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Biomedical subjects

D Webster

Publications and source records attributed to D Webster.

At least 19 recordsLinked to original sources
PubMed2001

Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies in mice.

Measles remains a significant problem in both the developed and developing world, and new measles vaccination strategies need to be developed. This paper examines the strategy of utilizing transgenic plants expressing a measles antigen for the development of an oral sub-unit measles vaccine. A 1.8 kb fragment encompassing the coding region of the measles virus hemagglutinin (H) protein was cloned into a plant expression cassette. Three different expression constructs were tested: pBinH (H gene alone), pBinH/KDEL (addition of a C-terminal endoplasmic reticulum-retention sequence SEKDEL) and pBinSP/H/KDEL (further addition of an authentic N-terminal plant signal peptide). The highest levels of recombinant H protein production were observed in plants transformed with pBinH/KDEL. Mice inoculated intraperitoneally with transgenic plant derived recombinant H protein produced serum anti-H protein antibodies that neutralized the measles virus (MV) in vitro. Mice gavaged with transgenic tobacco leaf extracts also developed serum H protein-specific antibodies with neutralizing activity against MV in vitro. These results indicate that the plant-derived measles H protein is immunogenic when administered orally and that, with further development, oral vaccination utilizing transgenic plants may become a viable approach to measles vaccine development.

Administration, Oral↗
PubMed2001

Does 77C-->G in PTPRC modify autoimmune disorders linked to the major histocompatibility locus?

A 77G allele of the gene encoding CD45, also known as the protein tyrosine phosphatase receptor-type C gene (PTPRC), has been associated with multiple sclerosis (MS). Here we determine allele frequencies in large numbers of MS patients, primary immunodeficiencies linked to major histocompatibility complex (MHC) locus and over 1,000 controls to assess whether aberrant splicing of PTPRC caused by the 77C-->G polymorphism results in increased susceptibility to these diseases. Our results show no difference in the frequency of the 77G allele in patients and controls and thus do not support a causative role for the polymorphism in the development of disorders with a strong autoimmune component in etiology.

Animals↗
PubMed2001

Treatment of resistant mycoplasma infection in immunocompromised patients with a new pleuromutilin antibiotic.

Patients with primary antibody deficiency (PAD) are prone to mycoplasma infection with unusual strains which may be resistant to conventional antibiotics. Mycoplasmas were isolated from the joint fluid (Ureaplasma urealyticum) of two PAD patients with arthritis and from the cerebral spinal fluid (Mycoplasma maculosum) in one with meningitis, the latter probably originating from the patient's dog. Combinations of doxycycline and quinolones or macrolides failed to clear the infections, but after demonstrating in-vitro sensitivity to the pleuromutilin, Econor, for two of the isolates, all three patients responded to oral treatment with Econor. The infection was completely eradicated in two patients, with the emergence of a resistant strain in the third. Mycoplasma infection should be considered in PAD patients with unexplained sepsis. Pleuromutilins such as Econor are powerful new anti-mycoplasmal agents which provide an additional therapeutic option when patients fail to respond to conventional antibiotics.

Adolescent↗
PubMed2001

The role of alcohol use in intimate partner femicide.

The purpose of this study was to examine alcohol use by victims and perpetrators as a risk factor for intimate partner violence and femicide. A case control design was used to describe alcohol use among Femicide/Attempted Femicide victims (n = 380), Abused Controls (n = 384) and Non-Abused Controls (n = 376), and their intimate partners. Telephone interviews of proxies (family members or friends) of femicide victims and actual survivors of attempted femicide were conducted in 10 cities. The purpose of the interviews was to gather information about relationship violence and alcohol use by femicide victims, attempted femicide survivors, and their perpetrators. Telephone interviews of controls, recruited from the same cities by random digit dialing, were also conducted. Perpetrator problem drinking was associated with an eight fold increase in partner abuse (e beta = 8.24, p < .0001) and a two fold increased risk of femicide/attempted femicide (e beta = 2.39, p = .001), controlling for demographic differences.

Adolescent↗
PubMed2001

Long term recovery of IgG and IgM production during HIV infection in a patient with common variable immunodeficiency (CVID).

