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Biomedical subjects

A Richardson

Publications and source records attributed to A Richardson.

At least 73 records · Page 4Linked to original sources

Techniques for obtaining specimens for culture to confirm onychomycosis.

A study was conducted to determine whether fungal culture results in cases of suspected onychomycosis differ depending on the location from which the specimen is obtained. Specimens were taken from the nail plate, subungual debris, and nail bed in 30 patients with clinical evidence of onychomycosis. Cultures from the subungual debris were more likely to be positive for dermatophytes, nondermatophytic molds, and yeasts than were cultures from the deeper nail bed or nail plate.

Adult↗

A cephalometric study of the effect of extraction of lower first permanent molars.

The sample consisted of 28 patients (16 female: 12 male) from the records of the Orthodontic Department for whom the extraction of both lower first permanent molars was considered due to caries. The age ranged from 8-14 years (mean age 12.4). A cephalometric radiograph was taken prior to the extraction and after a mean of 18 months. No other treatment was done during the observation period. The radiographs were traced arid digitized using the GeLa program. A total of 16 points were digitized yielding 19 measurements (7 angular and 12 linear). The data were analyzed using 't' test and Pearson Correlation Coefficients in SPSS PC and compared to a control group matched for age and sex. Results showed that on average, the lower second molar moved forwards 5.9 mm. On average there was no change in angulation of the incisors to the bases. There was no significant change in the vertical relations of the jaws save that caused by normal growth and development. A significant correlation was found between the change in overbite and original overbite (r = -0.55, P < 0.01), the change in Li/A-Pog (r = 0.41, P < 0.05) and the change in facial proportions (r = -0.59, P < 0.001). The change in overjet was correlated with the change in Li/A-Pog (r = 0.58, P < 0.001) and change in Li/mand (r = -0.55, P < 0.01). The extraction of the lower first molars results in deepening of the overbite on average, but has no effect on the anterior facial height or any other vertical relationship. However, the increase in overbite is associated with lingual positioning of the lower incisor and the change in facial proportions. The change in overjet is related to lingual positioning and retroclination of the lower incisors.

Adolescent↗

Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3.

Akt (also known as PKB or RAC-PK) is an intracellular serine/threonine kinase involved in regulating cell survival. Although this makes it a promising target for the discovery of drugs to treat human cancer, a complicating factor may be the role played by Akt in insulin signalling. Two human isoforms, Akt-1 and Akt-2, have been described previously and a third isoform has been identified in rats (here termed Akt-3, but also called RAC-PK-gamma or PKB-gamma). We describe the identification of the corresponding human isoform of Akt-3. The gene encoding human Akt-3 was localized to chromosome 1q43-44. The predicted protein sequence is 83% identical to human Akt-1 and 78% identical to human Akt-2, and contains a pleckstrin homology domain and a kinase domain. In contrast to the published rat Akt-3 isoform, human and mouse Akt-3 also possess a C-terminal 'tail' that contains a phosphorylation site (Ser472) thought to be involved in the activation of Akt kinases. In addition to phosphorylation of Ser472, phosphorylation of Thr305 also appears to contribute to the activation of Akt-3 because mutation of both these residues to aspartate increased the catalytic activity of Akt-3, whereas mutation to alanine inhibited activation. Akt-3 activity could be inhibited by the broad spectrum kinase inhibitor staurosporine and by the PKC inhibitor Ro 31-8220, but not by other PKC or PKA inhibitors tested. Although Akt-3 is expressed widely, it is not highly expressed in liver or skeletal muscle, suggesting that its principle function may not be in regulating insulin signalling. These observations suggest that Akt-3 is a promising target for the discovery of novel chemotherapeutic agents which do not interfere with insulin signalling.

Amino Acid Sequence↗

Cognitive disorders: A question of misattribution.

A recent study indicates that schizophrenia patients are prone to auditory hallucinations because they have difficulty recognising their 'inner speech' as their own, and consequently tend to misattribute it to an external source.

Auditory Perception↗

Expression of heat shock protein 70 decreases with age in hepatocytes and splenocytes from female rats.

