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Biomedical subjects

R J Jackson

Publications and source records attributed to R J Jackson.

At least 19 recordsLinked to original sources
PubMed2007

Verifiable CPD paper: factors that influence the dental attendance pattern and maintenance of oral health for people with multiple sclerosis.

OBJECTIVE: To determine the impact of multiple sclerosis (MS) on patient attendance at dental practices and maintenance of oral health. DESIGN: A cross-sectional postal questionnaire-based study. SETTING: Leicestershire, United Kingdom. SUBJECTS AND METHODS: People with MS in Leicestershire identified from local health authority records (n = 476). MAIN OUTCOME MEASURES: Number registered at dental practice, frequency of attendance, issues and perspectives relating to attendance and maintenance of oral health. RESULTS: A response rate of 61% (n = 289) was obtained. When compared to the general population, a higher number of people with MS were registered with a dentist (49%:88%) and displayed more frequent practice attendance (71%:81%) in the past year. People with MS reported difficulties in attending a dentist and maintaining oral health, which were exacerbated by deterioration in general health. Problems relating to reduced personal mobility had the greatest impact on attendance. CONCLUSIONS: MS has a negative impact on perceived patient attendance and maintenance of oral health. Patients with a progressive disability could benefit greatly from the provision of preventive oral health care. The importance of seeking care earlier rather than later needs to be emphasised to both professionals and patients alike. Further efforts are required to increase awareness of the importance of oral health to the quality of life of people with MS and ensure that individuals with physical disabilities receive the same access to dental services as the able-bodied.

Architectural Accessibility↗
PubMed2005

Immunocontraceptive effects on female rabbits infected with recombinant myxoma virus expressing rabbit ZP2 or ZP3.

Recombinant myxoma viruses expressing rabbit zona pellucida 2 (rZP2) or rabbit zona pellucida 3 (rZP3) glycoproteins were constructed and tested in domestic rabbits to assess their potential to induce autoimmune infertility. The recombinant virus expressing rZP2 had no effect on fertility or ovarian histology, despite all animals developing antibodies against the rZP2 antigen. However, recombinant viruses expressing rZP3 induced infertility in 70% of animals at the first breeding. Serum antibodies were relatively short-lived, but antibody was bound to zona pellucida of all rabbits from Day 10 onward. There was no obvious correlation between infertility and rZP3 antibody titer. There was a transient inflammatory response in the ovaries of rZP3-immunized rabbits at Day 15 but no T-cell response to rZP3 could be detected at any time. Dysfunctional follicular formation was present in ovaries from rabbits infected with rZP3-expressing viruses 15-40 days postinfection but this had disappeared at later time points. A recombinant myxoma virus expressing a modified rZP3 antigen with the C-terminal hydrophobic putative anchor sequence deleted was also tested. This virus did not induce either infertility or an antibody response against the zona pellucida. Thus, the context of antigen presentation was crucial for an autoimmune response.

Animals↗
PubMed2005

Alternative mechanisms of initiating translation of mammalian mRNAs.

Of all the steps in mRNA translation, initiation is the one that differs most radically between prokaryotes and eukaryotes. Not only is there no equivalent of the prokaryotic Shine-Dalgarno rRNA-mRNA interaction, but also what requires only three initiation factor proteins (aggregate size approximately 125 kDa) in eubacteria needs at least 28 different polypeptides (aggregate >1600 kDa) in mammalian cells, which is actually larger than the size of the 40 S ribosomal subunit. Translation of the overwhelming majority of mammalian mRNAs occurs by a scanning mechanism, in which the 40 S ribosomal subunit, primed for initiation by the binding of several initiation factors including the eIF2 (eukaryotic initiation factor 2)-GTP-MettRNA(i) complex, is loaded on the mRNA immediately downstream of the 5'-cap, and then scans the RNA in the 5'-->3' direction. On recognition of (usually) the first AUG triplet via base-pairing with the Met-tRNA(i) anticodon, scanning ceases, triggering GTP hydrolysis and release of eIF2-GDP. Finally, ribosomal subunit joining and the release of the other initiation factors completes the initiation process. This sketchy outline conceals the fact that the exact mechanism of scanning and the precise roles of the initiation factors remain enigmatic. However, the factor requirements for initiation site selection on some viral IRESs (internal ribosome entry sites/segments) are simpler, and investigations into these IRES-dependent mechanisms (particularly picornavirus, hepatitis C virus and insect dicistrovirus IRESs) have significantly enhanced our understanding of the standard scanning mechanism. This article surveys the various alternative mechanisms of initiation site selection on mammalian (and other eukaryotic) cellular and viral mRNAs, starting from the simplest (in terms of initiation factor requirements) and working towards the most complex, which paradoxically happens to be the reverse order of their discovery.

