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C A Jones

Publications and source records attributed to C A Jones.

At least 37 records · Page 2Linked to original sources
PubMed2003

Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro.

Dendritic cells (DC) are critical for stimulation of naive T cells. Little is known about the effect of herpes simplex virus type 2 (HSV-2) infection on DC structure or function or if the observed effects of HSV-1 on human DC are reproduced in murine DC. Here, we demonstrate that by 12 h postinfection, wild-type (wt) HSV-2 (186) abortively infected murine bone marrow-derived DC and induced early cell death compared to UV-inactivated HSV-2 or mock-infected DC. HSV-2-induced loss of DC viability was more rapid than that induced by HSV-1 and was due, in part, to apoptosis, as shown by TEM, caspase-3 activation, and terminal deoxynucleotidyl transferase-mediated dCTP biotin nick end labeling. HSV induced type-specific changes in the murine DC immunophenotype. At 12 h postinfection, wt HSV-2 upregulated DC major histocompatibility complex (MHC) class II expression, and in contrast to UV-inactivated HSV-2, downregulated expression of MHC class I, but it had no effect on surface CD40, CD80, or CD86. Wt HSV-1 (MC-1) induced only CD40 upregulation. More-profound effects on the DC immunophenotype were observed in HSV-2-infected neonatal DC. Wt HSV of either serotype impaired murine DC-induced T-cell alloproliferation and lipopolysaccharide-induced DC interleukin-12 secretion. Thus, there are marked differences in the levels of HSV-induced cytolysis in DC according to the HSV serotype, although HSV-2 displays immunomodulatory effects on the DC immunophenotype and function similar to those of HSV-1.

Animals↗
PubMed2002

Impact of HIV seropositivity on graft and patient survival after cadaveric renal transplantation in the United States in the pre highly active antiretroviral therapy (HAART) era: an historical cohort analysis of the United States Renal Data System.

BACKGROUND: National statistics are presented for patient survival and graft survival in patients seropositive for the human immunodeficiency virus (HIV+) at the time of renal transplantation in the era prior to highly active antiretroviral therapy (HAART). METHODS: Historical cohort analysis of 63, 210 cadaveric solitary renal transplant recipients with valid HIV serology entries in the United States Renal Data System (USRDS) from 1 January 1987 to 30 June 1997. The medical evidence form was also used for additional variables but, because of fewer available values, was analyzed in a separate model. Outcomes were patient characteristics and survival associated with HIV+ status. RESULTS: Thirty-two patients (0.05%) in the study period were HIV+ at transplant. HIV+ patients were comparable to the national renal transplant population in terms of gender and ethnic distribution but were younger and had younger donors and better HLA matching than the USRDS population. Patient and graft three-year survival were significantly reduced in HIV+ recipients (53% graft, 83% patient survival) relative to the USRDS population (73% and 88%, respectively). In multivariate analysis, HIV+ status was independently associated with patient mortality and decreased graft survival in recipients of cadaveric kidney transplants. CONCLUSIONS: This analysis was retrospective and may underestimate the number of HIV+ patients transplanted in the United States. Although the clinical details of patient selection for transplant were unknown, these results show HIV+ patients can have successful outcomes after cadaveric renal transplantation, although outcomes are significantly different from HIV- recipients.

Adult↗
PubMed2002

A hypothesis: antenatal sensitisation to respiratory syncytial virus in viral bronchiolitis.

AIM: To investigate the possibility of antenatal sensitisation to respiratory syncytial virus (RSV). METHODS: A total of 36 cord blood specimens were obtained from newborn infants; serum IgA was measured to exclude maternal blood contamination. Cord peripheral blood mononuclear cells were separated and cultured in the presence of either uninfected negative control cells or cells containing ultraviolet (UV) inactivated RSV. Proliferation was assessed by tritiated thymidine incorporation. Supernatant cytokine concentrations were measured using ELISA. RESULTS: Significantly higher proliferative response rates to UV inactivated RSV were shown in those infants exposed in utero to the RSV epidemic after 22 weeks gestation. UV inactivated RSV stimulation induced significantly higher interferon gamma production from specimens with a positive proliferative response (sensitised) than from those with a negative response (not sensitised). CONCLUSIONS: Antenatal sensitisation to RSV occurs in one third of infants exposed to an RSV epidemic at the appropriate time of gestation. This sensitisation is associated with increased interferon gamma production, suggesting a type 1 memory response. We hypothesise that priming of fetal T cells to RSV results in a reduced severity of subsequent RSV disease in these individuals and that this will explain much of the clinical diversity of RSV disease.

