-phox (NCF1) gene.

The cytosolic factor p47-phox, encoded by the NCF1 gene, is an essential component of the phagocyte NADPH-oxidase system. Upon activation of this multicomponent system, p47-phox translocates to the membrane and participates in the electron transfer from NADPH to molecular oxygen. A deficiency or absence of p47-phox is the most common autosomal form of chronic granulomatous disease (CGD). We have cloned and characterized the NCF1 gene from four bacteriophage clones, a P1 clone and genomic DNA from normal individuals. The gene is 15,236 base pairs long and includes 11 exons. It is 98.6% homologous in sequence to at least one pseudogene that maps to the same region of chromosome 7q11.23. Slightly more than half (50.37%) of the wild-type NCF1 gene consists of repetitive elements. In particular, the density of Alu sequences is high (1.4 Alu/kb); there are 21 Alu repeats interspersed through 10 introns. These findings are consistent with the observation that recombination events between the wild-type gene and its highly homologous pseudogenes account for the majority of potentially lethal mutations in p47-phox-deficient chronic granulomatous disease. Analysis of 1.96 kb of sequence 5' of the start of translation revealed a high homology (99.6%) between wild-type and pseudogene clones. Characterization of NCF1 establishes a foundation for detailed molecular analysis of p47-phox-deficient CGD patients as well as for the study of the regulation of the NCF1 gene and pseudogenes, both of which are present as full-length transcripts in normal individuals.

5' Untranslated Regions↗
PubMed2000

The ultraviolet environment of Mars: biological implications past, present, and future.

A radiative transfer model is used to quantitatively investigate aspects of the martian ultraviolet radiation environment, past and present. Biological action spectra for DNA inactivation and chloroplast (photosystem) inhibition are used to estimate biologically effective irradiances for the martian surface under cloudless skies. Over time Mars has probably experienced an increasingly inhospitable photobiological environment, with present instantaneous DNA weighted irradiances 3.5-fold higher than they may have been on early Mars. This is in contrast to the surface of Earth, which experienced an ozone amelioration of the photobiological environment during the Proterozoic and now has DNA weighted irradiances almost three orders of magnitude lower than early Earth. Although the present-day martian UV flux is similar to that of early Earth and thus may not be a critical limitation to life in the evolutionary context, it is a constraint to an unadapted biota and will rapidly kill spacecraft-borne microbes not covered by a martian dust layer. Microbial strategies for protection against UV radiation are considered in the light of martian photobiological calculations, past and present. Data are also presented for the effects of hypothetical planetary atmospheric manipulations on the martian UV radiation environment with estimates of the biological consequences of such manipulations.

Atmosphere↗
PubMed2000

Confocal imaging of N-methyl-D-aspartate receptors in living cortical neurons.

The fluorescence-conjugated N-methyl-D-aspartate receptor-selective antagonist, BODIPY-conantokin-G, was employed to label N-methyl-D-aspartate receptors in living neurons derived from the visual cortex of embryonic rats. The fluorescent labeling was visualized and analysed using confocal microscopy and digital imaging techniques. BODIPY-conantokin-G binding sites were homogeneously distributed across somata four days after neurons (E17-20) were placed in culture. In five-day-old cultures, BODIPY-conantokin-G binding sites became clusters of fluorescently labeled spots which were arranged irregularly on somata and proximal neurites. Distal neurites displayed fluorescent labeling after 10-15 days in culture. Displacement experiments showed that spermine and unlabeled conantokin-G compete with BODIPY-conantokin-G labeling at the N-methyl-D-aspartate receptor-associated polyamine site. The N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid also depressed the labeling but with a weaker effect, probably due to interactions occurring between the N-methyl-D-aspartate receptor agonist binding site and the polyamine modulatory site. The fluorescent dyes FM 1-43 and FM 4-64 were used in double-labeling studies to compare the distribution of nerve terminals with that of BODIPY-conantokin-G binding sites. BODIPY-conantokin-G binding clusters were associated with presynaptic nerve terminals while isolated BODIPY-conantokin-G binding sites were not always opposed to terminals. The aggregation of receptors to form clusters may lead to the functional formation of excitatory synapses. To investigate whether modulation of membrane potentials affected the formation of N-methyl-D-aspartate receptor clusters, cultured neurons were chronically treated for a week with either tetrodotoxin (to block membrane action potentials) or a high concentration of potassium to depolarize the membrane. While neurons in the tetrodotoxin-treated group showed a similar number of fluorescently labeled clusters compared with the control group, neurons in the high potassium group exhibited a higher number of fluorescently labeled receptor clusters. These results suggest that more active neurons may tend to form more N-methyl-D-aspartate synapses during early development.

