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Biomedical subjects

C Adams

Publications and source records attributed to C Adams.

At least 73 records · Page 4Linked to original sources

Influence of the chemical nature of side chain at beta 108 of hemoglobin A on the modulation of the oxygen affinity by chloride ions. Low oxygen affinity variants of human hemoglobin expressed in transgenic pigs: hemoglobins Presbyterian and Yoshizuka.

Hemoglobin A (HbA) and two low oxygen affinity variants of HbA, HbPresbyterian and HbYoshizuka, were produced in transgenic pigs and purified to homogeneity by ion-exchange chromatography. These two variants contain either lysine (HbPresbyterian) or aspartic acid (HbYoshizuka) instead of the normal asparagine residue at position beta 108 in HbA. Transgenic pigs expressed these variants at a level up to 11% and were healthy. Both HbPresbyterian and HbYoshizuka exhibited low O2 affinity (P50 of 21.2 and 18.9, respectively, compared with control HbA value of 11.8 in 0.1 M NaCl, pH 7.5) and retained normal cooperativity with Hill coefficients of 2.9 and 2.5, respectively. HbPresbyterian exhibited Bohr effect comparable with HbA. In contrast, HbYoshizuka had a diminished response to changes in pH. Thus the structural basis of reduced O2 affinity of these variants appears to be distinct: the consequence of mutation at beta 108 is a function of the chemical nature of the side chain. This is further confirmed by the sensitivity of the O2 affinity of the variants to the presence of Cl-. The O2 affinity of HbYoshizuka is insensitive to changes in Cl- concentration, whereas the O2 affinity of HbPresbyterian exhibited a pronounced and dramatic chloride effect. In fact, P50 of HbPresbyterian was identical to that of HbA at very low Cl- concentrations, and the P50 increased to >40 at 0.5 M Cl-. The chloride effect was completely abolished when HbPresbyterian was stabilized at the 2,3-diphosphoglycerate pocket by interdimeric cross-linking. Molecular modeling studies demonstrate that in HbPresbyterian, Cl- can bridge the epsilon-amino group of Lys beta 108 with either the guanidino group of Arg beta 104 or the epsilon-amino group of Lys alpha 99, resulting in the stabilization of the "T" structure. The utility of these low O2 affinity hemoglobins as cell-free oxygen carriers is discussed.

Allosteric Regulation

Isolation of a gene (pbsC) required for siderophore biosynthesis in fluorescent Pseudomonas sp. strain M114.

An iron-regulated gene, pbsC, required for siderophore production in fluorescent Pseudomonas sp. strain M114 has been identified. A kanamycin-resistance cassette was inserted at specific restriction sites within a 7 kb genomic fragment of M114 DNA and by marker exchange two siderophore-negative mutants, designated M1 and M2, were isolated. The nucleotide sequence of approximately 4 kb of the region flanking the insertion sites was determined and a large open reading frame (ORF) extending for 2409 bp was identified. This gene was designated pbsC (pseudobactin synthesis C) and its putative protein product termed PbsC. PbsC was found to be homologous to a family of enzymes involved in the biosynthesis of secondary metabolites, including EntF of Escherichia coli. These enzymes are believed to act via ATP-dependent binding of AMP to their substrate. Several areas of high sequence homology between these proteins and PbsC were observed, including a conserved AMP-binding domain. The expression of pbsC is iron-regulated as revealed when a DNA fragment containing the upstream region was cloned in a promoter probe vector and conjugated into the wild-type strain, M114. The nucleotide sequence upstream of the putative translational start site contains a region homologous to previously defined -16 to -25 sequences of iron-regulated genes but did not contain an iron-box consensus sequence. It was noted that inactivation of the pbsC gene also affected other iron-regulated phenotypes of Pseudomonas M114.

Amino Acid Sequence

The tryptophan repressor sequence is highly conserved among the Enterobacteriaceae.

Tryptophan biosynthesis in Escherichia coli is regulated by the product of the trpR gene, the tryptophan (Trp) repressor. Trp aporepressor binds the corepressor, L-tryptophan, to form a holorepressor complex, which binds trp operator DNA tightly, and inhibits transcription of the tryptophan biosynthetic operon. The conservation of trp operator sequences among enteric Gram-negative bacteria suggests that trpR genes from other bacterial species can be cloned by complementation in E. coli. To clone trpR homologues, a deletion of the E. coli trpR gene, delta trpR504, was made on a plasmid by site-directed mutagenesis, then crossed onto the E. coli genome. Plasmid clones of the trpR genes of Enterobacter aerogenes and Enterobacter cloacae were isolated by complementation of the delta trpR504 allele, scored as the ability to repress beta-galactosidase synthesis from a prophage-borne trpE-lacZ gene fusion. The predicted amino acid sequences of four enteric TrpR proteins show differences, clustered on the backside of the folded repressor, opposite the DNA-binding helix-turn-helix substructures. These differences are predicted to have little effect on the interactions of the aporepressor with tryptophan, holorepressor with operator DNA, or tandemly bound holorepressor dimers with one another. Although there is some variation observed at the dimer interface, interactions predicted to stabilize the interface are conserved. The phylogenetic relationships revealed by the TrpR amino acid sequence alignment agree with the results of others.

