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PubMed2000

Amazonian onchocerciasis: parasitological profiles by host-age, sex, and endemicity in southern Venezuela.

This paper describes, for the human onchocerciasis focus of southern Venezuela, the age profiles of Onchocerca volvulus microfilarial (mf) and nodule prevalence, mf intensity, and mf aggregation for the whole examined population (836 Yanomami people) living in 20 villages, and for these communities classified according to endemicity levels (hypoendemic: < or = 20 %; mesoendemic: 21-59 %; hyperendemic: < or = 60 % infected). Mf prevalence and intensity increased with age, particularly in the hyperendemic areas, and there were no marked differences between the sexes. The prevalence of nodules followed the same age pattern. Fifty percent mf prevalence was reached in the 15-19 year age-class when the population was taken as a whole; nearly in the 10 to 14-year-olds for the hyperendemic level, in those aged 20-29 years in mesoendemic areas, and not reached at all in hypoendemic villages. The degree of mf aggregation was measured by the k value of the negative binomial distribution and by the variance to mean ratio (VMR). The relationship between the standard deviation (S.D.) of mf counts and the mean mf density was also explored. These 3 indices (k, VMR, and S.D.) showed a tendency to increase with both mean mf load and host age. Since infection intensity and host age were themselves positively related, it was not possible to draw definite conclusions about age-specific changes of parasite aggregation. There was not a significant decrease of mf intensity after an earlier peak neither was there a shift towards younger ages of the maximum no. of mf/mg reached as the endemicity level increased. These results are discussed in relation to detection of density dependence in the human host, selection of an indicator age-group for rapid epidemiological assessment (REA) methods, and strategies of ivermectin distribution in the Amazonian focus. It is recommended that, for the Amazonian onchocerciasis focus, the indicator group for REA consists of all those aged 15 years and over.

Adolescent↗
PubMed1992

A new approach to morbidity risk assessment in hookworm endemic communities.

The relationship between paired hookworm prevalence and mean intensity of infection data from geographically defined communities was examined. The results show that, in spite of major socio-economic and environmental differences between communities, the relationship is consistent and non-linear. A generalized value of k (the exponent of the negative binomial distribution) for hookworms was estimated to be 0.34, which is consonant with previous estimates from cross-sectional data. Maximum likelihood analysis indicates that the severity of hookworm aggregation in humans has an inverse relationship to mean worm burden which is less marked than for Ascaris lumbricoides. A simple model, based on published estimates of hookworm burdens associated with hookworm anaemia, was used to predict prevalence of morbidity from prevalence of infection data for Tanzania, Kenya and Zambia. Predictions correspond to the observation that hookworm anaemia is highly focal, and largely coastal, in distribution. These analyses suggest that locality-targeting of chemotherapy is particularly appropriate for the control of hookworm morbidity.

Ancylostomiasis↗
PubMed1983

Facile oxygen exchanges of phosphoenolpyruvate and preparation of [18O]phosphoenolpyruvate.

Phosphoenolpyruvate when heated in acidic solution exchanges its phosphoryl and carboxyl oxygens rapidly and its enolic oxygen much more slowly with oxygens from water. The incorporation of 18O into phosphoenolpyruvate was measured by gas chromatography-mass spectrometry and phosphorus-31 nuclear magnetic resonance after heating in H218O at 98 degrees C. The rates of exchange of all six oxygens of phosphoenolpyruvate with water increase with increasing acidity, and the phosphoryl oxygens exchange more rapidly than the carboxyl oxygens. The rate of exchange of each oxygen of the phosphoryl group is 16-fold greater than the hydrolysis rate at 1 N HCl. This provides a simple and useful method for the synthesis of [18O]phosphoenolpyruvate highly enriched in its phosphoryl-group oxygens. An enrichment of 89% was obtained with a 50% yield. The [18O]-phosphoenolpyruvate showed a binomial distribution of 18O in the phosphoryl-group oxygens. The exchange may be explained by the reversible formation of a transient cyclic phosphate and, for exchange of the enolic oxygen, a transient acyl phosphate. Preparation of [18O]phosphoenolypyruvate from [18O]Pi by a chemical synthesis from beta-chlorolactate was not satisfactory because of drastic loss of 18O during the procedures used. Some loss of 18O also occurred during an enzymic synthesis with KCNO, [18O]Pi, carbamate kinase, and pyruvate kinase.

Gas Chromatography-Mass Spectrometry↗
PubMed1989

In vitro dissociation and reassociation of human alcohol dehydrogenase class I isozymes.