Age Factors↗
PubMed2000

Publication bias in meta-analysis: its causes and consequences.

Publication bias is a widespread problem that may seriously distort attempts to estimate the effect under investigation. The literature is reviewed to determine features of the design and execution of both single studies and meta-analyses leading to publication bias, and the role the author, journal editor, and reviewer play in selecting studies for publication. Methods of detecting, correcting for, and preventing publication bias are reviewed. The design of the meta-analysis itself, and the studies included in it, are shown to be important among a number of sources of publication bias. Various factors influence an author's decision to submit results for publication. Journal editors and reviewers are crucial in deciding which studies to publish. Various methods proposed for detecting and correcting for publication bias, though useful, all have limitations. However, prevention of publication bias by registering every trial undertaken or publishing all studies is an ideal that is hard to achieve.

Epidemiologic Research Design↗
PubMed2000

Phakomatosis pigmentovascularis IIb with renal anomaly.

Phakomatosis pigmentovascularis (PPV) is a rare congenital naevoid syndrome; most case reports originate in Japan. The major clinical manifestations consist of coexisting extensive naevus flammeus and pigmentary naevus with or without systemic involvement. We report an 8-year-old Taiwanese boy, who was born with extensive naevus flammeus and other anomalies comprising persistent aberrant Mongolian spot-like pigmentary patches, leg-length discrepancy, pelvic obliquity, scoliosis and bilateral melanosis oculi bulbi. Further investigation also revealed agenesis of the right kidney. The cutaneous lesions remained unchanged over a 3-year follow-up period. Within the classification of PPV, this boy's disorder represents an example of PPV IIb. Right kidney agenesis, which has never been observed in PPV, may be an incidental finding.

Child↗
PubMed2000

Pretransplantation tumor necrosis factor-alpha production predicts acute rejection after liver transplantation.

Immunosuppressive therapy has many adverse effects in both the short and longer term. Tailoring immunosuppression might be possible if pretransplantation parameters predicted rejection. We investigated production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokine, interleukin-10 (IL-10), pretransplantation to determine whether there is a relation with acute rejection. Peripheral-blood mononuclear cells were obtained from patients with chronic liver disease on the waiting list for orthotopic liver transplantation and healthy controls. Cells (0.5 x 10(6)) were stimulated with 200 ng of lipopolysaccharide. Preincubation for 30 minutes with tacrolimus, cyclosporine, and dexamethasone at concentrations of 10 and 100 ng was also performed. TNF-alpha and IL-10 levels were measured by enzyme-linked immunosorbent assay. Acute rejection was defined on clinical and histological grounds. Pretransplantation in vitro production of TNF-alpha significantly (P <.05) increased in the group of patients with acute rejection (n = 9) compared with those who did not develop rejection (n = 12). Preincubation with dexamethasone significantly (P <.001) reduced TNF-alpha and IL-10 production in both patients and controls (n = 8). IL-10 production pretransplantation was not different in those who developed acute rejection (n = 9) compared with those who did not (n = 9). Preincubation with tacrolimus augmented (P <.05) the production of IL-10 in patients (n = 18), but not controls (n = 6). Pretransplantation TNF-alpha production is increased in patients who go on to develop acute rejection posttransplantion.

Acute Disease↗
PubMed2000

Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression.

Neuropilin-1 (NRP1) is a VEGF(165) and semaphorin receptor expressed by vascular endothelial cells (EC) and tumor cells. The function of NRP1 in tumor cells is unknown. NRP1 was overexpressed in Dunning rat prostate carcinoma AT2.1 cells using a tetracycline-inducible promoter. Concomitant with increased NRP1 expression in response to a tetracycline homologue, doxycycline (Dox), basal cell motility, and VEGF(165) binding were increased three- to fourfold in vitro. However, induction of NRP1 did not affect tumor cell proliferation. When rats injected with AT2.1/NRP1 tumor cells were fed Dox, NRP1 synthesis was induced in vivo and AT2.1 cell tumor size was increased 2.5- to 7-fold in a 3-4 wk period compared to controls. The larger tumors with induced NRP1 expression were characterized by markedly increased microvessel density, increased proliferating EC, dilated blood vessels, and notably less tumor cell apoptosis compared to noninduced controls. It was concluded that NRP1 expression results in enlarged tumors associated with substantially enhanced tumor angiogenesis.

Animals↗
PubMed2000

Rabbit facial nerve regeneration in autologous nerve grafts after antecedent injury.

