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Biomedical subjects

E A Jones

Publications and source records attributed to E A Jones.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prevalence of appendectomy among ulcerative colitis patients and their relatives.

BACKGROUND: It has been suggested that appendectomy may protect against ulcerative colitis (UC). However, the incidences of appendectomy and UC in developed countries have diverged over the last 50 years, possibly as a consequence of environmental factors. AIM: To determine whether the incidence of appendectomy is lower in patients with UC than in the general population. METHODS: Patients with UC (153), their relatives (116) and members of the general population (306) that had been matched for age, sex and educational status were studied. RESULTS: Six per cent of UC patients had undergone appendectomy. The corresponding figure for non-family controls was 20% (P < 0.0001; OR = 0.27; 95% CI = 0.15-0.45). The rate of appendectomy within families (cases plus siblings) was 17/269 (6.3%) and was similar to that for UC patients alone(P < 0.001). CONCLUSIONS: A negative association between appendectomy and UC exists in our patients with UC. In addition, the appendectomy rate in families of UC patients was lower than that in the general population, possibly implying that common environmental and genetic factors could play an important role in the divergent incidences of appendicitis and UC over the last 50 years.

Adolescent↗
PubMed2001

Liver transplantation for intractable pruritus is contraindicated before an adequate trial of opiate antagonist therapy.

A woman with stage III (pre-cirrhotic) primary biliary cirrhosis was referred for liver transplantation because of intractable pruritus. Oral administration of 50 mg naltrexone precipitated a severe opioid withdrawal-like reaction. Subsequently, when oral naltrexone therapy was reintroduced following a cautious infusion of naloxone, no reaction occurred and the pruritus resolved completely. Liver transplantation should not be considered for apparently intractable pruritus of cholestasis before an adequate trial of opiate antagonist therapy.

Contraindications↗
PubMed2000

Identification of a novel gp130-responsive site in the vasoactive intestinal peptide cytokine response element.

The neuropoietic cytokine ciliary neurotrophic factor (CNTF) potently induces transcription of the vasoactive intestinal peptide (VIP) gene through a 180-base pair (bp) cytokine response element (CyRE) in the VIP promoter. We have previously shown that CNTF induction of STAT and AP-1 protein binding within the CyRE is necessary to mediate CNTF induction of VIP gene transcription. We now show that a third, previously uncharacterized site at the 3'-end of the CyRE is also critical to CNTF induction of CyRE transcription. A 4-bp mutation in this 3'-region reduced CNTF-mediated induction of transcription approximately 80%. Whereas mutations in both the STAT and AP-1 sites substantially reduced CNTF induction of transcription, mutations in these sites together with the novel 3'-site completely abolished the ability of CNTF to induce CyRE-mediated transcription. Gel shift analysis indicated that a complex in neuroblastoma cells bound specifically to this 3'-site. This complex was not altered by CNTF treatment. Mutations in an 8-bp sequence (TTACTGGA) eliminated binding of this protein complex and markedly reduced transcriptional activation of the CyRE by CNTF. Thus, we have identified a protein complex binding to a novel DNA sequence that is necessary for full CNTF induction of VIP gene transcription.

Base Sequence↗
PubMed2000

Modulation of apoptotic and inflammatory genes by bioflavonoids and angiotensin II inhibition in ureteral obstruction.

OBJECTIVES: Ureteral obstruction results in an injury response that can progress to irreversible renal fibrosis and tubular atrophy by apoptosis. The molecular events leading to apoptosis from obstruction are not well understood. We investigated the effect of bioflavonoids and angiotensin II inhibition on apoptotic and inflammatory gene expression in a model of unilateral ureteral obstruction (UUO). METHODS: Complete UUO was produced in rats by ureteral ligation. The rats were treated with dimethyl sulfoxide (control), enalapril, losartan, curcumin, or quercetin. The animals were killed on day 7 and both obstructed and contralateral unobstructed kidneys were harvested. Expression of the inflammatory chemokine monocyte chemotactic protein-1, apoptosis effector genes Fas and Fas ligand, and oxidative stress gene HO-1 was evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: Ureteral obstruction was associated with a 6.3-fold increase in monocyte chemotactic protein-1 expression compared with sham-operated rats (P = 0.01). Monocyte chemotactic protein-1 expression was severely attenuated in all other treatment groups (P <0.05). Similarly, Fas and Fas ligand expression were increased in control UUO kidneys compared with sham-operated ones (P <0.05). Fas gene expression was significantly inhibited by quercetin but not enalapril, losartan, or curcumin compared with the control. The induction of Fas ligand was attenuated in all treatment groups (P <0.05). HO-1 was expressed at low levels in both unobstructed and obstructed kidneys. Treatment with curcumin increased HO-1 expression fourfold (P <0.05). CONCLUSIONS: The expression of apoptotic and chemokine genes is significantly upregulated in UUO. Bioflavonoids and angiotensin inhibitors are able to attenuate the expression of these genes and thus may be beneficial in renal protection.