AIMS: Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency. This paper describes the immunological consequences of human immunodeficiency virus (HIV) infection in a patient with familial CVID subsequently treated with highly active antiretroviral therapy (HAART). METHODS: Serial measurements over 11 years of serum immunoglobulins, specific antibodies to tetanus toxoid and pneumococcal polysaccharides, lymphocyte phenotypes, and HIV viral load were made. RESULTS: The patient recovered total serum IgG and IgM, but not IgA production, with adequate concentrations of specific antibodies, allowing withdrawal of intravenous immunoglobulin without an increase in infections. T cell numbers gradually declined and the patient developed a high grade B cell lymphoma. After successful chemotherapy, HAART was commenced, viral load fell from 472 000 to < 50 copies/ml, and CD4+ T cell numbers increased from 13 to 661 x 10(6)/litre. Antibody production was maintained after suppression of viral load. CONCLUSIONS: This is the first definitive report of reversal of IgG and IgM deficiency in familial CVID after HIV infection. Failure to normalise IgA supports the concept of separate predisposing genetic factors for selective IgA deficiency, which when combined with others lead to CVID. Furthermore, a persistently high viraemia is not required to maintain the recovery of immunoglobulin values, suggesting this depends either on a transitory effect of a high viral load, or a persistence of low amounts of virus.

Adult↗
PubMed2001

Cochlear implantation of a patient with a previously undescribed mitochondrial DNA defect.

Mitochondrial DNA (mtDNA) defects are responsible for symptom complexes that are characteristically heterogeneous but are typically represented by muscle weakness and neurological deficits. One common feature of mitochondrial disease is deafness. This report details the assessment and outcome of a patient with a previously undescribed mtDNA rearrangement who underwent cochlear implantation. The patient shows a marked improvement in sentence recognition tests and recognition of environmental sounds. Patients with profound sensorineural hearing loss due to mtDNA defects should be considered as candidates for cochlear implantation when they no longer benefit from conventional hearing aids.

Adult↗
PubMed2000

Impaired antibody affinity maturation process characterizes a subset of patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is an heterogeneous syndrome characterized by decreased levels of serum Ig and recurrent bacterial infection. Here, we were interested to study whether a qualitative defect of the affinity Ab maturation process could be combined to the low level of serum Ig in a cohort of 38 CVID patients. For this, we designed a novel and rapid screening test for the detection of hypomutated V gene expressed by memory B cells. This test delineated a subset of 9/38 (23%) CVID patients with an abnormal pattern of Ig V gene mutation. The mean frequency of V gene mutation of this subset was significantly lower (1.74%) compared with other CVID patients (5.46%) and normal donors (6.5%) (p<0.0001). The mean age of this subgroup was significantly higher than other hypogammaglobulinemic patients with normal levels of V gene mutation (p<0.02), whereas no difference in the duration of symptoms was noted between the two groups. This suggests that hypomutation characterizes patients who began CVID late in life. Recently, it was shown that non-Ig sequences, such as the intronic BCL-6 gene, could be the target of the somatic hypermutation process in normal memory B cells. Our finding of a normal mutation frequency of the BCL-6 gene in two hypomutated CVID point to a defect of the Ig targeting of hypermutation machinery in these cases.

Adult↗
PubMed2000

Randomized trial of a specialist genetic assessment service for familial breast cancer.

BACKGROUND: Because of the growing demand for genetic assessment, there is an urgent need for information about what services are appropriate for women with a family history of breast cancer. Our purpose was to compare the psychologic impact and costs of a multidisciplinary genetic and surgical assessment service with those of current service provisions. METHODS: We carried out a prospective randomized trial of surgical consultation with (the trial group) and without (the control group) genetic assessment in 1000 women with a family history of breast cancer. All P: values are from two-sided tests. RESULTS: Although statistically significantly greater improvement in knowledge about breast cancer was found in the trial group (P: =.05), differences between groups in other psychologic outcomes were not statistically significant. Women in both groups experienced statistically significant reductions in anxiety and found attending the clinics to be highly satisfying. An initial specialist genetic assessment cost pound 14.27 (U.S. $22.55) more than a consultation with a breast surgeon. Counseling and genetic testing of affected relatives, plus subsequent testing of family members of affected relatives identified as mutation carriers, raised the total extra direct and indirect costs per woman in the trial group to pound 60.98 (U.S. $96.35) over costs for the control subjects. CONCLUSIONS: There may be little benefit in providing specialist genetics services to all women with a family history of breast cancer. Further investigation of factors that may mediate the impact of genetic assessment is in progress and may reveal subgroups of women who would benefit from specialist genetics services.

