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Biomedical subjects

R Presley

Publications and source records attributed to R Presley.

At least 19 recordsLinked to original sources

Truncation of the Mll gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos.

The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted Mll (the murine homologue of MLL) in exon 5 causing expression of three truncated in-frame Mll transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2-cell stage. Embryos cultured in vitro progress to the 2-cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives.

Animals↗

Dlx5 regulates regional development of the branchial arches and sensory capsules.

We report the generation and analysis of mice homozygous for a targeted deletion of the Dlx5 homeobox gene. Dlx5 mutant mice have multiple defects in craniofacial structures, including their ears, noses, mandibles and calvaria, and die shortly after birth. A subset (28%) exhibit exencephaly. Ectodermal expression of Dlx5 is required for the development of olfactory and otic placode-derived epithelia and surrounding capsules. The nasal capsules are hypoplastic (e.g. lacking turbinates) and, in most cases, the right side is more severely affected than the left. Dorsal otic vesicle derivatives (e. g. semicircular canals and endolymphatic duct) and the surrounding capsule, are more severely affected than ventral (cochlear) structures. Dlx5 is also required in mandibular arch ectomesenchyme, as the proximal mandibular arch skeleton is dysmorphic. Dlx5 may control craniofacial development in part through the regulation of the goosecoid homeobox gene. goosecoid expression is greatly reduced in Dlx5 mutants, and both goosecoid and Dlx5 mutants share a number of similar craniofacial malformations. Dlx5 may perform a general role in skeletal differentiation, as exemplified by hypomineralization within the calvaria. The distinct focal defects within the branchial arches of the Dlx1, Dlx2 and Dlx5 mutants, along with the nested expression of their RNAs, support a model in which these genes have both redundant and unique functions in the regulation of regional patterning of the craniofacial ectomesenchyme.

Animals↗

Role of the Dlx homeobox genes in proximodistal patterning of the branchial arches: mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 alter morphogenesis of proximal skeletal and soft tissue structures derived from the first and second arches.

The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.

Animals↗

Randomized trial of breast self-examination in Shanghai: methodology and preliminary results.

BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated. PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China. METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer. RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups. CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination. IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination.

Adult↗

Prediction of group membership in developmental dyslexia, attention deficit hyperactivity disorder, and normal controls using brain morphometric analysis of magnetic resonance imaging.

This study explored the utility of using selected brain morphometric indices for predicting group membership for children with developmental dyslexia (n = 10), attention deficit hyperactivity disorder: combined type (n = 10), and a control group (n = 10). Subjects ranged in age from 6.1 to 16 years (M = 10.5 years, SD = 2.8). None of the subjects were diagnosed with mental retardation, nor did any of the subjects have a history of seizure disorder, head trauma, or other neurodevelopmental disorders. WISC-R Full Scale IQ ranged from 87 to 149 (M = 114.4, SD = 13.3) with no significant differences noted between the clinical groups. Six brain regions, as defined by MRI scans, were selected a priori for inclusion in a discriminant function analysis. Reliability of the morphometric measures ranged from 0.94 to 0.97. One significant discriminant function was generated which accounted for about 61.4% of the variance between groups. The predictive discriminant analysis using the six morphometric MRI measurements classified subjects with an overall 60% accuracy with the best accuracy found for the developmental dyslexia and control groups. A predictive discriminant analysis incorporating these six morphometric measures as well as chronological age and FSIQ increased the overall classification accuracy to 87% with the misclassfied subjects assigned to one of the clinical groups. The findings support the presumed neurological basis for many neurodevelopmental disorders. They also underline the importance of including brain morphometric measures in predictive models.

Journal Article↗

A survey of marketing practices by family practice residency programs.

The purpose of the study reported in this article was to identify marketing practices that are being utilized by family practice residencies in the United States and to differentiate which strategies were felt to be most useful. A survey questionnaire on marketing strategies was mailed to 361 civilian family practice residencies listed in the 1992 Director of Family Practice Residency Programs. A total of 151 questionnaires were returned for a total response rate of 42.1 percent. The results were summarized using descriptive statistics and Chi-square analysis. Family practice residency programs use a number of different strategies to attract patients. The effectiveness of a given program is dependent on local factors, program strengths and the target population desired. The three most useful marketing strategies reported in the survey were HMO listings, emergency department referrals, and patient referrals. The three least effective strategies were health fairs, sports physicals, and school presentations.

Academic Medical Centers↗

Toward a structure of preschool temperament: factor structure of the temperament assessment battery for children.

Much of the research and thinking in the area of childhood temperament has been guided by the structural and measurement model of Thomas, Chess, and colleagues. Recently, researchers have called into question this structural conception and have explored the factor structure of the instruments based on the Thomas and Chess model. A review of the literature indicates that there are few studies at any one age level, and that much of the research is limited by small samples. The results of a large sample factor analysis of parent and teacher ratings of preschool children are reported. A five-factor solution was judged most appropriate for parent ratings, and a three-factor solution seemed most appropriate for teacher ratings. Relations of these factors to the Big Five personality factors found in adult personality research are discussed.