Freezing (-78 degrees C) and thawing (25 degrees C) a heterodimeric human alcohol dehydrogenase class I isozyme in the presence of 0.1 M sodium phosphate/0.1 mM DTT, pH 7.0, and the subsequent separation of the scrambled isozymes by HPLC are used to prepare homodimers from heterodimers, with recovery of enzyme activity ranging from 80 to 95%. The ratio of the three isozymes obtained from a heterodimer follows the binomial distribution of 1:2:1, indicating random reassociation of the two subunits. The physical and enzymatic properties of the reassociated isozymes are the same as those obtained directly from human liver preparations. The nature of subunit-subunit interactions of human ADH class I isozymes is examined by optimizing the conditions required for the formation of the new dimers "in vitro". The effect of a number of reagents previously used in the reversible dissociation of dehydrogenases is investigated. The coenzyme NAD+ is a potent inhibitor of the dissociation of dimers during the freeze/thaw procedure. The presence of sodium phosphate in the enzyme solution is essential during the freezing and thawing experiment. No appreciable dissociation/reassociation occurs in TES, HEPES, or even potassium phosphate. The reversible dissociation is due primarily to the decrease in pH because of the low solubility of Na2HPO4 at low temperatures. The reassociation occurs after thawing in a temperature-dependent process. There is no reactivation if the enzyme is incubated at 0 degrees C after thawing, while at 25 degrees C high recovery in activity is achieved in a time period ranging from 15 to 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗
PubMed1997

Kinetic and spectroscopic investigations of wild-type and mutant forms of apple 1-aminocyclopropane-1-carboxylate synthase.

Two catalytically inactive mutant forms of 1-aminocyclopropane-1-carboxylate (ACC) synthase, Y85A and K273A, were mixed in low concentrations of guanidine hydrochloride (GdnHCl). About 15% of the wild-type activity was recovered (theoretical 25% for a binomial distribution), proving that the functional unit of the enzyme is a dimer, or theoretically, a higher order oligomer. The enzyme catalyzes the conversion of S-adenosyl-L-methionine (SAM) to ACC. The value of kcat/KM is 1.2 x 10(6) M-1 s-1 at pH 8.3. Viscosity variation experiments with glycerol and sucrose as viscosogenic reagents showed that this reaction is nearly 100% diffusion controlled. The sensitivity to viscosity for the corresponding reaction of the less reactive Y233F mutant is much reduced, thus the latter reaction serves as a control for that of the wild-type enzyme. The kcat/KM vs pH profile for wild-type enzyme exhibits pKa values of 7.5 and 8.9. The former is assigned to the pKa of the alpha-amino group of SAM, while the latter corresponds to the independently determined spectrophotometric pKa of the internal aldimine. The kcat vs pH profile exhibits similar pKas, which means that the above pKa values are not perturbed in the Michaelis complex. The phenolic hydroxyl group of Tyr233 forms a hydrogen bond to the 3'-O- of PLP. The spectral and kinetic pKa (kcat/KM) values of the Y233F mutant are not identical (spectral 10.2, kinetic 8.7). A model that accounts quantitatively for these data posits two parallel pathways to the external aldimine for this mutant, the minor one has the alpha-amino group free base form of SAM reacting with the protonated imine form of the enzyme with kcat/KM approximately 6.0 x 10(3) M-1 s-1, while the major pathway involves reaction of the aldehyde form of PLP with SAM with kcat/KM approximately 7.0 x 10(5) M-1 s-1. The spectral pKa is defined only by the less reactive species.

Binding Sites↗
PubMed1999

A biochemical and biophysical characterization of recombinant mutants of fetal hemoglobin and their interaction with sickle cell hemoglobin.