OBJECTIVE: The effect of incomplete antecedent injuries on subsequent facial nerve regeneration within cable graft repairs is not known. The purpose of this study is to compare facial nerve regeneration after an immediate and delayed neural cable graft repair. METHOD: Rabbit facial nerve regeneration after complete transectional injuries of the buccal division was compared in two experimental models. In one, a 10-mm segment of the nerve was transected, rotated 180 degrees, and immediately repaired as a cable graft (N=8). In the second, a preliminary nerve crush was allowed to recover over a 4-week period and a 10-mm segment of nerve centered on the crush site was then transected, rotated 180 degrees, and delay repaired as a cable graft (N = 7). Data are presented as total numbers of regenerating myelinated axons that traverse the surgical repair to innervate the cable graft and distal nerve stumps, as well as the percentage of regenerating neurites compared with preoperative pooled and individual controls. Subpopulations of regenerating neurons are delineated to quantify the pattern of neural innervation. RESULTS: Five weeks after cable graft repair both groups had similar myelinated outgrowth from the proximal nerve stump across the proximal anastomosis to innervate the cable graft (3995 +/- 1209 vs. 3284 +/- 651; P = .89). However, the delayed repair group had more intrafascicular regeneration within cable grafts (2261 +/- 931 vs. 1660 +/- 1169; P = .02) and distal nerve stump (1532 +/- 281 vs. 445 +/- 120; P = .004) than the immediate repair group. The immediate repair group had greater extrafascicular nerve regeneration in the cable graft (2335 +/- 1954 vs. 437 +/- 236; P = .001) and more myelin and axonal debris in pre-existing neural fascicles of the cable graft (P = .02) and distal nerve stump (463 +/- 187 vs. 103 +/- 87; P = .02). CONCLUSIONS: Antecedent priming lesions do not enhance axonal survival as determined by regenerating myelinated axonal counts. However, antecedent injuries enhance the efficiency of neural innervation of the affected mimetic musculature by increasing the number of myelinated intrafascicular neural regenerants in the cable graft and distal nerve stump. This is accomplished by two factors: increased perineural fibrosis and decreased intrafascicular myelin and axonal debris.

Animals↗
PubMed2000

Conformational behavior of ionic self-complementary peptides.

Several de novo designed ionic peptides that are able to undergo conformational change under the influence of temperature and pH were studied. These peptides have two distinct surfaces with regular repeats of alternating hydrophilic and hydrophobic side chains. This permits extensive ionic and hydrophobic interactions resulting in the formation of stable beta-sheet assemblies. The other defining characteristic of this type of peptide is a cluster of negatively charged aspartic or glutamic acid residues located toward the N-terminus and positively charged arginine or lysine residues located toward the C-terminus. This arrangement of charge balances the alpha-helical dipole moment (C --> N), resulting in a strong tendency to form stable alpha-helices as well. Therefore, these peptides can form both stable alpha-helices and beta-sheets. They are also able to undergo abrupt structural transformations between these structures induced by temperature and pH changes. The amino acid sequence of these peptides permits both stable beta-sheet and alpha-helix formation, resulting in a balance between these two forms as governed by the environment. Some segments in proteins may also undergo conformational changes in response to environmental changes. Analyzing the plasticity and dynamics of this type of peptide may provide insight into amyloid formation. Since these peptides have dynamic secondary structure, they will serve to refine our general understanding of protein structure.

Amino Acid Sequence↗
PubMed2000

Antiapoptotic herpesvirus Bcl-2 homologs escape caspase-mediated conversion to proapoptotic proteins.

The antiapoptotic Bcl-2 and Bcl-x(L) proteins of mammals are converted into potent proapoptotic factors when they are cleaved by caspases, a family of apoptosis-inducing proteases (E. H.-Y. Cheng, D. G. Kirsch, R. J. Clem, R. Ravi, M. B. Kastan, A. Bedi, K. Ueno, and J. M. Hardwick, Science 278:1966-1968, 1997; R. J. Clem, E. H.-Y. Cheng, C. L. Karp, D. G. Kirsch, K. Ueno, A. Takahashi, M. B. Kastan, D. E. Griffin, W. C. Earnshaw, M. A. Veliuona, and J. M. Hardwick, Proc. Natl. Acad. Sci. USA 95:554-559, 1998). Gamma herpesviruses also encode homologs of the Bcl-2 family. All tested herpesvirus Bcl-2 homologs possess antiapoptotic activity, including the more distantly related homologs encoded by murine gammaherpesvirus 68 (gammaHV68) and bovine herpesvirus 4 (BHV4), as described here. To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. Only the viral Bcl-2 protein encoded by gammaHV68 was susceptible to caspase digestion. However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-x(L), and Bid, which are potent inducers of apoptosis, the cleavage product of gammaHV68 Bcl-2 lacked proapoptotic activity. KSBcl-2, encoded by the Kaposi's sarcoma-associated herpesvirus, was the only viral Bcl-2 homolog that was capable of killing cells when expressed as an N-terminal truncation. However, because KSBcl-2 was not cleavable by caspases, the latent proapoptotic activity of KSBcl-2 apparently cannot be released. The Bcl-2 homologs encoded by herpesvirus saimiri, Epstein-Barr virus, and BHV4 were not cleaved by apoptotic cell extracts and did not possess latent proapoptotic activities. Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death.