Age Factors↗

The segmental Bauplan of the rostral zone of the head in vertebrates.

Observations in a wide selection of lower vertebrate embryos have confirmed classical descriptions concerning segmentation of the early head mesoderm. The premandibular (PM) segment is seen as the most rostral representative of a continuous rostro-caudal series of condensations in the paraxial mesoderm, luminisations within which are secondary and variable in occurrence and form. The premandibular condensations are typically in continuity across the midline; the confluence, which comes to lie behind Rathke's pouch, marks the site of first mesoderm formation behind the oral membrane. The underlying consistency of pre-otic segmental pattern throughout the vertebrates is frequently obscured by superimposed variation in morphological detail between species, reflecting the dynamic nature of the morphogenetic tissue processes. Luminisation is one such morphogenetic epiphenomenon. Variations in it account for the terminal (Platt's) vesicle and "proboscis pores": such structures cannot therefore be safely used to infer evolutionary homologies. Many previous difficulties facing segmentation theory are explained as the result of failure to take account of the dynamic nature of the responsible morphogenetic events.

Animals↗

Morphine or U-50,488 suppresses Fos protein-like immunoreactivity in the spinal cord and nucleus tractus solitarii evoked by a noxious visceral stimulus in the rat.

Immunohistochemical visualization of Fos protein, the nuclear phosphoprotein product of the early-immediate gene c-fos, permits identification of populations of neurons that are activated in response to a variety of stimuli. This study examined the distribution of Fos-like immunoreactive (FLI) neurons in the spinal cord and the nucleus tractus solitarii (NTS) of the caudal medulla evoked by a noxious visceral stimulus in the unanesthetized rat. It also compared the inhibition of pain behavior and Fos expression by a mu-selective opioid agonist, morphine, and a kappa-selective opioid agonist, U-50,488. Intraperitoneal injection of 3.5% acetic acid in the unanesthetized rat evoked the expression of FLI in a discrete population of spinal cord neurons, the distribution of which closely mirrored the spinal terminations of visceral primary afferents. Specifically, FLI neurons were concentrated in laminae I, IIo, V, VII, and X. Large numbers of Fos-immunoreactive neurons were also present in the NTS of the caudal medulla, most likely as a result of spinosolitary tract and vaginal afferent input. The number of labeled neurons in both the spinal cord and the NTS was significantly correlated with the number of abdominal stretches, a pain behavior measure. Both morphine (1-10 mg/kg s.c.) and U-50,488 (3-30 mg/kg s.c.) produced a dose-dependent inhibition of the pain behavior in these animals and a dose-dependent suppression of the number of FLI neurons in both the spinal cord and in the NTS; complete suppression of FLI neurons was, however, not necessary for the production of antinociception. Furthermore, although equianalgesic doses of morphine and U-50,488 reduced the number of labelled neurons in the spinal cord to a comparable extent, morphine reduced the number of immunoreactive neurons in the NTS to a greater extent than did U-50,488. These results suggest that morphine and U-50,488 have comparable effects on the transmission of visceral nociceptive messages by spinal neurons, but differentially affect the autonomic response to noxious visceral stimuli.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Treatment trial of oxiracetam in Alzheimer's disease.

Twenty-four carefully assessed patients with probable Alzheimer's disease were enrolled in a double-blind, placebo-controlled treatment study of oxiracetam, a nootropic agent reported to improve memory performance in patients with dementia. A broad battery of neuropsychological tests failed to reveal any improvement in the treated group or in any treated patient when individual test scores were analyzed. These findings indicate that oxiracetam is ineffective in reducing cognitive impairment due to Alzheimer's disease.

Aged↗

Dysnomia in Alzheimer's disease: an evaluation of neurobehavioral subtypes.

The relative influence of perceptual and semantic features on naming performance was investigated with reference to the neurobehavioral profiles displayed by patients with Alzheimer's disease (AD). Forty-one patients were classified as manifesting a verbal, visual, or global subtype based upon their pattern of neuropsychological functioning. Perceptual characteristics of to-be-named pictures were varied by manipulating the amount of line detail, whereas semantic qualities were varied by altering word frequency norms. All AD subtypes were less accurate than normal elderly controls in naming low frequency pictures. Patients and controls took longer to name low frequency and high complexity pictures, and this effect was comparable across the AD groups. Patients with predominantly visual deficits were significantly slower in naming than controls, and those with verbal impairments made a higher proportion of semantic naming errors when compared to patients displaying visual or severe global impairments. These results suggest that deficits in semantic processing contribute to naming dysfunction in AD, and they highlight the importance of examining dissociations among neurobehavioral subtypes.

Alzheimer Disease↗

The foramen ovale and sphenoidal angle in man.

