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Biomedical subjects

G P Moore

Publications and source records attributed to G P Moore.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of epidermal growth factor receptor expression in human melanocytes.

The epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor alpha (TGFalpha), are reportedly involved in autocrine growth of melanoma cells. The signal pathway has also been implicated in early events of transformation, suggesting a function for EGFR in normal cells. This study reports the presence of EGFR in cultured melanocytes and examines some cellular responses to TGFalpha. Western analysis revealed 170 kDa bands in extracts of cultured neonatal human melanocytes, corresponding to the receptor Mr. Protein expression was more pronounced in cells during active growth. EGFR were less evident in cultures populated predominantly by melanized cells, indicating that receptor expression became reduced in differentiating cells. Immunocytochemistry confirmed these observations and also showed that EGFR reactivity was predominantly localized in the cell body but absent from dendrites. Addition of TGFalpha to early cultures induced a rapid increase in phosphotyrosine signal of the 170 kDa protein. Longer treatment (24-48 h) increased the intensity of the EGFR signal, suggesting that receptors had been upregulated. However, inclusion of TGFalpha in cultures did not result in an increase in cell numbers when compared to controls. The observations provide evidence of the existence of a receptor-mediated pathway in melanocytes which has transforming potential in vivo.

Cell Division↗
PubMed2001

Extracellular matrix molecules and follicle morphogenesis in ovine skin.

Chondroitin sulphate, fibronectin, laminin and the hyaluronan receptor, CD44, were localized in ovine skin during follicle morphogenesis. Prior to initiation, chondroitin sulphate was detected in the mesenchyme adjacent to the dermal-epidermal junction and showed an approximately regular periodicity in staining intensity. With the appearance of follicle primordia, the more strongly stained regions of the matrix were associated with mesenchymal condensations. During later development and in the mature follicle, staining was localized to the matrices of cells of the dermal sheath and papilla. CD44 was also localized in the mesenchymal condensations at follicle initiation and, subsequently, in the dermal sheath. Fibronectin staining was confined to the mesenchyme prior to follicle formation and became associated with presumptive papilla and dermal sheath cells during follicle formation and maturation. Fibronectin antisera detected an approximately 220 kDa protein in western blots of adult and fetal skin. An additional band of 150 kDa was also observed prior to follicle initiation. In contrast, laminin was predominantly restricted to the basal laminae of developing and mature follicles. The aggregative behaviour of ovine papilla cells was examined in vitro. The number and size of aggregates were not affected by inclusion of chondroitin sulphate or fibronectin in the culture medium, but both increased in the presence of hyaluronidase. Chondroitinase had the opposite effect and beta-D-xyloside completely abolished aggregative behaviour. In conclusion, the appearance of certain matrix molecules may presage morphogenetic movements of cells at follicle initiation and regulate patterns of follicle distribution in skin during fetal life.

Animals↗
PubMed2001

Ethics seminars: the practice of medical procedures on newly dead patients--is consent warranted?

The use of the newly dead to teach procedures is widely practiced in training institutions. This model allows a realistic opportunity both to become more familiar with lifesaving maneuvers before they are actually necessary and to maintain proficiency. Whether to notify the next of kin first has been an issue of ethical debate. Some argue a "don't ask, don't tell" policy is justified, while others mandate open consent by family members prior to the practice. Several medical studies have found that patients and families are likely to consent to the procedures but prefer to be asked permission first. Multiple legal cases have addressed the issue of usage of cadavers postmortem without expressed permission. Earlier cases emphasized the concept of "pseudo-property" rights and declared that the next of kin do not have constitutional ownership of the deceased person's body. More recent legal cases are declaring that families do, in fact, possess these rights. In this day and age of increasing recognition of personal autonomy, it is probably prudent to approach the next of kin for permission before performing procedures on the newly deceased.

Attitude to Death↗
PubMed2000

Concurrent Parkinson tremors.

1. Concurrent resting and postural tremors of patients with idiopathic Parkinson's disease were monitored using transducers responding to angular velocity of rotation. Spectra and correlation functions were calculated for each pair of records. 2. When concurrent tremor spectra share indistinguishable fundamental frequencies, have statistically significant peaks in their coherence spectra at those fundamental frequencies, and show significant peaks in their cross-correlation functions near zero delay, they are classified as linearly dependent. When such tremor records are superimposed, their phase-locked behaviour is evident. 3. Pairs of correlated concurrent tremors, of varying duration, have been observed in both hands, both feet and in either hand and the contralateral or ipsilateral foot. Correlated tremors may be concurrent with other tremors that are independent. We hypothesize that correlated Parkinson tremors arise from one or more common (and possibly unilateral) central sources.

