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Biomedical subjects

J Cross

Publications and source records attributed to J Cross.

At least 19 recordsLinked to original sources
PubMed2000

Acute systemic inflammation impairs endothelium-dependent dilatation in humans.

BACKGROUND: We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation. METHODS AND RESULTS: Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal. CONCLUSIONS: S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.

Acetylcholine↗
PubMed2000

The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin.

The AF-6 protein is a multidomain protein that contains two potential Ras-binding domains within its N terminus. Because of this feature, AF-6 has been isolated in both two-hybrid and biochemical approaches and is postulated to be a potential Ras-effector protein. Herein, we show that it is specifically the first Ras-binding domain of AF-6 that mediates this interaction and that the Ras-related Rap1A protein can associate with this motif even more efficiently than the oncogenic Ha-, K-, and N-Ras GTPases. We further demonstrate that both Ras and Rap1 interact with full-length AF-6 in vivo in mammalian cells and that a fraction of Rap1 colocalizes with AF-6 at the membrane. Dominant active Rap1A, in contrast to Ras, when introduced into epithelial MDCK and MCF-7 cells, does not perturb AF-6-specific residency in cell-cell adhesion complexes. In a pursuit to gain further understanding of the role of AF-6 in junctions, we identified profilin as an AF-6-binding protein. Profilin activates monomeric actin units for subsequent polymerization steps at barbed ends of actin filaments and has been shown to participate in cortical actin assembly. To our knowledge, AF-6 is the only integral component in cell-cell junctions discovered thus far that interacts with profilin and thus could modulate actin modeling proximal to adhesion complexes.

Actins↗
PubMed2000

Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia.

Pre-eclampsia, a common complication of first pregnancies, is thought to result from a poorly perfused placenta and may reflect an abnormal maternal immune reaction to the hemiallogenic fetus. Human leukocyte antigen (HLA)-G, a major histocompatibility tissue-specific antigen expressed in extravillous trophoblast cells (fetal-derived), may protect trophoblasts from maternal-fetal immune intolerance and allow these cells to invade the uterus. Through RNA in-situ hybridization analysis, we studied the expression pattern of HLA-G in normal placentae and placentae from pregnancies complicated by severe pre-eclampsia. In normal placenta we found HLA-G expression in the anchoring extravillous trophoblasts with an increasing gradient of expression in the more invasive cells. However, in nine out of 10 pre-eclamptic placentae HLA-G expression was absent or reduced. We conclude that HLA-G is normally expressed in invasive trophoblasts and HLA-G expression is defective in most pre-eclamptic placentae. We propose that trophoblasts lacking HLA-G are vulnerable to attack by the maternal immune system. These defective trophoblasts will be unable to invade the maternal spiral arteries effectively, thereby developing vessels which cannot adequately nourish the developing placenta. This poorly perfused placenta may initiate the systemic cascade of events associated with pre-eclampsia.

Female↗
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↗
PubMed1994

Latex allergy in hospital employees.

To investigate the incidence of latex IgE-mediated hypersensitivity, 224 hospital employees were interviewed and prick skin tests were performed to six common aeroallergen extracts, one non-latex "synthetic" glove extract, and four different latex glove extracts. Of the 224 subjects, there were 136 nurses, 41 laboratory technicians, 13 dental staff, 11 physicians, 6 respiratory therapists, and 17 housekeeping and clerical workers. All 224 subjects tested negative for the nonlatex glove (Tactylon) extract but 38 (17%) tested positive for latex extracts. The incidence ranged from 0% in housekeeping staff to 38% in dental staff. Eighty-four percent of the latex skin test-positive employees complained of itching and 68% of rash upon exposure to latex, whereas the latex skin test-negative employees reported these symptoms in 29% and 17%, respectively. Urticaria was a symptom in 55% of the latex skin test-positive and 0.5% of the skin test negative-subjects. Anaphylaxis occurred in 10.5% of the skin test-positive and in none of the skin test-negative employees. Symptoms of sneezing (34% vs 7%), nasal congestion (39% vs 7%), and lacrimation and ocular itching (45% vs 6%) were also significantly different between the latex skin test-positive and latex skin test-negative subjects. We conclude that the incidence of latex IgE-mediated allergy in hospital employees is 17%. The symptoms of anaphylaxis and hives when using latex gloves are sensitive predictors of IgE-mediated latex allergy.

Female↗