Adult↗
PubMed2000

Morphological and biochemical evaluation of RAW 264.7 cells exposed to polychlorinated biphenyl.

The effects of PCBs exposure, at low doses ranging between 10-100 mg PCB (Arclor-1254), on the viability of RAW 264.7 macrophage cells after 24, 48, and 72 hours of incubation was investigated. Furthermore, this study was designed to determine the interrelationship between PCBs and estrogen (E, 10 mg) and its role in the viability of RAW cells. Macrophages were cultured and plated in 24 well-plates according to standard protocols. The wells were divided into eight groups (n = 4 wells/group, 1 x 10(4) cells/well). The cells in groups 1-3 were treated with vehicle (serum-control for estrogen, DMSO-control for PCB, and media alone, respectively). Cells in groups 4 and 5 were treated with low (10 mg) and high (100 mg) doses of PCB. Cells in group 6 were treated with E, and cells in groups 7 and 8 were treated with low dose PCB + E and high dose PCB + E, respectively. Cell viability and damage (Malianodialdehyde, MDA level) were determined after 24, 48, and 72 hours, as well as, cell morphology. The results of this study showed that low and high doses of PCB depressed cell number by 52%. Estrogen treatment caused no effect on cell number in comparison to cells treated with serum alone. Cell number in response to E and low and high doses of PCB decreased cell number by 50%. Similar results were also observed at 48 hour time phase. In contrast, at the 72 hour phase, no significant changes were observed for cell count. Morphological evaluation of the cells revealed healthy spindle shaped multinucleated cells in the control group but, groups exposed to PCB induced morphological changes that included: cells became small, round, and increased evidence of cellular injury and debris. Estrogen treatment did not show changes from the control group. However E and PCB treatments caused the cells to become round, tightly compact nuclei with evidence of cell fragmentation. The results of this investigation showed that exposure to either 10 or 100 mg of PCB had detrimental effects on the RAW 264.7 macrophage cells as early as 24 hours. Combination treatment with E didn't provide any protective measures to the viability of RAW cells exposed to PCBs.

Animals↗
PubMed2000

Brain abscess at the University Hospital of the West Indies.

Surgical infections of the central nervous system are still attended by high rates of morbidity and mortality, although substantial progress has been made since the advent of computed tomography (CT) scanning technology. In this retrospective review of 25 surgically treated patients with either brain abscess or subdural empyema at the University Hospital of the West Indies, the majority of patients were male and between the ages of 10 and 30 years with a mean age of 16.9 years. Almost half the patients had a hemiparesis on presentation while 60% had fever. Subdural empyema was more common than a localized intracerebral abscess which was most frequently located in the frontal lobe. The most common predisposing factors were sinusitis and congenital heart disease. Streptococci spp and Staphylococci spp were the most frequently isolated organisms. All patients underwent CT scanning and surgical intervention. The mortality rate was 20%, and 21% of the survivors had late seizures. There must be a high index of clinical suspicion and early referral to specialist centres where neuroradiological investigation and prompt neurosurgical intervention can be carried out to minimize morbidity and mortality.

Adolescent↗
PubMed1999

Quality evaluation of newborn screening programs.

