Biomedical subjects

E Allen

Publications and source records attributed to E Allen.

At least 37 records · Page 2Linked to original sources

PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome V.

Here we report the sequence of 569,202 base pairs of Saccharomyces cerevisiae chromosome V. Analysis of the sequence revealed a centromere, two telomeres and 271 open reading frames (ORFs) plus 13 tRNAs and four small nuclear RNAs. There are two Tyl transposable elements, each of which contains an ORF (included in the count of 271). Of the ORFs, 78 (29%) are new, 81 (30%) have potential homologues in the public databases, and 112 (41%) are previously characterized yeast genes.

Base Sequence↗

PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.

The nucleotide sequence of the 948,061 base pairs of chromosome XVI has been determined, completing the sequence of the yeast genome. Chromosome XVI was the last yeast chromosome identified, and some of the genes mapped early to it, such as GAL4, PEP4 and RAD1 (ref. 2) have played important roles in the development of yeast biology. The architecture of this final chromosome seems to be typical of the large yeast chromosomes, and shows large duplications with other yeast chromosomes. Chromosome XVI contains 487 potential protein-encoding genes, 17 tRNA genes and two small nuclear RNA genes; 27% of the genes have significant similarities to human gene products, and 48% are new and of unknown biological function. Systematic efforts to explore gene function have begun.

Base Sequence↗

PubMed1997

The Genome Sequence DataBase version 1.0 (GSDB): from low pass sequences to complete genomes.

The Genome Sequence DataBase (GSDB) has completed its conversion to an improved relational database. The new database, GSDB 1.0, is fully operational and publicly available. Data contributions, including both original sequence submissions and community annotation, are being accomplished through the use of a graphical client-server interface tool, the GSDB Annotator, and via GIO (GSDB Input/Output) files. Data retrieval services are being provided through a new Web Query Tool and direct SQL. All methods of data contribution and data retrieval fully support the new data types that have been incorporated into GSDB, including discontiguous sequences, multiple sequence alignments, and community annotation.

Animals↗

PubMed1997

Massive hemoptysis as the presenting manifestation in a child with histoplasmosis.

A previously healthy and asymptomatic 7-year-old white boy presented with a history of two episodes of hemoptysis productive of bright red blood in the 5 days preceding admission. After admission he developed massive hemoptysis that, on bronchoscopy, was noted to be emanating from the right lower lobe. An emergency right lower lobe resection was done. Pathological examination revealed hilar adenopathy and peripheral lesions with caseating granulomas containing yeast, morphologically consistent with Histoplasma capsulatum.

Amphotericin B↗

PubMed1997

Alterations in dopamine clearance and catechol-O-methyltransferase activity by dopamine infusions in children.

OBJECTIVE: To determine the role of catechol-O-methyltransferase (COMT) in the biodisposition of pharmacologic concentrations of dopamine. DESIGN: The study was an open-label dose escalation trial in which dopamine was employed as the sole exogenous catecholamine. The dosage was adjusted to achieve improvements in cardiac output or to augment renal function. SETTING: A 16-bed pediatric intensive care unit serving both medical and surgical patients. PATIENTS: The study was performed using 14 dopamine-treated and five untreated control patients. Children ranged in age from 16 days to 12 yrs; five of the treated patients and two of the untreated controls were female. All but one of the study patients were enrolled within 24 hrs of palliative or corrective surgery for congenital heart disease. Control patients had noncardiac surgical procedures. Both treated and control groups were similar with respect to severity of illness, as judged by Therapeutic Intervention Scoring System score. INTERVENTIONS: All treated patients received dopamine as a continuous intravenous infusion. Infusion rates were determined by caregivers and ranged from 3.0 to 20 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Serial, timed blood samples were obtained from patients and control subjects for the determination of plasma dopamine concentrations and for the determination of mononuclear cell COMT activity. Measured rates of dopamine infusion (3.0 to 18.3 micrograms/kg/min) were consistently less than the nominal rates (3.0 to 20.0 micrograms/kg/min) of infusion (p < .0001) due in part to calculations based on the hydrochloride salt rather than dopamine base. At similar steady-state infusion rates, plasma dopamine concentrations varied over a four-fold range, with steady-state concentrations at even the lowest infusion rate exceeding endogenous concentrations by at least ten-fold. Variations in steady-state plasma dopamine concentration reflected large age-associated variations in dopamine clearance, which was found to be saturable at concentrations of > 200 ng/mL. Mononuclear cell COMT activity was assessed simultaneously in these patients. Baseline COMT activity varied over a six-fold range and was unrelated to dopamine clearance or patient age. COMT activity increased two- to six-fold in dopamine-treated patients with plasma steady-state dopamine concentrations of > 100 ng/mL. CONCLUSIONS: These data demonstrate marked age and concentration-dependent differences in dopamine clearance that account for large interindividual differences in the steady-state plasma dopamine concentrations in patients receiving similar infusion rates. While concomitant variability in COMT activity is observed, the lack of correlation between dopamine clearance and COMT activity suggests that COMT is not rate-limiting for the clearance of exogenously administered dopamine.

