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Biomedical subjects

J E Jones

Publications and source records attributed to J E Jones.

At least 37 records · Page 2Linked to original sources
PubMed1998

The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: a mechanism for persistence.

The hepatitis B precore Ag (HBeAg) is a secreted nonparticulate version of the viral nucleocapsid hepatitis B core Ag (HBcAg), and its function is unknown. A proportion of HBeAg-specific Th cells evade deletion/anergy in HBeAg-transgenic (Tg) mice and mediate anti-HBe "autoantibody" (autoAb) production after in vivo activation with the appropriate Th cell peptide. This model system was used to determine how secretory HBeAg may effect deletion of Th cells in the periphery. For this purpose, HBeAg-Tg mice were bred with Fas and Fas ligand (FasL)-defective lpr/lpr and gld/gld mutant mice. Fas-FasL interactions mediate activation-induced apoptosis in the periphery. In HBeAg-Tg/+ mice, high-titrated anti-HBe autoAb was produced that was exclusively composed of the IgG1 isotype (i.e., Th2-like profile). In contrast, HBeAg-Tg/lpr and HBeAg-Tg/gld mice produced significantly less anti-HBe autoAb, and the IgG isotype patterns were broadened to include IgG2a, IgG2b and IgG3 as well as IgG1 (i.e., mixed Th1/Th2-like profile). These results suggest that HBeAg-specific Th1 cells are preferentially depleted by Fas-FasL-mediated interactions. The effect of circulating HBeAg on HBcAg-specific Th1 cells was also examined by transferring HBe/HBcAg-specific Th cells into dual HBeAg- and HBcAg-expressing Tg recipient mice. The presence of serum HBeAg ablated the expected Th1-mediated anti-HBc Ab response and shifted it toward a Th2 phenotype. These results suggest that in the context of a hepatitis B viral infection, circulating HBeAg has the potential to preferentially deplete inflammatory HBeAg- and HBcAg-specific Th1 cells that are necessary for viral clearance, thereby promoting hepatitis B virus persistence.

Adoptive Transfer↗
PubMed1998

The carriage of Pasteurella haemolytica in sheep and its transfer between ewes and lambs in relation to mastitis.

The possible presence of Pasteurella haemolytica in the mouth of lambs and on the skin of the teats of ewes was investigated. The organism was found in the mouth of ewes and lambs and, soon after lambing, on the teat skin of ewes. It was not isolated from the teat skin of pregnant ewes 1-14 days before lambing or from the teat skin one week after the lambs had been weaned. The transfer of P. haemolytica to the teat skin is undoubtedly mediated by the lamb. There is ample opportunity for the teat orifice to be exposed to P. haemolytica during the suckling period and it is known that only a few colony-forming units of virulent organisms are required to initiate mastitis.

Animals↗
PubMed1998

Gender and research productivity in US and Canadian schools of dentistry. A preliminary investigation.

The purpose of this study was to evaluate individual faculty research productivity with respect to gender among clinical faculty in 66 United States and Canadian schools of dentistry. A comprehensive survey instrument was developed to collect information on factors associated with research productivity of individual faculty. The present investigation focused on time spent per week in various work related activities (teaching, administration, research, and private practice), external grant money obtained for research, and responses to 12 variables evaluating the subject's perceptions of their research background, work environment, attitude and outcome effects from publishing, and the use of colleagues in conducting research. The 833 respondents represented a response rate of 69.4% (833/1200) from a 50% stratified random sample of faculty who (1) had full-time appointments and held at least the DMD or DDS degree or the foreign equivalent, (2) taught in a clinical department of the dental school, and (3) were not departmental chairpersons or administrators. The majority of subjects responding to the survey were male (705 males, 84.6%; 128 females, 15.4%). Respondents reported a mean of 10.3 years (males = 10.8, females = 7.5) in full-time dental education and a mean of 10.1 career publications (males = 11.6, females = 6.5; P < 0.001). Although there was no significant difference in weekly hours devoted to academic responsibilities between males and females, several factors did demonstrate significant gender differences (external grant money obtained for research purposes, P < 0.03; feeling that the departmental chair did not emphasize research, P < 0.05; feeling a lack of autonomy within their institution, P < 0.007; and feeling a lack of available colleagues for research purposes, P < 0.001). The implications of the findings are discussed concerning strategies for improving research productivity for females in academic dentistry.

Canada↗
PubMed1997

Role of B cells in antigen presentation of the hepatitis B core.

