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Biomedical subjects

R J Jackson

Publications and source records attributed to R J Jackson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Identification and analysis of a collagenolytic activity in Streptococcus mutans.

Streptococcus mutans is an important pathogen in coronal caries and is implicated in dental root decay by its ability to bind collagen from various sources. In the present study, electron microscopic analysis demonstrated the ability of S. mutans to bind and to disrupt collagen fibrils of the amniotic membrane. The synthetic peptide FALGPA, which is similar in structure to collagen, was degraded by S. mutans, with a lower level of FALGPA hydrolytic activity observed in sucrose-grown cells compared with cells grown in the absence of sucrose. Inhibition studies of FALGPA hydrolytic activity showed a pattern characteristic of collagenase activity, with inhibition by 1,10-phenanthroline and EDTA, but not by phenylmethylsulfonyl fluoride (PMSF). Additionally, immunological cross-reactivity was observed between proteins from disrupted cells of S. mutans and antiserum to collagenase from Clostridium histolyticum. Gelatinolytic activity was demonstrated by gelatin zymogram analysis. These findings suggest that collagenolytic activity by S. mutans may be an important virulence factor in dental root decay.

Amnion↗
PubMed1997

Is nasogastric tube decompression necessary after major abdominal surgery in children?

Nasogastric (NG) decompression has traditionally been used after major abdominal surgery in pediatric patients. This study was designed to determine if NG tubes could be routinely omitted in pediatric patients undergoing major abdominal procedures. Between January 1993 and December 1995, 83 patients had follow-up prospectively without NG decompression after a variety of major abdominal surgeries. NG tubes were inserted for persistent vomiting or abdominal distension. Exclusion criteria included bowel obstruction, intestinal atresia, and perforation of the stomach or duodenum. Ages ranged from 13 days to 22 years. Seventy-four patients (89%) were treated successfully without postoperative NG decompression. There were no cases of pneumonia, wound dehiscence, anastomotic leak, or delay in return of gastrointestinal function. Nine patients required NG tubes for persistent vomiting or abdominal distension. An anastomotic leak developed in one patient after endorectal pull-through. NG decompression is unnecessary after most major abdominal operations in pediatric patients. The endorectal pull-through may represent a group of patients that benefit from routine decompression.

Adolescent↗
PubMed1997

The protective role of gastric acidity in neonatal bacterial translocation.

The acid environment of the stomach serves as an important defense against intestinal colonization by potentially pathogenic bacteria. The purpose of this study was to examine the effect of increased gastric pH on bacterial translocation in a neonatal rabbit model. Fifty-nine rabbit pups were delivered by cesarean section and randomly divided into normal acid (NA) and reduced acid (RA) groups. All were gavage fed and challenged with Enterobacter cloacae, 1 x 10(6) CFU/mL. The RA group received ranitidine, 20 mg/kg/d with all feeds. Gastric pH was measured by pH probe before and 4 hours after bacterial challenge. Mesenteric lymph node (MLN), spleen, liver, midjejunum, and cecum were harvested for culture at 72 hours. Gastric pH in the RA group was significantly increased before and 4 hours after the bacterial challenge. The incidence of bacterial translocation to the MLN, spleen, and liver was significantly higher in the RA group. Log cecal and jejunal colony counts were significantly increased in the RA animals. The authors conclude that the gastric acidity is protective against intestinal colonization and translocation of potentially pathogenic bacteria in this neonatal rabbit model.

Animals↗
PubMed1997

Effect of use of 0.05% cetylpyridinium chloride mouthwash on normal oral flora.

OBJECTIVES: The aims of this study were to examine the effect of the use of a mouthwash containing 0.05% cetylpyridinium chloride (CPC) on (1) the composition of the normal oral microbial flora and (2) the establishment of non-oral bacterial species in the mouth. METHOD: In a double-blind study, 129 subjects used, twice daily for 6 weeks, either a randomly assigned test or placebo mouthwash. At baseline and at the completion of the study, a sample of the oral flora was obtained by asking each subject to "swish" around the mouth for 30 s, 10 ml of distilled water. The numbers of total colony forming units (CFU), facultative bacteria, streptococci, mutans streptococci, lactobacilli, staphylococci, yeasts and enterococci were enumerated after culture on eight non-selective and selective media. RESULTS: After 6 weeks use of either the test or placebo mouthwashes, there were no significant differences (analysis of variance) between the counts (CFU/ml of sample) for any of the microbial taxa. CONCLUSIONS: These data indicate that the use of a CPC-containing mouthwash does not alter the composition of the normal oral flora or result in the establishment of non-oral and potentially pathogenic bacteria in the mouth.