Catechol O-Methyltransferase↗

PubMed1997

Fluorescent dye assay for detection of DNA in recombinant protein products.

A homogeneous fluorescence-based DNA detection system has been developed to measure DNA in protein solutions. The technique relies on the increase in fluorescence of a dye molecule when it intercalates into double-stranded (ds) DNA. The increased fluorescence is a direct measurement of the amount of DNA in the sample. The analysis time required per sample is less than 5 min. The dye has absorbance and emission maxima at 485 and 530 nm, respectively. The assay is linear from 98 pg/mL to 200 ng/mL of DNA in buffers containing no proteins with typical relative standard deviation values of less than 2.4%. The assay performance was evaluated under various matrix conditions, including buffers, pH, ionic salts, detergents, denaturants and organic solvents. Each reagent was tested at several concentrations to determine how the slope and linearity (r value) of the standard curve were affected. Even in the presence of matrix components and protein, the assay was able to quantitatively detect picogram to nanogram levels of DNA. The fluorescence can be removed by DNase treatment. This method is specific for dsDNA with RNA emitting less than 2% intensity of an equivalent mass of DNA.

Buffers↗

PubMed1997

Cerebral infarction in patients with AIDS.

PURPOSE: To establish the frequency, distribution, and pathogenesis of cerebral infarction as confirmed with MR imaging in a cohort of patients with acquired immunodeficiency syndrome (AIDS). METHODS: We reviewed all (71) abnormal cranial MR studies obtained at our institution in human immunodeficiency virus (HIV)-positive patients over a 2-year period and recorded the number and distribution of ischemic lesions, any associated abnormalities, and the MR angiographic findings, where available. Patients' charts were studied for relevant clinical data, biochemical and culture results, and potential etiologic factors. RESULTS: Twenty-two infarcts were seen in 13 of the 71 patients. Of these 22, the basal ganglia area was affected in 15, the middle cerebral artery territory in two, and the vertebrobasilar territory in five. Five patients had concomitant evidence of infection, six others used cocaine or were intravenous drug abusers. MR angiography was performed in eight patients; two of these had multiple lesions consistent with vasculitis, two had isolated lesions that corresponded with their parenchymal infarct, and four had normal findings. CONCLUSIONS: The frequency of infarction was 18%, higher than previously reported. The pathogenesis of infarction was multifactorial. Underlying infectious causes were identified in 39% of patients. Two patients had an idiopathic vasculitis.

AIDS Dementia Complex↗

PubMed1996

Enhanced thrombolytic and antithrombotic potency of a fibrin-targeted plasminogen activator in baboons.

BACKGROUND: Thrombolytic therapy reduces mortality in patients with acute myocardial infarction, but significant limitations exist with the use of currently available agents. In the present report, we describe the thrombolytic and antithrombotic potencies of a hybrid recombinant plasminogen activator consisting of an antifibrin antibody 59D8 (AFA) and low-molecular-weight single-chain urokinase-type plasminogen activator (scuPA). METHODS AND RESULTS: A thrombolysis model in which thrombi are preformed in vivo in juvenile baboons was developed to compare the potencies of AFA-scuPA, recombinant tissue plasminogen activator (rTPA), and recombinant scuPA (rscuPA) in lysing nonocclusive 111In-labeled platelet-rich arterial-type thrombi and 125I-labeled fibrin-rich venous-type thrombi. Systemic infusion of 1.89 nmol/kg AFA-scuPA produced thrombolysis that was comparable to that obtained with much higher doses of TPA (14.2 nmol/kg) and rscuPA (28.5 nmol/kg). When steady-state plasma concentrations are normalized, AFA-scuPA lyses thrombi sixfold more rapidly than scuPA and TPA (P < .001) and reduces the rate of formation more than comparable doses of rscuPA (P < .0001). At equivalent thrombolytic doses, AFA-scuPA produced fewer antihemostatic effects than either rTPA or rscuPA. Template bleeding time measurements were shorter (3.5 +/- 0.12 minutes for AFA-scuPA versus 5.3 +/- 0.36 and 5.2 +/- 0.04 minutes for rTPA and rscuPA, respectively; P < .05), alpha 2-antiplasmin consumption was less (P < .05), and D-dimer generation was lower (P < .05). CONCLUSIONS: We conclude that antibody targeting of scuPA to fibrin increases thrombolytic and antithrombotic potencies with less impairment of hemostasis compared with rTPA and rscuPA.