Animals↗
PubMed2003

Contraceptive responses of mice immunized with purified recombinant mouse zona pellucida subunit 3 (mZP3) proteins.

Mouse zona pellucida subunit 3 (mZP3) was tested for efficacy as an immunocontraceptive antigen by comparing the fertility of mice immunized with recombinant mZP3 proteins. Recombinant protein was expressed using either the vaccinia virus T7 mammalian (vmZP3 protein) or baculovirus insect cell (bmZP3 protein)-expression systems. Female BALB/c or wild mice were immunized by i.p. injection using Freund's complete adjuvant and boosted three times with affinity purified recombinant proteins in Freund's incomplete adjuvant. Most mice developed antibodies that crossreacted to the respective mZP3 antigens by ELISA or western blot. In BALB/c mice immunized with vmZP3, fertility and mean litter size were reduced transiently to 25% and 10%, respectively, of those of control mice. However, immunization with bmZP3 did not affect either the fertility or mean litter sizes in BALB/c or wild mice immunized with bmZP3. The results demonstrate that reduction in fertility can be achieved in female BALB/c mice immunized using Freund's adjuvants and recombinant mZP3 protein produced in a mammalian, but not an insect, cell-expression system. Arguments are presented for the likely role of glycosylation of the mZP3 antigen in inducing contraceptive immune responses.

Animals↗
PubMed2001

Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation.

Picornavirus proteases cleave translation initiation factor eIF4G into a C-terminal two-thirds fragment (hereafter named p100) and an N-terminal one-third fragment, which interacts with the cap-binding factor eIF4E. As the timing of this cleavage correlates broadly with the shut-off of host cell protein synthesis in infected cells, a very widespread presumption has been that p100 cannot support capped mRNA translation. Through the use of an eIF4G-depleted reticulocyte lysate system, we show that this presumption is incorrect. Moreover, recombinant p100 can also reverse the inhibition of capped mRNA translation caused either by m7GpppG cap analogue, by 4E-BP1, which sequesters eIF4E and thus blocks its association with eIF4G, or by cleavage of endogenous eIF4G by picornavirus proteases. The concentration of p100 required for maximum translation of capped mRNAs is approximately 4-fold higher than the endogenous eIF4G concentration in reticulocyte lysates. Our results imply that picornavirus-induced shut-off is not due to an intrinsic inability of p100 to support capped mRNA translation, but to the viral RNA outcompeting host cell mRNA for the limiting concentration of p100.

Animals↗
PubMed2001

Oral QS-21 requires early IL-4 help for induction of mucosal and systemic immunity.