Analysis of Variance↗
PubMed1997

Life and death in the cytoplasm: messages from the 3' end.

The cytoplasmic life of an mRNA revolves around the regulation of its localization, translation and stability. Interactions between the two ends of the mRNA may integrate translation and mRNA turnover. Regulatory elements in the region between the termination codon and poly(A) tail - the 3' untranslated region - have been identified in a wide variety of systems, as have been some of the key players with which these elements interact.

Animals↗
PubMed1997

Translational controls impinging on the 5'-untranslated region and initiation factor proteins.

Translation of eukaryotic mRNAs is generally initiated by the scanning ribosome mechanism. This can be downregulated by high affinity protein binding to cap-proximal RNA motifs. Translation can also be regulated by short open reading frames within the 5' -untranslated region. A key factor for initiation is elF4F, in which one of the polypeptide chains, elF4G, seems to have a bridging function and binds three other factors at separate sites: elF4E (the cap-binding factor), the helicase elF4A, and elF3, which also interacts with 40S ribosomal subunits. Initiation is regulated by the MAP kinase and rapamycin-sensitive signalling pathways, which control phosphorylation of elF4E and 4E-BP1, a protein which in the dephosphorylated form binds and sequesters elF4E.

Animals↗
PubMed1997

The role of anxiety sensitivity in the pathogenesis of panic: prospective evaluation of spontaneous panic attacks during acute stress.

Expectancy theory posits that anxiety sensitivity may serve as a premorbid risk factor for the development of anxiety pathology (S. Reiss, 1991). The principal aim of the present study was to determine whether anxiety sensitivity acts as a specific vulnerability factor in the pathogenesis of anxiety pathology. A large, nonclinical sample of young adults (N = 1,401) was prospectively followed over a 5-week highly stressful period of time (i.e., military basic training). Anxiety sensitivity was found to predict the development of spontaneous panic attacks after controlling for a history of panic attacks and trait anxiety. Approximately 20% of those scoring in the upper decile on the Anxiety Sensitivity Index (R. A. Peterson & S. Reiss, 1987) experienced a panic attack during the 5-week follow-up period compared with only 6% for the remainder of the sample. Anxiety sensitivity also predicted anxiety symptomatology, functional impairment created by anxiety, and disability. These data provide strong evidence for anxiety sensitivity as a risk factor in the development of panic attacks and other anxiety symptoms.

Adolescent↗
PubMed1997

Dentine hypersensitivity and the placebo response. A comparison of the effect of strontium acetate, potassium nitrate and fluoride toothpastes.

A considerable number of varied agents are apparently effective in the treatment of dentine hypersensitivity. In particular, the literature supports the efficacy of strontium, potassium and fluoride containing toothpastes. This study was a double-blind, randomised, parallel group comparison of three products, namely strontium- and potassium-based desensitising toothpastes both containing fluoride, and a conventional fluoride toothpaste. A total of 131 subjects entered a 4-week wash-in phase using the conventional fluoride toothpaste, of whom 120 entered a 6-week treatment phase. Sensitive teeth were evaluated at wash-in baseline, treatment baseline and after 2 and 6 weeks use of the treatment pastes. Dentine hypersensitivity was assessed with tactile and cold air stimuli together with an overall subjective assessment. Analysis of the findings was performed using non-parametric statistical methods. Of the original 120 subjects, 112 completed the trial. All 3 toothpaste groups showed reductions in sensitivity over the 6 weeks; however, no significant differences were found between the three products at any given time. Interestingly, there was no significant change in sensitivity between wash-in baseline and treatment baseline for the cold air stimulus with the fluoride-only-based paste. However, for the group using the same fluoride toothpaste, there was significant improvement between wash-in baseline and week 6, and treatment baseline and week 6 for this stimulus, suggesting a substantial placebo effect occurred. There is a need for further investigation of a wash-in period and examination of the placebo effect when evaluating dentine hypersensitivity trials.

Acetates↗
PubMed1997

Gum health product formulations: what is in them and why?

