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Biomedical subjects

M Hall

Publications and source records attributed to M Hall.

At least 73 records · Page 4Linked to original sources
PubMed1998

Retinoid signaling distinguishes a subpopulation of olfactory receptor neurons in the developing and adult mouse.

We asked whether retinoic acid (RA) influences olfactory receptor neurons (ORNs) in the developing and mature mouse olfactory epithelium (oe). The distribution of retinoid receptors and binding proteins in the oe changes between embryonic days 11.5 and 13.5, the period when ORNs first differentiate and send axons into the nascent olfactory nerve. Coincident with this change, RA, which is produced in the frontonasal mesenchyme at these ages, begins to activate gene expression in a bilaterally symmetric subset of ORNs in the dorsolateral oe, as judged by the expression of an RA-responsive transgene. Axons from these RA-activated ORNs are segregated in the olfactory nerve as it extends through the frontonasal mesenchyme toward the forebrain. In vitro, RA potentiates ORN neurite growth on laminin, which, in the embryo, is found in a stripe of frontonasal mesenchyme directly associated with the olfactory nerve. RA does not modify growth on fibronectin, type IV collagen, or L1, which olfactory axons encounter in different regions of the territory between the olfactory epithelium and the brain. The pattern of RA-mediated transcriptional activation and axon segregation persists in early postnatal mice, and RA signaling can be recognized in a subset of adult ORNs in the dorsolateral oe. Thus, RA-mediated gene expression distinguishes a subpopulation of ORNs in a distinct region of the oe during the early development of the olfactory pathway, and may influence differentiation and axonal projections of ORNs in this region throughout life.

Animals↗
PubMed1998

A new family of cytokinin receptors from Cereales.

The highly specific recognition of a natural cytokinin, trans-zeatin, by cytokinin-binding protein (CBP) of 67 kDa from barley leaves was detected with an assay developed on the basis of cytokinin competition in ELISA with anti-idiotype antibodies (raised against antibodies to zeatin) for complex formation with CBP. Monoclonal antibodies (mAbs) raised against 70 kDa CBP from etiolated maize seedlings cross-reacted with barley 67 kDa CBP and prevented barley CBP and trans-zeatin induced activation of transcription elongation directed by RNA polymerase I associated with barley chromatin. One mAb (Z-6) had an agonistic effect. Maize CBP replaced barley CBP in activation of RNA synthesis with cytokinin in the barley transcription system. Hence, a new family of cytokinin receptors with common functions and immunodeterminants including maize and barley CBPs was found.

Antibodies, Anti-Idiotypic↗
PubMed1998

The role of interval underestimation in hyperactive children's failure to suppress responses over time.

The relationship between response inhibition and time estimation abilities was investigated in a group of hyperactive and non-hyperactive children. Children performed a discrete trials intertemporal response task under two conditions. Under both conditions children had to respond within a 2 s window, which was delayed for a set period (either 5 or 15 s). In condition one (signalled condition), these response requirements were signalled by changes in the expression of a face drawn on a computer screen. In condition two (unsignalled condition), always presented on the trial following the signalled condition, these changes in expression were obscured by a hand drawn over the mouth of the face so that effective performance depended on the childs ability to estimate the point at which the facial expression changed on the preceding trial. Both groups of children had little difficulty inhibiting responses when the response requirements were signalled. All children made far more errors under the unsignalled condition. Hyperactive children displayed a systematic tendency to respond before the response window occurred. Taken together, these data give no support to the idea that hyperactivity is essentially a problem of disinhibition and raise interesting questions about the role of time mis-estimation in the disorder.

Attention↗
PubMed1998

Low-velocity gunshot wounds of the proximal phalanx: treatment by early stable fixation.

