PubMed Health⌕ Search

Biomedical subjects

J Cross

Publications and source records attributed to J Cross.

At least 37 records · Page 2Linked to original sources
PubMed2000

CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis.

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibodies, accompanied by focal necrotizing glomerulonephritis with crescent formation. The role of T cells in the pathogenesis of EAG remains unclear. T-cell costimulation is provided by ligation of CD28 with either B7.1 (CD80) or B7.2 (CD86) on antigen-presenting cells, and can be inhibited by a soluble form of CTLA4 (CTLA4-Ig) that binds to both B7.1 and B7.2. We examined the effect of CD28-B7 blockade on the development of EAG using native CTLA4-Ig or mutant CTLA4-Ig (Y100F-Ig), which selectively blocks B7.1. Native CTLA4-Ig treatment ameliorated EAG by several measures, including the levels of circulating anti-GBM antibodies, albuminuria, the deposition of IgG and fibrin in the glomeruli, the severity of glomerular abnormalities, and the numbers of infiltrating T cells and macrophages. Y100F-Ig resulted in a similar reduction in the severity of nephritis, but produced no overall reduction in circulating anti-GBM antibodies, although there was a reduction in IgG2a antibodies. We concluded that CD28-B7 blockade reduced autoantibody production and cellular infiltration of glomeruli, and prevented target organ injury. Our results suggest a key role for B7. 1 in costimulation of Th1-like autoimmune responses in the rat, and show that glomerular injury in EAG is largely dependent on cell-mediated mechanisms.

Abatacept↗
PubMed1999

Wegener granulomatosis: MR imaging findings in brain and meninges.

PURPOSE: To determine the spectrum of intracranial magnetic resonance (MR) imaging appearances of Wegener granulomatosis. MATERIALS AND METHODS: MR imaging studies in 19 patients with Wegener granulomatosis and possible central nervous system involvement were reviewed by two neuroradiologists. Intermediate-weighted and T2-weighted fast spin-echo MR images of the brain had been acquired in all patients, and spin-echo T1-weighted nonenhanced and gadolinium-enhanced images had been acquired in 18 patients. RESULTS: MR imaging findings included diffuse linear dural thickening and enhancement (n = 6); focal dural thickening and enhancement contiguous with orbital, nasal, or paranasal disease (n = 5); infarcts (n = 4); nonspecific white matter areas of high signal intensity on intermediate-weighted and T2-weighted images (n = 10); enlarged pituitary gland with infundibular thickening and enhancement (n = 2); a discrete cerebellar lesion that was probably granulomatous in origin (n = 1); and cerebral (n = 8) and cerebellar atrophy (n = 2). CONCLUSION: MR imaging demonstrated the wide spectrum of findings of central nervous system involvement in patients with Wegener granulomatosis and was particularly useful for the evaluation of direct intracranial spread from orbital, nasal, or paranasal disease.

Adolescent↗
PubMed1998

Novel potentiation of interleukin 1alpha production in endotoxin-stimulated IC-21 cells by ambient pressure augmentation.

BACKGROUND: We hypothesized that increased ambient pressure would increase the production of interleukin 1alpha by endotoxin-stimulated macrophages, based on the clinical observation that patients with "pus under pressure" demonstrate systemic toxic effects (a priori hypothesis). DESIGN AND SETTING: In vitro experiment in the laboratory. INTERVENTIONS: A murine macrophage line, IC-21 cells, was seeded into 6-well plates, 25 x 10(4) cells per well. Cells were incubated under atmospheric (ATM) or increased (ATM+60 mm Hg) ambient pressure (AP) in the presence or absence of endotoxin (lipopolysaccharide [LPS]). The IC-21 production of interleukin 1alpha was determined at 2, 4, 8, and 12 hours. Four groups were examined: group 1: AP ATM, no LPS; group 2: AP ATM+60 mm Hg, no LPS; group 3: AP ATM and LPS, 500 ng/mL; and group 4: AP ATM+60 mm Hg and LPS, 500 ng/mL. MAIN OUTCOME MEASURES: The IC-21 production of interleukin 1alpha. RESULTS: Interleukin 1alpha production at 2, 4, 8, and 12 hours (mean [+/-SD] picograms per 10(6) cells) was as follows: group 1: 3.0 (+/-5.9), 8.1 (+/-10.3), 50.5 (+/-51.1), and 6.1 (+/-4.1), respectively; group 2: 228.7 (+/-110.2), 141.0 (+/-141.8), 112.5 (+/-98.5), and 118.2 (+/-79.8), respectively; group 3: 37.2 (+/-13.3), 191.5 (+/-86.5), 627.3 (+/-184.3), and 600.7 (+/-67.1), respectively; and group 4: 601.2 (+/-49.9), 1050.9 (+/-190.6), 2684.2 (+/-562.2), and 3144.7 (+/-388.4), respectively. The production of IL-1alpha by group 3 was significantly greater (P<.04, unpaired Student t test) at 4, 8, and 12 hours than that by groups 1 or 2. Likewise, the production of IL-1alpha by group 4 was significantly greater (P<.001, unpaired Student t test) at all time points than that by groups 1, 2, or 3. CONCLUSIONS: Our data support the hypothesis that pressure may be a novel potentiator of the macrophage proinflammatory cytokine response to endotoxin. This provides a possible explanation for the phenomenon of systemic illness seen with "pus under pressure."