The hepatitis B virus (HBV) nucleocapsid or core antigen (HBcAg) is extremely immunogenic during infection and after immunization. For example, during many chronic infections, HBcAg is the only antigen capable of eliciting an immune response, and nanogram amounts of HBcAg elicit antibody production in mice. Recent structural analysis has revealed a number of characteristics that may help explain this potent immunogenicity. Our analysis of how the HBcAg is presented to the immune system revealed that the HBcAg binds to specific membrane Ig (mIg) antigen receptors on a high frequency of resting, murine B cells sufficiently to induce B7.1 and B7.2 costimulatory molecules. This enables HBcAg-specific B cells from unprimed mice to take up, process, and present HBcAg to naive Th cells in vivo and to T cell hybridomas in vitro approximately 10(5) times more efficiently than classical macrophage or dendritic antigen-presenting cells (APC). These results reveal a structure-function relation for the HBcAg, confirm that B cells can function as primary APC, explain the enhanced immunogenicity of HBcAg, and may have relevance for the induction and/or maintenance of chronic HBV infection.

Animals↗
PubMed1997

Detection of K-ras point mutation by in situ PCR in cell suspensions: comparison of the indirect and direct methods.

In situ PCR is a new technique for the localization of low copy number sequences. We report here a method for the in situ visualization of a point mutation in K-ras codon 12 by indirect in situ PCR. Twenty-five primers were examined to select mutant-specific primers. Harvested cell lines were fixed and suspended in PCR mixture. Forty cycles of PCR in cell suspension was performed in a thermal cycler using a hot start method. Cells were cytocentrifuged onto slides, and post-fixation was performed. The specimens on the slides were then hybridized with a digoxigenin-labeled probe, followed by color reaction. Both Calu-1 (mutated: TGT) and NCI-H460 (wild type: GGT) cells had strong hybridization signals in the nuclei with general primers. But with mutant-specific primers, only Calu-1 cells had hybridization signals. No signal was observed without primers or Taq DNA polymerase. Southern blotting of the same preparation confirmed desired amplification. We also applied direct in situ PCR, but this method failed to detect the point mutation. We conclude that our indirect in situ PCR method shows the feasibility of in situ identification of single cells carrying point mutations.

Blotting, Southern↗
PubMed1997

The predictive value of tympanometry in the diagnosis of middle ear effusion.

Over a 12-month period 501 children (age range 11 months to 15 years) underwent surgery for a possible middle ear effusion. All had tympanometry performed within 2 h of surgery. The results of tympanometry were correlated with the surgical findings in 955 ears. A type-B tympanogram has a high sensitivity (0.91) in predicting middle ear effusion with good specificity (0.79). A type-A tympanogram has a very high specificity (0.99) in predicting a dry middle ear but low sensitivity (0.34). Both the positive (0.91) and negative (0.84) predictive values of a type-A tympanogram are high. The addition of a type-C tympanogram increases the sensitivity of predicting a dry middle ear to 0.79. The positive predictive value of a peaked (type-A or -C) tympanogram is 0.71 and should be considered strong evidence that the middle ear is dry. Tympanometry is the best clinical test for the presence or absence of a middle ear effusion, and on the basis of preoperative tympanometry alone the need for surgery should be carefully reassessed.

Acoustic Impedance Tests↗
PubMed1997

The hepatitis B virus core and e antigens elicit different Th cell subsets: antigen structure can affect Th cell phenotype.