Twenty-eight proximal phalangeal fractures secondary to low-velocity gunshot wounds in 27 patients treated by stable fixation were retrospectively reviewed. Definitive fixation was performed within 1 week of injury. Fractures were stabilized with either a plate, intramedullary spacer, or a combination of both. When necessary, supplemental fixation was achieved with cerclage wires or interfragmentary screws. Twenty fractures with bone loss or comminution were primarily supplemented with iliac crest bone graft. After surgery, the fingers were splinted in 90 degrees of metacarpophalangeal (MP) flexion. An aggressive supervised therapy program was initiated within 24 hours of surgery. The average length of follow-up care was 9 months (range, 3-29 months). Primary union was achieved in all fractures. The average range of motion was 83 degrees for the MP joint and 66 degrees for the proximal interphalangeal joint. The average total active motion (TAM) for the involved digits was 200 degrees (range, 65 degrees-250 degrees). Fractures without intra-articular extension had a significantly better average TAM (213 degrees) than did those with intra-articular extension (169 degrees; p = .05). Primary bone grafting did not adversely effect the final TAM. There were no infections. Early stable fracture fixation of these injuries achieved union, alignment, and early rehabilitation with no appreciable increase in morbidity.

Adult↗
PubMed1998

Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes.

1. The in vitro human liver metabolism of the alpha1-adrenoceptor blocker tamsulosin was investigated. When 14C-tamsulosin was incubated with human liver microsomes, it was converted to five known urinary metabolites and at least three unknown metabolites. Of the former group, the predominant metabolite was the O-deethylated metabolite (M-1), followed by the o-ethoxyphenoxy acetic acid (AM-1) and the m-hydroxylated metabolite (M-3). 2. There was a good linear relationship between AM-1 formation and testosterone 6beta-hydroxylase activity in microsomes from each of 10 individual donors. The rate of M-1 formation also correlated with the same activity, albeit the correlation curve did not pass through the origin. By contrast, the rates of M-3 and the O-demethylated metabolite (M-4) formation correlated with dextromethorphan O-demethylase activity. 3. Ketoconazole strongly inhibited AM-1 formation and reduced that of M-1 by c. 60%. Immunoinhibition studies using anti-rat antibodies supported these results. The formation of M-3 and M-4 was inhibited by quinidine and sparteine. 4. It is concluded that formation of tamsulosin metabolites, AM-1 and M-1, is catalysed by CYP3A4 whereas that of M-3 and M-4 is catalysed by CYP2D6. However, minor contributions from other CYPs cannot be excluded.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1998

Fatal multiple drug intoxication following acute sertraline use.

A 53-year-old Caucasian male victim of suicide was suspected of overdose with sertraline and alprazolam after death-scene investigation. The concentration of sertraline, a selective serotonin reuptake inhibitor, was determined by a gas chromatograph with mass selective detection. The concentration of alprazolam, a triazolobenzodiazepine, was determined by high-performance liquid chromatography. The sertraline concentration was reported at 1.0 mg/L in peripheral blood, which is greater than previously reported in other postmortem cases in which death was attributed to a multiple drug overdose. The N-desmethylsertraline concentration was reported at 0.2 mg/L in peripheral blood, which is far less than in other postmortem cases and suggests acute intoxication in this case. The alprazolam concentration was reported at 33 microg/L in heart blood, which is within the therapeutic range. The cause of death was multiple drug intoxication following acute use of sertraline, the manner of death was suicide, and the mechanism of death is an unexplained drug interaction and/or toxicity.

Alprazolam↗
PubMed1998

Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients.