The highly purified saponin derivative, QS-21, from the Quillaja saponaria Molina tree has been proved to be safe for parenteral administration and represents a potential alternative to bacterial enterotoxin derivatives as a mucosal adjuvant. Here we report that p.o. administration of QS-21 with the vaccine protein tetanus toxoid elicited strong serum IgM and IgG Ab responses, which were only slightly enhanced by further oral immunization. The IgG Ab subclass responses were predominantly IgG1 followed by IgG2b for the 50-microg p.o. dose of QS-21, whereas the 250-microg p.o. dose also induced IgG2a and IgG3 Abs. Low oral QS-21 doses induced transient IgE Ab responses 7 days after the primary immunization, whereas no IgE Ab responses were seen in mice given the higher QS-21 dose. Further, low but not high p.o. QS-21 doses triggered Ag-specific secretory IgA (S-IgA) Ab responses. Th cell responses showed higher IFN-gamma (Th1-type) and lower IL-5, IL-6, and IL-10 (Th2-type) secretion after the high QS-21 p.o. dose than after low doses. Interestingly, the mucosal adjuvant activity of low oral QS-21 doses was diminished in IL-4(-/-) mice, suggesting a role for this cytokine in the initiation of mucosal immunity by oral QS-21. In summary, our results show that oral QS-21 enhances immunity to coadministered Ag and that different doses of QS-21 lead to distinct patterns of cytokine and serum Ab responses. We also show that an early IL-4 response is required for the induction of mucosal immunity by oral QS-21 as adjuvant.

Adjuvants, Immunologic↗
PubMed2001

The built environment and children's health.

The built environment embraces a wide range of concepts, from the design and integrity of housing, to land-use urban planning. A high-quality environment is essential for children to achieve optimal health and development. Building and land-use policies, including the quality and design of a child's physical environment, can cause or prevent illness, disability, and injury, and can degrade or preserve natural resources. Though many common pediatric conditions such as obesity, asthma, and lead poisoning, as well as injuries, are associated with risk factors within a child's built environment, this issue has received little attention from researchers or policymakers. This new field is ripe for etiologic and prevention research, and we need pediatric advocates to speak out for children's needs within this arena.

Child↗
PubMed2001

Prospective results of a standardized algorithm based on hemodynamic status for managing pediatric solid organ injury.

BACKGROUND: Controversy surrounds the need for ICU admission, prolonged bed rest, and the duration of activity restrictions for children sustaining blunt trauma. Adult literature supports management based on hemodynamic status, not CT grade. STUDY DESIGN: A 3-year prospective study of a standardized management algorithm for hemodynamically normal pediatric patients with blunt liver or spleen injury was performed. Patient selection was based on vital signs, irrespective of injury grade on CT. Patients requiring ICU admission for nonliver or nonspleen injury were excluded. Patients were admitted to a surgical ward with serial hematocrit levels. Discharge occurred 48 hours postinjury if patients had no abdominal tenderness, tolerated a regular diet, and had a stable hematocrit. Patients were allowed noncontact activity, including school, after discharge. Patients were followed up at 1 month with ultrasonographic imaging. RESULTS: Eighty-nine patients sustained blunt liver or spleen injury. Forty-five patients were excluded for other injuries (Glasgow Coma Scale < 13, 32 of 45); the remaining 44 patients had a mean age of 8.9 years (range 2 to 17 years), Injury Severity Score 10.6 (range 4 to 33), liver grade 2.1, and splenic injury grade 2.3. Mechanisms of injury were predominately motor vehicle collisions (59%). All patients were managed nonoperatively without transfusion; 43 of 44 patients completed the algorithm. Mean observation was 55.2 +/- 12.3 hours. One-month followup occurred in 33 of 44 patients, with one complication detected and no delayed bleeding. CONCLUSION: Management of pediatric solid organ injury should be guided by hemodynamic status and not injury grade on CT. Hemodynamically normal children can be safely managed without intensive care monitoring, do not need prolonged hospitalization, and can resume school on discharge.

Adolescent↗
PubMed2001

Construction of regulatable picornavirus IRESes as a test of current models of the mechanism of internal translation initiation.

