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Biomedical subjects

J E Jones

Publications and source records attributed to J E Jones.

At least 55 records · Page 3Linked to original sources
PubMed1995

Preferential recognition of hepatitis B nucleocapsid antigens by Th1 or Th2 cells is epitope and major histocompatibility complex dependent.

Regulatory T-helper (Th) cells have been categorized into two functional subsets, Th1 and Th2 cells, which produce distinct lymphokines. In general, Th1 cells mediate cellular immune responses and Th2 cells mediate humoral immunity. Recent serological studies suggest that the Th1-Th2 balance may be relevant in acute and chronic hepatitis B virus (HBV) infections. The purpose of this study was to determine the potential of the nucleocapsid antigens (Ags) (hepatitis B core and e Ags [HBc/eAg]) of HBV to preferentially elicit either a Th1 or a Th2 dominant response. For this purpose, H-2 congenic B10.S and B10 mice were immunized with HBc/eAg, and Ag-specific T-cell proliferative responses, T-cell helper function, and T-cell cytokine production were analyzed. The results indicated that B10.S mice preferentially develop a Th1-like response whereas B10 mice preferentially develop a Th2-like response after immunization with HBc/eAg. Furthermore, the preferential Th1 and Th2 response patterns were reproduced when 12-residue peptides representing the dominant HBc/eAg-specific T-cell sites for B10.S (peptide 120-131) and B10 (peptide 129-140) mice were used as immunogens. Therefore, the combination of the T-cell site recognized and the major histocompatibility complex restricting element can in large part determine the Th phenotype of the HBc/eAg-specific T-cell response. Other factors that influenced Th phenotype were the presence of exogenous cytokines, Ag structure, and tissue distribution.

Amino Acid Sequence↗
PubMed1994

Clara cell 10 kDa protein mRNA in normal and atypical regions of human respiratory epithelium.

We used RNA-RNA in situ hybridization to study expression of the human CC10 gene in morphologically normal and atypical areas of 32 non-neoplastic lung specimens resected from 26 non-small cell lung cancer patients. We scored strong, moderate or weak levels of CC10 mRNA expression in 3 distinct lung compartments. In morphologically normal lungs, strong and moderate levels of CC10 mRNA were observed in bronchioli and bronchi, respectively, but the expression was rarely observed in the alveolar region. Distinct alterations in CC10 mRNA expression were noted in specific histologic abnormalities within bronchi and the alveolar region. CC10 hybridization signal decreased markedly in bronchi containing diffuse goblet cell hyperplasia or squamous metaplasia, while CC10 mRNA expression remained unchanged in bronchi with basal cell hyperplasia or focal goblet cell hyperplasia. Bronchiolar CC10 mRNA levels remained unchanged in sections containing abnormalities elsewhere. Interestingly, in alveoli with bronchiolization of the alveoli, high levels of CC10 mRNA were observed. These regions also contained strongly stained keratin 14-positive cells, which may indicate a concurrent metaplastic process. In lungs with morphologic atypias, no correlation was found between abnormalities detected in bronchi and alveoli from the same lung. A comparison of mRNA expression and clinicopathologic features demonstrated that the amount of histologic abnormalities increased with smoking history (pack years); however, no correlation between CC10 mRNA expression and sex, age or smoking history was found.

Age Factors↗
PubMed1994

Soluble CTLA-4 can suppress autoantibody production and elicit long term unresponsiveness in a novel transgenic model.

Activation of Ag-specific T cells often requires costimulatory signals in addition to the primary signal mediated through the TCR. The CD28-B7 interaction provides one important costimulatory signal. Previous studies have shown that a soluble CD28 homologue, CTLA4lg, binds B7 with high affinity and can inhibit CD28-B7-mediated costimulation in vitro and in vivo. In this study we examined the ability of soluble human CTLA4lg to inhibit autoantibody production in vivo. For this purpose we used a novel transgenic (Tg) model of autoantibody production. Hepatitis B eAg-expressing Tg mice can be induced to produce autoantibody to the circulating autoantigen (HBeAg) by the injection of a T cell recognition site that fails to elicit T cell tolerance in these mice. Autoimmunity in this model is quantitative because serum autoantibody and autoantigen concentration are inversely correlated and easily measurable by ELISA. In this system a single regimen of CTLA4lg treatment significantly suppressed primary autoantibody production and variably led to long term unresponsiveness. Furthermore, in vivo treatment with CTLA4lg inhibited both T cell activation and T cell-B cell interactions.

