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Biomedical subjects

C A Jones

Publications and source records attributed to C A Jones.

At least 109 records · Page 6Linked to original sources
PubMed1997

Type-1 and type-2 cytokines in human late-gestation decidual tissue.

Evidence suggests that successful pregnancy in rodents requires the preferential stimulation of type-2 cytokine production by gestation-associated tissues. The ability of human gestation-associated tissue to synthesize type-2 and type-1 cytokines has not been examined in detail and was the subject of this study. Decidual tissue collected at term, either before the onset of labor (elective caesarean section) or at the completion of labor, expressed mRNA for interleukin (IL)-10 and interferon gamma (IFN-gamma) and produced IL-10 and IFNgamma protein in vitro. IL-4 mRNA or protein was not detected. IFNgamma production in vitro was significantly decreased by decidual cells prepared from decidua collected after labor as compared with those collected before the commencement of labor, a change that may be associated with prostaglandin E2 (PGE2) production in conjunction with labor. IFNgamma, IL-4, and IL-10 were detectable in human amniotic fluid collected at term. There was no significant difference in the levels of IL-4, IFNgamma, or IL-10 in samples collected before labor onset or during labor. Thus, late-gestation human decidual tissue and amniotic fluid do not preferentially express a type-2 cytokine profile of cytokines. This is not consistent with observations of a predominant type-2 cytokine profile in gestation-associated tissues in murine pregnancy.

Amniotic Fluid↗
PubMed1997

Renal calcification in preterm infants: follow up at 4-5 years.

AIM: To determine the consequences of renal calcification in preterm infants. METHODS: A cohort of 11 preterm babies was studied at the age of 4 to 5 years. They had had renal calcification as neonates. Seventeen matched controls were also studied. Each child had a renal ultrasound scan, a calcium load test, and a desmopressin test for renal concentrating ability (RCA). The study group also had glomerular filtration rate (GFR) estimated, using the height:creatinine ratio, and tubular phosphate reabsorption, without phosphate load, per glomerular filtration rate (Tp/GFR) calculated, RESULTS: In the study group the median GFR was 61 ml/min/1.73m2 (range 46-79 ml/min/1.73m2) and the median calculated Tp/GFR SD score was -0.94 (range -2.8-0.68). Five children out of the study group had ultrasonic evidence of renal calcification. There was no significant difference between the two groups in renal size, calciuria, before or after calcium load, or RCA. Eight children (three patients, five controls) had an abnormal calcium load test. The RCA of the children in the study and control groups combined was below that of published values, with a median calculated SD score -0.71 (95% CI -1.21 to -0.23). CONCLUSIONS: There was evidence of renal dysfunction in children who had been born preterm. Renal calcification detected in the neonatal period does not seem to be a major predisposing factor for the abnormalities of renal function subsequently observed in these infants.

Calcinosis↗
PubMed1997

Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group.

African Americans (blacks) have a disproportionately high incidence of end-stage renal disease due to hypertension. The Modification of Diet in Renal Disease (MDRD) Study found that strict blood pressure control slowed the decline in glomerular filtration rate (GFR) only in the subgroup of patients with proteinuria. The present report compares the effects of blood pressure control in black and white MDRD Study participants. Fifty-three black and 495 white participants with baseline GFRs of 25 to 55 mL/min/1.73 m2 were randomly assigned to a usual or low mean arterial pressure (MAP) goal of < or = 107 or < or = 92 mm Hg, respectively. GFR decline was compared between randomized groups and correlated with the level of achieved blood pressure. The mean (+/-SE) GFR decline over 3 years in the low blood pressure group was 11.8+/-7.3 mL/min slower than in the usual blood pressure group among blacks (P=.11) compared with 0.3+/-1.3 mL/min slower among whites (P=.81) (P=.12 between blacks and whites). In both blacks and whites, higher baseline urine protein excretion was associated with a greater beneficial effect of the low MAP goal on GFR decline (P=.02 for both races). Combining both blood pressure groups and controlling for baseline characteristics, higher follow-up achieved MAP was associated with faster GFR decline in both blacks (P<.001) and whites (P=.002), with a sevenfold stronger relationship in blacks (P<.001). These secondary analyses support the prior recommendation for a lower than usual blood pressure goal (MAP < or = 92 mm Hg) in black and white patients with proteinuria (> 1 g/d). In addition, a lower level of blood pressure control may be even more important in blacks than in whites in slowing the progression of renal disease.

Adolescent↗
PubMed1997

Conserved enhancer elements in human and mouse renin genes have different transcriptional effects in As4.1 cells.