BACKGROUND: Despite the use of directly observed therapy (DOT) by tuberculosis control programs, patient treatment failure, relapse, and acquired drug resistance remain problematic in a small number. We investigated serum drug levels in non-HIV-infected tuberculosis patients who were receiving DOT by the health department and did not respond to treatment as expected. METHODS: The indications for checking levels were as follows: (1) slow clinical response or failure to convert the sputum culture within 12 weeks; (2) treatment failure, early disease relapse < 13 months since being declared cured; (3) relapse, late disease reactivation > or = 13 months since being declared cured; and (4) acquired drug resistance while receiving DOT. Baseline characteristics of control subjects who responded to therapy as expected were compared. Venous blood for analysis was obtained at 2 h after directly observed ingestion and measured by high-performance liquid chromatography. RESULTS: Twenty-four patients receiving daily or twice-weekly standard therapy with isoniazid (INH, 300 or 900 mg) and rifampin (RMP, 600 mg) were identified; 22 had drug levels evaluated at 2 h. For INH, 15 of 22 patients (68%) had levels less than the reported target range. For RMP, 14 of 22 patients (64%) had low levels. Among the 14 patients receiving INH, 900 mg, and RMP, 600 mg, 4 (29%) had very low levels of both. Use of a combination INH/RMP tablet was associated with lower INH levels (p=0.04); however, RMP levels were higher (p<0.02). Alcohol use was associated with significantly higher RMP (p<0.01) serum concentrations. CONCLUSIONS: Important questions remain concerning the utility and timing of serum drug measurements. However, if a patient is not responding to therapy as expected and one is assured that the Mycobacterium tuberculosis organism is susceptible to the drugs given and that the patient is taking the medication as prescribed, drug level monitoring should be considered.

Adult↗
PubMed1998

Genetic patterning of the posterior neuropore region of curly tail mouse embryos: deficiency of Wnt5a expression.

The mouse mutant curly tail (ct) develops tail flexion defects and spina bifida as the result of delayed or failed closure of the posterior neuropore (PNP). With the aim of identifying genes involved in the chain of events resulting in defective neurulation, which can be detected at day 10.5 of development, we examined the expression patterns of a number of genes implicated in patterning of axial structures, mesoderm and neuroepithelium. The genes analyzed were Shh, HNF3alpha, HNF3beta, Brachyury, Hoxb1, Evx1, Fgf8, Wnt5a and Wnt5b. No differences could be detected between non-mutant embryos and ct/ct embryos with normal PNP size for any of these genes. Comparisons between ct/ct embryos with enlarged PNP and phenotypically normal ct/ct or nonmutant embryos showed differences only for Wnt5a. Expression of this gene was greatly reduced in the ventral caudal mesoderm and hindgut endoderm. Analysis of younger embryos revealed that prior to the stage at which embryos at risk of developing neural tube defects can be detected, the same proportion of ct/ct embryos shows reduced Wnt5a expression. The proportion of embryos showing reduced expression and almost undetectable expression of Wnt5a reflects the proportions of tail defects and spina bifida seen at later stages. We suggest that deficiency of Wnt5a signaling in the ventral caudal region tissues is an important component of the mechanism of development of the defects in affected curly tail mutant mice, and that it is causally related to decreased cell proliferation within the ventral caudal region. A possible relationship between decreased Wnt5a expression and reduced levels of heparan sulphate proteoglycan is discussed.

Animals↗
PubMed1998

Palliative terminal cancer care in community hospitals and a hospice: a comparative study.

BACKGROUND: Despite palliative care being an accepted role of community hospitals, there is little quantitative evidence of the type of care provided. AIM: To obtain quantitative data comparing palliative cancer care provided in 12 community hospitals in 10 towns (approximately 350 medical beds) and in a consultant-led purpose-built hospice (12 beds). METHOD: Retrospective medical and nursing case note analysis over one year of cancer deaths in the former Exeter Health District. RESULTS: A total of 171 community hospital and 116 hospice casenotes were analysed. Hospice patients had significantly different reasons for admission compared with community hospital patients (P < 0.001), with pain and symptom control being more frequent and terminal nursing care less frequent reasons for admission to the hospice. Community hospital length of stay was significantly longer than hospice length of stay (P = 0.002; mean community hospital stay 16 days, mean hospice stay eight days). Symptoms on admission differed significantly. Drug prescribing on admission and at death and indications of active treatment of symptoms were broadly similar. Community hospital patients received more investigations than hospice patients, linked to the observation that around one in ten community hospital patients were admitted for investigation and active treatment. Community hospital medical notes were significantly less likely to meet minimum quality standards than were hospice notes (81/171 vs. 18/116; P < 0.001), with major deficiencies in the areas of examination, progress reporting, and absence of confirmation of death. CONCLUSIONS: This study confirms the role of community hospitals in palliative terminal cancer care. Differences in care between community hospitals and a hospice have been demonstrated that may reflect either different admission populations to each setting or differences in the way care was delivered.