Secretion of the hepatitis B virus (HBV) e antigen (HBeAg) has been conserved throughout the evolution of hepadnaviruses. However, the function of this secreted form of the viral nucleoprotein remains enigmatic. It has been suggested that HBeAg functions as an immunomodulator. We therefore examined the possibility that the two structural forms of the viral nucleoprotein, the particulate HBV core (HBcAg) and the nonparticulate HBeAg, may preferentially elicit different T helper (Th) cell subsets. For this purpose, mice were immunized with recombinant HBcAg and HBeAg in the presence and absence of adjuvants, and the immunoglobulin G (IgG) isotype profiles of anti-HBc and anti-HBe antibodies were determined. Second, in vitro cytokine production by HBcAg- and HBeAg-primed Th cells was measured. The immunogenicity of HBcAg, in contrast to that of HBeAg, did not require the use of adjuvants. Furthermore, HBcAg elicited primarily IgG2a and IgG2b anti-HBc antibodies, with a low level of IgG3, and no IgG1 anti-HBc antibodies. In contrast, the anti-HBe antibody response was dominated by the IgG1 isotype; low levels of IgG2a or IgG2b anti-HBe antibodies and no IgG3 anti-HBe antibodies were produced. Cytokine production by HBcAg- and HBeAg-primed Th cells was consistent with the IgG isotype profiles. HBcAg-primed Th cells efficiently produced interleukin-2 (IL-2) and gamma interferon (IFN-gamma) and low levels of IL-4. Conversely, efficient IL-4 production and lesser amounts of IFN-gamma were elicited by HBeAg immunization. The results indicate that HBcAg preferentially, but not exclusively, elicits Th1-like cells and that HBeAg preferentially, but not exclusively, elicits Th0 or Th2-like cells. Because HBcAg and the HBeAg are cross-reactive in terms of Th cell recognition, these findings demonstrate that Th cells with the same specificity can develop into different Th subsets based on the structural form of the immunogen. These results may have relevance to chronic HBV infection. Circulating HBeAg may downregulate antiviral clearance mechanisms by virtue of eliciting anti-inflammatory Th2-like cytokine production. Last, the influence of antigen structure on Th cell phenotype was not absolute and could be modulated by in vivo cytokine treatment. For example, IFN-alpha treatment inhibited HBeAg-specific Th2-mediated antibody production and altered the IgG anti-HBe isotype profile toward the Th1 phenotype.

Adjuvants, Immunologic↗
PubMed1997

Evaluation of an education package in leg ulcer management.

An experimental study was conducted with 224 nurses in the experimental group and 40 in a control group to evaluate the implementation of an education and training package in the management of leg ulceration. A knowledge and reported practice questionnaire was completed before and after an educational intervention was received by nurses in the experimental group only. There was no difference between groups in the initial scores. Following the implementation of the education and training package, nurses in the experimental group achieved a significant increase in score from 25 to 34. There was no change in score in the control group.

Community Health Nursing↗
PubMed1996

Regeneration of sensory cells after laser ablation in the lateral line system: hair cell lineage and macrophage behavior revealed by time-lapse video microscopy.

The regeneration of sensory hair cells in lateral line neuromasts of axolotls was investigated via nearly continuous time-lapse microscopic observation after all preexisting hair cells were killed by a laser microbeam. The laser treatments left neuromasts with one resident cell type, which was supporting cells. Over the course of 1 week, replacement hair cells arose either directly via differentiation of cells present in the epithelium from the beginning of the time-lapse period or via the development of cells produced after one or two divisions of supporting cells. All of the cell divisions that produced hair cells were asymmetrical. During the first hour after the treatment, macrophages and smaller leukocytes were attracted to the laser-treated neuromasts. The smaller leukocytes returned to control levels 48-60 hr after the treatment, whereas macrophages remained active there throughout the period of hair cell replacement. Macrophage incidence peaked 36-48 hr after the laser treatment. Macrophages phagocytosed damaged hair cells and supporting cells, as well as new cells and preexisting cells without recognizable damage. The results provide direct evidence of hair cells arising as progeny produced from the divisions of supporting cells, evidence of hair cells and supporting cells arising from the same cell division, evidence relating to the timing of hair cell differentiation, and indirect evidence pertaining to proposals that hair cells sometimes arise via conversion of cells without an intervening division. The results also suggest that macrophages may influence early stages in the process of hair cell regeneration.

Ambystoma↗
PubMed1996

Cervical thymic cysts.

Cervical thymic cysts are a rare cause of neck masses in children. This case report describes a three-year-old child with a several-month history of an enlarging neck mass, who was emergently admitted due to airway obstruction. Computed tomography revealed a large cystic mass extending from the oropharynx to the level of the mediastinum. Excision of the mass with pathologic examination revealed a thymic cyst. The clinical picture, the theories regarding development of these cysts, as well as surgical options for treatment, are discussed.

Airway Obstruction↗
PubMed1995

Human peptidylglycine alpha-amidating monooxygenase transcripts derived by alternative mRNA splicing of an unreported exon.