Despite the strong conservation of proximal 5'-flanking DNA sequences, cell transfection and transgenic animal studies have failed to provide a unifying hypothesis to explain the expression of both mouse and human renin genes. Recently, sequences contained in the mouse Ren-1c gene 5'-flanking DNA (-2866 to -2625) were shown to contain an enhancer-like element that stimulates Ren-1c promoter activity in renin-expressing As4.1 cells approximately 80-fold. Earlier studies using transgenic mice had suggested that this same region is required for the cell-specific expression of mouse renin genes. Since existing human renin genomic clones lack sequences homologous to the mouse renin enhancer, we isolated several human P1 and P1 artificial chromosome genomic clones that contain > 80 kb spanning the human renin gene. Analysis of these clones by Southern blot hybridization and long-rang polymerase chain reaction showed that they contain sequences homologous to the mouse enhancer at approximately 12 kb upstream of the transcription start site. Mouse and human sequences were 59% identical over a 650-bp region that contained the minimal enhancer from the mouse Ren-1c gene. However, a 1-kb fragment containing the entire human enhancer homology failed to stimulate human renin promoter activity in transiently transfected As4.1 cells. Further deletional analysis showed that a 220-bp region of the human sequence highly conserved in the mouse Ren-1c gene exhibited up to 47-fold transcriptional stimulation, although this was lower than the maximal effect exhibited by the minimal mouse enhancer (223-fold). Taken together, these observations suggest that sequences surrounding the conserved enhancer core stimulate enhancer activity in the mouse gene but suppress activity in the human gene. The high transcriptional activity of the mouse enhancer may have evolved to support the exceptionally high plasma renin concentrations found in mice. However, the enhancer core and surrounding conserved sequences may play an additional role in directing cell specificity.

Animals↗
PubMed1997

Immune responses during pregnancy and the development of allergic disease.

It is now established that allergen exposure in the first few months of life is important in the development of specific allergic sensitisation (1, 2). Furthermore, the immune response of infants born to families with a strong history of allergic disease is relatively immature at birth in comparison to infants with no family history of allergies, with reduced production of Interferon-gamma (IFN-gamma) (3-5) and lower levels of T cell activation and memory (6). It therefore seems logical that the interaction of these two factors must be important in the ontogeny of allergic disease.

Allergens↗
PubMed1996

Role of proximal promoter elements in regulation of renin gene transcription.

Mouse As4.1 cells, obtained after transgene-targeted oncogenesis to induce neoplasia in renal renin-expressing cells, express high levels of renin mRNA from the endogenous Ren-1(c) gene. We have used these cells to characterize the role of the Ren-1(c) proximal promoter (+6 to -117) in the regulation of renin gene transcription. It was found that 4.1 kilobases (kb) of Ren-1(c) 5'-flanking sequence, in combination with the proximal promoter, are required for strong activation (approximately 2 orders of magnitude over the basal level of the promoter alone) of the chloramphenicol acetyltransferase reporter in transfection assays. Within the 4.1-kb fragment, a 241-base pair region was identified that retains full activity in an orientation-independent manner in combination with the promoter. The resulting transcripts initiate at the normal renin start site. Electrophoretic mobility shift assays identified a sequence at approximately position -60 in the promoter region that binds nuclear proteins specific for renin-expressing As4.1 cells. Mutations in this sequence, which disrupt binding of nuclear protein(s), completely abolish activation of transcription by the 4. 1-kb fragment. Activation of transcription by the 241-base pair enhancer was still observed, although it was diminished in magnitude (60-fold over the mutated promoter alone). We present a model derived from the current data that suggests that regulation of renin expression is achieved through cooperation of transcription factors binding at the proximal promoter element and a distal enhancer element to abrogate or override the effects of an intervening negative regulatory region.

Animals↗
PubMed1996

The capacity to accumulate cyclic AMP in the preoptic-anterior hypothalamic area of the rat is affected by the exposition to low ambient temperature and the subsequent recovery.

The accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) was measured in the preopticanterior hypothalamic area, the cerebral cortex, and the hippocampus of rats exposed to different ambient temperatures: (1) 23 +/- 0.5 degrees C, for 53 h +/- 20 min (control); (2) -10 +/- 1 degrees C, for 53 h +/- 20 min (exposure to low ambient temperature); (3) -10 degrees C for 48 h and 23 degrees C for the following 5 h +/- 20 min (recovery). The capacity to accumulate cAMP was tested by subjecting animals to acute hypoxia, a stimulus which is known to induce a large increase in brain cAMP concentration. In the control condition, hypoxic stimulation increases cAMP concentration in all the brain regions studied. In contrast, during the exposure to low ambient temperature, whilst both the cerebral cortex and the hippocampus show the same levels of accumulation found in the control condition, cAMP accumulation is reduced in the preoptic-anterior hypothalamic area. However, during the first few hours of the recovery period, the preoptic-anterior hypothalamic area is able to reattain the capacity for cAMP accumulation observed in the control condition.