Aged↗
PubMed2000

Quantitative digitography (QDG): a sensitive measure of digital motor control in idiopathic Parkinson's disease.

This study introduces a new method for studying, quantitatively, the dynamics of finger movement using data obtained from sequences of key strikes on a computer-interfaced piano keyboard. We have called this quantitative digitography (QDG). This initial article introduces the method in a group of patients with Parkinson's disease and in a group of healthy subjects using simple, repetitive, alternating finger-tapping for 60 seconds. Patients with idiopathic Parkinson's disease (IPD) were studied "ON" and "OFF" dopaminergic medication before and after pallidotomy. Customized software allowed the independent analysis of key strike velocity, duration of key strike, and frequency of tapping along with a quantitative measure of the regularity of performance. Quantitative measures of the improvement in performance after medication are presented for each parameter of movement. The technique also reveals correlates of some clinical phenomena of the temporal disturbances of repetitive motion in IPD, such as fatigue, tremor, freezing, and festination. We demonstrate that the performance of 60 seconds of alternating finger tapping on a computerized keyboard yields objective measures of motor performance that are significantly different in patients with IPD "OFF" when compared with "ON" medication and when compared with healthy subjects. This is the first time that such a method has been used in the measurement of specific kinematics of digital motion in Parkinson's disease. The equipment is inexpensive and portable and the data are rapidly and easily collected, making it suitable for the outpatient setting.

Adult↗
PubMed2000

Expression of nerve growth factor mRNA and its translation products in the anagen hair follicle.

The cellular localization of NGF mRNA and its translation products have been identified in ovine hair follicles. NGF mRNA was detected in the proliferating cells of the follicle bulb and differentiating cells of the suprabulbar region, but was absent from the outer root sheath. Western analysis revealed the presence of a 73 kDa NGF prohormone in extracts of ovine flank skin, but the mature 13 kDa NGF was absent. Immunohistochemical analysis with antibodies specific to mouse NGF and a pro-NGF specific domain localized the NGF prohormone to outer root sheath cells in the upper bulb region of the follicle, adjacent to the zone of keratinization. Antibody binding was also associated with the luminal epithelium of the apocrine sweat gland and the pilary canal of the follicle at its junction with the epidermis. These observations, together with the reported presence of high- and low-affinity NGF receptors in the follicle, implicate the NGF prohormone-responsive neuronal system in the regulation of hair growth.

Animals↗
PubMed2000

Commercial recombinant human beta-nerve growth factor and adult rat dorsal root ganglia contain an identical molecular species of nerve growth factor prohormone.

Examination of commercial recombinant human beta-nerve growth factor (rh-beta-NGF) preparations with polyclonal antibodies specific to 13-kDa NGF and pro-NGF-specific domains revealed the presence of high-molecular-mass immunoreactive proteins, including a 60-kDa NGF prohormone. On incubation with a mixture of N- and O-specific glycosidases, the 60-kDa NGF pro-hormone generated a 32-kDa protein corresponding to the molecular size of NGF precursor predicted by the cloned human NGF cDNA. Highly sensitive chemiluminescence immunoblot analysis of adult rat dorsal root ganglia, spinal cord, and colon tissues with NGF- and pro-NGF domain-specific antibodies also revealed the presence of high-molecular-mass proteins, including the 60-kDa NGF prohormone. Based on the presence of the 60-kDa NGF prohormone in dorsal root ganglia and its efferent tissues, we suggest that proteolytically unprocessed, glycosylated NGF prohormone may mediate interactions between neurons and the tissues they innervate.

Animals↗
PubMed1999

Do parents want to be present during invasive procedures performed on their children in the emergency department? A survey of 400 parents.

STUDY OBJECTIVES: No large study has addressed whether parents want to be present when invasive procedures are performed on their children in the emergency department. We conducted a survey to address this question. METHODS: The study used a self-administered, written survey consisting of 5 pediatric scenarios with increasing level of procedural invasiveness. Parents in an urban, teaching hospital ED waiting area were asked to participate. RESULTS: Of 407 persons asked to participate, 400 (98%) completed the survey. The number of parents expressing a desire to be present during a procedure performed on their child was 387 (97.5%) for venipuncture of the extremity, 375 (94.0%) for laceration repair, 341 (86.5%) for lumbar puncture, and 317 (80.9%) for endotracheal intubation. For a major resuscitation scenario, 316 (80.7%) wished to be present if their child were conscious during the resuscitation, 277 (71.4%) wanted to be present if their child were unconscious during the resuscitation, whereas 322 (83.4%) indicated a desire to be present if their child were likely to die during the resuscitation. Of the 400, 261 (65.3%) wished to be present for all 5 scenarios. Only 26 (6.5%) wanted the physician to determine parental presence in all 5 scenarios. CONCLUSION: Most parents surveyed would want to be present when invasive procedures are performed on their children. With increasing procedural invasiveness, parental desire to be present decreased. However, most parents would want to be in attendance if their child were likely to die, and nearly all parents want to participate in the decision about their presence.