We are characterizing the alternatively spliced human peptidylglycine alpha-amidating monooxygenase (hPAM)-encoding mRNA transcripts expressed by human cells. Reverse transcription coupled to the polymerase chain reaction (RT-PCR) has been used to identify four alternatively spliced variants that differ in the region joining the two catalytic domains. Two of the transcripts represent previously reported splice variants differentiated by the presence (hPAM-A) or absence (hPAM-B) of a 321-nucleotide (nt) linker (optional exon A) which in the rat produce functionally distinct enzymes. Different mRNAs represent two splice variants, hPAM-C and hPAM-D, that show the presence of an exon unreported for PAM in any other species. This new exon, designated exon C, is 54 nt in length, encodes an 18-amino-acid (aa) peptide containing a conserved dibasic aa endoproteolytic processing motif, and is located 3' of exon A in human genomic DNA. We propose that cell-specific regulation of mRNA splicing would provide a mechanism for control of prohormone activation by these variants of the PAM enzyme.

Alternative Splicing↗
PubMed1995

Interleukin 12 suppresses autoantibody production by reversing helper T-cell phenotype in hepatitis B e antigen transgenic mice.

Helper T (Th) cells are classified as Th1 or Th2 cells by virtue of cytokine secretion and function as mediators of cellular or humoral immunity, respectively. Cytokines also regulate the differentiation of Th cells. For example, interleukin (IL)-12 promotes Th1 and suppresses Th2 cell development, suggesting that IL-12 may be useful therapeutically in Th2-mediated autoimmune and allergic disorders. Therefore, the effect of systemic IL-12 treatment on in vivo autoantibody synthesis in hepatitis B e antigen (HBeAg)-expressing transgenic mice, which is dependent on self-reactive Th2 cells, was examined. Low-dose IL-12 significantly inhibited autoantibody production by shifting the Th2-mediated response toward Th1 predominance. Additionally, previous studies suggest that a predominance of HBeAg-specific Th2-type cells may contribute to chronicity in hepatitis B virus infection. Therefore, IL-12 may also prove beneficial in modulating the HBeAg-specific Th response to favor viral clearance in chronic hepatitis B virus infection.

Animals↗
PubMed1995

Peripheral primitive neuroectodermal tumors of the head and neck.

OBJECTIVE: Primitive neuroectodermal tumor is a malignant small round cell tumor of neuroectodermal origin. The occurrence of these tumors in the head and neck is rare. Our objective is to document the frequency of presentation, methods of diagnosis, and forms of treatment used to combat primitive neuroectodermal tumors in the head and neck. DESIGN: Retrospective chart review. RESULTS: The most common location for primitive neuroectodermal tumors in our series was the thoracopulmonary region (46%); the next most common location was the head and neck (42%). Metastatic disease was present in 31% of patients at the time of diagnosis. Cytogenic analysis was found to be helpful in confirming the diagnosis of primitive neuroectodermal tumor. Therapy for primitive neuroectodermal tumors included surgery, chemotherapy, and radiation therapy. Survival statistics were poor, with 65% of the patients alive at 2 years' follow-up. CONCLUSIONS: Primitive neuroectodermal tumor is an aggressive malignant small round cell tumor that may present in the head and neck. Long-term survival for patients with primitive neuroectodermal tumor is still poor; however, the use of improved chemotherapeutic agents combined with aggressive surgical control of primary disease and, in some cases, radiation therapy should lead to improved long-term survival.

Adolescent↗
PubMed1995

Characterization of self-reactive T cells that evade tolerance in hepatitis B e antigen transgenic mice.

Previous studies of hepatitis B e antigen (HBeAg)-expressing transgenic (Tg31e) mice have indicated that the degree of T cell tolerance was epitope specific. For example, T cells specific for residues 120-131 of HBeAg are profoundly tolerant, whereas a proportion of T cells specific for residues 129-140 escape tolerance induction in B10. S x B10-Tg31e mice. To understand the basis for differential tolerance towards two T cell sites on the same self antigen, we characterized T cell recognition of HBeAg by primary T cells and T cell hybridomas derived from HBeAg-Tg and non-Tg mice. The self-reactive T cells surviving in B10-Tg31e mice exhibited a unique fine specificity, albeit still focussed on HBeAg residues 129-140, which could be distinguished from the HBeAg-specific T cell repertoire in non-Tg B10 mice. Further, self-reactive T cells were comprised predominantly of Th2-type cells that preferentially evaded tolerance induction as compared to their Th1 counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic hepatitis B virus (HBV) infection, these results suggest that a predominance of HBeAg-specific Th2 cells expressing a limited repertoire may influence the initiation or the maintenance of the HBV chronic carrier state.

Animals↗