Three recombinant mutants of human fetal hemoglobin (Hb F) have been constructed to determine what effects specific amino acid residues in the gamma chain have on the biophysical and biochemical properties of the native protein molecule. Target residues in these recombinant fetal hemoglobins were replaced with the corresponding amino acids in the beta chain of human normal adult hemoglobin (Hb A). The recombinant mutants of Hb F included rHb F (gamma 112Thr --> Cys), rHb F (gamma 130Trp --> Tyr), and rHb F (gamma 112Thr --> Cys/gamma 130Trp --> Tyr). Specifically, the importance of gamma 112Thr and gamma 130Trp to the stability of Hb F against alkaline denaturation and in the interaction with sickle cell hemoglobin (Hb S) was investigated. Contrary to expectations, these rHbs were found to be as stable against alkaline denaturation as Hb F, suggesting that the amino acid residues mentioned above are not responsible for the stability of Hb F against the alkaline denaturation as compared to that of Hb A. Sub-zero isoelectric focusing (IEF) was employed to investigate the extent of hybrid formation in equilibrium mixtures of Hb S with these hemoglobins and with several other hemoglobins in the carbon monoxy form. Equimolar mixtures of Hb A and Hb S and of Hb A(2) and Hb S indicate that 48-49% of the Hb exists as the hybrid tetramer, which is in agreement with the expected binomial distribution. Similar mixtures of Hb F and Hb S contain only 44% hybrid tetramer. The results for two of our recombinant mutants of Hb F were identical to the results for mixtures of Hb F and Hb S, while the other mutant, rHb F (gamma 130Trp --> Tyr), produced 42% hybrid tetramer. The sub-zero IEF technique discussed here is more convenient than room-temperature IEF techniques, which require Hb mixtures in the deoxy state. These recombinant mutants of Hb F were further characterized by equilibrium oxygen binding studies, which indicated no significant differences from Hb F. While these mutants of Hb F did not have tetramer-dimer dissociation properties significantly altered from those of Hb F, future mutants of Hb F may yet prove useful to the development of a gene therapy for the treatment of patients with sickle cell anemia.

Adult↗
PubMed2006

Stochastic analysis of the parity-violating energy differences between enantiomers and its implications for the origin of biological chirality.

A stochastic description of a racemic mixture is developed taking into account the slight energy difference between enantiomers originating from parity violation (DeltaE(PV) approximately equal to 10(-13) Jmol(-1)). The system can be described by an asymmetric binomial distribution. A method is developed to calculate the probability of forming the more-stable isomer in excess, which is not significantly larger than 50% under normal conditions. It is concluded that the parity-violating energy difference between enantiomers is very unlikely to be relevant in considerations about the origin of biological chirality.

Algorithms↗
PubMed1999

Diagnostic accuracy of MRI compared to CCT in patients with brain metastases.

OBJECTIVES: In patients with extracranial neoplasms, the occurrence and number of brain metastases (BM) are critical for further diagnostic approaches and therapeutic strategies and the patient's prognosis. Although widely accepted, there is surprisingly little evidence in the literature that MRI is superior to CCT. Therefore, in patients with solitary BM according to diagnostic contrast-enhanced computed tomography (CCT), we investigated, what additional information could be gained by contrast-enhanced magnetic resonance imaging (MRI). METHODS/RESULTS: Among 55 patients with solitary BM according to CCT, 17 had multiple BM on MRI (31%) and 38 had solitary BM in both. Based on a presumed binomial distribution of our data, we calculated a rate of at least 19% of patients with solitary BM on CCT, in which MRI would show multiple lesions (p = 0.05). The two main characteristics for BM missed by CCT were the smaller diameter, which averages 2 cm less than in BM identified with both modalities, and a preferential frontotemporal location. CONCLUSION: MRI is indeed superior to CCT in the diagnosis of BM the essential reasons besides detection of smaller lesions being a better soft tissue contrast, significantly stronger enhancement with paramagnetic contrast agents, the lack of bone artifacts, fewer partial volume effects, and direct imaging in three different planes. Therefore, MRI is indispensable in the diagnostic workup of patients with BM for choosing the optimum therapeutic approach, especially with regard to the decision whether to operate or to primarily irradiate the patient's metastases.

Adolescent↗
PubMed2003

Psychosocial and behavioral functioning among pediatric brain tumor survivors.

OBJECTIVE: To describe the psychosocial and behavioral functioning, as described by patient, parent and teacher, of a cohort of adolescents who have been previously treated for a brain tumor. METHODS: A cohort of 32 patients, 12-18 years old, were evaluated between 1 and 5 years post-treatment for brain tumor during the patient's regularly scheduled follow-up clinic appointment at the Dana-Farber Cancer Institute. The Self-Report questionnaire and the Parent-Report of the Behavioral Assessment System for Children (BASC) were administered to the patient and to one of the patient's parents, respectively. In addition, the BASC Teacher-Report was completed by the patient's teacher. Descriptive statistics were generated; binomial distribution analyses were carried out to assess whether the proportion of individuals with impaired performance on each measure exceeded normative expectations. RESULTS: Comparison of the proportion of patients with elevated scores to normative expectations indicated no excess of elevated scores on any of the BASC scales of the Self-Report. However, parents endorsed items in the areas of attention problems and leadership; teachers endorsed items concerning learning problems; and both parents and teachers endorsed items indicative of somatization behaviors. CONCLUSIONS: Parent and teacher feedback indicate some level of psychosocial and behavioral morbidity for adolescents treated for a brain tumor; this finding contrasts with adolescent Self-Report indicating no difficulties in behavioral and psychosocial functioning. The extent to which these vulnerabilities impact quality of life and the discrepancy between reporters should be assessed in follow-up studies with a larger cohort of patients.