The structure of the greater wing of the sphenoid in the region of the foramen ovale and sphenoidal angle is described in both the adult human and in two partly ossified human embryos. It is shown that the foramen ovale of man is enclosed by membrane bone, derived from a medial process associated with the scaphoid fossa, and a lateral tongue, the most dorsal part of which is present in many adults as a process on the lateral margin of the foramen. These structures are parts of an extensive membrane bone which forms the larger part of the greater wing of the sphenoid. It is shown that the foramen of Vesalius represents the site of fusion between this membrane bone and the more medial, cartilaginous, ala temporalis. Various inconstant patterns of grooves and foramina in the vicinity of the foramen ovale can be interpreted as arising from the interplay of the various parts of the membrane bone and the emissary venous plexus from the middle meningeal veins to the pterygoid plexus. The embryonic anlagen of the pterygo-sphenoidal and pterygo-spinous ligaments are described, and the association of these structures with the parts of the membrane bone are discussed.

Humans↗

The primitive course of the internal carotid artery in mammals.

In all recent mammals the internal carotid artery at the level of the auditory capsule is derived from the embryonic dorsal aorta. In adults of various groups, the artery lies in positions which are classified as medial or promontory. It is shown that these character states arise by a process of differential growth affecting the relative positions of the dorsal aorta and the cochlear promontory. There is no evidence for separate vessels in the embryo which could give rise to non-homologous internal carotid arteries in the two positions. It follows that the concept of a primitive mammalian morphotype with both a medial and a promontory internal carotid artery in the same individual presents a formidable embryological problem. It is recommended that, in the absence of supporting evidence, the widespread current taxonomic and palaeontological use of this hypothetical morphotype should be regarded with suspicion.

Anatomy, Comparative↗

The pterygoid and ectopterygoid in mammals.

A dorsal pterygoid element and a ventral ectopterygoid element can be recognised during the development of monotremes, marsupials and eutherian mammals. Their homology with the elements so named in fossils ancestral to mammals can be established by positional evidence. In monotremes the elements remain distinct and show specialised features, including a hamular cartilage in the ectopterygoid of one specimen of Ornithorhynchus. In most higher mammals the pterygoid element is much reduced and is replaced anteriorly by the perpendicular plate of the palatine. Posteriorly the pterygoid element fuses with the ectopterygoid, in many cases before the onset of ossification. The hamular cartilage arises by chondrification within the ectopterygoid element and shows no sign of being a separate morphological entity, but must be regarded as a specialised feature associated with the architecture of the palatal musculature. There is a strong case for the value of recognising that the 'pterygoid process' of higher mammals includes both a pterygoid and an ectopterygoid moiety.

Animals↗

Measurements of noradrenaline fluorescence in axons of chick embryo sympathetic ganglia grown in three day culture.

Chicken embryo sympathetic ganglion fragments, grown in culture for three days, were incubated for short periods in appropriate experimental and control media to provide information on axonal uptake of exogenous noradrenaline in the presence and absence of the uptake-blocking drugs, protriptyline and phenoxybenzamine. The cultures were dried, gassed in formaldehyde vapour and examined by fluorescence microscopy. Spot readings were taken on axon-bundles using a microspectrophotometer. Readings were corrected for the amount of tissue present in each field, using graticule and interferometric methods. Brightness was uniform along individual axon-bundles, but varied from bundle to bundle within the same culture. Despite this range in brightness the readings fell into a normal distribution about the mean. Dose-dependent increases in brightness were obtained following incubation with noradrenaline. A clear indication of the effect of the blocking drugs was observed but the range in brightness prevented reliable quantitative data on these effects from being obtained. It was concluded that the wide range of brightness within each culture reflected a lack of equivalence in the intrinsic noradrenaline-uptake properties of the axon-bundles developing in such cultures.

Animals↗

Electron probe x-ray microanalysis of small granulated cells in rat sympathetic ganglia after sequential aldehyde and dichromate treatment.

Rat adrenal medulla and celiac-mesenteric sympathetic ganglia were fixed by a glutaraldehyde/formaldehyde-potassium dichromate-osmium treatment sequence and plastic-embedded. Fine sections were examined by electron probe x-ray microanalysis. Comparable peaks for chromium (Kalpha = 5.4 keV) were obtained from cytoplasmic fields containing membrane-bounded inclusion granules in both adrenomedullary noradrenaline cells and a type (type II) of sympathetic small granulated cell whose inclusion granules closely resemble those of the adrenomedullary noradrenaline cell. Chromium was not detected in granules within adrenomedullary adrenaline cells nor in two other sympathetic small granualted cell types. In no material was chromium detected in agranular cytoplasmic or nuclear fields. Since chromium binds to the Schiff monobase formed by glutaraldehyde and noradrenaline during fixation, we infer that noradrenaline is present in the granules of the type II sympathetic small granulated cell, as well as in adrenomedullary noradrenaline cells.

Adrenal Medulla↗

A numerical relationship between chromaffin-positive and small intensely fluorescent cells in sympathetic ganglia.

A statistical analysis of counts of small intensely fluorescent (SIF) and chromaffin-positive (CH+) cells in superior cervical, thoracic and coeliac-mesenteric ganglia of rats at various ages (Santer et al. 1975) has been carried out. The results indicate that the numerical distribution of CH+ cells closely follows that of yellow SIF cells but not that of green SIF cells. This relationship holds both for different ganglia and for different ages.

Age Factors↗