Angiotensin II↗
PubMed2000

Xbra3 induces mesoderm and neural tissue in Xenopus laevis.

Homologues of the murine Brachyury gene have been shown to be involved in mesoderm formation in several vertebrate species. In frogs, the Xenopus Brachyury homologue, Xbra, is required for normal formation of posterior mesoderm. We report the characterisation of a second Brachyury homologue from Xenopus, Xbra3, which has levels of identity with mouse Brachyury similar to those of Xbra. Xbra3 encodes a nuclear protein expressed in mesoderm in a temporal and spatial manner distinct from that observed for Xbra. Xbra3 expression is induced by mesoderm-inducing factors and overexpression of Xbra3 can induce mesoderm formation in animal caps. In contrast to Xbra, Xbra3 is also able to cause the formation of neural tissue in animal caps. Xbra3 overexpression induces both geminin and Xngnr-1, suggesting that Xbra3 can play a role in the earliest stages of neural induction. Xbra3 induces posterior nervous tissue by an FGF-dependent pathway; a complete switch to anterior neural tissue can be effected by the inhibition of FGF signalling. Neither noggin, chordin, follistatin, nor Xnr3 is induced by Xbra3 to an extent different from their induction by Xbra nor is BMP4 expression differentially affected.

Amino Acid Sequence↗
PubMed2000

Visual event-related potentials in cirrhotic patients without overt encephalopathy.

UNLABELLED: Ambulant patients with cirrhosis and no clinical evidence of encephalopathy were screened for impaired brain function by neuroelectrophysiological testing dependent on cognitive function. Infrequent large checkerboard visual stimuli were randomly interleaved with frequent small ones to elicit P300 event-related potentials (ERPs). Three ERP components, N200, P3a and P3b, were derived from the electroencephalogram (EEG) by computer averaging. The use of 10% contrast and a minimum of four precisely placed scalp electrodes were found to be necessary for optimal separation of ERPs from sensory evoked potentials. Visual ERPs, onset/offset and pattern-reversal visual evoked potentials (VEPs), the spontaneous EEG and the time taken to complete a standard number connection test (NCT) were obtained from 20 normal adult subjects and 19 age-matched patients with histologically-confirmed cirrhosis and no clinical evidence encephalopathy. The latencies and amplitudes of evoked potentials and the alpha rhythm of the EEG were determined. In 6 of the 19 patients the latencies of P3a and/or P3b exceeded the corresponding mean for controls + 2 standard deviations of that mean. In 4 other patients the NCT was prolonged. In all of the patients the N200, VEPs and alpha rhythm of the EEG were normal. IN CONCLUSION: (i) Optimal isolation of ERPs is critically dependent on stimulus contrast and electrode placement; (ii) ERPs appear to be more sensitive than primary sensory evoked potentials or the EEG in detecting impaired brain neuroelectrophysiological function; and (iii) Cirrhotic patients without overt encephalopathy in whom P3a and/or P3b latencies are prolonged may have subclinical hepatic encephalopathy.

Adult↗
PubMed2000

Florid opioid withdrawal-like reaction precipitated by naltrexone in a patient with chronic cholestasis.