Bronchiolitis, Viral↗
PubMed2001

Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).

Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.

Adult↗
PubMed2001

Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein.

The products of Polycomb group (PcG) genes are required for the epigenetic repression of a number of important developmental regulatory genes, including homeotic genes. Enhancer of zeste (E(Z)) is a Drosophila PcG protein that previously has been shown to bind directly to another PcG protein, Extra Sex Combs (ESC), and is present along with ESC in a 600-kDa complex in Drosophila embryos. Using yeast two-hybrid and in vitro binding assays, we show that E(Z) binds directly to another PcG protein, Polycomblike (PCL). PCL.E(Z) interaction is shown to be mediated by the plant homeodomain (PHD) fingers domain of PCL, providing evidence that this motif can act as an independent protein interaction domain. An association was also observed between PHF1 and EZH2, human homologs of PCL and E(Z), respectively, demonstrating the evolutionary conservation of this interaction. E(Z) was found to not interact with the PHD domains of three Drosophila trithorax group (trxG) proteins, which function to maintain the transcriptional activity of homeotic genes, providing evidence for the specificity of the interaction of E(Z) with the PCL PHD domain. Coimmunoprecipitation and gel filtration experiments demonstrate in vivo association of PCL with E(Z) and ESC in Drosophila embryos. We discuss the implications of PCL association with ESC.E(Z) complexes and the possibility that PCL may either be a subunit of a subset of ESC.E(Z) complexes or a subunit of a separate complex that interacts with ESC.E(Z) complexes.

Amino Acid Motifs↗
PubMed2001

Critical roles of a cyclic AMP responsive element and an E-box in regulation of mouse renin gene expression.

Mouse As4.1 cells, obtained after transgene-targeted oncogenesis to induce neoplasia in renal renin expressing cells, express high levels of renin mRNA from their endogenous Ren-1(c) gene. We have previously identified a 242-base pair enhancer (coordinates -2866 to -2625 relative to the CAP site) upstream of the mouse Ren-1(c) gene. This enhancer, in combination with the proximal promoter (-117 to +6), activates transcription nearly 2 orders of magnitude in an orientation independent fashion. To further delimit sequences necessary for transcriptional activation, renin promoter-luciferase reporter gene constructs containing selected regions of the Ren-1(c) enhancer were analyzed after transfection into As4.1 cells. These results demonstrate that several regions are required for full enhancer activity. Sequences from -2699 to -2672, which are critical for the enhancer activity, contain a cyclic AMP responsive element (CRE) and an E-box. Electrophoretic mobility shift assays demonstrated that transcription factors CREB/CREM and USF1/USF2 in As4.1 cell nuclear extracts bind to oligonucleotides containing the Ren-1(c) CRE and E-box, respectively. These two elements are capable of synergistically activating transcription from the Ren-1(c) promoter. Moreover, mutation of either the CRE or E-box results in almost complete loss of enhancer activity, suggesting the critical roles these two elements play in regulating mouse Ren-1(c) gene expression. Although the Ren-1(c) gene contains a CRE, its expression is not induced by cAMP in As4.1 cells. This appears to reflect constitutive activation of protein kinase A in As4.1 cells since treatment with the protein kinase A inhibitor, H-89, caused a significant reduction in Ren-1(c) gene expression and this reduction is mediated through the CRE at -2699 to -2688.

Animals↗
PubMed2001

REM sleep enhancement due to rhythmical auditory stimulation in the rat.

