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A Dean

Publications and source records attributed to A Dean.

At least 19 recordsLinked to original sources
PubMed2004

Compact sources as the origin of the soft gamma-ray emission of the Milky Way.

The Milky Way is known to be an abundant source of gamma-ray photons, now determined to be mainly diffuse in nature and resulting from interstellar processes. In the soft gamma-ray domain, point sources are expected to dominate, but the lack of sensitive high-resolution observations did not allow for a clear estimate of the contribution from such sources. Even the best imaging experiment revealed only a few point sources, accounting for about 50% of the total Galactic flux. Theoretical studies were unable to explain the remaining intense diffuse emission. Investigating the origin of the soft gamma-rays is therefore necessary to determine the dominant particle acceleration processes and to gain insights into the physical and chemical equilibrium of the interstellar medium. Here we report observations in the soft gamma-ray domain that reveal numerous compact sources. We show that these sources account for the entirety of the Milky Way's emission in soft gamma-rays, leaving at most a minor role for diffuse processes.

Journal Article↗
PubMed2002

Differential expression and induction of two Drosophila cytochrome P450 genes near the Rst(2)DDT locus.

Previous studies have shown that the major metabolic resistance locus in the insecticide-resistant Drosophila line Rst(2)DDT(Wisconsin) maps between the markers cn and vg on chromosome 2. Six cytochrome P450 genes exist in this region. We investigated the expression levels of these P450 genes in DDT-resistant and -susceptible fly lines. We report: (i) DDT resistance is significant (> 30-fold) and dominant, (ii) resistance is reduced by the cytochrome P450 inhibitor PBO, (iii) there is constitutive over-expression relative to susceptible flies of two genes encoding cytochrome P450 enzymes within the cn-vg region (CYP6G1 = 4.3-fold; CYP12D1 = 6.0-fold), and (iv) exposure to DDT results in an increased expression of only one of these two P450 genes (CYP12D1 > or = 6-fold above constitutive resistant fly baselines).

Animals↗
PubMed2001

Extracorporeal photopheresis in Sézary syndrome: hematologic parameters as predictors of response.

Data were analyzed from 23 patients with Sézary syndrome (defined by erythroderma, more than 10% circulating atypical mononuclear cells, and peripheral blood T-cell clone) undergoing monthly extracorporeal photopheresis as the sole therapy for up to 1 year. The cohort showed a significant reduction of skin scores during treatment (P =.001). Thirteen patients (57%) achieved a reduction in skin score greater than 25% from baseline at 3, 6, 9, or 12 months (responders). Reduction in skin score correlated with reduction in the Sézary cell count as a percentage of total white cell count (P =.03). Responders and nonresponders were compared. None of the measured parameters was significantly different between the 2 groups. It was assessed whether any of the baseline parameters predicted outcome. A higher baseline lymphocyte count was significantly associated with a decrease in skin score at 6 months (P <.05). A higher baseline Sézary cell count as a percentage of total white cell count predicted a subject was more likely to be a responder after 6 months of treatment (P =.021). No other parameters predicted responder status. These data show that the modest falls in CD4, CD8, and Sézary cell counts were seen in all patients and might have resulted from lymphocyte apoptosis. This mechanism could explain the more favorable response seen in patients with higher percentages of Sézary cells in the peripheral blood. Alternatively, minimum tumor burden might be required for the induction of a cytotoxic response. Analysis of tumor-specific cytotoxic T cells is needed to investigate these possibilities further.

Adult↗
PubMed2001

Prognostic significance of tumor burden in the blood of patients with erythrodermic primary cutaneous T-cell lymphoma.

Erythrodermic cutaneous T-cell lymphoma (CTCL) includes patients with erythrodermic mycosis fungoides who may or may not exhibit blood involvement and Sézary syndrome and in whom hematological involvement is, by definition, present at diagnosis. These patients were stratified into 5 hematologic stages (H0-H4) by measuring blood tumor burden, and these data were correlated with survival. The study identified 57 patients: 3 had no evidence of hematologic involvement (H0), 8 had a peripheral blood T-cell clone detected by polymerase chain reaction (PCR) analysis of the T-cell receptor gene and less than 5% Sézary cells on peripheral blood smear (H1), and 14 had either a T-cell clone detected by Southern blot analysis or PCR positivity with more than 5% circulating Sézary cells (H2). Twenty-four patients had absolute Sézary counts of more than 1 x 10(9) cells per liter (H3), and 8 patients had counts in excess of 10 x 10(9) cells per liter (H4). The disease-specific death rate was higher with increasing hematologic stage, after correcting for age at diagnosis. A univariate analysis of 30 patients with defined lymph node stage found hematologic stage (P =.045) and lymph node stage (P =.013) but not age (P =.136) to be poor prognostic indicators of survival. Multivariate analysis identified only lymph node stage to be prognostically important, although likelihood ratio tests indicated that hematologic stage provides additional information (P =.035). Increasing tumor burden in blood and lymph nodes of patients with erythrodermic CTCL was associated with a worse prognosis. The data imply that a hematologic staging system could complement existing tumor-node-metastasis staging criteria in erythrodermic CTCL.