Amino Acid Sequence

Anatomical urinary stress incontinence in women with rheumatoid arthritis: its frequency and coping strategies.

OBJECTIVE: The objectives of this study were to develop a valid screening tool for anatomical urinary stress incontinence (AUSI), to use it to determine the frequency of AUSI in women with RA, and to identify the cognitive, behavioral, and psychological coping strategies used by these women to deal with incontinence. METHODS: A screening tool concerning AUSI was validated by comparing self-reported incidences of AUSI with clinical evaluation. Questionnaires regarding presence of AUSI and cognitive, behavioral, and psychological coping strategies were sent to 750 women clinically diagnosed with RA. RESULTS: Of the 262 respondents (35% response rate), 21% had characteristics of AUSI, a rate similar to general population studies. Coping strategies varied depending on whether the women were at home or away from home and whether the women were alone or with others. CONCLUSIONS: There is a need for women with incontinence and the health care workers who serve them to be educated about AUSI and its treatments.

Adaptation, Psychological

Primary hypothyroidism with intracranial hypertension and pituitary hyperplasia.

A 12-year-old girl presented with primary hypothyroidism, secondary pituitary hyperplasia, and intracranial hypertension. Cranial computed tomography revealed a sellar mass with suprasellar extension. She responded to medical treatment. Intracranial hypertension may be associated with primary hypothyroidism prior to thyroxine treatment. Because significant pituitary hyperplasia can be associated with primary hypothyroidism, it is vital to have endocrine investigation prior to consideration of surgical removal of an apparent pituitary tumor.

Cerebrospinal Fluid Pressure

Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives.

We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling.

Canada

Genetic selection for mutations that impair the co-operative binding of lambda repressor.

Bacteriophage lambda repressor binds co-operatively to adjacent pairs of DNA target sites. A novel combination of positive genetic selections, involving two different operon fusions derived from P22 challenge phages, was used to isolate mutant lambda repressors that have lost the ability to bind co-operatively to tandem sites yet retain the ability to bind a strong, single site. These cb (co-operative binding) mutations result in 10 different amino acid changes, which define eight residues in the carboxyl-terminus of repressor. Because challenge phage derivatives may be applied to study essentially any specific protein-DNA interaction, analogous combinations of genetic selections may be used to explore the ways that a variety of proteins interact to assemble regulatory complexes.

Amino Acid Sequence

International headache society criteria and childhood headache.

The objective of this study was to determine whether the intuitive clinical diagnosis of a headache type made by paediatric neurologists would also have fulfilled International Headache Society (IHS) criteria for that type. Clinical information was recorded on data sheets. The neurologists made clinical diagnoses without referring to a fixed set of criteria. An independent physician then used the information on the data sheets to classify the child's headache by IHS criteria. Complete data sheets were available for 72 children, aged between four and 18 years. The intuitive clinical diagnosis was completely concordant with the criterion diagnosis of the IHS in 61 per cent, partially concordant in 31 per cent and at complete variance in 8 per cent. These data suggest that the IHS criteria can be applied to a majority of children in a referral-based population such as this, but that minor revisions to the criteria are necessary to make them even more applicable to children.

Adolescent

Inter-observer agreement in the diagnosis of childhood headache.

We prospectively assessed inter-observer agreement in the diagnosis of recurrent headaches in children. Clinical letters containing information on 40 children with headaches (age 4.3 to 17.8 years, median 10.4 years) were given to four Pediatric Neurologists. One or more headache types could be checked off on a data sheet that listed the main types recognized by the International Headache Society and an additional one, "combined migraine and tension-type headache". There were six combinational pairs of neurologists. The six pairs yielded 240 sets of diagnoses. Percentage agreement ranged from 45% to 78%, Kappa values from 0.20 to 0.59, and weighted Kappa from 0.19 to 0.52 within the six pairs. Agreement was 76% when both neurologists in a pair assigned single headache types and 4% when one or both neurologists diagnosed multiple types. The International Headache Society suggests that patients may have multiple types of headache and recommends that all types be classified. We suggest that the option of diagnosing more than one headache type from data in clinical letters may reduce inter-observer agreement.

Adolescent

Problem solving styles of school nurses.

School nurses are challenged on a daily basis to solve complex problems and generate creative solutions to meet the health needs of children. This study focused on how school nurses go about solving problems in the delivery of school health services. The results showed that school nurses' problem-solving style allows them to act as "bridgers" within the educational environment and to promote collaboration among many types of school personnel.

Humans

Serosurvey of some major zoonotic infections in children and teenagers in Bali, Indonesia.

