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Biomedical subjects

I Jones

Publications and source records attributed to I Jones.

At least 73 records · Page 4Linked to original sources
PubMed1998

IL-8 and the activation of eosinophils and neutrophils following nasal allergen challenge.

BACKGROUND: A growing body of evidence suggests that proinflammatory cytokines play a role in allergic inflammation by attracting and activating inflammatory cells. In this study, we have investigated the relationship between interleukin-8 (IL-8) in nasal lavage fluid and the local activation of eosinophils and neutrophils following nasal allergen challenge of allergic patients. METHODS: Nasal challenges were performed with grass pollen extract in 14 allergic patients and 5 nonallergic controls. Nasal lavage fluid was collected repeatedly for 10 h, and the levels of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were used as markers of eosinophil and neutrophil activation, respectively. The levels of these molecules were compared with that of IL-8 in nasal lavage fluid. RESULTS: Allergen challenge of allergic patients produced a significant late-phase increase in the levels of ECP and MPO. Furthermore, the level of MPO showed a highly significant correlation with the level of IL-8 in lavage fluid (r = 0.8, p< 0.0001), whereas there was no significant relationship between the levels of ECP and IL-8. CONCLUSION: Interestingly, our findings suggest that both eosinophils and neutrophils are activated following nasal allergen challenge. In addition, our results are consistent with the hypothesis that IL-8 acts as a chemoattractant/activator of neutrophils during the late phase of the allergic inflammation. In contrast, we were not able to demonstrate any significant relationship between the level of IL-8 in lavage fluid and the activation of eosinophils.

Adult↗
PubMed1998

Protective mucosal immunity elicited by targeted lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

Prevention of sexually transmitted HIV infection was first investigated in non-human primates by mucosal immunization via the rectal, vaginal or male urethral route. This was compared with subcutaneous targeted iliac lymph node (TILN) and systemic intramuscular immunization in non-human primates. TILN immunization elicited the most consistent mucosal sIgA and IgG antibody response in the rectum, vagina, urine and seminal fluid, as well as in blood. Both mucosal and TILN immunization induced a specific CD4+ T cell proliferative response in the iliac lymph nodes which drain these mucosal surfaces, and in the splenic and circulating T cells. In the next experiment macaques were immunized by the TILN route with SIV gp120 and p27 in alum. Rectal mucosal challenge with SIVmac 32H J5 molecular clone (or cell-free virus) induced total protection in four out of seven macaques, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (p = 0.025). The remaining three macaques immunized by the TILN route showed either decrease in viral load (> 90%) or transient viraemia, indicating that all seven TILN immunized macaques showed total or partial protection of rectal transmission by SIV (p = 0.001). Protection was associated with significant increase in the iliac lymph nodes IgA antibody secreting cells to p27 (p < 0.02), CD8-suppressor factor inhibiting replication of SIV in CD4+ T cells (p < 0.01) and the chemokines RANTES and MIP-1 beta (p < 0.01). We suggest that administration of gp120 and p27 by the TILN route may elicit protective B and T cell immunity which can significantly prevent rectal transmission of SIV or HIV.

Animals↗
PubMed1998

Why do some patients not cash their prescriptions?

BACKGROUND: A small number of studies have used different methodologies to measure primary non-compliance, but they have not established the reasons for patients not cashing their prescriptions. It has been suggested that the number of uncashed prescriptions is a measure of the quality of doctor-patient communication, but this hypothesis remains untested. AIM: To establish the feasibility of obtaining data on a sensitive subject from patients by interview and to seek patients' reasons for not cashing prescriptions using qualitative data. METHOD: Questionnaire administered to 1000 consecutive patients attending surgery, followed by interview with those patients who indicated that they had not cashed the index prescription. RESULTS: The response rate was 93.5%. Twenty-two patients were included in the study. There was wide variation in the number of uncashed prescriptions issued by each doctor (1-13). A total of nine out of 22 patients reported that their medication was cheaper over the counter and obtained it in this way; 13 out of 22 did not obtain their medication. Five patients indicated that cost was a factor in not obtaining their medication. Other factors included the doctor's permission not to cash the prescription, poor understanding of the illness, and the wish to maintain control. CONCLUSION: It is feasible to ask patients about aspects of their behaviour that may indicate, or cause, difficulties in the doctor-patient relationship. Prescribing behaviour varies widely between doctors and, although cost is a factor in determining whether a prescription will be cashed, other variables, such as the patient's desire to maintain control over the illness, may be more important.

Adolescent↗
PubMed1998

Postnatal depression in the community.