Findings consistent with the hypothesis that increased central opioidergic tone contributes to the pruritus of cholestasis provide a rationale for treating this form of pruritus with opiate antagonists. However, initiation of therapy with an opiate antagonist in a cholestatic patient may precipitate a transient opioid withdrawal-like reaction. A woman with chronic cholestasis and disabling pruritus experienced severe transient opioid withdrawal-like reactions after oral administration of 12.5 and 2 mg naltrexone. Subsequently, naloxone was administered by intravenous infusion. Initially, the infusion rate was low and subtherapeutic. It was gradually increased to a rate known to be effective in inducing opioid antagonism. Oral naltrexone was then reintroduced without any reaction occurring. During the ensuing 12 months, while taking naltrexone, 25 mg daily, the patient has been completely free from pruritus. These observations strongly support the hypothesis that increased central opioidergic tone is a component of the pathophysiology of cholestasis.

Administration, Oral↗
PubMed2000

Pathogenesis of hepatic encephalopathy.

Hepatic encephalopathy is considered to be a reversible metabolic encephalopathy, which occurs as a complication of hepatocellular failure and is associated with increased portal-systemic shunting of gut-derived nitrogenous compounds. Its manifestations are most consistent with a global depression of CNS function, which could arise as a consequence of a net increase in inhibitory neurotransmission, due to an imbalance between the functional status of inhibitory (e.g., GABA) and excitatory (e.g., glutamate) neurotransmitter systems. In liver failure, factors that contribute to increased GABAergic tone include increased synaptic levels of GABA and increased brain levels of natural central benzodiazepine (BZ) receptor agonists. Ammonia, present in modestly elevated levels, may also augment GABAergic tone by direct interaction with the GABAA receptor, synergistic interactions with natural central BZ receptor agonists, and stimulation of astrocytic synthesis and release of neurosteroid agonists of the GABAA receptor. Thus, there is a rationale for therapies of HE that lower ammonia levels and incrementally reduce increased GABAergic tone towards the physiologic norm.

Ammonia↗
PubMed2000

Pruritus and fatigue in primary biliary cirrhosis.

Pruritus is experienced by about 80% of patients with primary biliary cirrhosis. It can have a marked negative impact on the quality of life of patients, and it can be an indication for liver transplantation. There is evidence to suggest that the pruritus of cholestasis is mediated, at least in part, by endogenous opioids. A central component has been proposed. Behavioural data have shed light on the pathogenesis of this form of pruritus. Fatigue affects the majority of patients with primary biliary cirrhosis. It interferes with work performance and family life. An idea is emerging that suggests that fatigue in primary biliary cirrhosis also may be mediated centrally. Research tools need to be developed to study fatigue objectively in patients with primary biliary cirrhosis.

Fatigue↗
PubMed2000

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals.

AIMS: To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. METHODS: The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. RESULTS: Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. CONCLUSIONS: The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.

Biopsy, Needle↗
PubMed2000

JAGGED1 expression in human embryos: correlation with the Alagille syndrome phenotype.

Alagille syndrome (AGS, MIM 118450) is an autosomal dominant disorder with a variable phenotype characterised by hepatic, eye, cardiac, and skeletal malformations and a characteristic facial appearance. Mutations within the gene JAGGED1 (JAG1), which encodes a ligand for NOTCH receptor(s), has been shown to cause Alagille syndrome. Interactions of NOTCH receptors and their ligands influence cell fate decisions in several developmental pathways. We report the tissue expression of JAG1 in human embryos. We have performed tissue in situ hybridisation on human embryos aged 32-52 days using (35)S labelled riboprobes for JAG1. JAG1 is expressed in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas, mesocardium, around the major bronchial branches, and in the neural tube. We conclude that JAG1 is expressed in the structures affected in Alagille syndrome, such as the pulmonary artery, anterior chamber of the eye, and face.

Alagille Syndrome↗
PubMed2000

Abnormal signal intensity in skeletal muscle at MR imaging: patterns, pearls, and pitfalls.

