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Biomedical subjects

J M White

Publications and source records attributed to J M White.

At least 19 recordsLinked to original sources
PubMed1992

The epidemiology of pertussis in England and Wales.

Recovery in the uptake of whole-cell pertussis vaccine from 30% in 1978 to 91% in 1992 has resulted in a major reduction in the incidence of pertussis and in the proportion of cases occurring in pre-school children. This has been accompanied by a decline in pertussis mortality rates, with no deaths reported since September 1990. Seventy-four per cent of the 50 fatal cases reported since 1980 have been infants under one year of age, demonstrating the importance of completing primary immunisation as early as possible after birth. There is no evidence, as yet, that introduction of the accelerated immunisation schedule in June 1990 has reduced the proportion of cases occurring in infants, suggesting that the decline in mortality during the last two years is largely due to indirect protection provided by the current high level of vaccine-induced herd immunity. If 90% coverage is sustained and there is no significant waning of immunity with age, the circulation of Bordetella pertussis should be sufficiently reduced to interrupt the four year epidemic cycle for the first time in the United Kingdom. The hypothesis that vaccine-induced immunity has a serotype-specific component is supported by recent changes in serotype prevalence which have followed the increase in vaccine coverage. Given the successful reinstatement of whole-cell vaccine in the UK immunisation programme, the case for replacing it with a new acellular preparation will require careful evaluation.

Adolescent↗
PubMed1992

Membrane fusion.

Common themes are emerging from the study of viral, cell-cell, intracellular, and liposome fusion. Viral and cellular membrane fusion events are mediated by fusion proteins or fusion machines. Viral fusion proteins share important characteristics, notably a fusion peptide within a transmembrane-anchored polypeptide chain. At least one protein involved in a cell-cell fusion reaction resembles viral fusion proteins. Components of intracellular fusion machines are utilized in multiple membrane trafficking events and are conserved through evolution. Fusion pores develop during and intracellular fusion events suggesting similar mechanisms for many, if not all, fusion events.

Biological Transport↗
PubMed1992

Anti-human IgG causes basophil histamine release by acting on IgG-IgE complexes bound to IgE receptors.

We have reexamined the ability of anti-human IgG antibodies to induce histamine release from human basophils. A panel of purified murine mAbs with International Union of Immunological Societies-documented specificity for each of the four subclasses of human IgG was used. Of the 24 allergic subjects studied, the basophils of 75% (18/24) released greater than 10% histamine to one or more anti-IgG1-4 mAb, whereas none of the 13 nonatopic donor's basophils released histamine after stimulation with optimal amounts of anti-IgG mAb. The basophils of 85% (11/13) of the nonatopic donors did respond to anti-IgE challenge, as did 92% (22/24) of the atopic donor cells. Histamine release was induced most frequently by anti-IgG3, and 10/18 anti-IgG responder cells released histamine with mAb specific for two or more different subclass specificities. The rank order for induction of histamine release was anti-IgG3 greater than anti-IgG2 greater than IgG1 greater than anti-IgG4. As in our previous study using polyclonal anti-IgG, 100- to 300-micrograms/ml quantities of the anti-IgG mAb were required for maximal histamine release, about 1000-fold higher than those for comparable release with anti-human IgE. Specificity studies using both immunoassays and inhibition studies with IgE myeloma protein indicated that anti-IgG induced histamine release was not caused by cross-reactivity with IgE. Ig receptors were opened by lactic acid treatment so that the cells could be passively sensitized. Neither IgE myeloma nor IgG myeloma (up to 15 mg/ml) proteins could restore the response to anti-IgG mAb. However, sera from individuals with leukocytes that released histamine upon challenge with anti-IgG mAb could passively sensitize acid-treated leukocytes from both anti-IgG responder and nonresponder donors for an anti-IgG response. The only anti-IgG mAb that induced release from these passively sensitized cells were those to which the serum donor was responsive. Sera from non-IgG responders could not restore an anti-IgG response. These data led to the hypothesis that the IgG specific mAb were binding to IgG-IgE complexes that were attached to the basophil through IgE bound to the IgE receptor. This was shown to be correct because passive sensitization to anti-IgG could be blocked by previous exposure of the basophils to IgE. We conclude that anti-IgG-induced release occurs as a result of binding to IgG anti-IgE antibodies and cross-linking of the IgE receptors on basophils.

