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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 703 records · Page 39Linked to original sources
PubMed1994

Physical mapping studies at D15S10: implications for candidate gene identification in the Angelman syndrome/Prader-Willi syndrome chromosome region of 15q11-q13.

The Angelman syndrome (AS) and Prader-Willi syndrome (PWS) loci have been mapped to chromosome 15q11-q13. Chromosomal deletions of differing parental origin in the two syndromes have been interpreted as being due to genetic imprinting. Molecular analysis of patients with varying deletions has localized the AS locus to the interval between D15S113 and GABRB3 and the PWS locus between D15S13 and D15S113. In the present study, DNA cloning and physical mapping techniques have been used to characterize the AS/PWS chromosome region in the vicinity of D15S10, a locus that is telomeric to D15S113 and centromeric to GABRB3. A CpG island near TD3-21 at D15S10 has been cloned, allowing the identification of a widely expressed 4.5-kb transcript and providing a novel DNA marker, OP3, at this locus. OP3 and TD3-21 have been used to construct a long-range physical map extending over approximately 2800 kb. Clusters of rare-cutting restriction sites on this map locate four other CpG islands. Since these CpG islands lie within the minimum deletion intervals for AS and PWS, they mark the possible locations of candidate genes for the two syndromes.

Angelman Syndrome↗
PubMed1994

A comparison of 67Cu- and 131I-labelled forms of monoclonal antibodies SEN7 and SWA20 directed against small-cell lung cancer.

The intact anti-SCLC monoclonal antibody (MAb) SEN7 and its F(ab')2 were labelled with the beta-emitting isotope 67Cu. Both materials retained their biological activity in vitro as determined by the Lindmo assay. In a direct comparison of in vivo distribution in a xenograph model, 131I- and 67Cu-labelled intact SEN7 showed similar absolute tumour accumulation. Blood levels were markedly lower in the case of the 67Cu-labelled antibody, resulting in improved tumour:blood ratios which reached a maximum of 13:1 compared with only 4.5:1 for 131I-SEN7. In the case of the 67Cu-labelled F(ab')2, very high accumulation of the nuclide was observed in the kidney. Levels of radio copper in liver and spleen were also found to be significantly raised when compared with radio iodine. SWA20, a MAb which had previously failed to show any selective in vivo accumulation in tumour xenografts when labelled with radio iodine showed higher and more stable tumour accumulation when labelled with 67Cu.

Animals↗
PubMed1994

Removal/neutralization of hepatitis A virus during manufacture of high purity, solvent/detergent factor VIII concentrate.

Recent reports have suggested an increased risk of type A viral hepatitis in hemophilic patients treated with high purity factor VIII concentrates prepared using ion exchange chromatography coupled with solvent/detergent treatment for inactivation of viruses. To determine the capacity for removal or inactivation of hepatitis A virus during the factor VIII manufacturing process, human plasma and various factor VIII production intermediates were spiked with cell culture-propagated virus and subjected to scaled down conditions mimicking the manufacture of solvent/detergent factor VIII. The combination of antibody-mediated neutralization, cryoprecipitation, anion exchange chromatography, and lyophilization in the absence of sucrose resulted in a minimal reduction of 5.5 to 8.55 log10 in the infectivity of hepatitis A virus.

Animals↗
PubMed1994

Prenatal diagnosis and post-mortem study of a fetus with mosaic trisomy 14 due to a dic(14)(p11).

Amniocentesis at 17 weeks' gestation revealed a mosaic karyotype--46,XX/46,XX,-14,+dic(14)(p11). No abnormalities were detected on ultrasound. Growth and placentation were normal. The fetus was examined after termination of pregnancy and micrognathia and pulmonary hyperlobation were the only abnormalities detected. Several tissues were set up for cytogenetics, including fetal skin, kidney, ovary, and placenta. The diagnosis was confirmed by these studies. The level of mosaicism varied between tissues, with the trisomy 14 cell line highest in amniotic fluid.

Adult↗
PubMed1994

Nebulizer delivery of tobramycin to the lower respiratory tract.

