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Biomedical subjects

P Middleton

Publications and source records attributed to P Middleton.

At least 55 records · Page 3Linked to original sources
PubMed1989

Asthma and chronic airflow limitation in the highlands of Papua New Guinea: low prevalence of asthma in the Asaro Valley.

The prevalence of asthma in the South Fore region of Papua New Guinea was found to be 7.3%, which is thought exceptionally high for highland areas in this country. To investigate the prevalence of asthma and of chronic airflow limitation in a different highland region with similar living conditions, adults and children from 7 villages in the Asaro Valley were interviewed. Questions were asked about smoking history and about past and present symptoms of cough, of shortness of breath, of chest tightness and of asthma. Of 743 adults interviewed, 206 underwent a clinical study with measurements of lung function, bronchial responsiveness and skin prick tests. Dust was collected from the floors and blankets of 36 houses for counts of house dust mites. We did not find any children with symptoms of asthma. Only 2 adults (0.3%) had symptoms consistent with asthma, and a further 6.2% had symptoms and/or lung function consistent with chronic airflow limitation. Most bronchial hyperresponsiveness was associated with asthma or with chronic airflow limitation. The prevalence of atopy was similar in the Asaro and South Fore populations, but the South Fore had higher house dust mite counts in blanket dust. The low prevalence of asthma in the Asaro Valley is unexplained in terms of factors normally associated with asthma. Because asthma in this area does not appear in childhood and only develops in a small proportion of adults, it may be of different aetiology to asthma in Caucasian populations.

Adult↗
PubMed1988

Neural regulation of properties of the nicotinic acetylcholine receptor.

During nerve-muscle synapse formation, acetylcholine receptors become localized and modified to allow efficient transfer of information from nerve to muscle. In this paper we summarize our studies on two aspects of receptor modulation--their concentration at synaptic sites and their ability to desensitize in response to prolonged application of agonist. We demonstrate that receptor localization is a complex event which extensively reorganizes the structure of the junctional region. This allows the subsequent influences of contraction to be exerted differently in junctional and extrajunctional regions. We indicate that increases in muscle cell Ca2+ appear to mediate some of the effects of muscle contraction and suggest how regulation of Ca2+ levels may specify junctional and extrajunctional differences. Finally, we discuss the role of receptor phosphorylation in determining the rate of desensitization.

Acetylcholine↗
PubMed1988

Desensitization of acetylcholine receptors in rat myotubes is enhanced by agents that elevate intracellular cAMP.

Incubating skeletal muscle fibers with forskolin, an activator of adenylate cyclase, increases the rate at which nicotinic acetylcholine receptors (AChRs) desensitize when exposed to ACh. Several reports indicate that this is due to the phosphorylation of AChRs by cAMP-dependent protein kinase, but other studies suggest that forskolin interacts with AChRs directly and that second-messenger systems are not required. To help clarify this issue, we studied the effects of forskolin and several other drugs on AChR function in embryonic rat myotubes. AChR function was studied by recording ACh-induced membrane depolarizations and ACh-induced single-channel currents. Our results indicate that forskolin at low concentrations enhances AChR desensitization through the action of a second messenger, most likely cAMP. An analog of forskolin that is much less effective in activating adenylate cyclase (1,9-dideoxyforskolin) is also much less potent in enhancing desensitization. Forskolin at low concentrations does not alter single-channel conductance or mean channel open time. However, when used at concentrations above 20 microM, forskolin may also exert direct drug effects on AChRs.

Animals↗
PubMed1987

Biological properties of a tumour cell line (NB1-G) derived from human neuroblastoma.

The properties of a new tumour cell line (NB1-G) derived from human neuroblastoma by xenografting in nude rats followed by adaptation to tissue culture are described. Studies using a panel of monoclonal antibodies demonstrate the neuro-ectodermal nature of the cells and support the diagnosis of the primary tumour as neuroblastoma. Cytogenetic studies have revealed a human karyotype with several chromosomal abnormalities. Genetic analysis by in situ DNA hybridization has demonstrated the presence of multiple copies of the N-myc gene. Approximately 20-30 fold amplification of the gene is observed on Southern blot analysis. The cell line has been adapted to growth as multicellular tumour spheroids as well as monolayer culture. Radiobiological studies on spheroids show the cells to be radiosensitive with low capacity for sub-lethal damage accumulation and repair. The cell line should be useful for fundamental studies of human neuroblastoma as well as experimental therapy in vitro.

Animals↗
PubMed1986

Forskolin increases the rate of acetylcholine receptor desensitization at rat soleus endplates.

