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Biomedical subjects

M J Ward

Publications and source records attributed to M J Ward.

At least 19 recordsLinked to original sources

Identification of a chemotaxis operon with two cheY genes in Rhodobacter sphaeroides.

A large chemotaxis operon was identified in Rhodobacter sphaeroides WS8-N using a probe based on the 3' terminal portion of the Rhizobium meliloti cheA gene. Two genes homologous to the enteric cheY were identified in an operon also containing cheA, cheW, and cheR homologues. The deduced protein sequences of che gene products were aligned with those from Escherichia coli and shown to be highly conserved. A mutant with an interrupted copy of cheA showed normal patterns of swimming, unlike the equivalent mutants in E. coli which are smooth swimming. Tethered cheA mutant cells showed normal responses to changes in organic acids, but increased, inverted responses to sugars. The unusual behaviour of the cheA mutant and the identification of two homologues of cheY suggests that R. sphaeroides has at least two pathways controlling motor activity. To identify functional similarity between the newly identified R. sphaeroides Che pathway and the methyl-accepting chemotaxis protein (MCP)-dependent pathway in enteric bacteria, the R. sphaeroides cheW gene was expressed in a cheW mutant strain of E. coli and found to complement, causing a partial return to a swarming phenotype. In addition, expression of the R. sphaeroides gene in wild-type E. coli resulted in the same increased tumbling and reduced swarming as seen when the native gene is overexpressed in E. coli. The identification of che homologues in R. sphaeroides and complementation by cheW suggests the presence of MCPs in an organism previously considered to use only MCP-independent sensing. The MCP-dependent pathway, appears conserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

Associations among adult attachment representations, maternal sensitivity, and infant-mother attachment in a sample of adolescent mothers.

Associations among adolescent attachment organization, maternal sensitivity, and infant attachment organization were examined prospectively in 74 teenaged mother-infant dyads. Pregnant teenagers' attachment organizations predicted both sensitivity and infant-mother attachments. Mothers classified autonomous (F) in the prenatal period showed higher levels of sensitivity at both 3 and 9 months than mothers classified dismissing (Ds), preoccupied (E), or unresolved (U). Correspondence between maternal attachment (F vs. Ds/E/U) and infant attachment (secure [B] vs. avoidant [A]/resistant [C]/disorganized [D]) was observed in 58 of 74 (78%) dyads. Exact 4-group (Ds/E/F/U and A/B/C/D) agreement was observed in 50 of 74 (68%) families. In contrast, associations between maternal sensitivity and infant attachment were not significant, leading to questions about the processes that link attachment representations, maternal behavior, and infant attachment in adolescent mothers.

Adolescent

Sequence analysis and relationships between meningococcal class 3 serotype proteins and other porins from pathogenic and non-pathogenic Neisseria species.

The presence of highly conserved regions within previously determined porin gene sequences from Neisseria meningitidis and Neisseria gonorrhoeae permitted the construction of oligonucleotide primers for PCR amplification of other neisserial porin genes. Although two separate porin genes (porA and porB) are present in N. meningitidis only a single fragment, corresponding to porB, could be amplified from this species. The amplified porB genes from four different meningococcal serotypes, which express the class 3 outer membrane protein, were sequenced. Amplified fragments corresponding to porin genes from N. lactamica and N. sicca were also sequenced. In common with the known neisserial porins, models of the organisation of the predicted proteins indicated trans-membrane structures with eight surface exposed loops. In the meningococcal class 3 proteins the main regions of sequence variation, which must be responsible for serotype specificity, were located on loops 5 and 7. A phylogenetic analysis of the family of porins from the Neisseria confirmed the close relationship of the meningococcal class 3 protein with the gonococcal PIA protein, while the gonococcal PIB protein was shown to be closely related to the N. lactamica porin. The close relationship seen between porins of the pathogenic and non-pathogenic Neisseriae identified no obvious virulence-associated regions in the proteins, but did suggest that the current nomenclature for neisserial porin genes may need reviewing.

Alleles

Bacillus anthracis but not always anthrax.