Animals↗

PubMed1996

The single and multiple dose pharmacokinetics of pranlukast in healthy volunteers.

OBJECTIVE: The pharmacokinetics of pranlukast, a leukotriene LTD4 antagonist, were studied in 48 young, healthy subjects after single and repeated oral doses (given every 12 h) ranging from 112.5 to 675 mg. The doses were administered 30 minutes after a light breakfast. RESULTS: Maximal drug concentrations generally occurred between 2 and 6 h after dosing, and there was some evidence of an absorption lag-time. Secondary peaks were observed in the plasma concentration vs. time profiles of many of the study subjects after both single and repeated doses, particularly during the period of maximum drug absorption. In general, after both single and repeated doses, there were related increases in the corresponding Cmax and AUC with a rise in dose, although the increase was diminished at doses above 450 mg. With repeated dosing of pranlukast the mean AUC was generally higher (up to 1.6-fold), and the higher plasma concentrations allowed characterisation of a longer mean t 1/2 than after single dose administration. The mean steady-state trough plasma concentrations attained after evening doses were considerably higher (up to 14-fold) than those obtained after the morning dose. CONCLUSION: The data suggested that the pharmacokinetics of pranlukast are influenced by the time of dosing. Based on analysis of urinary 6 beta-hydroxycortisol excretion, there was no evidence that pranlukast modified the metabolic activity of cytochrome P-450 3A isoenzymes.

Adolescent↗

PubMed1996

Mice expressing a mutant desmosomal cadherin exhibit abnormalities in desmosomes, proliferation, and epidermal differentiation.

Desmogleins are members of the cadherin superfamily which form the core of desmosomes. In vitro studies indicate that the cytoplasmic domain of desmogleins associates with plakoglobin; however, little is known about the role of this domain in desmosome recognition or assembly in vivo, or about the possible relation of desmoglein mutations to epidermal differentiation and disease. To address these questions we used transgenic mouse technology to produce an NH2-terminally truncated desmoglein (Pemphigus Vulgaris Antigen or Dsg3) in cells known to express its wild-type counterpart. Within 2 d, newborn transgenic animals displayed swelling of their paws, flakiness on their back, and blackening of the tail tip. When analyzed histologically and ultrastructurally, widening of intercellular spaces and disruption of desmosomes were especially striking in the paws and tail. Desmosomes were reduced dramatically in number and were smaller and often peculiar in structure. Immunofluorescence and immunoelectron microscopy revealed no major abnormalities in localization of hemidesmosomal components, but desmosomal components organized aberrantly, resulting in a loss of ultrastructure within the plaque. In regions where desmosome loss was prevalent but where some adhesive structures persisted, the epidermis was thickened, with a marked increase in spinous and stratum corneum layers, variability in granular layer thickness, and parakeratosis in some regions. Intriguingly, a dramatic increase in cell proliferation was also observed concomitant with biochemical changes, including alterations in integrin expression, known to be associated with hyperproliferation. An inflammatory response was also detected in some skin regions. Collectively, these findings demonstrate that a mutation in a desmoglein can perturb epidermal cell-cell adhesion, triggering a cascade of changes in the skin.

Animals↗

PubMed1996

The effects of the menstrual cycle on the incidence of emesis and efficacy of ondansetron.

Postoperative nausea and vomiting after general anesthesia remains a complex and perturbing phenomenon associated with several factors. In women, the phase of the menstrual cycle as a factor in postoperative nausea and emesis is controversial. This retrospective study was performed to assess the effects of the menstrual cycle and efficacy of the antiemetic ondansetron on postoperative emesis. A total of 1169 ASA grade I-II patients from two double-blind, placebo-controlled studies were enrolled in 18 centers. Patients with irregular cycles or taking estrogens or progesterones were excluded from the analysis, leaving 873 patients eligible for this study. The patients were stratified on the basis of their last menses into four groups: 1) 1-8, 2) 9-16, 3) 17-28, and 4) 29-35 days. All patients received a general anesthetic with endotracheal intubation. Patients received either 1, 4, or 8 mg ondansetron or placebo given intravenously before induction of anesthesia. All patients were studied for a 24-h period. Emesis rates were compared with respect to the phase of the menstrual cycle and between menstruating and nonmenstruating patients. There was no relationship (P = 0.100) between the incidence of emesis and the phase of the menstrual cycle in the group receiving the placebo. There was, however, a significant reduction (P < 0.001) in emesis for the ondansetron-treated patients regardless of the phase of the menstrual cycle. In addition, ondansetron had a similar dose-response curve in both menstruating and nonmenstruating women.