Adult↗
PubMed2001

The buccal fat pad flap in oral reconstruction.

BACKGROUND: The aim of this study is to describe the surgical technique, indications, advantages, and possible complications of the buccal fat pad flap and to report our clinical experience with this flap for intraoral reconstruction after tumor removal. METHODS: The flap has been used to reconstruct oral defects after tumor resection in 32 patients, who have been retrospectively analyzed. RESULTS: Adequate closure of the defect was achieved during surgery in all cases. In one case, there was partial loss of the flap; this was treated conservatively. In five cases there was some retraction in the reconstructed area. CONCLUSIONS: Buccal fat pad as a flap offers an adequate reconstructive option to be born in mind when reconstructing small to medium defects in the oral cavity. It is a simple and quick surgical technique with a low incidence of complications.

Adipocytes↗
PubMed2001

Phenotypic and neuropathologic heterogeneity of anti-Hu antibody-related paraneoplastic syndrome presenting with progressive dysautonomia: report of two cases.

The anti-Hu antibody (HuAb) is directed against RNA-associated neuronal proteins and is known to cause paraneoplastic encephalomyelitis/sensory neuronopathy syndrome mostly when associated with small cell lung cancer (SCLC). Paraneoplastic encephalomyelitis/sensory neuronopathy syndrome with concurrent autonomic neuropathy has been reported to occur in paraneoplastic syndromes, although its occurrence concomitant with acute pandysautonomia is less frequent. The authors describe the clinical, neuropathologic, and serologic features of two cases with an anti-Hu-related paraneoplastic syndrome presenting with progressive autonomic neuropathy. Both patients showed features of dysautonomia, including postural dizziness, abdominal pain, and diarrhea, and symptoms of sensory neuropathy. Investigations disclosed severe sensory and autonomic neuropathy and positive HuAb titers. The disease of patient 1 had a very rapid progression, and the patient died of cardiac arrest within 2 months of the onset of symptoms. The autopsy revealed SCLC. In contrast, the disease of patient 2 had a less aggressive course. An extensive tumor search disclosed SCLC only 28 months after onset of symptoms, and the patient died 1 month later of cardiorespiratory arrest. Autopsies in both cases showed inflammation involving the intermediolateral columns and the dorsal root ganglia. These two cases illustrate the association of early dysautonomia with HuAb-related paraneoplastic syndrome and the variations of clinical, neuropathologic, and serologic findings in these types of cases.

Aged↗
PubMed2001

Relevance of residual histologic and electrocorticographic abnormalities for surgical outcome in frontal lobe epilepsy.

PURPOSE: To estimate the significance of residual electrocorticographic and neuropathologic abnormalities on seizure control after surgery for frontal lobe epilepsy with the purpose of determining their relevance in deciding the extent of the surgical procedure. METHODS: The presence of epileptiform discharges in intraoperative electrocorticograms (ECoGs) and the nature and extent of neuropathologic abnormalities were reviewed for 35 patients who underwent frontal lobe resections for the treatment of epilepsy at our institution. The relations between surgical outcome and presence of the following features were studied: (a) presence of abnormal tissue at the limits of the resection; (b) presence of sporadic spikes and seizure patterns in the preresection ECoG; (c) their abolition in the postresection ECoG; and (d) the topography of residual discharges with respect to the margins of the resection. RESULTS: On neuropathologic examination, 18 patients showed focal cortical dysplasia (CD), and 17 showed other abnormalities (non-CD). Ten CD patients and 11 non-CD patients experienced a favourable outcome. Seizure patterns were significantly more common in patients with focal cortical dysplasia than in those without, with a sensitivity of 94% and a specificity of 75%. Abolition of seizure patterns was associated with a favourable surgical outcome (p = 0.031). Abolition of sporadic spikes or their presence in the postresection ECoG did not influence outcome. There was no clear relation between outcome and location of residual sporadic discharges. Seizure patterns persisted in the postresection ECoG in three CD patients, were located at the margins of the resection in all three, and these patients had a poor outcome. Incomplete removal of abnormal tissue was not associated with a poorer outcome in either patient group or in the complete sample. CONCLUSIONS: Seizure patterns were significantly more common in patients with cortical dysplasia, and their abolition on postresection ECoG recordings was associated with a favourable surgical outcome. Persistence of sporadic ECoG spikes and incomplete removal of histologic abnormalities did not affect outcome significantly.