One hundred and ninety serum samples, mainly from children and teenagers, from northeast Bali were tested for the presence of antibodies against five zoonotic agents: Brucella abortus, Coxiella burnetii, Toxoplasma gondii, Toxocara canis and Trichinella spiralis. All children were negative for brucellosis and Q fever. A high prevalence rate was found for toxocariasis (63.2%) and trichinosis (19.5%). Antibody prevalence against T. gondii was found to be rather low (3.1%). To our knowledge, this is the first evidence of toxoplasmosis, toxocariasis and trichinosis infection in humans on Bali. Eating habits and poor hygiene may explain the frequency of parasitic infestations in the children and teenagers in Bali.

Adolescent

Accident prevention. Getting the message across on safety.

Child accident prevention is a key part of the health visitor's role. But faced with the demands of a large and busy caseload, health visitors may not be able to give the subject the priority it needs. Cheryll Adams describes a uniquely simple way to ensure that parents get the message about child safety.

Accident Prevention

A comparative study of pH/activity profiles for the anaerobic H2O2 and alkyl hydroperoxide supported N demethylation of N methylaniline catalyzed by alkaline haematin and microsomal cytochrome P-450.

A comparative study of the effect of pH on haemin-mediated H2O2 and alkyl hydroperoxide-supported N-demethylation of N-methylaniline and the corresponding cytochrome P-450 mediated process has been carried out. This extends previous studies and provides quantitative evidence that the same active oxygen species are involved in both the enzymic and metalloporphyrin mediated processes. Furthermore, this evidence clearly indicates that the environment at the point of catalysis in the enzyme active site differs considerably from that of the bulk solution.

Anaerobiosis

Comprehension problems in children with specific language impairment: literal and inferential meaning.

A group of 61 schoolchildren with specific language impairment (SLI) was compared with a control group on a comprehension task, in which the child was questioned about a story that had been presented either orally or as a series of pictures. Half the questions were literal, requiring the child to provide a detail that had been mentioned or shown explicitly in the story. The remainder required the child to make an inference about what had not been directly shown or stated. SLI children were impaired on this task, even after taking into account "comprehension age," as assessed on a multiple-choice test. However, the effects of mode of presentation and question type were similar for control and SLI groups. Children who fitted the clinical picture of semantic-pragmatic disorder had lower scores than other SLI children on this task. In addition, they were more prone to give answers that suggested they had not understood the question. However, as with the other SLI children, there was no indication that they had disproportionate difficulty with inferential questions. It is concluded that SLI children are impaired in constructing an integrated representation from a sequence of propositions, even when such propositions are presented nonverbally.

Child

Flagellar microtubule dynamics in Chlamydomonas: cytochalasin D induces periods of microtubule shortening and elongation; and colchicine induces disassembly of the distal, but not proximal, half of the flagellum.

To study the mechanisms responsible for the regulation of flagellar length, we examined the effects of colchicine and Cytochalasin D (CD) on the growth and maintenance of Chlamydomonas flagella on motile wild type cells as well as on pf 18 cells, whose flagella lack the central microtubules and are immobile. CD had no effect on the regeneration of flagella after deflagellation but it induced fully assembled flagella to shorten at an average rate of 0.03 microns-min. Cells remained fully motile in CD and even stubby flagella continued to move, indicating that flagellar shortening did not selectively disrupt machinery necessary for motility. To observe the effects of the drug on individual cells, pf 18 cells were treated with CD and flagella on cells were monitored by direct observation over a 5-hour period. Flagella on control pf 18 cells maintained their initial lengths throughout the experiment but flagella on CD-treated cells exhibited periods of elongation, shortening, and regrowth suggestive of the dynamic behavior of cytoplasmic microtubules observed in vitro and in vitro. Cells behaved individually, with no two cells exhibiting the same flagellar behavior at any given time although both flagella on any single cell behaved identically. The rate of drug-induced flagellar shortening and elongation in pf 18 cells varied from 0.08 to 0.17 microns-min-1, with each event occurring over 10-60-min periods. Addition of colchicine to wild type and pf 18 cells induced flagella to shorten at an average rate of 0.06 microns-min-1 until the flagella reached an average of 73% of their initial length, after which they exhibited no further shortening or elongation. Cells treated with colchicine and CD exhibited nearly complete flagellar resorption, with little variation in flagellar length among cells. The effects of these drugs were reversible and flagella grew to normal stable lengths after drug removal. Taken together, these results show that the distal half to one-third of the Chlamydomonas flagellum is relatively unstable in the presence of colchicine but that the proximal half to two-thirds of the flagellum is stable to this drug. In contrast to colchicine, CD can induce nearly complete flagellar microtubule disassembly as well as flagellar assembly. Flagellar microtubules must, therefore, be inherently unstable, and flagellar length is stabilized by factors that are sensitive, either directly or indirectly, to the effects of CD.

Actins