Picornavirus internal ribosome entry sites (IRESs) are approximately 450 nt. RNA elements that direct internal initiation of translation, such that when placed between the two cistrons of a dicistronic construct, they drive independent translation of the downstream cistron. Consequently they have been widely used for coordinated expression of two or more proteins. All picornavirus IRESs have an AUG triplet at the very 3' end, which is thought to be the actual site of internal ribosome entry. However with some IRESs, such as foot-and-mouth disease virus, and especially poliovirus, the majority of ribosomes do not initiate translation at this putative entry site AUG, but at the next AUG further downstream, which is thought to be accessed by a process of linear ribosome scanning from the entry site. If this is so, then it should be possible to regulate IRES-dependent translation by inserting an iron responsive element (IRE) between the putative entry site AUG and the main functional initiation site. This should make IRES-dependent translation sensitive to the concentration of iron regulatory protein (IRP), the protein that specifically binds to the IRE. This has been attempted with both the foot-and-mouth disease virus and poliovirus IRESs, and was successful in so far as an inhibition specifically of IRES-dependent translation was observed that was strictly dependent on both the presence of IRP and of a functional IRE motif inserted in the sense orientation. However, the range over which expression could be varied was rather limited (three- to fourfold maximum), because some IRES-dependent translation remained completely refractory to inhibition by even very high IRP concentrations. In contrast, with a cap-proximal IRE in the 5' untranslated region of an mRNA translated by the scanning mechanism, addition of sufficient IRP results in complete inhibition. These results support the model of IRES-promoted ribosome entry at an upstream site followed by strictly linear scanning to the main functional initiation site for the majority of internal initiation events, but imply that some ribosomes must access the functional initiation site by another route, possibly a nonlinear shunting-like mechanism.

Aphthovirus↗
PubMed2001

Development of a tRNA-dependent in vitro translation system.

A method is described for depleting rabbit reticulocyte lysates and wheat germ extracts of endogenous tRNAs by affinity chromatography using a matrix generated by coupling ethanolamine to epoxy-activated Sepharose 6B. Greater than 90% depletion of tRNA is achieved with the result that translation becomes in effect absolutely dependent on added tRNA. This depletion procedure should prove very useful for studying the influence of tRNA concentration, and the spectrum of the tRNA population, on recoding events such as programmed frameshifting and readthrough of termination codons.

Animals↗
PubMed2001

Differential alternative splicing activity of isoforms of polypyrimidine tract binding protein (PTB).

Polypyrimidine tract binding protein (PTB) is an RNA-binding protein that regulates splicing by repressing specific splicing events. It also has roles in 3'-end processing, internal initiation of translation, and RNA localization. PTB exists in three alternatively spliced isoforms, PTB1, PTB2, and PTB4, which differ by the insertion of 19 or 26 amino acids, respectively, between the second and third RNA recognition motif domains. Here we show that the PTB isoforms have distinct activities upon alpha-tropomyosin (TM) alternative splicing. PTB1 reduced the repression of TM exon 3 in transfected smooth muscle cells, whereas PTB4 enhanced TM exon 3 skipping in vivo and in vitro. PTB2 had an intermediate effect. The PTB4 > PTB2 > PTB1 repressive hierarchy was observed in all in vivo and in vitro assays with TM, but the isoforms were equally active in inducing skipping of alpha-actinin exons and showed the opposite hierarchy of activity when tested for activation of IRES-driven translation. These findings establish that the ratio of PTB isoforms could form part of a cellular code that in turn controls the splicing of various other pre-mRNAs.

Alternative Splicing↗
PubMed2001

The slipping rib syndrome in children.

The slipping rib syndrome is an infrequent cause of thoracic and upper abdominal pain and is thought to arise from the inadequacy or rupture of the interchondral fibrous attachments of the anterior ribs. This disruption allows the costal cartilage tips to sublux, impinging on the intercostal nerves. Children with this entity are seldom described in the literature. We present a retrospective review of 12 children and young adults with slipping rib syndrome and a systematic approach for evaluation and treatment.

Adolescent↗
PubMed2001

Acidification of formula reduces bacterial translocation and gut colonization in a neonatal rabbit model.