Animals↗
PubMed1996

Effect of frequency of prenatal care visits on perinatal outcome among low-risk women. A randomized controlled trial.

OBJECTIVES: In 1989, the Expert Panel on the Content of Prenatal Care established guidelines on the timing and content of prenatal care, including a schedule consisting of fewer prenatal visits than traditionally provided, for women at low risk of adverse perinatal outcomes. We tested the hypothesis that there are no significant increases in adverse perinatal outcomes when low-risk women are seen in a prenatal care visit schedule of fewer visits than routinely advised. DESIGN: Randomized controlled trial. SETTING: Group-model health maintenance organization. PATIENTS: A total of 2764 pregnant women, judged to be at low risk of adverse perinatal outcomes. INTERVENTIONS: Following risk assessment, participants were randomly assigned to an experimental schedule (nine visits) or a control schedule (14 visits) with additional visits as indicated or as desired by the patient. MAIN OUTCOME MEASURES: Preterm delivery, preeclampsia, cesarean delivery, low birth weight and patient's satisfaction with care. RESULTS: On average, there were 2.7 fewer visits observed in the experimental group than in the control group. There were no significant increases in the main outcomes of the experimental group; preterm delivery (relative risk [RR], 1.08; 95% confidence interval [CI], 0.92 to 1.27; P = .19), preeclampsia (RR, 0.94; 95% CI, 0.78 to 1.14, P = .74), cesarean delivery (RR, 1.04; 95% CI, 0.93 to 1.17; P = .25), and low birth weight (RR, 0.94; 95% CI, 0.78 to 1.12; P = .76). There were no differences between the two groups in patients' satisfaction with quality of prenatal care. CONCLUSION: In this study, good perinatal outcomes and patient satisfaction were maintained when the prenatal visit schedule proposed by the Expert Panel on the Content of Prenatal Care was observed.

Adult↗
PubMed1996

Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia.

Fanconi anaemia (FA) is an autosomal recessive disease characterized by bone marrow failure, variable congenital malformations and predisposition to malignancies. Cells derived from FA patients show elevated levels of chromosomal breakage and an increased sensitivity to bifunctional alkylating agents such as mitomycin C (MMC) and diepoxybutane (DEB). Five complementation groups have been identified by somatic cell methods, and we have cloned the gene defective in group C (FAC)(7). To understand the in vivo role of this gene, we have disrupted murine Fac and generated mice homozygous for the targeted allele. The -/- mice did not exhibit developmental abnormalities nor haematologic defects up to 9 months of age. However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to MMC and DEB. Homozygous male and female mice also had compromised gametogenesis, leading to markedly impaired fertility, a characteristic of FA patients. Thus, inactivation of Fac replicates some of the features of the human disease.

Animals↗
PubMed1996

Molecular phylogenetic analysis of Cyclospora, the human intestinal pathogen, suggests that it is closely related to Eimeria species.