A decline in the induction of heat shock protein 70 (hsp70) expression with age has been shown to occur in a variety of tissues from male rodents. Because the age-related change in the expression of many genes often differ in male and female rodents, we have measured the induction of hsp70 expression in hepatocytes and splenocytes from young/adult (4-8 months) and old (20-22 months) female Fischer 344 rats. Hepatocytes and splenocytes isolated from old female rats showed a marked decrease in the induction of hsp70 mRNA and protein levels by heat shock when compared to hepatocytes and splenocytes isolated from young/adult female rats. Because the heat shock transcription factor HSF1 mediates the heat-induced transcription of hsp70, the effect of age on HSF1 was also studied. The ability of extracts from heat-shocked splenocytes to bind to the heat shock element (HSE) decreased with age. Interestingly, the levels of HSF1 protein were similar in splenocytes and hepatocytes from old female rats compared to young/adult female rats, even though the levels of HSE-binding were lower for splenocytes isolated from old rats. In this study, we show an age-related decline in the expression of hsp70, and this decline was similar to what we had previously observed in male Fischer 344 rats.

Aging↗

Characterization of the antioxidant status of the heterozygous manganese superoxide dismutase knockout mouse.

The antioxidant status of several tissues (liver, kidney, lung, brain, heart, muscle, stomach, and spleen) from heterozygous manganese superoxide dismutase (MnSOD) mutant mice (Sod2-/+) was characterized. The activity of MnSOD was decreased (30 to 80%) in all tissues examined. The levels of mRNA coding for the major antioxidant enzymes (CuZnSOD, catalase, and glutathione peroxidase) were not significantly altered in liver, kidney, heart, lung, or brain in the Sod2-/+ mice. The activities of the enzymes were not altered in any of these tissues, with the exception of a decrease in glutathione peroxidase activity in muscle in the Sod2-/+ mice compared to the Sod2+/+ mice. Thus, there was no up-regulation of the activities of the major antioxidant enzymes to compensate for the decrease in MnSOD activity. Reduced glutathione levels were 30 to 50% lower in the lung, brain, and muscle of the Sod2-/+ mice compared to the wild-type Sod2+/+ mice. In addition, the ratio of GSH/GSSG was decreased approximately 50% in Sod2-/+ muscle, indicating that the decrease in MnSOD activity in the Sod2-/+ mice results in some degree of oxidative stress in this tissue.

Animals↗

Compensatory changes in GroEL/Gp31 affinity as a mechanism for allele-specific genetic interaction.

Previous work has shown that the GroEL-GroES interaction is primarily mediated by the GroES mobile loop. In bacteriophage T4 infection, GroES is substituted by the gene 31-encoded cochaperonin, Gp31. Using a genetic selection scheme, we have identified a new set of mutations in gene 31 that affect interaction with GroEL; all mutations result in changes in the mobile loop of Gp31. Biochemical analyses reveal that the mobile loop mutations alter the affinity between Gp31 and GroEL, most likely by modulating the stability of the GroEL-bound hairpin conformation of the mobile loop. Surprisingly, mutations in groEL that display allele-specific interactions with mutations in gene 31 alter residues in the GroEL intermediate domain, distantly located from the mobile loop binding site. The observed patterns of genetic and biochemical interaction between GroES or Gp31 and GroEL point to a mechanism of genetic allele specificity based on compensatory changes in affinity of the protein-protein interaction. Mutations studied in this work indirectly alter affinity by modulating a folding transition in the Gp31 mobile loop or by modulating a hinged conformational change in GroEL.

Alleles↗

Impaired auditory frequency discrimination in dyslexia detected with mismatch evoked potentials.

Deficits in phonological skills appear to be at the heart of reading disability; however, the nature of this impairment is not yet known. The hypothesis that dyslexic subjects are impaired in auditory frequency discrimination was tested by using an attention-independent auditory brain potential, termed mismatch negativity (MMN) while subjects performed a visual distractor task. In separate blocks, MMN responses to graded changes in tone frequency or tone duration were recorded in 10 dyslexic and matched control subjects. MMN potentials to changes in tone frequency but not to changes in tone duration were abnormal in dyslexic subjects. This physiological deficit was corroborated by a similarly specific impairment in discriminating tone frequency, but not tone duration, which was assessed separately. Furthermore, the pitch discrimination and MMN deficit was correlated with the degree of impairment in phonological skills, as reflected in reading errors of regular words and nonwords. It is possible that in dyslexia a persistent sensory deficit in monitoring the frequency of incoming sound may impair the feedback control necessary for the normal development of phonological skills.

Acoustic Stimulation↗

Opposite patterns of P300 asymmetry in schizophrenia are syndrome related.