BACKGROUND/PURPOSE: The authors hypothesized that gastric acidity is protective because it is bactericidal. They tested acidified formula for protection against gut colonization and bacterial translocation. METHODS: In vitro: Formula was acidified to pH of 2, 3, 4, 5 and innoculated with Enterobacter. Growth over time was quantitatively assessed. In vivo: 442 premature rabbit pups were sorted randomly and fed formula of pH 2, 3, 4, or 7, with ranitidine. Two models were utilized: (1) with bacterial challenge using a known acid sensitive organism, (2) without bacterial challenge to simulate natural gut colonization and to test against organisms of unknown acid sensitivity. Normal acid animals received pH 7 formula, no ranitidine. On day 3, the mesenteric lymph nodes (MLN), spleen, liver, and cecum were harvested and cultured. RESULTS: Bacterial growth was inhibited at pH 2 and 3, growth was logarithmic above pH 4 (P<.001). Total and organ-specific translocation was reduced at pH 3 and below in both models (P<.05). Translocation with formula pH 3 equaled normal acid animals. Quantitative cecal colonization was reduced in pups receiving pH 3 and below in both models (P<.05). CONCLUSION: Acidification of formula below pH 4 is bactericidal to enteric organisms. Acidified formula decreases bacterial translocation and gut colonization.

Animals↗
PubMed2001

Recurrent congenital diaphragmatic hernia: A novel repair.

BACKGROUND/PURPOSE: Repair of recurrent diaphragmatic hernia continues to be a difficult problem. An innovative method using a nonabsorbable polypropylene prosthetic mesh plug placed via the thoracic approach using minimal dissection is presented. METHODS: A retrospective analysis showed 39 children with congenital diaphragmatic hernia (CDH) who underwent repair between January 1997 and March 2000. Five children suffered a recurrence and underwent repair via the thoracic approach using the Bard Marlex Mesh Perfix Plug (C.R. Bard Inc, Billerica, MA). Follow-up was available in all children and ranged from 1 to 33 months (average, 13.8 months). RESULTS: Age at recurrence ranged from 2 to 48 months (average, 14.8 months), and the average time between initial repair and recurrence was 8.2 months (range, 2 to 16 months). There were no recurrences after the transthoracic mesh plug diaphragmatic hernioplasty. One child died of multiple congenital anomalies 6 months after repair. CONCLUSION: The transthoracic repair of recurrent diaphragmatic hernias using a nonabsorbable polypropylene prosthetic mesh plug represents an innovative approach to a difficult problem in which 5 repairs have been accomplished without recurrence in nearly 14 months of follow-up. J Pediatr Surg 36:1768-1769.

Child, Preschool↗
PubMed2001

A revisit of mucosal IgA immunity and oral tolerance.

Induction of mucosal immunity by oral immunization with protein antigen alone is difficult: potent mucosal adjuvants, vectors, or other special delivery systems are required. Cholera toxin (CT) has been shown to be an effective adjuvant for the development of mucosal vaccines and, when given with vaccine, induces both mucosal and systemic immune responses via a Th2 cell-dependent pathway. However, and in addition to potential type-I hypersensitivity, a major concern for use of mucosal adjuvants such as CT is that this molecule is not suitable for use in humans because of its inherent toxicity. When we examined the potential toxicity of CT for the central nervous system, both CT and CT-B accumulated in the olfactory nerves/epithelium and olfactory bulbs of mice when given by the nasal route. The development of effective mucosal vaccines for the elderly is also an important issue; however, only limited information is available. When mucosal adjuvanticity of CT was evaluated in aged mice, an early immune dysregulation was evident in the mucosal immune system. The present review discusses these potential problems for effective mucosal vaccine development. Tolerance represents the most common and important response of the host to environmental antigens, including food and commensal bacterial components, for the maintenance of an appropriate immunological homeostasis. We have examined whether Peyer patches could play a more important role for the maintenance of oral tolerance. Using Peyer patch-null mice, we found that mice lacking this gut-associated lymphoid tissue retained their capability to produce secretory IgA antibodies but did not develop normal oral tolerance to protein antigens.