Adaptation, Psychological↗
PubMed1977

Binomial assessment of behavioral-phenotypic variations: constancy of choices, trial effects, and social interaction effects in mass-screened color preferences of quail chicks (Coturnix coturnix japonica).

Individual variations in repeated approach choices between colors by quail chicks were efficiently and reliably identified by methods of binary mass screening and binomial assessment. Choices between a pair of identical white stimuli showed only random variations, which indicated that position habit, systematic alternation, and extraneous stimulus factors did not influence performances. Choices between blue and red colors showed significant individual variations, which were free of influences from changes in the probabilities of choices on repeated trials, interdependence between trials, and interdependence between individual performances of mass-screened subjects. Genetic determination of individual variations were shown by strong responses to bidirectional genetic selection of choices between blue and red, which also introduced small social interaction effects in mass-screened performances. Results are discussed in relation to the use of binomial distribution for identifying phenotypic units and variations in choice behaviors.

Animals↗
PubMedDate not supplied

Multi-barrelled K channels in renal tubules.

Most ion-channels have several kinetically distinct open and closed states. However, a number of groups have reported the presence of sub-conductance states within the open states. It is not clear whether these sub-conductance states represent a partially-occluded open state (with restricted diffusion), or whether they indicate the presence of parallel conductive units. Here we present evidence for the presence of four parallel, equally-conductive subunits that make up a K-selective channel in the apical membrane of early distal tubule in the kidney of Amphiuma. The overall open probability of the channel is controlled by a main gate, the kinetics of which can be described by a simple two-state (open or closed) model. This main gate acts either to occlude or to expose the four subunits in unison. The subunits seem to gate independently both of the main gate and of one another, their open probability obeying the binomial distribution.

Animals↗
PubMed1998

Fractional allelic loss in gastric carcinoma correlates with growth patterns.

To gain an insight into the genetic events underlying morphological phenotypes, we analysed 58 gastric carcinoma tissues for the genome-wide allelotype study using microsatellite markers. Based on a binomial distribution, loss of heterozygosity (LOH) that was significantly more frequent than expected (P<0.05) thus interpreted as nonrandom LOH selected during tumorigenesis. The overall extent of chromosomes undergoing LOH i.e. fractional allelic loss (FAL, the ratio of LOH-positive markers to the total number of informative markers) was measured in each tumor patient. Nonrandom LOH was found on 17p (48.0%), 18q (38.4%), 13q (38.1%) and 9p (36.4%). Overall, there were no significant phenotypes correlated with allelic loss on specific chromosome regions. Based on a bimodal distribution of FAL values with two peaks bordered by a mean of 0.233, tumors were classified into LOH-related (>0.233) and LOH-unrelated (<0.233) types. Among 24 patients with LOH-related tumors, increase in the infiltrative type of growth pattern was found to correspond with a significant trend of increasing FAL values. This study shows that the growth pattern of gastric carcinoma is correlated with FAL, suggesting that a malignant phenotype is influenced by LOH event.

Adenocarcinoma↗
PubMed1998

Risk of avascular necrosis following short term megadose methylprednisolone treatment.

We conducted a prospective cohort study to determine whether administration of large doses of the corticosteroid methylprednisolone following spinal cord injury as recommended in the National Acute Spinal Cord Injury Study-2 (NASCIS-2) protocol results in an increased incidence of avascular necrosis (AVN) of the femoral or humeral head. All subjects were patients treated by a spinal cord injury physician in an Acute Spinal Cord Injury Unit between 1989 and 1996 where some received the megadose steroids while others did not. Patients younger than 15 years and older than 75 years were excluded, as were those with any hip or shoulder disease, with pelvic fracture, or with a history of predisposition to AVN by hip dislocation, excessive alcohol consumption, previous high dose steroid use, or systemic lupus erythematosus. Screening for AVN of the femoral and humeral heads was performed at a minimum of 6 months following injury, using magnetic resonance imaging (MRI). The films were read by a radiologist blinded to the treatment protocol received by the individual subject. Among the 59 spinal cord injured patients who received steroids (age 15-64 years (mean 32 years)), five were female. Among the 32 spinal cord injured subjects who did not receive steroids (age 16 to 65 years (mean 34 years)), seven were female. There was no case of AVN found in either group. Using binomial distribution, we conclude that the true incidence of AVN among the methylprednisolone treated group is less than 5% (alpha < 0.05) and therefore continue to recommend short term (24 h) methylprednisolone therapy.