We have studied the function of acetylcholine (AcCho) receptors (AcChoRs) in rat soleus endplates before and after exposing the muscles to forskolin, a potent activator of adenylate cyclase. AcChoR function was tested by recording the membrane depolarization evoked by pulses of ionophoretically applied AcCho. Brief (2 msec) AcCho pulses delivered at 7 Hz evoked constant responses at untreated endplates. In contrast, after 10-100 microM forskolin was added to the bath, responses to similar pulse trains fell by as much as 80% within 1 sec. AcCho sensitivity recovered completely in less than 1 min after the pulses were stopped but fell again when the pulses were resumed. Similarly, longer (1 sec) ionophoretic AcCho pulses evoked roughly constant responses at control endplates, but after forskolin treatment the depolarization fell by one-half within less than 200 msec. These results indicate that forskolin increases the rate at which AcChoRs desensitize when exposed to agonist. Focal extracellular recordings showed that 20-100 microM forskolin also increased the decay rate of miniature endplate currents, indicating that forskolin may decrease AcChoR channel open time. Inhibitors of cAMP phosphodiesterase increased the potency of forskolin. When used alone, these inhibitors had effects similar to those of forskolin but smaller. Patch-clamp experiments indicated that forskolin at 100 microM may also interact with AcChoR channels directly, but at 20 microM this effect is negligible. Therefore, it is likely that the forskolin effects were mediated primarily by increased levels of intracellular cAMP.

Adenylyl Cyclases↗
PubMed1979

The lactulose hydrogen breath test as a diagnostic test for small-bowel bacterial overgrowth.

The lactulose hydrogen breath test has been evaluated as a diagnostic test for small-bowel bacterial overgrowth using the 14C-glycocholate breath test for comparison. Twenty-seven patients with suspected bacterial overgrowth and 37 control patients were studied. The lactulose test was positive in 8 out of 9 patients with Subsequently proven bacterial overgrowth, all of whom had positive 14C-glycocholate tests. However, 6 patients with ileal disease or resection had positive 14C-glycocholate tests but negative lactulose tests. subsequent bacteriological study of duodenal juice from these patients was negative. Negative results were obtained by both tests in the remaining 12 patients, none of whom were subsequently shown to have bacterial overgrowth. All 37 control subjects had negative lactulose tests. The lactulose breath test is a simple and promising diagnostic test for the detection of small-bowel bacterial overgrowth and, unlike the 14C-glycocholate test, has the advantage of being able to distinguish bacterial overgrowth from ileal disease.

Breath Tests↗
PubMed1978

Interpretation of the Mössbauer spectra of the four-iron ferredoxin from Bacillus stearothermophilus.

The Mössbauer spectra of both oxidized and reduced ferredoxin from Bacillus stearothermophilus have been analysed using computer fits to theoretical spectra obtained from a spin Hamiltonian. A consistent set of parameters was obtained from fits to spectra obtained over a wide range of temperature and magnetic field. These results are interpreted in terms of a model for the active centre which is consistent with its electronic and magnetic properties in both redox states. In the model for the oxidized centre all four iron atoms have essentially the same valence, intermediate between ferric and ferrous, with one pair spin-up and the other pair spin-down. On reduction the extra electron goes predominantly to one pair of iron atoms which become ferrous with the other pair remaining substantially unchanged. Using this model it is possible to obtain relationships between the spin Hamiltonian parameters for individual iron atoms and those for the coupled centre. This can give further insight into the relation between the observed electron paramagnetic resonance and Mössbauer spectra.

Ferredoxins↗
PubMed1978

A test of Sarbin's self-role congruency theory within a role-playing therapy analogue situation.

Explored the application of role playing, as a research technique, in a test of Sarbin's self-role congruency theory. Forty male Ss volunteered to play either the role of a therapist or client in a simulation of psychotherapy. The CPI dominance scale was used to select high dominant Ss to play the role of therapists. Half of these high dominant Ss were instructed in directive therapy (creating a self-role congruent condition with high dominance and directiveness being congruent) and half were instructed in non-directive therapy (creating a self-role incongruent condition). Judges' ratings were used to compare Ss' role playing ability and visible comfort between the self-role congruent and self-role incongruent conditions. The results supported Sarbin's theory of self-role congruence. These findings suggest methodological improvements in psychotherapy research via the use of role playing and have practical implications for the practice of psychotherapy.

Dominance-Subordination↗
PubMed1977

Clinical, laboratory, and epidemiologic features of a viral gastroenteritis in infants and children.

We studied 27 infants admitted to the hospital with acute diarrhea caused by human rotavirus (HRV) and obtained additional data on fecal excretion from ten outpatients with the same infection. The disease was characterized by watery diarrhea with fever and vomiting at the onset, isotonic dehydration, compensated metabolic acidosis, and increased concentrations of sodium and chloride but low concentrations of sugar in stools. Diarrhea usually ceased in three to four days when oral feedings were reduced or stopped but recurred mildly in four patients. Of 57 household contacts, 12 were symptomatic, 6 had HRV in their stools, and 19 had significantly increased serum HRV antibody titers. These features of the disease accord with available information on the pathogenesis of HRV infection. Knowledge of the clinical pattern of this newly diagnosable infection should help physicians to recognize and treat quickly this highly infectious, potentially dangerous illness.

Adult↗