Adolescent↗
PubMed2001

Acetylation of a specific promoter nucleosome accompanies activation of the epsilon-globin gene by beta-globin locus control region HS2.

On stably replicating episomes, transcriptional activation of the epsilon-globin promoter by the beta-globin locus control region HS2 enhancer is correlated with an increase in nuclease sensitivity which is limited to the TATA-proximal nucleosome (N1). To elucidate what underlies this increase in nuclease sensitivity and the link between chromatin modification and gene expression, we examined the nucleoprotein composition and histone acetylation status of transcriptionally active and inactive promoters. Micrococcal nuclease digestion of active promoters in nuclei released few nucleosome-like nucleoprotein complexes containing N1 sequences in comparison to results with inactive promoters. We also observed that N1 DNA fragments from active promoters are of a subnucleosomal length. Nevertheless, chromatin immunoprecipitation experiments indicate that histones H3 and H4 are present on N1 sequences from active promoters, with H3 being dramatically hyperacetylated compared with that from inactive promoters and vector sequences. Strikingly, H3 in the adjacent upstream nucleosome (N2) does not appear to be differentially acetylated in active and inactive promoters, indicating that the nucleosome modification of the promoter that accompanies transactivation by HS2 is highly directed and specific. However, global acetylation of histones in vivo by trichostatin A did not activate transcription in the absence of HS2, suggesting that HS2 contributes additional activities necessary for transactivation. N1 sequences from active promoters also contain reduced levels of linker histone H1. The detection of a protected subnucleosomal sized N1 DNA fragment and the recovery of N1 DNA sequences in immunoprecipitations using anti-acetylated H3 and H4 antibodies argue that N1 is present, but in an altered conformation, in the active promoters.

Acetylation↗
PubMed2001

In vivo regulation of Na/Ca exchanger expression by adrenergic effectors.

The Na/Ca exchanger encoded by the NCX1 gene plays an important role in calcium homeostasis in cardiac muscle. We previously identified three in vitro signaling pathways that are of major importance in the regulation of Na/Ca exchanger gene expression in neonatal cardiac myocytes, the protein kinase A (PKA) and protein kinase C (PKC) pathways, and intracellular Ca(2+). To determine whether these pathways are important in vivo, we stimulated the PKA and PKC pathways and examined functional expression of the Na/Ca exchanger in adult rat heart. After a 3- and 7-day treatment, norepinephrine (200 microg x kg(-1) x h(-1)), isoproterenol (150 microg x kg(-1) x h(-1)), and phenylephrine (200 microg x kg(-1) x h(-1)) each stimulated a significant increase in NCX1 mRNA levels (35-85%, P < 0.05). Norepinephrine also stimulated a 35% increase in protein abundance (P < 0.05), a 20% decrease in relaxation duration (P < 0.05), and a 25% reduction in the fluorescence decay constant (P < 0.05) after a 7-day treatment. We conclude that a 7-day treatment of alpha- and beta-adrenergic agonists increases the expression of functional Na/Ca exchangers in adult rat heart.

Adrenergic alpha-Agonists↗
PubMed2001

The palliative effects of octreotide in cancer patients.

Octreotide is an extremely useful compound for palliative care physicians. It appears to be active in a number of different pain states and may be given by the spinal and intraventricular route. Its actions in reducing gut motility and secretions make it a valuable adjunct in the management of inoperable bowel obstruction. The same actions make it a potent antidiarrheal agent. Octreotide will often succeed where other antidiarrheal agents fail. Its ability to reduce gut secretions has led to its use in the treatment of fistulae. It has also been proposed as a useful drug in the management of cachexia and ascites. Most of the existing evidence is based on small numbers of case reports and further larger trials are necessary.