Hospices↗
PubMed1998

Dying from cancer in community hospitals or a hospice: closest lay carers' perceptions.

BACKGROUND: Despite there being around 400 community hospitals in the United Kingdom, there is little published research on the quality of service provided by these hospitals. AIM: To compare the quality of terminal cancer care in community hospitals with a hospice as assessed by patients' closest lay carer (relative or friend). METHOD: Structured interview (or questionnaire based on the interview proforma) with closest lay carers of all patients dying over one year in 12 community hospitals in east Devon and a purpose-built hospice in the city of Exeter. RESULTS: A total of 292 cases (176 in community hospitals and 116 in a hospice) were identified, resulting in 238 carers being eligible for interview or questionnaire survey. Overall, 106 successful interviews and 55 questionnaires were completed, giving a response rate of 67.6%. Carers gave a near unanimous vote of excellence for the total care given by the hospice, while around 40% of carers of patients in community hospitals considered that improvements were possible. Community hospitals attracted more negative comments than hospices, with criticism being directed at problems of communication, lack of nursing staff, and lack of support in bereavement. Carers of hospice patients were significantly more likely to be present at the time of death than those of community hospital patients [45/70 (64%) vs. 31/89 (35%); chi 2 = 13.6, P < 0.001], an observation possibly because nursing staff in community hospitals are less experienced at dealing with terminally ill patients and such hospitals have fewer adequate facilities. CONCLUSIONS: Lay carers indicated great satisfaction with care given in the hospice and less satisfaction with care given in the community hospitals. However, the community hospitals are non-specialist units with far lower levels of trained staff. Improvements in terms of the communication skills of doctors and nurses, specific training for nurses in palliative care, and structured bereavement care could be made without necessarily increasing staffing numbers.

Attitude to Health↗
PubMed1997

Maintenance nortriptyline effects on electroencephalographic sleep in elderly patients with recurrent major depression: double-blind, placebo- and plasma-level-controlled evaluation.

Our aim was to contrast the effects of maintenance nortriptyline and placebo on electroencephalographic sleep measures in elderly recurrent depressives who survived 1-year without recurrence of depression. Patients on nortriptyline took longer to fall asleep and did not maintain sleep better than patients on placebo; however, maintenance nortriptyline was associated with more delta-wave production and higher delta-wave density in the first non-REM (NREM) period relative to the second. Nortriptyline levels were positively but weakly related to all-night delta-wave production during maintenance (accounting for 6.6% of the variance in delta-wave counts). Total phasic REM activity increased 100% under chronic nortriptyline relative to placebo, with a robust increase in the rate of REM activity generation across the night. Effective long-term pharmacotherapy of recurrent major depression is associated with enhancement in the rate of delta-wave production in the first NREM period (i.e., delta sleep ratio) and of REM activity throughout the night.

Aged↗
PubMed1997

Pacifastin, a novel 155-kDa heterodimeric proteinase inhibitor containing a unique transferrin chain.

A 155-kDa proteinase inhibitor, pacifastin, from plasma of the freshwater crayfish, Pacifastacus leniusculus, was found to be composed of two covalently linked subunits. The two subunits are encoded by two different mRNAs, which were cloned and sequenced. The heavy chain of pacifastin (105 kDa) is related to transferrins, containing three transferrin lobes, two of which seem to be active for iron binding. The light chain of pacifastin (44 kDa) is the inhibitory subunit, and has nine cysteine-rich inhibitory domains that are homologous to each other and to low molecular weight proteinase inhibitors isolated from the grasshopper, Locusta migratoria. The nine light chain domains and the Locusta inhibitors share a characteristic cysteine array (Cys-Xaa9-12-Cys-Xaa2-Cys-Xaa-Cys-Xaa6-8-Cys-Xaa4++ +-Cys) distinct from any described proteinase inhibitor family, suggesting that they constitute a new family of proteinase inhibitors. Pacifastin is the first known protein that has combined properties of a transferrin-like molecule and a proteinase inhibitor.