Gram-positive bacilli isolated during epidemiological investigations which, on the basis of conventional tests, resemble Bacillus anthracis but which fail to produce the capsule or to induce anthrax in test animals have long been dismissed in clinical and veterinary laboratories as B. cereus or simply as unidentified Bacillus spp. and thereupon discarded as inconsequential. In this study, the application of newly available DNA probe, polymerase chain reaction and specific toxin antigen detection technology has revealed that a proportion of such strains are B. anthracis which lack the plasmid carrying the capsule gene (pXO2). While these techniques cannot, of course, be used to confirm the identities of strains resembling B. anthracis but which also lack the plasmid carrying the toxin genes (pXO1), the likelihood that these also are bona fide B. anthracis becomes more acceptable. (As yet no naturally occurring pXO1-/2+ strains have been found.) At this point, the significance of the presence of such avirulent forms of B. anthracis in specimens can only be a subject for speculation, but the possibility that they may be indicators of virulent parents somewhere in the system being examined must be considered.

Animals

High frequency of independent IS50 transposition during Tn5 mutagenesis of Bordetella pertussis virulence-associated genes.

Transposon Tn5-generated mutants of Bordetella pertussis were selected on the basis of their inability to bind the dye Congo red (Crb-). No mutants which were solely Crb- were found. Ten mutants were phenotypically equivalent to previously described strains with mutations in the virulence regulatory (bvg) locus and failed to express a range of virulence-associated factors. Two of these mutants were shown to have Tn5 insertions within the bvg locus, while another two mutants showed deletions in this regulatory region. Complementation studies indicated that the other six mutants had spontaneous mutations in the bvg locus, but with Tn5 inserted elsewhere in the chromosome. Several of the mutants, besides having a single Tn5 insertion, also showed additional IS50 insertions, indicating that the IS50 element contained within Tn5 had transposed independently. Such additional insertion events, which themselves would have the potential to cause mutation, could complicate the interpretation of mutant phenotypes which could thus arise from the insertional inactivation of more than one gene.

Bordetella pertussis

Disturbances of affect expression in failure-to-thrive.

Positive and negative affects were assessed in 28 6- to 36-month-old children with failure-to-thrive and 14 normally growing children in feeding and nonfeeding situations. The roles of malnutrition and severity of organic effects also were examined. Failure-to-thrive children expressed less positive affect in the feeding and nonfeeding situations and more negative affect in feeding than normally growing children. Among failure-to-thrive children, the presence of both acute and chronic malnutrition was associated with heightened negative affect during feeding, whereas the degree of organic contribution had no effect. These results, if replicated, may have implications for clinical assessment and are discussed in terms of current theories of failure-to-thrive.

Affective Symptoms

Family data determine all parameters in Mendelian incomplete penetrance models.

We show that data on the frequency of occurrence of an hereditary trait in family members can be used to determine all four parameters in a Mendelian genetic model with incomplete penetrance. Thus previous statements in the literature that such data can determine only three combinations of the parameters are incorrect.

Alleles

Mycobacterium fortuitum lung abscess treated with ciprofloxacin.

Mycobacterium fortuitum rarely causes lung disease. Although treatment in the past has included intravenous antibiotics, this is the first report of a Mycobacterium fortuitum lung abscess that resolved with a prolonged course of oral ciprofloxacin alone. There is no evidence of recurrence 14 months after the end of treatment.

Ciprofloxacin

Bone turnover during high dose inhaled corticosteroid treatment.

This study was performed to determine the effects of high doses of two inhaled corticosteroids, beclomethasone dipropionate and budesonide, on biochemical indices of bone turnover (urinary hydroxyproline:creatine and calcium:creatinine ratios, plasma alkaline phosphatase, and parathyroid hormone). Twelve healthy male doctors, aged 25-36 (mean 30) years, were studied. After a week's run in period eight subjects inhaled beclomethasone dipropionate 2000 micrograms/day and eight inhaled budesonide 1800 micrograms/day for 28 days; this was followed by a week without any treatment. During treatment with beclomethasone dipropionate there was a significant increase in the hydroxyproline:creatinine ratio (a 46% increase at 28 days), and a fall in serum alkaline phosphatase activity (a 7.4% fall at 28 days). There were no significant changes during budesonide treatment. Thus high dose inhaled beclomethasone dipropionate increased biochemical markers of bone resorption and reduced serum alkaline phosphatase, a marker of bone mineralisation. A prospective study in asthmatic patients is indicated to assess the long term effects of high dose inhaled corticosteroids on bone mass.

Administration, Inhalation

Mothers' mental representations and their relationship to mother-infant attachment.