Antidiarrheals↗
PubMed2001

Otitis externa in UK general practice: a survey using the UK General Practice Research Database.

BACKGROUND: Otitis externa is a common clinical problem in general practice and yet there are remarkably few data available on the demographic characteristics of patients with this condition and the approaches used by general practitioners (GPs) in the United Kingdom (UK) to manage it. AIM: To define the descriptive epidemiology of otitis externa in the general population, to describe the first-line drug treatment used by UK GPs, and to determine factors related to second disease episodes. DESIGN OF STUDY: Epidemiological data survey. SETTING: All cases of otitis externa occurring in 1997 in practices contributing data to the UK General Practice Research Database. METHOD: Data were extracted on age, sex, date of episode of otitis externa, treatment prescribed, co-existing diagnoses of eczema and diabetes, referral to ear, nose, and throat departments and occurrence of subsequent episodes of disease. Arbitrarily a second episode of disease was defined as persistence if it occurred at 28 days or fewer after the first episode and recurrence if it occurred at more than 28 days after the first episode. RESULTS: A diagnosis of otitis externa was common in all age groups and, except in the elderly, was more common in females than males. There was an increase in disease episodes at the end of the summer in all age groups except the 60 years and over group. In the majority of cases GPs prescribed ear drops (85%), but a significant proportion of patients were also prescribed oral antibiotics (21%). Referral to secondary care was uncommon (3%). Among patients prescribed ear-drop formulations, those containing both steroid and antibiotic or steroid alone were used most commonly and were associated with the lower rates of disease persistence but not recurrence. Among patients prescribed antibiotics, penicillins were prescribed most commonly. Disease persistence rates, and to a lesser extent disease recurrence rates, were higher in patients prescribed oral antibiotics. CONCLUSION: Otitis externa is a common condition and GPs can expect to see an excess of cases at the end of the summer. Topical ear drops are the most common treatment used in the UK. Patients prescribed steroid or steroid/antibiotic combination ear drops have fewer subsequent consultations for otitis externa over the following 28 days.

Adolescent↗
PubMed2000

Locations of the regulatory sites for isocitrate dehydrogenase kinase/phosphatase.

Isocitrate dehydrogenase (IDH)(1) of Escherichia coli is regulated by a bifunctional protein, IDH kinase/phosphatase. In this paper, we demonstrate that the effectors controlling these activities belong to two distinct classes that differ in mechanism and in the locations of their binding sites. NADPH and isocitrate are representative members of one of these effector classes. NADPH inhibits both IDH kinase and IDH phosphatase, whereas isocitrate inhibits only IDH kinase. Isocitrate can "activate" IDH phosphatase by reversing product inhibition by dephospho-IDH. Mutations in icd, which encodes IDH, had parallel effects on the binding of these ligands to the IDH active site and on their effects on IDH kinase and phosphatase, indicating that these ligands regulate IDH kinase/phosphatase through the IDH active site. Kinetic analyses suggested that isocitrate and NADPH prevent formation of the complex between IDH kinase/phosphatase and its protein substrate. AMP, 3-phosphoglycerate, and pyruvate represent a class of regulatory ligands that is distinct from that which includes isocitrate and NADPH. These ligands bind directly to IDH kinase/phosphatase, a conclusion which is supported by the observation that they inhibit the IDH-independent ATPase activity of this enzyme. These effector classes can also be distinguished by the observation that mutant derivatives of IDH kinase/phosphatase expressed from aceK3 and aceK4 exhibited dramatic changes in their responses to AMP, 3-phosphoglycerate, and pyruvate but not to NADPH and isocitrate.

Adenosine Monophosphate↗
PubMed2000

The use of Mitek pins in the mandibular lingual releasing approach to oral and/or oropharyngeal carcinomas: a technical note.

Resection of carcinoma of the oral cavity and oropharynx requires adequate exposure. The purpose of this paper is to demonstrate the approach employed (mandibular lingual releasing approach) for resection of some oral cavity or oropharyngeal carcinomas and to point out the indications, advantages, complications, and refinements of this technique. The technique was carried out on 23 patients with oral cavity or oropharyngeal squamous cell carcinomas. A lingual floor-of-mouth flap was created allowing delivery of the tongue and floor of mouth without lip splitting, mandibulotomy, or mandibulectomy. After resection of the tumour and repair of the defect, the musculature of the floor of the mouth was reattached to the lingual cortex of the mandible using Mitek minianchors. There was adequate exposure in all the patients. Wound margin dehiscence occurred in four patients resulting in an orocervical fistula in three patients. Mandibular osteotomy and subsequent osteosynthesis were avoided. Thus instability and infection of the osteotomy site were avoided. However, additional mandibular osteotomy is feasible.