Amino Acid Sequence↗
PubMed2000

Evaluation of molecular techniques to biotype Giardia duodenalis collected during an outbreak.

Twenty-seven Giardia duodenalis cyst-positive specimens (human, animal, or drinking water) were obtained from a waterborne outbreak in a community in British Columbia, western Canada. Parasite isolates were characterized using molecular techniques at 4 different steps of organism retrieval. None of the drinking water samples (n = 20) infected gerbils and none was successfully amplified using polymerase chain reaction (PCR). We were able to genotype 4 of 7 (human and animal) isolates by amplification of DNA from original specimens at the triosephosphate isomerase (tpi) gene locus using PCR followed by restriction fragment length polymorphism (RFLP) analysis. Five of the original specimens inoculated into Mongolian gerbils (Meriones unguiculatus) were infective and genotyped at the tpi locus using parasite material collected from the gerbil (cysts and trophozoites). Pulsed field gel electrophoresis (PFGE) was used to biotype trophozoites collected from the gerbils as well as trophozoites from the 4 isolates that adapted to culture. Four of these 5 isolates displayed the same (designated outbreak) biotype at all parasite retrieval steps with all molecular techniques including the originally amplified isolates. PCR-RFLP identified an additional biotype group. The 4 isolates that adapted to in vitro culture were also characterized by isoenzyme electrophoresis (IE). Biotype groups identified in these axenized isolates were all the same with each molecular technique (PCR-RFLP, PFGE, IE) tested. Results of this study demonstrate a need for more sensitive molecular methods to detect and characterize Giardia in original host and environmental samples. Results are also consistent with evidence of biotype changes that occur during the presently used process of isolate retrieval.

Animals↗
PubMed2000

The subspecialty training, practice type, and geographical distribution of recently trained ophthalmologists: a study of male and female physicians.

OBJECTIVE: To characterize the distribution of male and female ophthalmologists with regard to practice type, subspecialty training, rural-urban distribution, and regional distribution. METHODS: Ophthalmology Matching Program files containing the records of residents who began their second year at accredited programs between 1986 and 1990 (inclusive), were compared to membership files of the American Academy of Ophthalmology. Practice locations for each individual were classified according to region, stage, and Rural-Urban Continuum County Code, as defined by the US Department of Agriculture. RESULTS: This cohort comprised 2,494 individuals, 77.1% (1922) of whom were male and 22.9% (572) of whom were female. Group practice was most common (55.9% for women and 61.3% for men). More women were in salaried positions associated with health maintenance organizations (p = 0.006) and academic settings (p < 0.001) than were men. Notable differences in subspecialty choice were restricted to pediatric ophthalmology, chosen three times more frequently by women, and vitreoretinal diseases/surgery, chosen twice as often by men. Only 5.6% of women selected nonmetropolitan practice locales compared to approximately twice that percentage of men. The Middle Atlantic and New England regions attracted more women, while the South Atlantic attracted more men.

Cohort Studies↗
PubMed2000

A case report of Aspergillus hypersensitivity syndrome with obstructing bronchial aspergillosis.

INTRODUCTION: A 62-year-old Indian male with diabetes mellitus presented with atypical, overlap features of Aspergillus hypersensitivity syndrome and obstructing bronchial aspergillosis. CLINICAL PICTURE: He was febrile and tachypnoeic with diffuse crepitations and wheezing. Chest X-ray was normal but eosinophil count was 2900/mm3 and Ig E > 10,000 IU/ml. TREATMENT AND OUTCOME: He responded initially to high dose steroid therapy but deteriorated subsequently from extensive mucus plugging of the bronchial tree which resulted in respiratory failure and death. He was HIV-negative. CONCLUSION: Culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs should be performed as early treatment may be life-saving.

Airway Obstruction↗