Two dominant factors dictate which ingredients are used in formulating toothpaste and mouthwashes. The major one is the type of active ingredient chosen, especially cationic active ingredients such as chlorhexidine; the other factor is the needs of the consumer. Apart from gum health benefits, the consumer expects to obtain from gum health toothpaste and mouthwashes other benefits of clean teeth (abrasive and detergent), fresh breath (antimicrobial agents and flavor) and protection from caries and possibly tartar. Exhaustive testing involving experimental design and validated laboratory and clinical tests is essential to ensure that all these benefits are delivered. Unless products are developed systematically, then products with relatively poor activity can find their way on to the market.

Chemistry, Pharmaceutical↗
PubMed1997

Oral immunization with PspA elicits protective humoral immunity against Streptococcus pneumoniae infection.

Streptococcus pneumoniae is a major respiratory mucosal pathogen affecting infants and children. Although a polysaccharide-based vaccine has been useful in adult populations, it does not elicit protective immunity in infants and young children. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein produced by all strains of Streptococcus pneumoniae. Previous studies have shown that systemic immunization of mice with PspA can elicit protective immunity against fatal pneumococcal infection. In this study, we demonstrated that oral immunization with PspA could elicit protective immune responses against pneumococcal infection. When mice were orally immunized with PspA alone, low levels of PspA-specific immunoglobulin G (IgG) responses were induced in serum; none was induced in secretion. On the other hand, when PspA was given orally with the mucosal adjuvant cholera toxin (CT), significant levels of IgG and IgA anti-PspA responses were induced in serum. The major IgG subclass was IgG1, followed by IgG2b, a profile of antibody response supported by Th2-type cells. In addition, all mice orally immunized with PspA and CT were protected from the lethal challenge with capsular serotype 3 S. pneumoniae A66. These results suggested that an oral PspA vaccine may be a useful means of preventing pneumococcal disease.

Adjuvants, Immunologic↗
PubMed1997

Reproductive toxins and alligator abnormalities at Lake Apopka, Florida.

The alligator population at Lake Apopka in central Florida declined dramatically between 1980 and 1987. Endocrine-disrupting chemicals and specifically DDT metabolites have been implicated in the alligators' reproductive failure. The DDT metabolite hypothesis is based largely on the observation of elevated concentrations of p,p-DDE and p,p-DDD in alligator eggs obtained from Lake Apopka in 1984 and 1985. In the following commentary, we draw attention to two nematocides that are established reproductive toxins in humans, dibromochloropropane (DBCP) and ethylene dibromide (EDB), which could also have played a role in the reproductive failure observed in alligators from Lake Apopka in the early 1980s.

Alligators and Crocodiles↗
PubMed1997

Hypospadias trends in two US surveillance systems.

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.

Humans↗
PubMed1996

Interleukin-12 alters helper T-cell subsets and antibody profiles induced by the mucosal adjuvant cholera toxin.

We have shown that systemic administration of rmIL-12 could trigger Th1-type responses to a protein antigen delivered orally with CT as mucosal adjuvant. The most striking finding was that IL-12 could retain its regulatory effects when orally administered and could redirect the immune response to the oral vaccine toward a Th1-type. However, regulation by orally administered IL-12 differed from parenteral treatment with IL-12 since only the latter treatment affected mucosal S-IgA responses. These findings have important implications for the development of mucosal vaccines that induce the desired immune response.

Adjuvants, Immunologic↗
PubMed1996

Luminometry: a novel bioluminescent immunoassay enhances the quantitation of mucosal and systemic antibody responses.