Animals↗
PubMed1996

Recruitment experience in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Several approaches for recruitment of African American adults with renal insufficiency due to hypertension (glomerular filtration rate between 25 and 70 ml/min/1.73 m2) were explored in the Pilot Study for the African American Study of Kidney Disease and Hypertension (AASK). Over a period of 42 weeks, prescreening information was obtained on 2880 individuals, of whom 498 (17%) were evaluated at a screening visit. Two hundred and twenty-five (8%) had an 125I-iothalamate assessment of glomerular filtration rate. Ninety-four of 97 participants who met all the study eligibility criteria were enrolled in the trial. The most common reasons for ineligibility during screening were absence of renal insufficiency or hypertension, presence of diabetes mellitus, and a body mass index above the acceptable level. Overall, an average of 31 prescreen contacts and 8 screening visits were conducted for every randomization (3.3% yield from prescreening to randomization). Screening in clinical practice was the most efficient method for recruitment (12.6% yield from prescreen contact to randomization compared to 1.1% from mass mailing campaigns, 1.3% from mass media campaigns, and 1.7% from referrals by patients with end-stage renal disease). Randomization yields increased with progressively higher age ranges (2.4%, 3.3%, and 6.0% prescreen to randomization yields for those aged < or = 50, 51-60, and 61-70, respectively). A slight majority (51%) of the prescreen contacts were women, but 75% of the randomized participants were men. Our results suggest that clinic-based screening is an effective approach for recruitment of African Americans with hypertension and renal insufficiency into clinical trials. They also suggest that enrollment of African American women in such studies is a special challenge.

Adult↗
PubMed1996

Relationship of dose of hemodialysis and cause-specific mortality.

A number of studies have found a relationship of lower all-cause mortality risk for ESRD patients treated with increasing dose of dialysis. The objective of this study was to determine the relationship of delivered dose of dialysis with cause-specific mortality. Data from the USRDS Case Mix Adequacy Study, which includes a national random sample of hemodialysis patients, were utilized. To minimize the contribution of unmeasured residual renal function, the sample used in this analysis (N = 2479) included only patients on dialysis for one year or more. Cox proportional hazards models, stratified for diabetes, were used to analyze the effect of delivered dose of dialysis (measured and reported by both Kt/V and URR) on major causes of death and withdrawal from dialysis, adjusting for other covariates including demographics, comorbid diseases present at start of study, functional status, laboratory values and other dialysis parameters. Patient follow-up for mortality was censored at the earliest of time of transplantation, 60 days after a switch to peritoneal dialysis or at the time of data abstraction. For each 0.1 higher Kt/V, the adjusted relative risk of death due to coronary artery disease was 9% lower (RR = 0.91, P < 0.05), due to other cardiac causes was 12% lower (RR = 0.88, P < 0.01), due to cerebrovascular disease (CVD) was 14% lower (RR = 0.86, P < 0.05), due to infection was 9% lower (RR = 0.91, P = 0.05), and due to other known causes was 6% lower (RR = 0.94, P < 0.05). There was no statistically significant relationship of Kt/V and risk of death among patients who died of malignancy (RR = 0.84, P = 0.10) or among patients whose death cause was missing (RR = 0.95, P = 0.41). The risk of withdrawal from dialysis prior to death due to any cause was 9% lower (RR = 0.91, P < 0.05) for each 0.1 higher Kt/V. The relationships of delivered dose of dialysis, as measured by URR, and cause-specific mortality were essentially similar in relative magnitude and statistical significance as the relationships observed using Kt/V as the measurement of dialysis dose, with the exception that the relationship was less significant for cerebrovascular disease and withdrawal from dialysis. The relationship of dialysis dose with risk of death due to each cause of death category except other cardiac causes and "other" causes appeared to be of greater magnitude and of greater statistical significance among diabetics than non-diabetics. These results indicate that low dose of dialysis is not associated with mortality due to just one isolated cause of death, but rather is due to a number of the major causes of death in this population. This study is consistent with hypotheses that low doses of dialysis may promote atherogenesis, infection, malnutrition and failure to thrive through a variety of pathophysiologic mechanisms. Further study is necessary to confirm these results and to test hypotheses that are developed.