Amino Acid Sequence↗
PubMed1997

Corticosteroids inhibit lymphocyte binding to endothelium and intercellular adhesion: an additional mechanism for their anti-inflammatory and immunosuppressive effect.

Glucocorticosteroids (GCS) are potent anti-inflammatory and immunosuppressive agents widely used in the treatment of many medical conditions, but their mechanism of action is not yet fully understood. Some of the anti-inflammatory effects of GCS have been attributed to the synthesis of lipocortins, whereas the immunosuppressive effects are thought to be mediated through the inhibition of several immune functions through a down-regulation of cytokine gene expression. Another important mechanism of action of GCS may relate to their ability to interfere with the phenomena of adhesion and migration of inflammatory cells. In this study, the direct effects of GCS on lymphocyte adhesion capacity in vitro were investigated. We demonstrate that GCS inhibit lymphocyte adhesion to endothelium through the down-modulation of lymphocyte adhesion molecules. We also provide evidence that GCS inhibit cell aggregate formation induced by TCR ligation, which directly correlates with the down-modulation of LFA-1 and CD2, but not LFA-3 or ICAM-1. Such down-modulation was paralleled by a decrease in the steady state mRNA level of LFA-1 and CD2 gene products, which suggests a direct GCS control of the expression of these genes. Finally, we show that GCS effects are mediated through the GCS receptor, since they can be completely reversed by the GCS-R antagonist RU-486. This study supports the concept that some of the immunosuppressive and anti-inflammatory effects of GCS are likely to be exerted by the inhibition of adhesion-dependent lymphocyte functions.

Adrenal Cortex Hormones↗
PubMed1997

Sleep in the wake of complicated grief symptoms: an exploratory study.

Our aim was to explore the concept that the symptoms of complicated grief may be a form of posttraumatic distress, rather than depression, and thus may have different effects on sleep. Sixty-five recently bereaved elders with varying levels of symptoms of complicated grief and depression were stratified by high versus low levels of symptoms; a two-way analysis of variance examined main effects of level of complicated grief symptoms and depressive symptoms on selected sleep measures, as well as interactions. Complicated grief symptoms were independently associated with mild subjective sleep impairment but showed no main effects on electroencephalographic (EEG) sleep measures. In a multiple regression analysis, complicated grief symptoms interacted with depressive symptoms to increase REM sleep percent. Thus, it appears that complicated grief symptoms do not entail the changes of EEG sleep physiology seen in depression, with the possible exception of an interaction with coexisting depression to enhance REM sleep percent.

Aged↗
PubMed1997

Cdk2-dependent phosphorylation of Id2 modulates activity of E2A-related transcription factors.

The helix-loop-helix (HLH) protein Id2 is thought to affect the balance between cell growth and differentiation by negatively regulating the function of basic-helix-loop-helix (bHLH) transcription factors. Id2 acts by forming heterodimers that are unable to bind to specific (E-box) DNA sequences. Here we show that this activity can be overcome by phosphorylation of a serine residue within a consensus target site for cyclin-dependent kinases (Cdks). In vitro, Id2 can be phosphorylated by either cyclin E-Cdk2 or cyclin A-Cdk2 but not by cyclin D-dependent kinases. Analogous phosphorylation occurs in serum-stimulated human diploid fibroblasts at a time in late G1 consistent with the appearance of active cyclin E-Cdk2. The phosphorylation of Id2 in these cells correlates with the restoration of a distinct E-box-dependent DNA-binding complex, suggesting that the levels of this complex are modulated by both the abundance and phosphorylation status of Id2. These data provide a link between cyclin-dependent kinases and bHLH transcription factors that may be critical for the regulation of cell proliferation and differentiation.

3T3 Cells↗