Abatacept↗
PubMed1994

Extrathymic expression of the intracellular hepatitis B core antigen results in T cell tolerance in transgenic mice.

We previously developed a transgenic (Tg) murine lineage (B10.S-Tg31e), which secretes the hepatitis B e Ag (HBeAg) into the serum at a concentration of 10 ng/ml. This serum concentration was sufficient to render B10.S-Tg31e mice functionally tolerant at the T cell but not B cell level. To determine the tolerogenic potential of an intracellular form of this Ag, namely the hepatitis B core Ag (HBcAg), expressed outside the thymus, the B10.S-Tg10c lineage was developed. In B10.S-Tg10c mice the HBcAg is expressed as an intracellular "self"-Ag predominantly in the liver, and cannot be detected in the serum, the thymus or in nonthymic lymphoid tissue. Despite the liver-specific and intracellular location of this transgenic self-protein, B10-STg10c mice demonstrate a significant degree of HBcAg-specific T cell tolerance at the level of T cell proliferation. Similarly, in vivo anti-HBc antibody production after HBcAg immunization is significantly reduced as compared with non-Tg littermate controls. No spontaneous anti-HBc antibody is produced in B10.S-Tg10c mice, however, adoptive transfer of HBcAg-specific T cells from non-Tg B10.S mice elicits anti-HBc specific "autoantibody" production. Interestingly, antibodies with specificity for the HBeAg as well as the HBcAg are produced. Antibody production in B10.S-Tg10c mice adoptively transferred with T cells indicates that sufficient native HBcAg can gain access to the extracellular compartment to engage HBcAg-specific B cells that are clearly not tolerant in this model. No liver injury was observed as a consequence of HBcAg expression, even in B10.S-Tg10c mice adoptively transferred with HBcAg-specific T cells. Unless HBcAg is unique in this regard, these results suggest that organ-specific, intracellular self-Ag may be released during normal cell turnover in sufficient concentrations to elicit systemic T cell tolerance. B10.S-Tg10c mice also serve as an immunologic model system for chronic infection with the HBeAg-negative mutant of the hepatitis B virus.

Animals↗
PubMed1994

Modelling the growth, survival and death of microorganisms in foods: the UK food micromodel approach.

Techniques for the development of mathematical models in the area of predictive microbiology have greatly improved recently, allowing better and more accurate descriptions of microbial responses to particular environmental conditions, thus enabling predictions of those responses to be made with greater confidence. Recognising the potential value of applying these techniques in the food industry, the Ministry of Agriculture, Fisheries and Food (MAFF) initiated a nationally coordinated five-year programme of research into the growth and survival of microorganisms in foods, with the aim of developing a computerised Predictive Microbiology Database in the UK. This initiative has resulted in the systematic generation of data, through protocols which ensure consistency of methodology, so that data in the database are truly comparable and compatible, and lead to reliable predictive models. The approaches taken by scientists involved in this programme are described and the various stages in the development of mathematical models summarized. It is hoped that this initiative and others being developed in the USA, Australia, Canada and other countries, will encourage a more integrated approach to food safety which will influence all stages of food production and, eventually, result in the development of an International Predictive Microbiology Database.

Bacteria↗
PubMed1994

Mathematical modelling of the growth, survival and death of Yersinia enterocolitica.

This paper discusses the development of a novel mathematical equation capable of handling the growth, survival and death of microorganisms. The equation was used in combination with second-order polynomials to fit a response surface to data representing the growth, survival and death of Yersinia enterocolitica as affected by temperature (0-30 degrees C), sodium chloride (0-10.5% w/v), pH (3.5-7.0) and undissociated lactic acid (0-9.63 g/l). The resulting predictive model showed a good correlation over the entire range of the experimental data. Predictions from the model have been compared with independent data from both published literature and inoculated food studies. Analysis of the results showed a good correlation, particularly for data from milk and meat products.

Hydrogen-Ion Concentration↗
PubMed1994

Dental-care experiences of people living with HIV/AIDS in Aotearoa New Zealand.