Antibodies, Anti-Idiotypic↗
PubMed1992

Identification of a prenylation site in delta virus large antigen.

During replication, hepatitis delta virus (HDV) switches from production of small to large delta antigen. Both antigen isoforms have an HDV genome binding domain and are packaged into hepatitis B virus (HBV)-derived envelopes but differ at their carboxy termini. The large antigen was shown to contain a terminal CXXX box and undergo prenylation. The large, but not the small, antigen formed secreted particles when expressed singly with HBV surface antigen. Mutation of Cys211 in the CXXX box of the large antigen abolished both prenylation and particle formation, suggesting that this site is important for virion morphogenesis.

3T3 Cells↗
PubMed1992

A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion.

The union of sperm and egg is a special membrane fusion event that gives a signal to begin development. We have hypothesized that proteins mediating cell-cell fusion events resemble viral fusion proteins and have shown that PH-30, a sperm surface protein involved in sperm-egg fusion, shares biochemical characteristics with viral fusion proteins. We report here the complementary DNA and deduced amino-acid sequences of the mature alpha and beta subunits of PH-30. Both are type-I integral membrane glycoproteins. The alpha subunit contains a putative fusion peptide typical of viral fusion proteins and the beta subunit contains a domain related to a family of soluble integrin ligands found in snake venoms. Thus, the PH-30 alpha/beta complex resembles many viral fusion proteins in both its membrane topology and its predicted binding and fusion functions.

ADAM Proteins↗
PubMed1992

Vaccine coverage: recent trends and future prospects.

OBJECTIVE: To assess the feasibility of achieving the target of 95% coverage for the childhood immunisation schedule by 1995 and to determine the influence of sociodemographic factors and information systems on recent trends. DESIGN: Analyses of trends in quarterly vaccination data for diphtheria, pertussis, and measles in health districts between February 1988 and February 1991. SETTING: District health authorities in England and Wales, and health and social services boards in Northern Ireland. SUBJECTS: Cohorts of children whose youngest member had reached the target age of 18 months for receiving the third doses of diphtheria and pertussis vaccines and 2 years for receiving measles vaccine. RESULTS: Predicted coverage levels for mid-1995 were in excess of 95% for diphtheria, pertussis, and measles vaccines. In the 118 districts that continuously reported between February 1988 and February 1991 the increase in coverage was 6% for diphtheria and 13% for pertussis and measles vaccines. 1991 coverage depended primarily on 1988 coverage. The additional effects of deprivation, change in computer system, and child population size achieved at most only marginal statistical significance. CONCLUSIONS: The government's target of 95% coverage by 1995 is realistic, although projections should be viewed with caution. Several national vaccination initiatives are likely to have contributed to the recent steady increase in coverage. Updating and validation exercises are likely to improve recorded coverage.

Child, Preschool↗
PubMed1992

Spatial localization without visual references.

To explain the veridical percept of the spatial ordering of objects and the generation of eye movements to peripheral targets, Lotze (1885 Microcosmos. Edinburgh: T. & T. Clark) proposed that there is a position label (local sign) for each retinal element. To estimate the precision of local sign information, we measured absolute localization thresholds at various eccentricities in the nasal visual field, in the complete absence of visual references. To eliminate perception of the visual surround, observers viewed a large display screen through a neutral density filter (2.0 log unit) in a dark room. The fixation target was extinguished at various times (interstimulus intervals or ISIs) prior to the onset of the test stimulus. In general, our results show that localization thresholds are proportional to the target eccentricity at all ISIs. At each eccentricity, localization thresholds are elevated after the extinction of the visual reference compared to thresholds when the reference is present. However, relative to the referenced threshold, unreferenced thresholds are elevated by a greater proportion at smaller eccentricities than at larger eccentricities. Our threshold vs ISI data can be adequately modeled on the basis of an intrinsic positional uncertainty, which increases with eccentricity, and additive and multiplicative sources of noise. The additive noise appears to reflect primarily the increasing scatter in eye position when the fixation target is extinguished. Our model's estimate of intrinsic positional uncertainty in the isoeccentric direction appears to reflect primarily the intrinsic positional uncertainty of the peripheral retina (the local sign), being very similar to cumulative cone position uncertainty and to the spacing between ON-P beta ganglion cells. In the isoeccentric direction, the estimated precision of the local sign mechanism across eccentricities is slightly better than the precision of saccadic endpoints, suggesting that noise in the motor system must also contribute to the scatter of saccadic endpoints in the isoeccentric direction. Interestingly, in the radial direction, we find a surprising similarity in our observers' positional uncertainty and the precision of saccadic endpoints.