Abnormal signal intensity within skeletal muscle is frequently encountered at magnetic resonance (MR) imaging. Potential causes are diverse, including traumatic, infectious, autoimmune, inflammatory, neoplastic, neurologic, and iatrogenic conditions. Alterations in muscle signal intensity seen in pathologic conditions usually fall into one of three recognizable patterns: muscle edema, fatty infiltration, and mass lesion. Muscle edema may be seen in polymyositis and dermatomyositis, mild injuries, infectious myositis, radiation therapy, subacute denervation, compartment syndrome, early myositis ossificans, rhabdomyolysis, and sickle cell crisis. Fatty infiltration may be seen in chronic denervation, in chronic disuse, as a late finding after a severe muscle injury or chronic tendon tear, and in corticosteroid use. The mass lesion pattern may be seen in neoplasms, intramuscular abscess, myonecrosis, traumatic injury, myositis ossificans, muscular sarcoidosis, and parasitic infection. Some of these conditions require prompt medical or surgical management, whereas others do not benefit from medical intervention. The ability to accurately diagnose these conditions is therefore necessary, and biopsy may be required to establish the correct diagnosis. Clues to the correct diagnosis and whether biopsy is necessary or appropriate are often present on the MR images, especially when they are correlated with clinical features and the findings from other imaging modalities.

Adolescent↗
PubMed2000

Neuropathic osteoarthropathy: diagnostic dilemmas and differential diagnosis.

The purpose of this pictorial essay is to illustrate the radiologic spectrum of imaging findings of neuropathic osteoarthropathy. Typical findings include joint destruction, disorganization, and effusion with osseous debris. A variety of other imaging findings related to neuropathic osteoarthropathy such as resorption of the ends of tubular bones and neuropathic fracture are shown. The two prevailing theories for the pathophysiology of neuropathic bone and joint disease, the neurovascular and neurotraumatic theories, are briefly described. Examples of osteoarthropathy from diverse causes are presented including syringomyelia, spinal cord injury, meningomyelocele, diabetes mellitus, congenital insensitivity to pain, steroid injections, syphilis, leprosy, and others. The discussion focuses on key imaging features with emphasis on disease patterns and differential diagnosis, which vary by skeletal location.

Adolescent↗
PubMed2000

Evolving concepts of the pathogenesis and treatment of the pruritus of cholestasis.

The site of the pathogenic events responsible for initiating the pruritus of cholestasis has been assumed to be the skin. This assumption cannot be excluded but is not supported by convincing data. Empirical therapies such as anion exchange resins and rifampicin often appear to be partially efficacious. Recent evidence suggests that altered neurotransmission in the brain may contribute to this form of pruritus. In particular, the hypothesis that increased central opioidergic tone is involved is supported by three observations: opiate agonists induce opioid receptor-mediated scratching activity of central origin, central opioidergic tone is increased in cholestasis and opiate antagonists reduce scratching activity in cholestatic patients. Apparent subjective ameliorations of pruritus following intravenous administration of ondansetron to cholestatic patients suggest that altered serotoninergic neurotransmission may also contribute to this form of pruritus.

Brain↗
PubMed2000

The effect of mycophenolate mofetil and polyphenolic bioflavonoids on renal ischemia reperfusion injury and repair.

PURPOSE: Chronic renal allograft nephropathy is associated with both immune and ischemic injury which may act synergistically to promote an inflammatory response. The immunosuppressant mycophenolic acid and the polyphenolic agents curcumin and quercetin possess properties that might ameliorate such injury. We studied the effects of these agents in models of ischemic renal injury and skin allograft rejection. MATERIALS AND METHODS: Ischemic acute tubular necrosis was produced in rats by renal pedicle occlusion with contralateral nephrectomy. Animals were treated with mycophenolic acid, quercetin and curcumin, or a combination of agents. Animals were killed on days 2 and 7 after operation and tissue samples were collected. Renal tubular apoptosis and cellular proliferation were assessed by immunohistochemistry. Expression of the cytokines RANTES and AIF were evaluated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Treatment with the polyphenolic compounds alone or in combination with mycophenolic acid was associated with less tubular damage, attenuation of renal inflammation, and prolongation of skin graft survival. A combination of agents decreased serum creatinine on day 2 from 4.5 to 0.9 mg./dl. (p< or =0.01) and at day 7 from 3.8 to 0.6 mg./dl. (p< or =0.01). Treatment with the polyphenolic compounds inhibited apoptosis at day 2. By RT-PCR, RANTES and AIF were detected at high levels on days 2 and 7. Treatment with these agents alone or in combination strongly attenuated this increased expression. CONCLUSIONS: The combination of mycophenolic acid with curcumin and quercetin reduces renal injury and facilitates repair. These agents may have a role in therapeutic regimens that are both immunosuppressive and renoprotective.

Animals↗