In schizophrenia reduction of the P300 amplitude is a robust statistical finding but with inconsistent evidence of symptom correlates and of lateral asymmetry. Here relations were examined with active and withdrawn syndromes which in other cognitive and electrophysiological measurement modalities have been associated with opposite functional asymmetries. A standard oddball detection task was used to elicit auditory evoked potentials from dextral DSM-IV schizophrenic patients. On clinical ratings blind to the psychophysiology, eight were classified as withdrawn and 12 had a predominance of active syndrome features. Both patient groups had congruent P300 maxima at Pz or P4, attesting to their application to the detection task. Syndromes were differentiated by opposite asymmetries in P300, N200-P300 and N100 amplitudes at the posterior temporal sites: a reduction in P300 and N200-P300 amplitudes on the left in the active patients, and a reduction on the right in the withdrawn patients, with the opposite asymmetries in N100 amplitudes. The syndrome-related asymmetries in P300, also manifested in earlier attentional (N100) components are interpreted in terms of thalamo-cortical arousal systems having generalised, internalised influences, rather than in terms of later cognitive processes underpinning the P300. The findings endorse a syndromal approach to laterality research in schizophrenia.

Adult↗

Cognitive asymmetry patterns in schizophrenia: retest reliability and modification with recovery.

In schizophrenia syndrome-related recognition memory impairments have been demonstrated to be dependent on hemispheric specialisation--word deficits (left hemisphere) in a Withdrawn syndrome and face deficits (right hemisphere) in an Active syndrome. Deficits were largely absent in recovered patients. Here the in state/trait nature was examined through longitudinal investigation of 33 patients. In 19 patients who were tested when psychotic and when symptoms remitted (with order randomised) memory improved with recovery, particularly word memory in Withdrawn patients and face memory in Active patients. In patients who presented with different syndromes on separate admissions there was evidence that cognitive asymmetry patterns reversed with syndrome changes. In nine patients in whom the retest reliability of syndrome-asymmetry relations was examined across repeat admissions or periods or recovery, the asymmetries were stable. In sum, further evidence was disclosed of reliable associations between left vs. right preferential hemispheric impairment and syndromes based on activity vs. withdrawal. Acknowledgement of the importance of this individual difference may assist in elucidating heterogeneity of cognitive function in schizophrenia. Reversals of asymmetry support a functional component to recognition memory deficits in schizophrenia with possible relevance to the recovery process.

Adult↗

Focus groups.

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England↗

The effect of odour priming on long latency visual evoked potentials of matching and mismatching objects.

This study reports a cross-modal, olfactory/visual event related potential (ERP) using odours as olfactory primes. The results show a difference in the ERP waveform for the N400 waveform when a visual image does not match the priming odour. An N400 peak was produced for both the matched and mismatched conditions but the peaks were significantly more negative for the mismatched condition. By the use of non-food odours this study extends an earlier finding by Grigor, who, using the same ERP paradigm, obtained similar results for food odours and photographs of food.

Adult↗

Visual event related potentials modulated by contextually relevant and irrelevant olfactory primes.

Visual evoked potentials were recorded from 16 scalp locations on 10 young subjects during presentation of a series of high-quality photographs on a computer screen. The photographs consisted of equal numbers of pictures of fruit (citrus and non-citrus fruits), flowers (roses and other flowers) and objects (e.g. buildings, vehicles, animals etc.). Every picture was different in order to avoid repetition effects. The pictures were presented under four odour conditions: no odour, rose odour, jasmine odour and citrus odour. In order to keep the subjects alert they were asked to make categorizing decisions for the visual stimuli (e.g. flower or fruit). No decision was required concerning the relationship between the visual stimulus and the odour. As expected, the N400 peak was more negative when the picture stimulus did not match the odour. It is hypothesized that the N400 peak can be used as a measure of relatedness of a sensory stimulus to a previous or on-going prime, irrespective of the mode of the stimuli.

Adult↗

Ectopic eruption of the maxillary canine quantified in three dimensions on cephalometric radiographs between the ages of 5 and 15 years.

The eruption paths of 20 ectopic maxillary canine teeth (10 right, 10 left) were measured in three dimensions on annual lateral and depressed postero-anterior cephalometric radiographs of 15 patients between the ages of 5 and 15 years and compared with the eruption of normal canines. It was found that between the ages of 8 and 12 years ectopic canines on the left side moved more anteriorly than the normally erupting canines and the same was true of the right canines between the ages of 7 and 12 years. While the ectopic canines moved occlusally, their vertical movement was less than normal which accounts for the clinical finding that canines are impacted in the palate at a high level. The average palatally ectopic canine always moves palatally, and never shares in the buccal movement shown by normally erupting canines between the ages of 10 and 12 years. It was interesting to find that the differences between growth of normal and ectopic canines in the lateral plane of space are present as early as 5-6 years.