Previous surveys of people living with HIV/AIDS suggest that such persons may have difficulty in securing dental care and that some dentists would prefer to refer such individuals. This study aimed to assess the experiences of people living with HIV/AIDS in Aotearoa New Zealand in obtaining and undergoing dental treatment. Survey forms were distributed through organisations working with people with HIV/AIDS. Fifty-seven questionnaires were analysed. The majority of respondents were gay white males. Seventy-five percent of participants felt that dental care was important, or very important, and 37 percent had increased the frequency of visits to the dentist since being diagnosed as HIV-positive. Forty-two (74 percent) participants had disclosed their HIV status to their dentists. Of this group, the majority had experienced either supportive or sympathetic reactions. Of those who concealed their status, 31 percent feared rejection by the dental practitioner, and 31 percent felt the dentist was taking adequate precautions and that there was no need to volunteer information on HIV status. Only three people reported denial of treatment on the grounds of their HIV status. An additional two people were immediately referred on by their practitioner after disclosure. Almost half the participants had changed dentists after they were diagnosed as HIV-positive. The main reasons stated included cost of treatment, fear of breach of confidentiality, or shifting to a new centre. Even though 33 percent received dental care in a hospital environment, 63 percent suffered systemic manifestations of HIV-infection, and 51 percent had oral manifestations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Incongruence of existing practice management curricula content and actual medical practice need.

BACKGROUND AND OBJECTIVES: Practice management is an important, but often overlooked, element of medical training, especially for physicians in primary care. The objective of this study was to evaluate our program's practice management curriculum to determine if it meets the needs of its graduates. METHODS: A questionnaire, developed and sent to 1986-1991 graduates of the residency program (n = 76), determined their perceptions of how well the practice management curriculum prepared them to operate a practice. Fifty (65.8%) usable surveys were returned. RESULTS: The respondents perceived deficits in areas of preparing for office management, starting and building a practice, using professional services (especially in the areas of financial decisions and use of professionals), and reimbursement procedures. CONCLUSIONS: Physicians need an understanding of business fundamentals such as economics, organization management, contract evaluation, negotiation and mediation skills, methods of allocation of limited resources, information science, and consumerism. This article offers a process through which other family practice residency programs can begin evaluating and restructuring their practice management curricula to meet these needs.

Curriculum↗
PubMed1993

Structure of hepatitis B virus core and e-antigen. A single precore amino acid prevents nucleocapsid assembly.

The hepatitis B virus core gene codes for two polypeptides: the core protein, which assembles to form particles (HBcAg), and the secreted precore protein (HBeAg). Expression vectors directing the synthesis in Escherichia coli of a recombinant HBeAg corresponding in sequence to serum-derived HBeAg encompassing the 10 precore amino acids remaining after cleavage of the precursor and residues 1-149 of HBcAg (PC-HBeAg) were constructed. Recombinant PC-HBeAg, HBcAg, and C-terminally truncated HBcAg were isolated from E. coli and analyzed by sucrose velocity sedimentation, electron microscopy, anti-HBc/e specific monoclonal antibody analysis, and for immunogenicity. HBcAg and truncated HBcAg formed 27-nm particles and displayed HBc antigenicity. In contrast, PC-HBeAg was nonparticulate and did not band in sucrose gradients. PC-HBeAg was recognized efficiently by HBeAg-specific antibodies and displayed little HBc antigenicity. Immunogenicity studies including T and B cell recognition confirmed that PC-HBeAg demonstrates HBe antigenicity. The presence of the 10 precore amino acids therefore prevented particle formation. To analyze which precore amino acids might be responsible for the prevention of particle formation a cysteine to glutamine substitution at amino acid position -7 was introduced into PC-HBeAg (-7C-->Q)PC-HBeAg. This single amino acid change at position -7 restored particle formation and HBc antigenicity. The evolutionarily conserved cysteine at position -7 thus appears responsible for the prevention of particle assembly in the HBeAg biosynthesis pathway.

Animals↗
PubMed1993

Asymmetric radiographic findings in the pediatric chest: approach to early diagnosis.

Several conditions in children produce a mass effect within one hemithorax, which may be life threatening. The different radiographic appearances of these conditions provide a basis on which they can be classified. The three major categories include a large cystic hemithorax, a large lucent hemithorax, and a large opaque hemithorax. Some disorders may be seen within more than one major group. Within the large cystic hemithorax group, congenital cystic adenomatoid malformation and congenital diaphragmatic hernia may be life-threatening conditions that require emergency surgery. The large lucent hemithorax is usually caused by pneumothorax, partial bronchial occlusion, or compensatory hyperinflation of the unobstructed lung. The majority of cases within the large opaque hemithorax group involve pleural fluid collections. Because many conditions that cause a mass effect require intervention or surgery, accurate interpretation of the plain chest radiograph is essential for an early diagnosis. Classification of radiographic features into these three groups often allows accurate diagnosis without additional studies.