Adult↗
PubMed1999

The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism.

OBJECTIVE: To investigate the effect of vigabatrin (VGB; gamma-vinyl gamma-aminobutyric acid [GABA]), a selective irreversible GABA-transaminase inhibitor, on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF) measured with 18F-fluorodeoxyglucose (FDG) PET and 15O water PET. BACKGROUND: Antiepileptic drugs (AEDs) reduce CMRGlc to varying degrees. Phenobarbital causes a mean decrease of 30 to 40%. Phenytoin, carbamazepine (CBZ), and valproate (VPA) cause milder reductions in CMRGlc. The combination of VPA with CBZ results in a greater decrease than either drug alone. The effect of novel AEDs on both CBF and CMRGlc has not been studied extensively. METHODS: Fourteen patients with refractory complex partial seizures on CBZ monotherapy for 4 weeks were included in the study. All patients had baseline 18F-FDG and 15O water PET studies followed by double-blind randomization to placebo (PLC) or VGB while on continuous CBZ treatment. PET scans were repeated after an interval of 2 months on target dose of VGB (50 mg/kg) or PLC. Quantitative PET data analysis was performed using a region of interest template. Significance was tested with the Wilcoxon rank sum test. RESULTS: No statistically significant difference in age, duration of epilepsy, or CBZ levels was observed in the two patient groups. VGB reduced global CMRGlc by 8.1+/-6.5% and global CBF by 13.1+/-10.4%. The change in CMRGlc was different in patients taking VGB compared with those on PLC (p < 0.04). VGB patients showed regional decreases in both CMRGlc and CBF, particularly in temporal lobes. CSF total GABA increased in the VGB patient group (1.48+/-1.06 versus 4.03+/-4.19 nm/mL). The increase differed from the PLC group (p < 0.03). We found a strong relation between decreased total CSF GABA and increased CMRGlc in the VGB patient group (R2 = 0.82, p < 0.01). CONCLUSIONS: Vigabatrin (VGB) causes mild reductions in both cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMRGlc) in contrast to other drugs such as barbiturates, which are direct agonists at the gamma-aminobutyric acid-benzodiazepine receptor complex. Conventional AEDs depress CBF and CMRGlc to a greater degree than does VGB. The relatively mild reduction could be due to pre- as well as postsynaptic effects or a use-dependent mechanism.

Adult↗
PubMed1999

Malignant myoepithelioma of the salivary glands: clinicopathological and immunohistochemical features.

Malignant myoepitheliomas (myoepithelial carcinomas) are uncommon, and we know of only 29 reported cases. We present a new case together with its clinical, histological, and immunohistochemical features. The tumour was located in the inferior vestibular sulcus of a 64-year-old woman. She was treated by wide local resection. Malignant myoepitheliomas are distinguished from benign myoepithelial neoplasms by their infiltrating and destructive growth. The tumour cells may be spindle-shaped or more rounded (plasmacytoid cells) and contain cellular pleomorphism and mitotic activity. The clinical and biological behaviour of this tumour is not yet known and there is little information about treatment and prognosis.

Diagnosis, Differential↗
PubMed1999

Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.

A large English family with autosomal dominant segregation of presenile dementia, ataxia and other neuropsychiatric features is described. Diagnoses of demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome have been attributed to particular individuals at different times. An Irish family, likely to be part of the same kindred, is also described, in which diagnoses of multiple sclerosis, dementia, corticobasal degeneration and new variant CJD have been considered in affected individuals. Molecular genetic studies have enabled the classification of this disease at the molecular level as one of the group of inherited prion diseases, with the substitution of valine for alanine at codon 117 of the prion protein gene (PRNP). Only three other kindreds have been described world-wide with this mutation and only limited phenotypic information has been reported. Here we describe the phenotypic spectrum of inherited prion disease (PrPA117V). The diversity of phenotypic expression seen in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopathological syndrome. Indeed, inherited prion disease should be excluded by PRNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new variant CJD.

Adult↗