We characterized a tobramycin aerosol generated by five nebulizers: Micron One, Pulmosonic, Pulmo-Aide, DeVilbiss Model 65, and UltraNeb 100 by particle size and drug concentration. The Micron One nebulizer did not produce a recoverable aerosol, while the Pulmosonic had a minimal output; therefore three machines were examined for their ability to deliver tobramycin to the lower respiratory tract of patients with cystic fibrosis (CF). The DeVilbiss 65 had the greatest output: with air as the carrier gas it produced an aerosol with > 60% of the particles having a mean mass aerodynamic diameter (MMAD) of > 5.5 microns. Using helox shifted the MMAD so that > 65% of the particles were < 5.5 microns. Increasing the power in the DeVilbiss 65 increased the output of particles > 9.2 microns, without a change in the particles < 3.3 microns. With air as the carrier gas the Pulmo-Aide and the UltraNeb 100 produced an aerosol with > 60% particles, < 3.3 microns MMAD. Using helox the UltraNeb 100 increased the amount of aerosol with a < 3.3 microns MMAD to 98%. Tobramycin delivery to the lower respiratory tract with the Pulmo-Aide and UltraNeb 100 was compared using air or helox by measuring sputum drug concentration. Pulmo-Aide failed to produce detectable tobramycin in sputum in 2 out of 9 patients with CF. With the UltraNeb 100, all patients had measurable sputum tobramycin immediately after administration (range, 16.2-3385 micrograms/g), but no statistically significant difference was found when using either compressed air, helox, or ambient air.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effects of breakfast and caffeine on cognitive performance, mood and cardiovascular functioning.

Two experiments examined the effect of breakfast (1.89 MJ) and caffeine (4 mg/kg) on cognitive performance, mood and cardiovascular functioning. In the first experiment, breakfast had no effect on performance of sustained attention tasks, but it increased pulse rate and influenced mood. The mood effects after breakfast differed between a cooked breakfast and a cereal/toast breakfast. In contrast to the effects of breakfast, this relatively high dose of caffeine improved performance of the sustained attention tasks, increased blood pressure and increased mental alertness. In the second experiment, effects of a breakfast and caffeine on mood and cardiovascular functions confirmed the results of the first study. The breakfast improved performance on free recall and recognition memory tasks, had no effect on a semantic memory task and impaired the accuracy of performing a logical reasoning task. In contrast to this, caffeine improved performance on the semantic memory, logical reasoning, free recall and recognition memory tasks. Overall, these results show that breakfast can improve performance in some but not all cognitive tasks and that these changes are very different from those observed after lunch, and those produced by caffeine.

Affect↗
PubMed1994

Effects of evening meals and caffeine on cognitive performance, mood and cardiovascular functioning.

An experiment was carried out to examine the effects of an evening meal and caffeine (3 mg/kg) on performance, mood and cardiovascular functioning. Subjects given a meal reported that they felt stronger, more proficient and more interested than subjects in the no-meal condition. They also performed a logical reasoning task more quickly than the no-meal group. However, no effects were found on sustained attention tasks or tasks involving recall or recognition of word lists. The effects of evening meals are, therefore, different from either those observed after lunch or breakfast. Caffeine improved alertness and performance on sustained attention tasks for the group as a whole. Interactions between caffeine conditions and levels of impulsivity of the subjects were also found in memory tasks.

Affect↗
PubMed1994

Derivation of germline competent embryonic stem cells with a combination of interleukin-6 and soluble interleukin-6 receptor.

In this report we document the derivation of pluripotential embryonic stem (ES) cells in the absence of a feeder layer by supplementation of culture media with either ciliary neurotrophic factor or oncostatin M, or with a combination of interleukin-6 (IL-6) plus soluble interleukin-6 receptor (sIL-6R). These factors all activate gp130-associated signaling processes, as does the previously characterized ES cell maintenance factor Differentiation Inhibiting Activity (Leukemia Inhibitory Factor). In particular, the IL-6/sIL-6R complex is thought to act exclusively through gp130. All ES cell lines derived using IL-6/sIL-6R contributed extensively to chimeras and were transmitted through the germline at high frequency. These findings point to a pivotal role for gp130 in ES cell propagation and may be relevant to attempts to derive ES cells from species other than mouse.

Animals↗
PubMed1994

The effects of phonetic similarity and list length on children's sound categorization performance.

Three experiments investigating children's performance on tests of sound categorization are reported. In two experiments, the children had to decide which was the "odd one out" in a sequence of three, four, and five words. In each case the "oddity" judgement required selecting the word which differed in its final consonant, producing a different rime segment. The odd word differed either by one phonetic feature (voice or place) or by both voice and place, from the others in the sequence. Oddity judgements were easier when the odd word was phonetically dissimilar to the background items but, contrary to expectation, performance did not decline as list length increased. Experiment 3 extended these findings by showing that place-only changes were more difficult than voice-only changes. Sound categorization performance correlated with memory span for words, but memory span did not make an independent contribution to sound categorization once age and reading skills had been controlled. The experiments show that the sound categorization task taps individual differences in speech perception mechanisms but that memory load is less crucial to this task than has often been supposed.