In the last four decades in many countries and regions all over the world newborn screening programs have been developed. Traditionally, most programs focus on phenylketonuria and congenital hypothyroidism. However, with development of new technologies, screening for a large variety of other disorders has become available. The decision-making process on what to screen or not to screen for is usually driven by personal interest of the professionals involved, by local legislation and access to funding, resulting in large differences among countries. In general, quality evaluation is only applied to the pure laboratory analytical phase. Less attention is given to the pre-analytical phase (e.g. timely sampling, maximum coverage) and the post-analytical phase (follow-up and treatment, evaluation of long-term effects, cost-effectiveness, etc.). In order to gain more insight into the current situation worldwide we developed a questionnaire which was sent to leading screening centers in more than 30 countries. As expected, the results show large differences in degree of organization, turnover times, completeness of coverage and follow-up. There appears to be no relationship between screening procedures and the degree of legislation or the system of funding. In presenting the more detailed results we hope to be of service to program organizers.

Asia↗
PubMed1999

Quality assurance and standardization: summary of the satellite meeting, Turku, Finland, 11-12 June 1999.

The Quality Assurance (QA) and Standardization satellite meeting addressed five major issues in newborn screening: (i) Pre- and post-analytical phases are important in the overall quality of screening, and quality assurance programs should include these aspects. (ii) It is possible to run a single screening program using laboratories on more than one site, as is done in Europe, California and Cuba. Special quality assurance procedures are necessary for success. (iii) It is possible to achieve improved analytical quality and international comparison of results by use of common reference materials such as the amino acid materials developed in Europe and the US. It will be important to use tested paper with defined performance characteristics. (iv) It is appropriate for newborn screening programs to be accredited, but it will also be important to develop criteria for pre- and post-analytic phases of screening. (v) A new QA program is being developed for Latin America. The Australasian QA program now includes amino acids and acylcarnitines in a form suitable for tandem mass spectrometry blind QA. The European Society for Paediatric Endocrinology has developed guidelines for CAH screening.

Accreditation↗
PubMed1999

Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia.

We investigated the feasibility and diagnostic utility of genotyping 9 CYP21 mutations, linked chromosome 6p markers, and a dimorphic X-Y marker from neonatal screening samples. Blood-impregnated filter papers (Guthrie cards) from 603 randomly chosen New Zealand neonates were genotyped blind to 17-hydroxyprogesterone (17-OHP) levels. Another 50 samples from Swiss and North American infants with correlative hormonal data were also genotyped. DNA was extracted, and gene-specific PCR was performed. CYP21 PCR products were subjected to ligase detection reaction, simultaneously analyzing 9 CYP21 mutations; PCR products of other genes were subjected to direct gel analysis. CYP21 genotyping indicated a heterozygote rate of 2.8% for classic mutations (excluding CYP21 deletions), and 2.0% for nonclassic mutations in New Zealanders. Ten full-term affected neonates showed a wide range of 17-OHP levels (15-1400 nmol/L). Sick or preterm infants or infants screened on the first day of life with high 17-OHP proved genetically unaffected. Genetic linkage disequilibrium was found between two CYP21 mutations and chromosome 6p markers. Guthrie cards can be used to accurately genotype CYP21 and other relevant markers, potentially enhancing the specificity and sensitivity of congenital adrenal hyperplasia screening. CYP21 heterozygote frequency for classic mutations is higher than expected based on genotype compared with that predicted by hormonal newborn screening.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Comparisons of magnitude estimation scaling of rock music by children, young adults, and older people.

The present study concerned the perceptual processing of complex auditory stimuli in 10 children (M age = 8.1) as compared to 10 young adults (M age = 19.3) and 10 older adult subjects (M age = 54.2). The auditory stimulus used was 10 sec. of rock music (Led Zeppelin, 1969). All three groups provided numerical responses to nine intensities of the rock music stimulus (10, 20, 30, 40, 50, 60, 70, 80, 90 dB above threshold). Analysis showed that the children reported a wider range of numerical responses than both adult groups. The mean numerical responses for the children ranged from .54 to 54.24. For the young adults the range was .76 to 11.37, and for the older subjects it was 1.6 to 23.31. Results suggest that the children were not bound by the same set of rules as the adults with regard to magnitude estimation scaling of the loudness of the rock music stimulus. Their internal scaling mechanisms appeared to be more flexible and broader based than those of the adults who participated in this study.

Acoustic Stimulation↗
PubMed1998

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults (</= 39 yr) with CD4 counts in the range 300-500 cells/microl and in older subjects (> 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease.

Acquired Immunodeficiency Syndrome↗