Fovea Centralis↗
PubMed1992

Structure, function and evolutionary relationship of proteins containing a disintegrin domain.

Disintegrins are soluble integrin ligands from snake venoms that disrupt cell-matrix interactions. Recently, the nuclear magnetic resonance structures of two disintegrins were determined, providing provocative molecular insight into how a disintegrin may engage an integrin. In addition, it has recently been realized that disintegrins are derived from larger multifunctional proteins, and that there is a family of membrane-anchored, disintegrin domain-containing proteins that may promote important cell-cell interactions.

Amino Acid Sequence↗
PubMed1992

Intermonomer disulfide bonds impair the fusion activity of influenza virus hemagglutinin.

At a low pH, the influenza virus hemagglutinin (HA) undergoes conformational changes that promote membrane fusion. While the critical role of fusion peptide release from the trimer interface has been demonstrated previously, the role of globular head dissociation in the overall fusion mechanism remains unclear. To investigate this question, we have analyzed in detail the fusion activity and low pH-induced conformational changes of a mutant, Cys-HA, in which the globular head domains are locked together by engineered intermonomer disulfide bonds (L. Godley, J. Pfeifer, D. Steinhauer, B. Ely, G. Shaw, R. Kaufmann, E. Suchanek, C. Pabo, J. J. Skehel, D. C. Wiley, and S. Wharton, Cell 68:635-645, 1992). In this paper, we show that Cys-HA expressed on the cell surface is predominantly a disulfide-bonded trimer. Cell surface Cys-HA is impaired in its membrane fusion activity, as demonstrated by both content-mixing and lipid-mixing fusion assays. It is also impaired in its ability to change conformation at a low pH, as assessed by proteinase K sensitivity. The fusion activity and low pH-induced conformational changes of cell surface Cys-HA are, however, restored to nearly wild-type levels upon reduction of the intermonomer disulfide bonds. By using a set of conformation-specific monoclonal and anti-peptide antibodies, we found that purified Cys-HA trimers are impaired in changes that occur in the globular head domain interface. In addition, changes that occur at a great distance from the engineered intermonomer disulfide bonds, notably release of the fusion peptides, are also impaired. Our results are discussed with respect to current views of the fusion-active conformation of the HA trimer.

Animals↗
PubMed1992

Modification of the behavioural effects of ethanol by nifedipine.

Nifedipine (10.0 mg/kg) was administered to mice together with graded doses of ethanol (0, 2.5, 3.0, 3.5, 4.0 and 4.5 g/kg), and activity measured over a 2-hr period following administration. Low ethanol doses increased activity, whereas the highest dose decreased it. By itself, nifedipine had no effect on activity, but when combined with ethanol it produced a consistent decrease in comparison with ethanol alone. This occurred irrespective of whether the ethanol dose alone increased or decreased activity. These results demonstrate a clear interaction between nifedipine and ethanol which cannot be characterized as simple potentiation or antagonism. Time-course data showed that the effects of nifedipine were apparent within 10-20 min of drug administration, but, in the case of the highest ethanol dose, increased toward the end of the 2-hr period. Retardation of the development of acute tolerance may contribute to the interaction between ethanol and nifedipine.

Adult↗
PubMed1992

Music therapy: an intervention to reduce anxiety in the myocardial infarction patient.

The purpose of this study was to examine the effects of relaxing music on elevated state anxiety in patients with a confirmed medical diagnosis of acute myocardial infarction. In addition, the relationship between trait anxiety and state anxiety was analyzed. A purposive sample of 40 myocardial infarction patients was randomly assigned to an experimental or control group. Statistically significant reduction in heart rate, respiratory rate, and state anxiety scores were found in the group that listened to relaxing music. A statistically significant positive correlation was found between trait anxiety scores and baseline state anxiety scores. Statistically significant negative correlations were found between trait anxiety scores and the degree of change in posttreatment state anxiety scores when examined as a net change, as well as a percent change. Results suggested that music therapy may be an effective intervention to reduce state anxiety levels in the acute myocardial infarction patient.

Adult↗