Age Factors↗
PubMed1994

Latency of skeletal muscle contraction after pulse train stimulation: an important factor in correct timing of skeletal muscle cardiac assist devices.

Various configurations of conditioned skeletal muscle are under investigation for cardiac assistance in patients with end-stage cardiac failure. Optimal timing of conditioned skeletal muscle contraction is essential for effective cardiac augmentation. However, unlike mechanical methods of assistance, skeletal muscle requires time to develop peak tension. We measured "time to 50% peak tension" and "time to 90% peak tension" using an electrical strain gauge in 12 canine latissimus dorsi muscles (6 untrained controls and 6 trained with 3 months of electrical stimulation at 25 Hz with a 15% duty cycle). The "time to 50% relaxation" and the "time to 90% relaxation" after discontinuation of the stimulus were also measured. Conditioned skeletal muscle required significantly more time to develop peak tension than unconditioned skeletal muscle. Relaxation was also significantly prolonged in conditioned muscle. Notably, conditioned lattisimus needed, on average, 0.35 sec to develop peak tension and 0.20 sec for 90% relaxation. Thus, 0.55 sec of each muscle contraction/relaxation cycle was devoted to development of peak tension and subsequent relaxation. At normal canine heart rates of approximately 120 beats per minute (0.50 sec per cardiac cycle), conditioned skeletal muscle may take up to 70% of each cardiac cycle (0.35 sec) to develop 90% of peak tension. The recognition of this phenomenon in conditioned skeletal muscle is important for effective contraction timing of both human and animal skeletal muscle assist devices. Development of proper conditioning regimens for such devices may benefit from identification of those training parameters which produce a minimal "time to peak tension."

Animals↗
PubMed1994

Differences in biodistribution of the anti-(carcinoembryonic antigen) murine monoclonal antibody CE-25, its F(ab')2 fragment and its intact mainly human chimeric form CE 4-8-13. Dependence on tumour size and amount of antibody injected.

The effect of the size of the tumour and the amount of antibody injected on the biodistribution of a family of radioiodinated antibodies was studied. The intact mouse anti-(carcinoembryonic antigen) (anti-CEA) monoclonal antibody CE-25, its F(ab')2 fragment and the intact human-mouse chimeric from CE 4-8-13 were evaluated in a model system using the human CEA-producing colon xenograft T 380 grown in nude mice. The relative retention (the percentage of the injected dose per gram of tissue), of mouse mAb and F(ab')2 in tumour and most normal tissues 1 day after injection was independent of the antibody dose; after 4 days the mAb values increased with increasing antibody dose. The relative retention of chimeric mAb increased with increasing antibody dose 1 day after injection and also slightly after 4 days. The relative retention in tumour tissue was lower in bigger xenografts for all antibodies. The relative retention of mouse mAb in small tumours increased from day 1 to day 4; for chimeric mAb this value decreased. In normal tissues the relative retention of mouse mAb decreased from day 1 to day 4, but the relative retention of chimeric mAb in normal tissue dropped rapidly and changed little afterwards. Thus the biokinetics of antibodies is "species"-dependent: foreign, mainly human, chimeric antibody clears faster from normal mouse tissue than mouse antibody and reaches lower concentrations.

Animals↗
PubMed1994

Cluster of an erythromycin-resistant variant of the Spanish multiply resistant 23F clone of Streptococcus pneumoniae in South Africa.

A multiply resistant serotype 23F pneumococcus was cultured from a 3-year-old child with otitis media and five carriers at the child's day-care centre in South Africa. Attempts to eradicate carriage with mupirocin failed. The strains were identical to the Spanish clone of multiply resistant pneumococci by serotype, antimicrobial susceptibility pattern, restriction analysis of the penicillin-binding protein 1A, 2B and 2X genes and by multilocus enzyme electrophoresis. The data suggest that this clone has acquired erythromycin resistance. A possible link between the index case and residence of a family member in Spain was found.

Adult↗
PubMed1994

Behavioral medicine treatment of ruminative vomiting and associated weight loss in an adolescent with autism.

Treated persistent ruminative vomiting of a 15-year-old boy with autism using a multicomponent behavioral medicine program within a residential facility. Preceding intervention the boy had lost 15 pounds associated with high-rate ruminating. The treatment program included a combination of dietary, nutritional, and behavioral procedures that emphasized food restrictions, satiation, and setting condition manipulations. Ruminative vomiting was reduced to near-zero levels and weight gain was achieved following treatment implementation. These therapeutic gains were sustained during a maintenance programming phase and at 1- through 4-month follow-up assessments. Issues related to functional assessment and treatment formulation in behavioral medicine intervention for ruminative vomiting are discussed.