Adolescent↗
PubMed1978

Subunit ratios of separated hybrid hexamers of Neurospora NADP-specific glutamate dehydrogenase containing complementing mutationally modified monomers.

The am1 and am3 mutational variants of the Neurospora crassa NADP-specific glutamate dehydrogenase show complementation activity in hybrid hexamers. A freeze-thaw hybridization method was used to construct hybrids from purified enzymes and the products were separated into species of different monomer ratio by affinity chromatography. Hexamers with am1:am3 ratios of 1:5, 2:4, 3:3, 4:2 and 5:1 were all recovered as resolved or partially resolved peaks in quantities approximating to a binomial distribution. Reassociation of monomers during the hybridization process was random, except for some differential loss of am3 protein by precipitation and an apparent absence of reassociated am1 homohexamers. Complementation activity was shown by hybrids of all five monomer ratios, owing to activation of am3 monomers by conformational constraints arising from the intrinsically inactive am1 monomers. The activating effect of such constraints was greatest in hexamers containing only a single am1 monomer and least in the 5 am1:1am3 species. When fully activated by L-glutamate all am3 monomers were equivalent in intrinsic catalytic activity, irrespective of the number of am1 monomers per hexamer.

Chemical Phenomena↗
PubMed1981

Markedness of features in the articulatory substitutions of children.

This study concerns an analysis of articulatory substitutions of 801 students using markedness theory and a distinctive feature model (Singh & Singh, 1976). The 556 male and 245 female students ranged in age from 3--7 years and were diagnosed as evidencing an articulatory disorder or a linguistic delay. Significantly more feature substitutions moved from marked to unmarked values than from unmarked to marked values (p less than .05, binomial distribution). The study proposed a hierarchy of distinctive features in terms of markedness rather than in terms of features per se. The applications of articulatory and acoustic data to phonological theory and the implications of the findings to speech treatment are discussed.

Articulation Disorders↗
PubMed1981

Pairwise listener preferences in hearing aid evaluation.

The relationships among pairwise judgments of the quality of connected discourse, pairwise judgments of the relative intelligibility of discourse, and measured intelligibility on a nonsense-syllable test were evaluated under identical conditions of primary talker and competitive babble. Stimuli were processed by eight hearing aids and presented in a repeated-measures design to 12 listeners with sensorineural hearing loss. Results revealed moderately high test-retest reliability for all three experimental conditions. Overall, a noteworthy positive relationship was evident between relative intelligibility judgments and measured phonemic identification, although this relationship varied considerably among individual listeners. The correspondence between quality judgments and relative intelligibility judgments was substantially lower, while the relationship between judgments of quality and phonemic identification scores was negligible. Findings demonstrate the potential importance of instructional set in producing valid judgments of the relative intelligibility of aided speech. The determination of measurement error inherent in pairwise preference data is discussed from the viewpoint of a probabilistic model encompassing a binomial distribution. It is concluded that experimental optimization of the agreement between relative intelligibility judgments and measured intelligibility performance of individual listeners will be required before the pairwise comparison technique can be considered a viable alternative to traditional hearing aid evaluation procedures.

Aged↗
PubMed1982

Responses to requests in the dialogues of mothers and their stage 1 children.

The development of conversation requires children to learn to relate their utterances to utterances from other speakers. This investigation examined one method in which children relate their utterances to preceding utterances in conversation, namely, response utterances to request utterances. Late Stage 1 children's responses were examined for their pragmatic and semantic relationships to five types of requests used by mothers. Conditional (child responses to mother's requests) and unconditional (child responses following mother's utterances) probabilities were generated using the lag sequential analysis. The level of significant difference between the conditional and unconditional probabilities was determined with the binomial distribution. The results indicate that the children produced contingent linguistic responses to the mothers' requests based on the pragmatic intent of the requests--specifically, those requesting semantic information, clarifying a misunderstood remark, and requesting agreement or disagreement with a proposition. Further, the children's responses to the mothers' requests for semantic information provided the appropriate semantic information requested by the mothers. The children produced contingent nonlinguistic responses to the mothers' requests for an action to be performed, whereas contingent nonlinguistic or linguistic responses following the mothers' requests for attention failed to achieve significance. These findings indicate that responses to requests are important in the development of early contingent speech and provide one means for structuring conversation with Late Stage I children.

Child Language↗