Adult↗

PubMed1995

Changes in incidence of and mortality from breast cancer in England and Wales since introduction of screening. United Kingdom Association of Cancer Registries.

OBJECTIVE: To assess the impact of the NHS breast screening programme on the incidence of and mortality from breast cancer. DESIGN: Comparison of age specific incidence and mortality before and after the introduction of screening in the late 1980s. SETTING: England and Wales. SUBJECTS: Women aged over 30 years. RESULTS: In 1992 the age standardised incidence of breast cancer was 40% higher than in 1979. After the introduction of screening in 1988 recorded incidence rates rose steeply in the screened age group (50-64 year olds) but not in others. In 1992 the rates levelled off at about 25% higher than in 1987. Total mortality from breast cancer has increased steadily since the 1950s; the rates increased earlier in the younger age groups. By the mid-1980s rates had begun to fall in the younger age groups; but total mortality was still among the highest in the world. Age standardised mortality in the 55-69 age group changed little during the first three years of screening but then fell steeply and in 1994 was 12% lower than in 1987. CONCLUSIONS: Since the introduction of screening there have been pronounced increases in recorded incidence in the screened age group. Cancer registries have an essential role in assessing screening programmes and cancer services. The steep decrease in mortality in 55-69 year olds which began three years after screening started is unlikely to be due to screening. The widespread adoption of treatment with tamoxifen during this period may be important. With the reduction in mortality already observed and the expected additional benefits from screening, the Health of the Nation target should be achieved.

Age Factors↗

PubMed1995

Phenotypic and genotypic characteristics of human immunodeficiency virus type 1 from patients with AIDS in northern Thailand.

Primary human immunodeficiency virus type 1 (HIV-1) isolates were obtained from 22 patients with AIDS from northern Thailand, where HIV-1 is transmitted primarily through the heterosexual route. Viral sequences were determined for the 22 patients with AIDS, and all were subtype E HIV-1 on the basis of sequence analysis of a region from the envelope protein gp120. Syncytium-inducing (SI) viruses were detected for 16 of 22 patients with AIDS by using MT-2 cells. Characteristics of amino acid sequences in V3 which have not been reported previously for subtype B SI HIV-1 were associated with the subtype E HIV-1 SI phenotype. The SI viruses from our study population contain predominantly a GPGR or GPGH motif at the tip of the V3 loop, in contrast to the previously described subtype E HIV-1 from Thailand which contained predominantly GPGQ. All the SI viruses lost a potential N-linked glycosylation site in V3 which is highly conserved among previously described subtype E HIV-1 isolates from asymptomatic patients from Thailand. HIV-1 envelope sequences including V3 from some patients with AIDS were significantly more divergent than viruses from asymptomatic patients in Thailand characterized 2 years ago or earlier. These results suggest that emergence of subtype E SI HIV-1 variants is associated with the development of AIDS, as it is for subtype B HIV-1. The divergence of subtype E HIV-1 in patients with AIDS as the disease progresses, and the divergence of subtype E HIV-1 in the infected population as the epidemic continues in Thailand, may have important implications for vaccine development.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Variability of human immunodeficiency virus type 1 group O strains isolated from Cameroonian patients living in France.

Human immunodeficiency virus type 1 (HIV-1) nucleotide sequences encoding p24Gag and the Env C2V3 region were obtained from seven patients who were selected on the basis of having paradoxical seronegativity on a subset of HIV enzyme-linked immunosorbent assay detection kits and having atypical Western blot (immunoblot) reactivity. Sequence analyses showed that all of these strains were more closely related to the recently described Cameroonian HIV isolates of group O (HIV-1 outlier) than to group M (HIV-1 major). All seven patients had Cameroonian origins but were living in France at the time the blood samples were taken. Characterization of a large number of group M strains has to date revealed eight distinct genetic subtypes (A to H). Genetic distances between sequences from available group O isolates were generally comparable to those observed in M intersubtype sequence comparisons, showing that the group O viruses are genetically very diverse. Analysis of sequences from these seven new viral strains, combined with the three previously characterized group O strains, revealed few discernable phylogenetic clustering patterns among the 10 patients' viral sequences. The level of diversity among group O sequences suggests that they may have a comparable (or greater) age than the M group sequences, although for unknown reasons, the latter group dispersed first and is the dominant lineage in the pandemic.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Coupled secretion of chloride and mucus in skin of Xenopus laevis: possible role for CFTR.