Child↗
PubMed1993

Attitudinal factors associated with individual faculty research productivity in academic dentistry.

The purpose of this study was to examine attitudinal factors associated with increased research productivity of individual clinical faculty in 66 United States and Canadian schools of dentistry. Thirteen variables, evaluating the subjects' perceptions of their research background, work environment, attitude and outcome effects from publishing, and the use of colleagues in conducting research, were evaluated. The 833 respondents represented a response rate of 64.9% (833/1200) from a 50% stratified random sample of faculty who (1) had full-time appointments and held at least the D.M.D. or D.D.S. degree or the foreign equivalent, (2) taught in a clinical department of the dental school, and (3) were not departmental chairpersons or administrators (assistant dean, associate dean, or dean). Respondents reported a mean of 10.3 yr. (range = 1 to 45, SD = 7.3) in full-time dental education (career age) and a mean of 10.1 career publications (range = 0 to 110, SD = 13.8). Analysis of variance for mean number of career publications, by increasing agreement in response to each attitudinal variable, yielded a significant positive association for each of the 13 attitudinal variables. Implications of the findings were discussed with respect to strategies for improving research productivity of individual faculty.

Adult↗
PubMed1993

Replacement of lateral line sensory organs during tail regeneration in salamanders: identification of progenitor cells and analysis of leukocyte activity.

It has been proposed that supporting cells may be the progenitors of regenerated hair cells that contribute to recovery of hearing in birds, but regeneration is difficult to visualize in the ear, because it occurs deep in the skull. Hair cells and supporting cells that are comparable to those in the ear are present in lateral line neuromasts, and in axolotl salamanders these cells are accessible to microscopic observation in vivo. After amputation of a segment of the tail that contains neuromasts, cells from the posteriormost neuromast on the tail stump divide rapidly and form a migratory regenerative placode. The cells of the regenerative placode represent a lineage that eventually produces both hair cells and supporting cells in replacement neuromasts. We sought to identify the progenitors of the regenerative placode by using differential interference contrast microscopy combined with time-lapse video recording in living axolotl salamanders. In response to amputation, the mantle-type supporting cells at the posteroventral edge of the neuromast that is nearest to the wound increased their frequency of cell division, and gave rise to the first cells of the placode. The increase in mitotic activity of mantle-type supporting cells was accompanied by an unexplained decrease in the frequency of divisions in the same neuromast's population of internal supporting cells. The time-lapse records suggested that the changes in the mitotic activity of supporting cells might have been linked to the presence of phagocytic leukocytes in the vicinity of the neuromast that was nearest to the wound. Leukocytes were evenly distributed around control neuromasts, but during regeneration leukocyte activity increased significantly in the vicinity of the posterior half of the posteriormost neuromast. The redistribution of leukocytes occurred early in the regenerative response, but a causal role for the leukocytes has not been conclusively established. It is possible that the leukocytes could contribute to the formation of the regenerative placode at that location by breaking down the glycocalyx that ensheaths the outermost cells of the neuromast, or through the secretion of mitogenic growth factors.

Ambystoma mexicanum↗
PubMed1993

The effect of a student summer assistantship program in family medicine on specialty selection.

BACKGROUND AND OBJECTIVES: Stimulating medical students' interest in family practice is a goal of family medicine education. Summer assistantship programs have been instituted to help address this issue. METHODS: This study evaluated the results of residency program selection for participants in a family medicine summer assistantship program during a five-year period. Students who applied for the assistantship but were not accepted were used as a comparison group to measure student interest in family medicine. Additional comparisons were made with students who neither applied to nor participated in the program. All students were followed until residency program selection had occurred, after which each participant in the assistantship program completed a questionnaire regarding the effect of the assistantship on residency selection. RESULTS: The difference in rate of family practice residency selection between the participants (n = 31) and those who applied but were not accepted (n = 57) was not significant (X2 = .3, df = 1, P = NS). However, the difference in family practice residency selection between the participants and those not applying (n = 403) was significant (X2 = 6.46, df = 1, P < .05). Participants selecting a family practice residency program were more likely to feel that the summer assistantship experience was their basis for selecting their residencies (mean 7.6 versus 4.7, P < .05 for t test). CONCLUSION: The difference in the rate of entry into family practice residency programs between the assistantship participants and those who applied but were not accepted was not significant.

Adult↗