We have directly compared enzyme-linked immunoassays (ELISAs) with bioluminescent immunoassays employing derivatives of the bioluminescent molecule aequorin, and have shown that detection of mucosal and serum antibodies is considerably more sensitive when detected by luminometry. Luminometry is based upon counting photons of light via phototubes and is generally similar to scintillation spectrometry. Current commercial luminometric technology employs a phototube which is most efficient for light emission in the 400-420 nm wavelength range. For this reason, we have chosen the bioluminescent molecule, aequorin, which upon the addition of Ca2+ undergoes a conformational change resulting in the emission of blue light at 469 nm. The high quantum yield is reflected by the fact that addition of Ca2+ to 1 ng of recombinant streptaequorin, a covalent conjugate of streptavidin and aequorin, resulted in the production of 7 x 10(8) relative light units. In this study, we show the superior sensitivity of biotin-streptaequorin when directly compared with biotin-streptavidin linked horseradish peroxidase commonly used for ELISA. For example, mice orally immunized once with cholera toxin (CT) did not exhibit detectable fecal IgA antibodies as determined by ELISA, whereas use of streptaequorin and the bioluminescent immunoassay revealed fecal IgA anti-CT-B subunit antibody titers of 1:24 500. In addition, no detectable anti-CT-B antibodies were noted in saliva samples by ELISA 7 days following oral immunization with CT, while IgA endpoint titers could be extrapolated to 1:393 000. The 21 day fecal IgA anti-CT-B titers were 1:512 by ELISA, whereas titers determined by luminometry reached 1:10(7) when Neutralite avidin and biotinylated aequorin were employed. In general, the bioluminescent immunoassay was > 10(4)-fold more sensitive when compared with ELISA for detection of mucosal and serum antigen- and isotype-specific antibody responses. Thus, the bioluminescent immunoassay is a more sensitive assay for detection of antibodies in dilute external secretions.

Administration, Oral↗
PubMed1996

The role of Th1 and Th2 cells for mucosal IgA responses.

We have used cytokine-knockout mice to help determine the precise requirements for CD4+ Th cell regulation of IgA responses. In these studies, we have used two different oral delivery systems to induce mucosal and systemic antibody responses to the vaccine TT. In normal mice, oral administration of TT with CT as adjuvant induces Th2 cells and cytokines, which give rise to mucosal IgA and serum IgG1, IgA, and IgE responses. On the other hand, oral immunization with rSalmonella expressing Tox C results in Th1-type responses as well as Th2 cell-derived IL-10 and macrophage-derived IL-6, which correlate with mucosal IgA and serum IgG2a antibody responses. Two major conclusions can be drawn from our studies with these two regimens in normal, IFN-gamma-/-, and IL-4-/- mice. First, oral administration of rSalmonella, which elicits classical Th1-type responses also induces significant mucosal IgA responses when given to mice with defective Th1- (IFN-gamma-/-) or Th2- (IL-4-/-) cytokine pathways. Interestingly, we detect Th2-type cells producing IL-10 and macrophage-secreting IL-6 in both normal and cytokine-deficient mice, and we postulate that these two cytokines are of most importance for murine IgA responses. Second, oral administration of TT plus CT as adjuvant induces classical Th2-type responses in both normal and IFN-gamma-/- mice. Further, lack of IL-4 results in failure to induce mucosal IgA responses. Thus, the IL-4 pathway is necessary for the CT adjuvant effect for mucosal IgA responses after oral immunization with a protein vaccine.

Administration, Oral↗
PubMed1996

Mucosal immunity: regulation by helper T cells and a novel method for detection.

The mechanisms which regulate mucosal IgA responses to orally administered protein vaccines are not yet fully elucidated. We have used two delivery systems, soluble tetanus toxoid (TT) with the mucosal adjuvant cholera toxin (CT) and recombinant Salmonella expressing Tox C, a fragment of TT, to assess the nature of CD4+ T helper (Th) cells and derived cytokines which support mucosal IgA responses in both normal and cytokine knockout (interferon gamma knockout; IFN-gamma-/- and IL-4-/-) mice. Our results provide important new information regarding Th cell and cytokine regulation of mucosal IgA responses. Whereas TT coadministered with CT induces predominant TT-specific Th2-type responses, rSalmonella delivery of Tox C induced dominant Th1-type responses along with synthesis of the Th2-cytokine IL-10. Both vaccine regimen elicited high levels of mucosal S-IgA and IL-6 production by macrophages. Further oral immunization of IFN-gamma-/- and IL-4-/- mice with rSalmonella Tox C also induced macrophage-derived IL-6 and Th2-derived IL-10 as well as S-IgA responses, suggesting that IFN-gamma from Th1-type cells as well as traditional Th2 cells producing IL-4 and IL-5 are not essential for mucosal IgA responses. Rather, induction of second level Th2 cells producing IL-10 together with high levels of IL-6 from other cell sources may be sufficient for mucosal IgA responses in the absence of traditional Th2 cells. These studies were facilitated by the development of a sensitive new luminometry assay which allowed detection of cytokines and cell surface molecules which are below the levels of detection by current solid phase assays.

Administration, Oral↗