Adolescent↗
PubMed1998

Pattern and morphogenesis in skin.

Models dealing with the development of hair and feather follicles commonly predict that the factors initiating morphogenesis also specify patterns of follicle distribution. The factors have been postulated as chemical or mechanical instabilities which, at certain threshold concentrations, determine both the location of follicles and their form. The models tend to focus on the earliest waves of induction, where follicles develop at separate, non-randomly spaced initiation sites in skin. However, in many animals, there are later waves of initiation, some of which give rise to compound follicles. These are bundles of follicles that arise by branching from the necks of those formed earlier and share a common pilary canal when mature. In some species, compound follicles make the greatest numerical contribution to the follicle population. Measurements of the frequencies of single and branched follicles in sheep selection lines with different follicle densities (from previous studies by Moore et al.) revealed that the follicles which formed first during foetal life (primary and original secondary populations) were established at separately identifiable sites in the skin, called here "initiation sites". However, there were also later waves of development, contributing follicles exclusively by the process of branching (the derived secondary population). Final follicle densities were not correlated with the densities of initiation sites. The observations suggested that mechanisms specifying the positional values of initiation sites differed from those determining follicle number. The final densities of the follicle populations in the sheep lines were also highly negatively correlated with the diameters of the wool fibres grown. The close statistical relationship suggested that the two parameters were developmentally linked. However, whereas fibre characteristics are realised when the follicle is mature, density is established earlier, during foetal life. We have reconciled these observations with the following hypothesis: a population of cells, committed to a follicular pathway of development, differentiates in the skin at or before the first wave of initiation. Subpopulations of the committed cells subsequently participate in each follicle initiation event, the number in each subpopulation ultimately determining fibre dimensions. Follicle initiation continues until most or all of the original population have been utilised. Transplantation and skin recombinant studies have demonstrated that the cells forming the dermal papilla of the follicle participate in follicle initiation and have inductive effects on epidermal tissue. Papilla size is also correlated with fibre diameter in the mature follicle. These attributes are consistent with those described for the committed cell population.

Animals↗
PubMed1998

Dietary fat manipulation and signal transduction in ovine skin.

Protection of dietary lipids in a protein matrix prevents biohydrogenation in ruminants and increases the availability of polyunsaturated fatty acids. This alters the composition of the tissue lipids, including the membrane phospholipids, which are important substrates for signal transduction. This study investigates the effects of a diet containing protected fatty acids on the activities of key intracellular kinases in the skin. Two groups of six sheep were offered either a control diet or one containing protected cottonseed, a source of linoleic acid (C18:2), for 3 months. Skin was taken from August to October, and analysed for protein kinase C (PKC), protein kinase A (PKA), mitogen-activated protein kinase (MAPK), phosphotyrosine activity and epidermal growth factor (EGF) receptor content. Skin and wool samples were also taken to measure changes in the fibre characters and follicle function. At the end of the experiment, the mean linoleic acid content of skin phospholipids from sheep fed the protected diet was twice that of the controls. In both groups, PKC activity was significantly elevated in skin taken during September and October compared with August values. However, activities measured in the experimental sheep were higher than in controls. This coincided with a decline in wool production. PKA activity decreased significantly in both groups between August and October. MAPK activities did not alter during the experiment. Western analyses did not reveal differences in phosphotyrosine-positive or EGF receptor bands between the groups.

Animals↗
PubMed1998

The effects of fibroblast growth factors 1 and 2 on fibre growth of wool follicles in culture.