We used the isolated skin of Xenopus laevis to investigate the relationship between the secretion of salt, water, and mucus by submucosal glands expressing the cystic fibrosis transmembrane conductance regulator (CFTR). In situ hybridization and immunofluorescence provided evidence for specific expression of CFTR in the mucus-secreting cells of the subepidermal glands. Stimulation of isolated sheets of skin with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate produced active Cl secretion and a marked increase in tissue conductance that was correlated with mucous cell degranulation and the distention of the glandular ducts. This coordinated increase in active secretion of salt and mucus was abolished by pretreatment of skins with bumetanide or by removing Cl from the bathing solutions. These results provide evidence for an intimate coupling between electrolyte transport and mucus secretion that may illuminate the pathophysiology of mucus-producing glands in cystic fibrosis lung disease.

Animals↗

PubMed1994

The contingent negative variation in positive and negative types of schizophrenia.

The authors analyzed the contingent negative variations of 20 medicated patients with schizophrenia diagnosed according to DSM-III-R and 20 age- and sex-matched normal comparison subjects. For the patients with schizophrenia, there were significant correlations between contingent negative variation amplitude and two items on the Scale for the Assessment of Negative Symptoms (affective flattening and avolition-apathy) and the total score on this scale. These findings have implications regarding the underlying pathology of negative and positive symptoms of schizophrenia.

Adult↗

PubMed1994

Tuberculosis in young adults and the elderly. A prospective comparison study.

OBJECTIVES: To compare the clinical, bacteriologic, and radiologic features of pulmonary and pleural tuberculosis in young adults and the elderly and determine if any differences exist between both groups. DESIGN: Prospective recruitment of all patients diagnosed as having pulmonary and pleural tuberculosis in British Columbia, Canada. SETTING: A population-based sample from a provincial control program TB registry. PATIENTS: A total of 218 consecutive patients whose conditions were diagnosed between January 1990 and May 1991. We excluded 15 HIV-positive patients whose conditions were diagnosed during this study. INTERVENTION: Standardized data collection of symptoms, bacteriology, and review of radiology by two readers blind to the clinical and epidemiologic data. MAIN RESULTS: There were 142 young adult patients and 76 elderly patients. The young adults had a mean age of 41.2 years and the elderly group had a mean age of 75 years of age. Fever (p = 0.002) and night sweats (p = 0.02) were more common in young adults. In culture-proven disease, hemoptysis, fever, and cough were more common in young adult (p = 0.03, 0.02, and 0.01, respectively). There was no difference in the duration of symptoms between the two groups. The odds ratio for cancers other than lung cancer, 3.98 (confidence interval, 1.49, 10.65) in the elderly group was the only significant risk factor to differ between the two groups. Skin test responses to 5TU PPD were positive in 86.2 percent of young adults and 67.6 percent of elderly patients tested (p = 0.03). A total of 79.6 percent of young adults and 88.15 percent of the elderly patients (not significant) were culture positive. Comparison of radiologic findings in young adults vs elderly patients showed no significant differences apart from those with miliary TB 0.7 percent vs 6.7 percent (p = 0.04). CONCLUSIONS: In this population-based study, young adults were more likely to have hemoptysis, fever, and cough and to have a positive PPD response. Cancer was significantly associated as a risk factor in the older age group. There was no difference in bacteriologically proven disease or radiologic findings between the two groups, apart from the more common occurrence of miliary TB in the elderly.

Adult↗

PubMed1994

Efficacy of electroconvulsive therapy after propofol and methohexital anesthesia.

Fifty-eight patients with major depression were randomly assigned to receive a hypnotic dose of either propofol or methohexital for their complete treatment series of electroconvulsive therapy (ECT). As expected, seizure duration was significantly shorter with propofol than with methohexital anesthesia. Both groups recovered from their depression at the same rate. There was a significant improvement in the Hamilton Rating Scale for Depression scores between the first and last ECT session. However, this was independent of the choice of propofol or methohexital as the anesthetic. This study supports previous reports that seizure duration does not influence recovery from depression.

Adolescent↗