From a physiological viewpoint, REM sleep (REMS) is a period during which homeostatic physiological regulations are impaired. In the rat, REMS occurs in two forms respectively characterized by episodes separated by long intervals (single REMS episodes) and by episodes which have short intervals and occur in sequences (REMS clusters). Since the partition of REMS in the form of either single or clustered episodes may reveal how the REMS drive and body homeostatic processes interact in the control of REMS occurrence, we have used this approach to clarify the effects of the rhythmical delivery of an auditory stimulus (1000 Hz, 63 or 88 dB, 50 ms, every 20 s), which has been previously observed by different authors to enhance REMS in the absence of a previous sleep deprivation. Stimuli were delivered to pairs of animals and triggered by the occurrence of REMS in one rat (REMS-selective stimulation), whilst the other animal received the same stimulus irrespectively of the stage of the wake-sleep cycle (REMS-unselective stimulation). The results showed that the REMS-selective stimulation did not change the overall amount of REMS, since an increase in the occurrence of REMS clusters was concomitant with a decrease in the occurrence of single REMS episodes. In contrast, under the REMS-unselective stimulation, the total amount of REMS was increased during the second day of stimulation through an increase in the duration of both types of REMS episodes. Since during the REMS-unselective stimulation 87% of the stimuli fell outside REMS (i.e., during the REMS interval), the results show that the occurrence of REMS is more consistently affected when the stimuli are delivered in a period during which homeostatic physiological regulations are fully operant.

Acoustic Stimulation↗
PubMed2001

An Abd-B class HOX.PBX recognition sequence is required for expression from the mouse Ren-1c gene.

Expression from the mouse Ren-1(c) gene in As4.1 cells is dependent on a proximal promoter element (PPE) located at approximately -60 and a 241-base pair enhancer region located at -2625 relative to the transcription start site. The PPE (TAATAAATCAA) is identical to a consensus HOX.PBX binding sequence. Further, PBX1b has been shown to be a component of a PPE-specific binding complex present in nuclear extracts from As4.1 cells. The binding affinities of different paralog HOX members to the PPE were examined in the absence or presence of PBX1b. HOXB6, -B7, and -C8 failed to bind the PPE alone but showed weak affinity in the presence of PBX1b. In contrast, HOXD10 and to a lesser degree HOXB9 bound the PPE with high affinities regardless of whether PBX1b was present. Abd-B HOX members, including HOXD10, -A10, -A9, -B9, and -C9, are expressed in As4.1 cells. The ability of HOX and PBX1b to form a ternary complex with PREP1 on the PPE is also demonstrated both in vivo and in vitro. Point mutations in either the HOX or PBX half-site of the PPE disrupted the formation of the HOX.PBX complex and dramatically decreased transcriptional activity of the Ren-1(c) gene demonstrating that both the HOX and PBX half-sites are critical for mouse renin gene expression. These results strongly implicate Abd-B class Hox genes and their cofactors as major determinants of the sites of renin expression.

Animals↗
PubMed2001

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Chromosomes, Human, Pair 1↗
PubMed2001

The effect of age on pain, function, and quality of life after total hip and knee arthroplasty.

BACKGROUND: As utilization rates for total joint arthroplasty increase, there is a hesitancy to perform this surgery on very old patients. The objective of this prospective study was to compare pain, functional, and health-related quality-of-life outcomes after total hip and total knee arthroplasty in an older patient group (> or =80 years) and a representative younger patient group (55-79 years). METHODS: In an inception community-based cohort within a Canadian health care system, 454 patients who received primary total hip arthroplasty (n = 197) or total knee arthroplasty (n = 257) were evaluated within a month prior to surgery and 6 months postoperatively. Pain, function, and health-related quality of life were evaluated with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and the 36-Item Short-Form Health Survey (SF-36). RESULTS: There were no age-related differences in joint pain, function, or quality-of-life measures preoperatively or 6 months postoperatively. Furthermore, after adjusting for potential confounding effects, age was not a significant determinant of pain or function. Although those in the older and younger groups had comparable numbers of comorbid conditions and complications, those in the older group were more likely to be transferred to a rehabilitation facility than younger patients. Regardless of age, patients did not achieve comparable overall physical health when matched with the general population for age and sex. CONCLUSIONS: With increasing life expectancy and elective surgery improving quality of life, age alone is not a factor that affects the outcome of joint arthroplasty and should not be a limiting factor when considering who should receive this surgery.