BACKGROUND: Postnatal depression affects 15% of all women derived. Good practice in antenatal and postnatal care suggests that regular contact should take place with members of the primary health care team (PHCT) but, despite this, many cases of postnatal depression are probably not detected. It is also widely perceived that depressed women consult more frequently about themselves and their babies, but it is not clear whether the number of contacts with the primary health care team as a whole reflects this. AIM: To determine whether the use of the Edinburgh Postnatal Depression Scale (EPNDS) at postnatal examination would detect women not recognized as depressed by the PHCT. To determine whether the number of contacts with the PHCT could be used as a screening tool for postnatal depression. METHOD: The EPNDS was administered at postnatal examination to 176 women delivering their babies between 1 April 1995 and 31 October 1995. Contacts with PHCT members were recorded up to the 42nd day after delivery, together with their assessment of the subjects' mental health. RESULTS: Of 30 women scoring > or = 12 on the EPNDS, only 13 were perceived to be depressed by the PHCT. The team as a whole identified more depressed women than any individual professional group. There was no significant difference in the number of contacts made with professionals by women who were or were not depressed. Asian women were more likely to be depressed than women from other ethnic groups. CONCLUSION: Despite the PHCT as a whole identifying more depressed women than any individual group, more than half were not identified by professionals. Tools such as the EPNDS should be used routinely in primary care; there is an urgent need to validate the EPNDS for non-Caucasian women.

Depression, Postpartum↗
PubMed1998

There is more to a test than technology-evaluation of testing for chlamydia infection in a charitable sector termination service.

In order to develop a possible strategy for chlamydia testing throughout the British Pregnancy Advisory Service (BPAS), it was decided to first find the prevalence of the infection in women attending and to examine the practicalities involved in offering tests and dealing with positive results. Urine samples at initial consultation were tested by a method based on the Ligase Chain Reaction (LCR). Five hundred and eighty seven women were tested with an overall chlamydia positivity of 8.1 per cent, but of 12.4 per cent (25/202) in women up to and including 20 years of age. Tests in women over 25 years showed a positivity of only 0.7 per cent (1/147). Urine testing proved to be a convenient, non-intrusive means of chlamydia detection with the potential to lead to prompt management of positive cases. However, in comparison with EIA testing of endocervical swabs, detection of chlamydia in the population studied was not enhanced and some limitations were demonstrated, imposed by requirements for controlled temperature for transport and storage of specimens. Alternative approaches to testing and management was discussed. The time and commitment required to offer this service effectively were observed to be important factors when staff and client were focused on the direct issues relating to the current pregnancy. Modified request forms enabled uniform data to be collated in the laboratory and compared with that from other services currently studied. Ongoing monitoring of chlamydia positivity in this nationwide termination service could provide useful sentinel data about the infection.

Abortion Applicants↗
PubMed1997

Mutant CD4 molecules with improved binding to HIV envelope protein gp120 selected by phage display.

Phage-display methodology has been used to select variant CD4 proteins exhibiting increased binding to the surface envelope glycoprotein, gp120, of Human Immunodeficiency Virus Type-1. To facilitate the selection, a library of mutant CD4 proteins was constructed by cloning a PCR-generated error prone population of the first two domains of CD4 into the phagemid expression vector pHEN1. Phage displaying CD4 in functional form were confirmed by Western blot with CD4-specific antibody and by phage ELISA on immobilized gp120. Biopanning of CD4 phage on immobilized gp120 followed by individual characterization identified five clones with increased binding to gp120. All of the selected variants had one or two amino acid substitutions within the V1 domain of CD4, notably at positions 15, 27, 30, 50, and 66 located in the strands surrounding the main binding loop. Variants which exhibited increased binding to recombinant gp120 in vitro were also shown to have an increased capacity for virus neutralization broadly in line with their in vitro binding activity.

Amino Acid Sequence↗
PubMed1997

Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT).

The human serotonin transporter gene (hSERT) is a strong candidate for involvement in the pathogenesis of mood disorder and, using a UK Caucasian case-control sample, Collier et al found a significant association between bipolar disorder and the 12 allele of the VNTR polymorphism in intron 2 of this gene. In a European collaborative sample, Collier et al found a significant association between affective disorder and a functional deletion polymorphism in the promoter of hSERT. We have undertaken association studies using these polymorphisms in a British Caucasian sample comprising 171 DSM-IV bipolar probands, 80 DSM-IV major depression probands and 121 unrelated controls matched to bipolar probands for age, sex and ethnicity. We found no association between the promoter deletion and affective disorder but our findings with the VNTR polymorphism are similar to those of Collier and colleagues: we found a significant excess of the 12 repeat allele in bipolar probands (P = 0.031, one-tall) with a suggestion of a gene dosage effect (using genotypes bearing no 12 repeat allele as baseline, the increased risks conferred by genotypes bearing 12 repeat alleles were: heterozygote, OR = 1.24; homozygote, OR = 1.76). Our findings add to the evidence that variation at or near hSERT influences susceptibility to bipolar disorder in the British Caucasian population.

Adult↗
PubMed1997

Differential regulation of the antibody responses to Gag and Env proteins of human immunodeficiency virus type 1.