Adult↗
PubMed1996

Control of major histocompatibility complex class II expression on human monocytes by interleukin-4: regulatory effect of lipopolysaccharide.

Interleukin-4 (IL-4), like interferon-gamma (IFN-gamma), stimulates monocyte major histocompatibility complex (MHC) class II expression and thus, by increasing antigen presentation, has the potential to increase immune reactivity. In this study, activation of human monocytes by lipopolysaccharide (LPS) prevented concomitant IL-4 stimulation of MHC class II expression. However, this was not a general observation for activated monocytes because although the high levels of MHC class II antigen expressed by monocytes stimulated in vitro with IFN-gamma were not further regulated by IL-4, the stimulatory effects of IL-4 persisted on cells activated with granulocyte macrophage colony-stimulating factor and tumour necrosis factor-alpha for enhanced MHC class II expression. MHC class II expression by monocytes cultured for 7 days with macrophage colony-stimulating factor was regulated by IL-4 and LPS in a manner very similar to that detected for freshly isolated monocytes. The inhibitory effect of LPS was not due to LPS-induced production of IL-10 or regulatory prostanoids. Furthermore, IFN-gamma-increased MHC class II expression was suppressed by LPS, suggesting that the regulation was at the level of MHC class II expression per se. This study suggests that during Gram-negative bacterial infections, IL-4 and IFN-gamma may not be able to signal enhanced MHC class II expression and thus, enhanced immune reactivity.

Antigen Presentation↗
PubMed1996

Papanicolaou staining of air-dried smears: value in rapid diagnosis.

Air-dried material normally submitted for Diff-Quik (modified Romanowsky stain) was rehydrated in normal saline, then fixed for a short period in formol alcohol, before staining by a modified Papanicolaou technique. Staining was performed by a rapid manual technique (< 2 min) if urgent or routinely on an automatic stainer. Comparisons were made between wet-fixed Papanicolaou-stained specimens and air-dried Papanicolaou-stained material. Air-dried material stained after rehydration showed superior nuclear definition compared with wet-fixed material; the removal of erythrocytes enhanced the staining of the remaining epithelial cells.

Biopsy, Needle↗
PubMed1996

Replication in UV-irradiated Caenorhabditis elegans embryos.

Replication continues in wild-type (but not rad mutant) Caenorhabditis elegans embryos even after exposure to massive fluences of UV radiation. It is of interest to elucidate the mechanism(s) for this "damage-resistant" DNA synthesis. In this study, DNA from unirradiated and UV-irradiated wild-type embryos was examined using the electron microscope. Large fluences of UV radiation (180 J m-2) had little effect on either replication bubble size or distances between bubbles in wild-type embryos, indicating that the damage-resistant DNA synthesis was not grossly aberrant. Conversely, UV irradiation significantly decreased center-to-center distances between bubbles in excision-repair-deficient rad-3 embryos. This suggests that the decreased DNA synthesis observed after UV irradiation in rad-3 embryos is due largely to blockage of elongation of DNA synthesis.

Animals↗
PubMed1996

Human herpesvirus-6 infections.

HHV-6 is ubiquitous in the community, appears to be acquired early in life, and has been proved to cause the clinical syndrome of exanthem subitum, and rarely to cause encephalitis. Like other herpesviruses, HHV-6 is capable of establishing latent infection and reactivating under a variety of stimuli. Improved diagnostic techniques have led to increased recognition of HHV-6 in the presence of many diseases, but much of the evidence for an aetiological role is inconclusive. There is accruing evidence for possible pathological roles in the immunocompromised host, but the evidence is less convincing for the range of associations otherwise listed for the normal host at the present time.

Child↗
PubMed1996

End-stage renal disease in the USA: data from the United States Renal Data System.

Treated end-stage renal disease continues to increase at an alarming rate in the US. There has been an exponential growth in the incidence rate between 1982 and 1991 at the rate of 8.76% per year. Approximately 218,042 patients received treatment for ESRD in 1991, of which 49,909 were new patients. Although the increase in the incidence rate is seen for all the major disease categories responsible for ESRD, diabetes mellitus, probably type 2, and hypertension are responsible for the bulk of the increase. African Americans and Native Americans have shown the most dramatic increase; diabetes being the major reason for both races, but for African Americans, hypertension is the leading cause of ESRD. A bulk of the increase in the ESRD patient population has been in the older age (greater than 65 years of age) group. The mortality rate for the ESRD patient population, and, specifically, for the dialysis population remains relatively high, with 1-year survival probabilities of approximately 78%. Some of the contributing factors cited for the high death rate, especially in the dialysis patient population include inadequate dialysis dose, low flux of the dialysis membranes, shortened dialysis times, an increase in the age of the ESRD population, and bioincompatible dialysis membranes. The effect of the widely practiced dialyzer reuse on dialysis patient morbidity and mortality remains unclear.