Age Factors↗
PubMed2001

A computationally simple test of homogeneity of odds ratios for twin data.

It is of interest to compare measures of association of binary traits among samples of bivariate data. One example is the comparison of association within a sample of monozygotic (MZ) twins to that within a sample of dizygotic (DZ) twins. A larger association in the MZ twins suggests that the trait of interest may have a genetic component. The Bivariate data in this example are binary traits for the twins in each pair. Another example is the comparison of a measure of Hardy-Weinberg disequilibrium across several populations. The bivariate data in this example are the two alleles comprising the genotype of interest. We propose using derived logistic regression equations from the full exponential model for the bivariate outcomes to test for homogeneity. We adjust for correlation among outcomes via generalized estimating equations. This modeling approach allows for adjustment for individual-level and pair-level covariates and thereby allows for testing for gene x environment interactions. Further, we extend the model to allow for simultaneous analysis of two diseases, which allows for testing for a genetic component to the coaggregation of two diseases. In contrast to approaches proposed by previous authors, no special software is required; our approach can be easily implemented in standard software packages. We compare our results to those of other methods proposed in the literature for data from the Vietnam Era Twins Study. We apply our methods also to the Anqing Twin Study and to data on major depression and generalized anxiety disorder from the Virginia Twin Register.

Disease↗
PubMed2001

Hypercalciuria in ex-preterm children, aged 7-8 years.

In a previous study, 8 of 28 ex-preterm infants, aged 4-5 years, had increased urinary calcium excretion. The aim of this study was to confirm this finding and to determine if raised urinary calcium excretion is associated with reduced bone mineralisation. Forty-six ex-preterm children, aged 7-9 years, and 40 age- and sex-matched controls were recruited. The calcium excretion measured from 3 separate 24-h urine collections was recorded and a dietary assessment made from a diary record. Data were retrieved from the neonatal case notes and included aminoglycoside usage. Dual energy X-ray absorptiometry was used to measure bone mineral content and bone mineral density (BMD) in all children. The mean maximum 24-h urinary calcium was significantly higher in the preterm group than the term group (P=0.01). Increased calcium excretion was associated with raised neonatal aminoglycoside levels (P=0.0013). Height standard deviation score and hip BMD were significantly lower in the 21 preterm children with a 24-h urinary calcium above 4 mg/kg per day than term controls (P=0.04 and P=0.004, respectively). Urinary calcium excretion had a negative relationship with hip BMD in the preterm group (P=0.004). This difference in BMD was not observed in the 25 preterm children with normocalciuria. In the 10 preterm girls with hypercalciuria, hip BMD was lower than in control females (P=0.01). This difference in hip BMD between the 11 preterm boys with hypercalciuria and term boys was not significant (P=0.05). In conclusion, preterm children are shorter and have a lower hip BMD than those with normocalciuria. Further prospective studies are required to assess this risk and its influence on subsequent impaired bone mineralisation.

Anthropometry↗
PubMed2001

Pattern of REM sleep occurrence in continuous darkness following the exposure to low ambient temperature in the rat.

The occurrence of REM sleep episodes, separated by intervals >3 min (single episodes) and < or =3 min (sequential episodes), was determined in the rat during the recovery (ambient temperature (Ta) 23 degrees C, L period of the LD [12 h:12 h]-cycle), which followed the exposure to low Ta (0 and -10 degrees C) during the D period of the previous LD-cycle, either in normal light (DL) or in continuous darkness (DD). Both exposures were characterized by an almost complete disappearance of REM sleep, whilst the recoveries showed an increase in the amount of REM sleep in the form of sequential episodes, which in DD was particularly prominent and concomitant with a decrease in the amount of REM sleep in the form of single episodes. The initial 2 h-rate of REM sleep occurrence was lower following the exposure to Ta -10 degrees C, than to Ta 0 degrees C. In DD, such an effect was due to the large reduction in the occurrence of sequential REM sleep episodes. A functional correlate of this finding is that the accumulation capacity of a second messenger (cAMP) was found to be lower at the end of the exposure to Ta -10 degrees C, with respect to both the control (Ta 23 degrees C) and the end of exposure to Ta 0 degrees C, in the preoptic-anterior hypothalamus, but not in the cerebral cortex.