The association between the constructs of mental representation posited by object relations theory and attachment theory was studied through an assessment of adolescent mothers' mental representations and their infants' security of attachment. Forty-two pregnant adolescents were given the Adult Attachment Interview (George, Kaplan, & Main, 1985) to assess their modes of attachment, and the Krohn Object Representation Scale for Dreams (Krohn & Mayman, 1974) to assess object-representations. When the 42 infants were 15 months old, they were videotaped in the Strange Situation (Ainsworth, Blehar, Waters, & Wall, 1978) with their mothers. Subjects were primarily low-income African-American and Hispanic mothers and infants. As measured by the significant association between classifications on the Adult Attachment Interview and the Krohn scale (p less than .001), the adolescents' attachment and object-representations were highly related. Both attachment and object relations were also significantly related to infant attachment (p less than .001 and p less than .01, respectively). Results suggest that the concepts of mental representation proposed by object relations theory and attachment theory overlap and that mothers' mental representations have heuristic value in predicting mother-infant attachment.

Adolescent

Bioavailability of intranasal metoclopramide.

After intranasal administration of metoclopramide, (5 mg in 0.5 ml sterile water) the maximum plasma concentration of 13.5 +/- 7.3 (mean +/- s.d.) ng ml-1 was achieved. Absolute bioavailability was 50.5 +/- 29.5%, 110 +/- 41 min later. We conclude that the intranasal route does not allow rapid absorption of the drug and is not associated with greater bioavailability than the oral route.

Absorption

Intravenous beta agonist in severe acute asthma.

STUDY OBJECTIVE: To determine whether salbutamol is more effective in treating severe asthma when given intravenously or by inhalation. DESIGN: Randomised trial of short term response to intravenous versus nebulised salbutamol in acute severe asthma. SETTING: District general hospital (secondary care centre). PARTICIPANTS: 76 patients aged 16-70 admitted to hospital with acute severe asthma (peak expiratory flow rate less than 50% of predicted) during study period. Five withdrawn because of adverse effects of treatment or non-response. Of remaining 71, 34 allocated to nebuliser group and 37 to intravenous treatment group. Patients with history of cardiovascular disease or recent corticosteroid or intravenous bronchodilator treatment excluded. Admission characteristics similar in the two groups. INTERVENTIONS: All patients given 5 mg nebulised salbutamol on admission before randomisation plus 200 mg hydrocortisone bolus intravenously and 35% inspired oxygen throughout. Nebuliser group received two more 5 mg doses of nebuliser salbutamol at 30 minutes and 2 hours; intravenous group received 4 hours' continuous salbutamol infusion (12 micrograms/min) starting at 30 minutes plus supplementary intravenous potassium chloride. No other bronchodilators used. ENDPOINT: Change in peak expiratory flow rate over 4 hours. MEASUREMENTS AND MAIN RESULTS: Peak expiratory flow rate improved more in intravenous group (25.2%) than in nebuliser group (14.3%) (p less than 0.01, 95% confidence interval 2.4 to 19.1%). Tachycardia caused two withdrawals from intravenous group; non-response caused three withdrawals from nebuliser group. CONCLUSIONS: Intravenous salbutamol is more effective than nebulised salbutamol in acute severe asthma but may have unacceptable cardiovascular effects.

Acute Disease

Social-emotional adaptation and infant-mother attachment in siblings: role of the mother in cross-sibling consistency.

We investigated concordance in social-emotional behavior and attachment of first- and secondborn siblings from 65 families. Both children were seen at 24 months in a problem-solving procedure and at 12 months in the Strange Situation. Maternal behavior at 24 months also was examined. Child behaviors at 24 months showed trends toward concordance across siblings. Maternal behavior was significantly stable across siblings and correlated significantly with child competence. In post-hoc analyses, the sample was split into 2 groups: maternal behavior stable (N = 36) and maternal behavior unstable. In the first group, cross-sibling correlations were significant and larger than for the whole sample; in the second group, cross-sibling correlations were low and nonsignificant. There also was significant concordance across siblings in attachment classification. These data suggest that it is essential to consider the care received by different children in investigating similarities in siblings' behavior.

Adaptation, Psychological

Hypernatraemia and hyperchloraemic acidosis after bleach ingestion.

The deliberate ingestion of household 'strong' bleach (NaOCl) caused severe metabolic disturbance. Hyperchloraemic acidosis was probably due to NaOCl reacting with hydrochloric acid in the stomach to form hypochlorous acid and chlorine. 'Strong' household bleach contains 10% NaOCl and this provides a large sodium load. The ingestion of 500 ml contained 673 mmol sodium and caused hypernatraemia.

Acidosis