Adolescent↗
PubMed1994

The hierarchical Bayesian approach to population pharmacokinetic modelling.

Compartmental models are widely used to model the profile of drug concentrations versus time from administration in an individual subject. Observed concentrations are then modelled as noisy departures from the underlying profile, the latter characterised for each individual by a small number of 'individual parameters'. When a population of individuals is studied, inter-individual variation is modelled by assuming that the individual profile parameters are drawn from a population distribution, the latter characterised by 'population parameters' describing, in effect, a mean population profile and individual variation around it. From a Bayesian statistical perspective, such models fit exactly into the so-called hierarchical modelling framework, which provides a coherent basis for individual and population inferences and prediction, as well as for decision-making (for example, the design of dosage regimens). This paper outlines the hierarchical model framework and describes how the required computations can be carried out in a straightforward manner by a Markov chain Monte Carlo technique known as Gibbs sampling, even when models involve mean-variance relationships and outliers.

Bayes Theorem↗
PubMed1994

Effects of fat content, weight, and acceptability of the meal on postlunch changes in mood, performance, and cardiovascular function.

This study examined the effects of fat content and meal size on postlunch changes in mood, performance, and cardiovascular function. Forty-six subjects (20 males, 26 females) were tested before and after lunch. Subjects were assigned to one of the following lunch conditions: a) low fat (23 g), large meal (860 g); b) low fat (18 g), small meal (600 g); c) high fat (84 g), large meal (840 g); d) high fat (79 g), small meal (530 g). The results showed only small effects of fat composition and meal size, with no cardiovascular effects being observed and no evidence of fat content or the weight of the meal influencing performance of logical reasoning or cognitive vigilance tasks. A few effects of meal type were significant in the mood data, but given the large number of analyses conducted, these could represent chance effects. Results from two selective attention tasks showed that subjects given the high-fat meals responded more slowly but more accurately, which differs from the effects of carbohydrate, protein, and calorie content reported in earlier papers. Weight of the meal influenced the degree of distraction from near and far distractors and also the accuracy of responses to central and peripheral targets. However, both the effects of fat and meal size were modified by task parameters, and further research is required before firm conclusions can be drawn about the functional importance of the influences of nutrient content and meal size on performance. The high-fat and large meals were rated as more acceptable than the low-fat and small meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The treatment-seeking woman at menopause.

Recent studies suggest that health care utilisation by women during menopause transition in general is highly idiosyncratic, despite the widespread advocation of prophylactic hormone therapy and increased health vigilance. The Melbourne Women's Midlife Health Study, a community-based cross-sectional study of 2001 urban Australian-born women aged 45-55 years, evaluated women's physical and emotional experiences, past and present health status, attitudes and beliefs about menopause, health behaviours and current menopausal status in a 30-min telephone interview. This paper reports on those factors related to help-seeking and health care utilisation. Findings show that treatment utilisers, in contrast to non-utilisers, reported a wider range of general symptoms, but reports on vasomotor symptoms did not contribute to the regression analysis. Treatment utilisers were further identified as problem-related or prevention-related utilisers. In three-way analyses, the past and present social and physical health of the problem-related treatment user was reportedly worse than either the prevention-related utiliser or non-utiliser. These findings suggest that medical and societal views about the health of middle-aged women during menopausal transition are likely to be based on the experiences of a particular segment of the population only. It is proposed that biased views of menopause as a time of considerable distress and ill-health are being perpetuated and over-generalised. This perspective appears to have little relevance for the majority of middle-aged women.

Australia↗
PubMed1994

Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways.

Propagation of the undifferentiated pluripotential phenotype of embryonic stem (ES) cells is dependent on the cytokine differentiation inhibiting activity/leukemia inhibitory factor (DIA/LIF). The DIA/LIF receptor complex is a heterodimer of DIA/LIF receptor (DIA/LIF-R) and gp130. The latter is also a component of the interleukin-6 (IL-6) receptor complex. We report that a combination of IL-6 and soluble IL-6 receptor (sIL-6R), which can induce homodimerisation of gp130 and activation of signalling processes, sustains self-renewal of pluripotential ES cells. Our findings indicate that the IL-6/sIL-6R complex acts on ES cells through gp130 alone, bypassing DIA/LIF-R, and therefore implicate gp130 as the key component in the signalling pathway responsible for stem cell renewal.

Amino Acid Sequence↗