Analysis of Variance↗
PubMed2001

Maternal transmission of infectious pathogens in breast milk.

Breast milk provides a superior source of nutrition and many other health benefits to the newborn infant. However, breastfeeding has also been recognized as a route of transmission to the newborn of some important pathogens that may result in disease. In the present article, up-to-date research and recommendations on the maternal transmission of infectious pathogens in breast milk or by breastfeeding are discussed in the context of local epidemiology and in the setting of an industrialized country.

Adult↗
PubMed2001

Using survival analysis to explore female cardiac rehabilitation program adherence.

Heart disease continues to be the predominant cause of death in the United States. Traditionally, coronary heart disease (CHD) has been considered to be a male disorder, but it is also a significant cause of death and disability among older women. Cardiac rehabilitation offers valuable tertiary prevention after myocardial infarction and other cardiac events and has proven to decrease CHD death risk. This study used survival analysis as a means to incorporate time as a variable in the analysis of cardiac rehabilitation program adherence with a sample of female CHD patients. Implications for the management of female cardiac rehabilitation are discussed.

Adult↗
PubMed2001

Costimulatory molecules in the developing human gastrointestinal tract: a pathway for fetal allergen priming.

BACKGROUND: Antigen-specific responses can be detected in umbilical cord blood mononuclear cells. The fetal immune system must therefore attain a level of maturity compatible with the initiation of such responses as well as be exposed to antigen. OBJECTIVE: We sought to assess the expression of costimulatory molecules in fetal gut and the presence of cytokines in amniotic fluid at this time as a preliminary analysis of the suitability of the fetal gut as a site of antigen priming during intrauterine life. METHODS: Human fetal gut was analyzed for cells expressing costimulatory molecules through use of immunohistochemistry. Amniotic fluid was studied by ELISA, for cytokines regulating the nature of the response, and as a source of the common dietary antigen ovalbumin. RESULTS: MHC class II--positive cells were abundant over the period examined (11-24 weeks of gestation), other surface antigens showing spatial and temporal variation in expression. From 11 to 14 weeks of gestation, CD68-positive and CD40-positive cells, like MHC class II--positive cells, were present throughout the lamina propria; few CD3-positive cells (T cells) were observed. With the emergence of lymphoid aggregates (14-16 weeks), CD83-positive cells (dendritic cells) and CD20-positive cells (B cells) could be detected in fetal gut; however, expression was restricted to the lymphoid aggregates. In contrast, MHC class II, CD40, and CD68 continued to be expressed in the lamina propria. CD28-positive cells were also evident from 14 weeks of gestation, occurring throughout the lamina propria and lymphoid aggregates; this corresponded to the increasing numbers of CD3-positive cells. The occasional CD86-positive, CD40L-positive, or CTLA4-positive cell could be seen in or around lymphoid aggregates after 14 weeks of gestation. Lymphoid follicles forming after 16 weeks of gestation contained MHC class II--positive, CD83-positive, CD20-positive, CD40-positive, CD86-positive, CD3-positive, CD28-positive, CD40L-positive, and CTLA4-positive cells. MHC class II--positive, CD40-positive, CD68-positive, CD3-positive, and CD28-positive cells continued to be present in the lamina propria at this time. At all times studied, CD14 was not expressed in the lamina propria or lymphoid follicles. Prostaglandin E(2), TGF beta(1), and IL-10 dominated the amniotic fluid cytokine milieu, and ovalbumin was also detectable in amniotic fluid from 3 of 26 women who had detectable circulating levels. CONCLUSION: Of the costimulatory molecules studied, CD40 was the most abundant. However, both of the ligand families studied (CD40-CD40L and CD86-CD28/CD152) could provide the costimulatory signals required for the initiation of antigenspecific reactivity in the gastrointestinal tract of the human fetus as early as 16 weeks of gestation. The cytokine milieu would favor the development of T(H)2-type reactivity to antigens, such as ovalbumin, that are present at this time.

Abatacept↗