A coccidian organism assigned to the genus Cyclospora has been increasingly recognized in association with prolonged diarrhea in humans throughout the world. Confusion surrounds the taxonomy of this fastidious organism, despite the availability of morphology and sporulation characteristics. The small subunit rRNA coding region from cyclosporan oocysts purified from a human fecal specimen was amplified and sequenced. The same sequence was present in specimens from 8 other patients with cyclosporan oocysts but absent in specimens from asymptomatic subjects and from cryptosporidiosis patients. Phylogenetic analysis of rDNA sequences reveals that the human-associated Cyclospora is closely related to members of the Eimeria genus. These results allow predictions concerning Cyclospora host specificity, life cycle, and epidemiology as well as the development of a specific polymerase chain reaction-based diagnostic assay.

Animals↗
PubMed1996

Diet in pregnancy and the offspring's blood pressure 40 years later.

OBJECTIVE: To determine how diet of the mother in pregnancy influences the blood pressure of the offspring in adult life. DESIGN: A follow up study of men and women born during 1948-1954 whose mothers had taken part in a survey of diet in late pregnancy. SETTING: Aberdeen, Scotland. POPULATION: Two hundred and fifty-three men and women born in Aberdeen Maternity Hospital. MAIN OUTCOME MEASURE: Systolic and diastolic blood pressure. RESULTS: The relations between the diet of mothers and their offsprings' blood pressure were complex. When the mothers' intake of animal protein was less than 50 g daily, a higher carbohydrate intake was associated with a higher blood pressure in the offspring (a 100 g increase in carbohydrate being associated with a 3 mmHg increase in systolic pressure (P = 0.02)). At daily animal protein intakes above 50 g, lower carbohydrate intake was associated with higher blood pressure (a 100 g decrease in carbohydrate being associated with an 11 mmHg rise in systolic blood pressure (P = 0.004)). These increases in blood pressure were associated with decreased placental size. CONCLUSION: Mothers' intakes of animal protein and carbohydrate in late pregnancy may influence their offsprings' adult blood pressure. This may be mediated through effects on placental growth.

Adult↗
PubMed1995

Prostate-specific membrane antigen: evidence for the existence of a second related human gene.

Prostate-specific membrane antigen (PSM) is a glycoprotein recognised by the prostate-specific monoclonal antibody 7E11-C5, which was raised against the human prostatic carcinoma cell line LNCaP. A cDNA clone for PSM has been described. PSM is of clinical importance for a number of reasons. Radiolabelled antibody is being evaluated both as an imaging agent and as an immunotherapeutic in prostate cancer. Use of the PSM promoter has been advocated for gene therapy applications to drive prostate-specific gene expression. Although PSM is expressed in normal prostate as well as in primary and secondary prostatic carcinoma, different splice variants in malignant tissue afford the prospect of developing reverse transcription-polymerase chain reaction (RT-PCR)-based diagnostic screens for the presence of prostatic carcinoma cells in the circulation. We have undertaken characterisation of the gene for PSM in view of the protein's interesting characteristics. Unexpectedly, we have found that there are other sequences apparently related to PSM in the human genome and that PSM genomic clones map to two separate and distinct loci on human chromosome 11. Investigation of the function of putative PSM-related genes will be necessary to enable us to define fully the role of PSM itself in the development of prostatic carcinoma and in the clinical management of this malignancy.

Antigens, Neoplasm↗
PubMed1994

The average daily energy expenditure of elderly males and females.

The aim of this study was to report on the average daily energy expenditure by elderly males and females in their normal day-to-day activities. The study was based on an analysis of data collected over six months from daily diary recording of activities. The subjects, 82 males and 93 females, were non-institutionalized volunteers with a mean age of 68 years. A multivariate analysis of variance indicated that there were no differences between males and females in total mean daily energy expended on Sporting activities. Females expended twice as much energy as males on Household Chores (F = 36.3,p < 0.001). Males expended over three times as much energy as females on gardening (F = 56.7, p < 0.001) and over seven times as much on Maintenance (F = 53.6, p < 0.001). There were also differences between males and females on energy expended while Walking (F = 6.1, p < 0.02) and on Miscellaneous activities (F = 6.3, p<0.05). It is concluded that sex stereotypical roles for activities required at younger ages are continued into old age. The implications of these findings for prescribing regular exercise in the elderly are discussed, indicating specific activities that might prove to be beneficial.

Aged↗