Adolescent↗
PubMed1996

Undetectable interleukin (IL)-10 and persistent IL-8 expression early in hyaline membrane disease: a possible developmental basis for the predisposition to chronic lung inflammation in preterm newborns.

We are interested in determining whether premature birth alters expression of counterregulatory cytokines which modulate lung inflammation. Production of proinflammatory cytokines tumor necrosis factor alpha. IL-1 beta, and IL-8 is regulated in part by the antiinflammatory cytokine IL-10. For preterm newborns with hyaline membrane disease, deficiencies in the ability of lung macrophages to express antiinflammatory cytokines may predispose to chronic lung inflammation. We compared the expression of pro- and antiinflammatory cytokines at the mRNA and protein level in the lungs of preterm and term newborns with acute respiratory failure from hyaline membrane disease or meconium aspiration syndrome. Four sequential bronchoalveolar lavage (BAL) samples were obtained during the first 96 h of life from all patients. All patients rapidly developed an influx of neutrophils and macrophages. Over time, cell populations in both groups became relatively enriched with macrophages. The expression of proinflammatory cytokine mRNA and/or protein was present in all samples from both patient groups. In contrast, IL-10 mRNA was undetectable in most of the cell samples from preterm infants and present in the majority of cell samples from term infants. IL-10 concentrations were undetectable in lavage fluid from preterm infants with higher levels in a few of the BAL samples from term infants. These studies demonstrate that 1) IL-10 mRNA and protein expression by lung inflammatory cells is related to gestational age and 2) during the first 96 h of life neutrophil cell counts and IL-8 expression decrease in BAL from term infants, but remain unchanged in BAL samples from preterm infants.

Bronchoalveolar Lavage↗
PubMed1996

A cohort analysis of pre-menopausal women with dysfunctional uterine bleeding.

OBJECTIVE: To examine the clinical and cost outcomes of patients with dysfunctional uterine bleeding (DUB) who are treated with hysterectomy or not. DESIGN: A retrospective analysis of DUB patients over 30 months of treatment after initial diagnosis. SETTING: Patients with DUB from an HMO with over 200,000 enrollees. PARTICIPANTS: Study patients, all women with an initial diagnosis of DUB, were divided into two cohorts. Cohort 1 was women who had a hysterectomy (not for cancer); Cohort 2 was women who did not have a hysterectomy. MAIN OUTCOME MEASURES: Visit counts and costs, prescription counts and costs, hospital costs, and procedure counts. RESULTS: Hysterectomy patients in our dataset tend to have more prescriptions, higher prescription costs, more visits overall, higher visit costs, higher hospitalization costs, and higher total costs per member per month (PMPM) than non-hysterectomy patients. After surgery, the hysterectomy patients' costs and utilization PMPM are higher than those for the non-hysterectomy patients. CONCLUSIONS: There is wide variation in the treatment of patients with DUB. Clinical practice improvement studies are needed to determine the appropriate treatments based on patient characteristics to achieve better outcomes for lower costs.

Adult↗
PubMed1995

cAMP accumulation in the hypothalamus, cerebral cortex, pineal gland and brown fat across the wake-sleep cycle of the rat exposed to different ambient temperatures.

The concentration of adenosine 3':5' cyclic monophosphate (cAMP) was determined in the anteroventro-medial hypothalamus, the cerebral cortex, the pineal gland and the interscapular brown adipose tissue, during the different stages of the wake-sleep cycle of rats kept, under a 12-12-h light-dark cycle, in different environmental conditions, i.e., control (47-52 h at ambient temperature (Ta) 23 +/- 0.5 degrees C), exposure (47-52 h at Ta 0 +/- 1 degree C) and recovery (1-4 h at Ta 23 degrees C after 48 h at Ta 0 degree C). The results show that cAMP concentration consistently changed: (1) during the wake-sleep cycle in the anteroventro-medial hypothalamus, decreasing from wakefulness to sleep; (2) during the dark-light transition in the pineal gland, increasing with the onset of the light phase; and (3) with the environmental condition in the interscapular brown adipose tissue increasing, with respect to the control condition, in exposure and recovery. No significant changes in cAMP concentration were observed in the cerebral cortex.

Adipose Tissue, Brown↗