The effects of fibroblast growth factor-1 (FGF-1) and FGF-2 on fibre growth and follicle function were examined using a previously described procedure to culture wool follicles. Because the FGFs bind to glycosaminoglycan components of the extra-cellular matrix, we also investigated interactions between FGF-1 and FGF-2 with heparin on wool fibre growth. Individual follicles were microdissected from Merino sheepskin and transferred to culture. Follicles increased in length for 6 days, and in all groups, no significant differences in follicle length were observed. Increase in follicle length was associated with fibre growth, follicles maintained normal anagen morphology and incorporated [3H]thymidine into the bulb and outer root sheath cells. Follicles in all treatments continued to produce fibre keratins, as detected by immunohistochemistry. However, the patterns of fibre and cytoskeletal proteins incorporating [35S]methionine in control and treated follicles were significantly different. We found a considerable decrease in the intermediate filament keratins or low sulphur proteins in follicles cultured in the presence of FGF-1 and FGF-2 compared to controls. The majority of proteins detected in these samples were acidic high sulphur proteins. These studies provide evidence for a specific role for the fibroblast growth factors in the regulation of fibre differentiation.

Animals↗
PubMed1998

Interactions between epidermal growth factor and the Tabby mutation in skin.

Mutations of the X-linked genes Tabby (Ta) in mice and EDA in humans result in developmental and functional abnormalities, primarily in the skin and hair follicles. Although both genes are believed to encode membrane-associated proteins, it has been suggested that, in the mouse, the mutation is linked to a deficiency of epidermal growth factor (EGF). This study investigated relationships between the skin abnormalities of Ta mice and the EGF signal pathway. The distribution of endogenous EGF in tissues of Ta/Y and +/Y animals was examined and, because of its reported morphogenetic actions and ability to overcome receptor signalling defects in vivo, the effects of exogenous EGF on the hair follicle population were determined. EGF levels were similar in a number of tissues of Ta/Y and +/Y mice, but amounts in Ta/Y submaxillary glands were reduced, probably due to a smaller gland size. Exogenous EGF inhibited hair follicle development and decreased follicle density in both genotypes. It was concluded from comparisons of the distributions of EGF and its effects in skin with those in mice bearing mutations in the EGF signal pathway that the normal phenotype results from interactions between EGF and the Ta peptide in skin.

Animals↗
PubMed1997

Eye, ear, nose, and throat.

Patients present to the emergency department with a number of eye, ear, nose, and throat (ENT) problems. This article updates some very common problems; identifies a few pearls on nasal foreign body removal, ophthalmologic medication, and epistaxis; and reviews a few pitfalls in identifying malignancies and sore throats.

Emergency Medicine↗
PubMed1997

Pearls, pitfalls, and updates for pain management.

Pain management is one of the most challenging areas we encounter as emergency physicians. However, many of us fail to adequately meet this challenge. This article discusses frequently encountered pain syndromes and pain management options.

Adult↗
PubMed1997

Is closed diagnostic peritoneal lavage contraindicated in patients with previous abdominal surgery?

OBJECTIVE: To compare the accuracies and complication rates of diagnostic peritoneal lavage (DPL) in trauma patients with and without previous abdominal surgery. METHODS: A retrospective review of DPL accuracy and complication rate was performed using all ED trauma patients who underwent DPL during 1993 as identified by the trauma registry. Care was provided at a Level-1 trauma center, a 1,100-bed, central-city teaching hospital with an annual ED census of 84,000. Records were reviewed for a history of previous surgery, DPL results, complications, mechanism of injury, and location of abdominal scars. DPL was performed using the Seldinger technique with a standard Arrow Diagnostic Peritoneal Lavage Kit using an 8-Fr catheter. Rates for patient groups with and without previous abdominal surgery were compared using Fisher's exact test. A "misclassified" DPL was defined as either a positive DPL with negative laparotomy or a negative DPL with subsequent need for laparotomy. "Complications" were defined as iatrogenic injury during the procedure or inability to obtain return of fluid during the lavage. RESULTS: A total of 372 DPLs were performed; 42 in patients with previous surgery and 330 in patients without prior surgery. The groups were similar with respect to proportion with blunt trauma (95% vs 97%), positive DPL (19% vs 19%), misclassified rate (2.4% vs 1.8%), and complication rate (2.4% vs 0.9%); no significant difference was found between groups. The previous abdominal surgeries were appendectomy (n = 20), tubal ligation (n = 5), abdominal hysterectomy (n = 4), cholecystectomy (nonlaparoscopic) (n = 4), pyloric stenosis (n = 1), uterine prolapse (n = 1), undescended testis (n = 1), partial gastrectomy (n = 1), and unknown (n = 5). The analysis had a 90% power of detecting a 10% difference between the 2 groups. CONCLUSION: The complication rate and accuracy of closed DPL in patients with previous abdominal surgery were similar to those for DPL performed in patients without previous abdominal surgery.

Abdomen↗