We have studied the antibody responses to Env and Gag antigens of human immunodeficiency virus type 1 (HIV-1) in several cohorts of HIV-1-infected individuals: long-term nonprogressors, progressors to disease, acute seroconvertors, and recipients of HIV-1 protease inhibitors. We conclude that the antibody responses to Env and Gag antigens are differentially regulated and that changes in the plasma viral load in the measurable range (500 to 10(8) RNA copies per ml) do not directly affect the antibody responses to these HIV-1 proteins. We provide quantitative estimates of HIV-1-specific immunoglobulin G concentrations in plasma, which can be in excess of 1 mg/ml for both anti-gp120 and anti-p24 once the immune response to HIV-1 has stabilized after seroconversion. We discuss the apparent paradox that the absence of anti-Gag antibodies (which have, at best, limited antiviral activity) is indicative of disease progression, while the retention of anti-Env antibodies (which do have antiviral activity) is of limited (or no) prognostic value. We show that the disappearance of anti-Gag antibodies during disease progression is highly unlikely to be due to immune complexing; instead, we believe that it reflects the loss of T-cell help that is more necessary for the anti-Gag than the anti-Env response.

AIDS Vaccines↗
PubMed1997

A survey of social outcome in schizophrenia in Tasmania.

OBJECTIVE: To survey the social outcome of patients with schizophrenia attending State mental health facilities in southern Tasmania. METHOD: Using the Statewide Mental Health Register, patients using inpatient and outpatient facilities who received a diagnosis of schizophrenia between 1981 and 1988 were identified (n = 771), and demographic and illness measures, and admissions and length of inpatient stay were compiled. The Life Skills Profile (LSP) was completed by mental health personnel for the 247 who were regular attenders or inpatients in 1991. RESULTS: Social morbidity as indexed by the LSP was highest in psychiatric hospital inpatients and patients in long-term rehabilitation programs, and lower in patients attending community centres. The majority of patients in suburban settings and attending community centres lived with their families, whereas patients in the inner city or in the rehabilitation service were mainly in hostel accommodation or living alone. Patients with schizophrenia attending State services were of a similar age range but had a longer duration of illness and more admissions, and had spent more days in hospital than patients who were not in regular contact with the service. CONCLUSIONS: The distribution of social morbidity in schizophrenia confirms that the public health system is supporting a group with high social morbidity. Patients with the highest morbidity are receiving the highest levels of care and intervention.

Adaptation, Psychological↗
PubMed1997

Myeloperoxidase and interleukin-8 levels in chronic sinusitis.

We have recently phenotyped inflammation in non-infectious allergic and non-allergic chronic maxillary sinusitis using sinus biopsies and lavage fluids. In this first paper, we have concentrated our work on the eosinophil, T cell, mast cell and macrophage infiltrates. However, many unresolved questions remain and particularly the role of neutrophils needed to be addressed. In the present study, we focused on the neutrophilic inflammation: myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured by immunoassays and neutrophils were enumerated by conventional staining in the sinus lavage fluids of 16 patients with chronic sinusitis and six control subjects. Both MPO and IL-8 levels were significantly higher in patients than in controls (P < 0.01 and 0.005, respectively). There was a significant correlation between MPO levels and neutrophil numbers, and between MPO and IL-8 levels in the sinus lavage fluid (P < 0.0001, Spearman rank correlation). The presence of high levels of IL-8 in the lavage fluids of patients suffering from chronic sinusitis, levels which correlate with those of MPO, suggests that this cytokine may activate neutrophils in this chronic disease.

Adolescent↗
PubMed1996

Baculovirus vectors for expression in insect cells.

Recombinant baculoviruses now represent a mature technology in which vector development, particularly for the control of expression level, has reached a plateau. However, other aspects of expression, such as the production of multiple proteins, improved product purification or maximizing protein processing, remain areas for novel vector and host cell development. This year has seen these topics come to the fore in descriptions of new expression systems.

Animals↗
PubMed1996

Assembly of macromolecular complexes in bacterial and baculovirus expression systems.

Many proteins exist normally as oligomers or complexes with other proteins. Recent advances in vector design have allowed this aspect of protein function to be mimicked in recombinant expression systems. Examples of the ordered oligomerization of a single protein through to the assembly of eight different proteins have been documented in recombinant Escherichia coli and recombinant baculovirus systems.

Animals↗
PubMed1996

Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

Prevention of sexually transmitted HIV infection was investigated in macaques by immunization with a recombinant SIV (simian immunodeficiency virus) envelope gp 120 and core p27 vaccine. In two independent series of experiments, we used the novel targeted iliac lymph node (TILN) route of immunization, aiming close to the iliac lymph nodes draining the genitorectal mucosa. Rectal challenge with the SIVmac 32H J5 molecular clone in two series induced total protection in four out of seven macaques immunized by TILN, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (P = 0.025). The remaining three macaques showed either a decrease in viral load ( > 90%) or transient viremia, indicating that all seven TILN-immunized macaques showed total or partial protection (P = 0.001). Protection was associated with significant increase in the iliac lymph nodes of IgA antibody-secreting cells to p27 (P < 0.02), CD8-suppressor factor (P < 0.01), and the chemokines RANTES and MIP-1 beta (P < 0.01).

Animals↗