Adolescent↗

Long-term effect of the chincap on hard and soft tissues.

The short- and long-term effects of the chincap used in combination with a removable appliance to procline upper incisors were analysed cephalometrically in 23 patients with Class III malocclusions. The overall changes were compared with growth changes in a closely matched control sample of untreated Class III patients. There was no evidence that the chincap retarded growth of the mandible. During treatment, there was an increase in mandibular length and facial height. The lower incisors retroclined and the upper incisors proclined. The incisor relationship was corrected. Soft tissue changes included an increase in nasolabial angle and improvement in soft-tissue profile, including the nose. Skeletal post-treatment changes included further mandibular growth associated with an increase in angle SNB and Wits measurement. Facial height also increased significantly. The Class I overjet was maintained, although slightly diminished. The soft tissue nose, upper and lower lip, and chin moved anteriorly, and the nasal tip and chin moved inferiorly. At the end of the study period there were no significant skeletal or soft tissue differences between the treated and control groups. The only significant contrasts were in the overjet and the overbite. Chincap therapy combined with an upper removable appliance to procline the upper incisors is effective in producing long-term correction of the incisor relationship by retroclination of lower incisors, proclination of upper incisors, and redirection of mandibular growth in a downward direction. The direction of growth at the chin is maintained subsequent to treatment, as are the changes in incisor inclination, although in diminished form. There are corresponding improvements in the soft tissue profile.

Case-Control Studies↗

Cephalometric changes in adult pharyngeal morphology.

This cephalometric study investigated morphological changes occurring in the pharynx between early and middle adult life. A sample of 16 young adults (mean age 20.2 years) had cephalometric films taken and repeated after an interval of 32 years. Changes in pharyngeal skeletal size, pharyngeal soft tissue thickness, pharyngeal airway depth, and soft palate dimensions were examined, in addition to standard craniofacial measurements. The results showed increases in maxillary prominence, and upper and lower anterior face height. The nasopharyngeal skeletal dimensions were unchanged over the 32-year interval, while the anteroposterior depth of the nasopharyngeal lumen increased as a result of a reduction in thickness of the posterior nasopharyngeal wall. In the oropharynx, the depth of the airway decreased with age, and the soft palate became longer and thicker. The findings indicate that pharyngeal morphology is not immutably established during childhood and adolescence, but changes throughout adult life. The tendency towards a longer and thicker soft palate, and narrower oropharynx during adulthood is discussed in relation to their possible role in explaining the increased prevalence of obstructive sleep apnoea and related disorders in later life.

Adult↗

Genetic analysis of the bacteriophage T4-encoded cochaperonin Gp31.

Previous genetic and biochemical analyses have established that the bacteriophage T4-encoded Gp31 is a cochaperonin that interacts with Escherichia coli's GroEL to ensure the timely and accurate folding of Gp23, the bacteriophage-encoded major capsid protein. The heptameric Gp31 cochaperonin, like the E. coli GroES cochaperonin, interacts with GroEL primarily through its unstructured mobile loop segment. Upon binding to GroEL, the mobile loop adopts a structured, beta-hairpin turn. In this article, we present extensive genetic data that strongly substantiate and extend these biochemical studies. These studies begin with the isolation of mutations in gene 31 based on the ability to plaque on groEL44 mutant bacteria, whose mutant product interacts weakly with Gp31. Our genetic system is unique because it also allows for the direct selection of revertants of such gene 31 mutations, based on their ability to plaque on groEL515 mutant bacteria. Interestingly, all of these revertants are pseudorevertants because the original 31 mutation is maintained. In addition, we show that the classical tsA70 mutation in gene 31 changes a conserved hydrophobic residue in the mobile loop to a hydrophilic one. Pseudorevertants of tsA70, which enable growth at the restrictive temperatures, acquire the same mutation previously shown to allow plaque formation on groEL44 mutant bacteria. Our genetic analyses highlight the crucial importance of all three highly conserved hydrophobic residues of the mobile loop of Gp31 in the productive interaction with GroEL.

Amino Acid Sequence↗