Administration, Inhalation↗
PubMed2001

Catheter materials affect the incidence of late blood-borne catheter infection.

BACKGROUND: Adherence of bacteria and subsequent catheter-related infections (CRI) are greatly enhanced by the fibrin sheath that develops on indwelling catheters. Since the infection rate of catheters without fibrin sheaths is low and the fibrin sheath mediates bacterial adherence, catheter material is not thought to affect the incidence of late catheter-related infection. METHODS: A total of 276 rats had catheters placed in the right jugular vein with the proximal end buried subcutaneously to eliminate exit site infection. Rats were divided into two groups: silastic catheters (SC; n = 133) and polyurethane catheters (PC; n = 143). Injections of 1 x 10(8) CFU/mL of Staphylococcus epidermidis were given via the tail vein on either the day of surgery, day 0 (n = 53 SC, n = 51 PC), or on postoperative day 10 (n = 50 SC, n = 62 PC). Thirty animals from each group (SC, PC) received sterile saline injections on day 10 and served as controls. Animals were sacrificed on postinjection day 3. Catheters were removed via the chest and placed into trypticase soy broth. Broth was incubated at 37 degrees C for 48 h. Microscopy for the fibrin sheath was done on 20 randomly selected catheters (10/group). Data were compared using Fisher's exact test, with p < 0.05 considered significant. RESULTS: Incidence of CRI was equal prior to the formation of the fibrin sheath, while CRI was significantly higher in silastic catheters in the presence of a fibrin sheath. Without a fibrin sheath (day 0), 8/53 silastic catheters and 3/51 polyurethane catheters were infected (p = NS). With a fibrin sheath (day 10), 31/50 silastic catheters were infected versus 20/62 polyurethane catheters (p < 0.05). Control catheters were all culture negative (30/group). With light microscopy, 20/20 catheters had fibrin sheaths at day 10 with no visible difference between silastic and polyurethane catheters. CONCLUSION: Catheter material does affect the incidence of catheter-related infection even when catheters are coated with a fibrin sheath. This difference may relate to a difference in the fibrin sheath itself as it forms on different catheter materials.

Animals↗
PubMed2001

Limitations of stereotactic biopsy in the initial management of gliomas.

Stereotactic biopsy is often performed for diagnostic purposes before treating patients whose imaging studies highly suggest glioma. Indications cited for biopsy include diagnosis and/or the "inoperability" of the tumor. This study questions the routine use of stereotactic biopsy in the initial management of gliomas. At The University of Texas M. D. Anderson Cancer Center, we retrospectively reviewed a consecutive series of 81 patients whose imaging studies suggested glioma and who underwent stereotactic biopsy followed by craniotomy/resection (within 60 days) between 1993 and 1998. All relevant clinical and imaging information was reviewed, including computerized volumetric analysis of the tumors based on pre- and postoperative MRI. Stereotactic biopsy was performed at institutions other than M. D. Anderson in 78 (96%) of 81 patients. The majority of tumors were located either in eloquent brain (36 of 81 = 44%) or near-eloquent brain (41 of 81 = 51%), and this frequently was the rationale cited for performing stereotactic biopsy. Gross total resection (>95%) was achieved in 46 (57%) of 81 patients, with a median extent of resection of 96% for this series. Diagnoses based on biopsy or resection in the same patient differed in 40 (49%) of 82 cases. This discrepancy was reduced to 30 (38%) of 80 cases when the biopsy slides were reviewed preoperatively by each of three neuropathologists at M. D. Anderson. Major neurologic complications occurred in 10 (12.3%) of 81 surgical patients and 3 (3.7%) of 81 patients undergoing biopsy. Surgical morbidity was probably higher in our series than it would be for glioma patients in general because our patients represent a highly selected subset of glioma patients whose tumors present a technical challenge to remove. Stereotactic biopsy is frequently inaccurate in providing a correct diagnosis and is associated with additional risk and cost. If stereotactic biopsy is performed, expert neuropathology consultation should be sought.

Adolescent↗