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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
PubMed1992

Epidermal growth factor alters the electrolyte profile of lactating ewes (Ovis aries).

1. Lactating ewes were treated with mouse epidermal growth factor (EGF) at a dose rate of 0.5 mg/day for 4 days and its effects on the electrolyte profile were observed. 2. There was no effect of EGF on plasma concentrations of sodium or potassium, although urinary and total (in urine and milk) losses of both were reduced. 3. EGF-induced hypocalcaemia was associated with reduced milk calcium secretion and increased urinary calcium excretion whereas EGF-induced hypermagnesaemia was associated with reduced urinary and total magnesium losses. 4. Glomerular filtration rate was reduced during EGF infusion. 5. Chronic intravenous EGF infusion affects the electrolyte profile by altering electrolyte secretion by the mammary gland and renal electrolyte excretion.

Animals↗
PubMed1992

Localization of epidermal growth factor immunoreactivity in sheep skin during wool follicle development.

Interactions among the cells and matrices of the epidermis and mesenchyme of skin are essential for hair follicle initiation and development. The identification of receptors for epidermal growth factor (EGF) on epithelial components of the follicle during growth has suggested that the ligand participates in some of these events. We have used affinity-purified antibodies together with an alkaline phosphatase detection procedure to investigate the distribution of EGF in the skin of the sheep during wool follicle formation. Immunoreactivity was restricted to the periderm and intermediate layers of fetal epidermis at 55 d of gestation, when the first wave of wool follicles are initiated. This particular distribution persisted during subsequent development but never became associated with the basal cells of the epidermis. The activity was lost around 118 d, coinciding with sloughing of the periderm. No immunoreactivity was found in the plugs or the dermal condensations of the developing follicles. At approximately 105 d of gestation, however, reactions were detected in the outer root sheath as the follicles matured and in the differentiating cells of the sebaceous glands. A similar distribution pattern was also noted at 140 d, just prior to birth, and in adult animals, indicating that EGF was sequestered and perhaps synthesized within the follicle. The presence of immunoreactive material was also associated with the pilary canals and the skin surface, suggesting that this may have had its origin in the sebaceous glands. We examined this using a radioreceptor assay for EGF. Material washed from the skin surface and sebaceous gland extracts were found to displace 125I-EGF from rat liver membranes, in parallel with mouse EGF.

Animals↗
PubMed1992

Epidermal growth factor alters milk composition and fluid balance of lactating ewes.

Lactating ewes were treated with murine epidermal growth factor (EGF) and its effects on concomitant milk production and composition were observed. Six ewes were infused via the jugular vein with 200 ml saline/day over 4 days (days 9-12 of lactation) followed by EGF at a dose rate of 0.5 mg/day in 200 ml saline over 4 days (days 13-16). All ewes then received a further infusion of 200 ml saline/day over 4 days (days 17-20). During the experiment a maintenance (lactation) diet was offered and ewes were machine-milked twice daily. An EGF-immunoreactive material was detected in mammary secretions and urine throughout the experiment, but only in plasma (1-9 micrograms/l) during the period of EGF infusion. The amount of EGF appearing in milk and urine increased from 37 micrograms and 10 micrograms respectively (day 1 of EGF infusion) to 56 micrograms and 17 micrograms respectively (day 4). EGF treatment resulted in lower milk yield and reduced concentration of lactose and protein; milk fat concentration fell after EGF infusion had ceased. Water intake increased markedly during EGF infusion and was 60% (4 kg) greater on day 4 than that measured during the first saline infusion. Urine volume also increased and was 164% (3.6 kg) greater by day 4 of EGF infusion compared with that recorded in the first saline infusion. Water retention (intake minus output in milk, urine and faeces) was significantly higher on the day after EGF infusion ceased than that found during the first saline infusion. The possibilities that the increased water intake was primary, or secondary, to a diuretic effect of EGF are discussed.

Animals↗
PubMed1992

Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor.

The infusion of low doses of epidermal growth factor (EGF) into lactating ewes stimulates water intake and urine volume. The plasma concentrations and daily output of various electrolytes in milk and urine are also affected. We have investigated this further by recording the effects of EGF infusion on fluid balance, electrolyte profiles and plasma concentrations of glucose and parathyroid hormone (PTH) in non-pregnant, non-lactating ewes. Twenty-four animals (n = 8 per group) received infusions of 100 ml saline/day into the jugular vein for 10 days (days 1-10) followed by EGF at a dose rate of either 1 (low dose), 5 (medium dose) or 10 (high dose) micrograms/kg liveweight per day in 100 ml saline for 5 days (days 11-15). All ewes then received an infusion of 100 ml saline/day for 10 days (days 16-25). Most plasma and urine samples had undetectable concentrations of EGF-immunoreactive material during the periods of saline infusion. During EGF infusion, the highest amounts of EGF infusate excreted in urine were 1.6, 5.9 and 5.6% for ewes in low, medium and high dose groups respectively. Water intake increased by 17% (0.5 kg), 88% (2.5 kg) and 89% (2.3 kg) and urine volume increased by 29% (0.5 kg), 108% (2.2 kg) and 134% (2.1 kg) for the three groups respectively. Fluid balance and feed intake were not affected by EGF infusion, but the output of faecal dry matter was reduced in ewes receiving the two higher doses of EGF. All levels of EGF resulted in hypocalcaemia, increased plasma PTH concentrations and hypermagnesaemia. There was no effect of EGF on plasma concentrations of K+ and glucose or on daily urinary excretion of K+ and Mg2+. The only response to the low dose was a reduced plasma concentration of Na+ and an increased daily urinary urate excretion. The two higher doses increased the daily urinary excretion of Na+, PO4(3-) and urate, but had no effect on the respective concentrations in plasma. Urinary Ca2+ excretion was reduced only during infusion of the medium dose of EGF. The responses of most variables were similar during infusion of the medium and high doses of EGF. All three doses of EGF induced polydipsic and diuretic responses in ewes, and infusions of 5-10 micrograms EGF/kg liveweight per day affected renal excretion of Ca2+, Na+ and PO4(3-). We interpret the responses of the kidney and plasma PTH concentrations as a means of maintaining the homeostasis of plasma profiles of electrolytes.

Animals↗
PubMed1991

Hair growth induction: roles of growth factors.

The hair follicles of eutheria arise during fetal life as a consequence of interactions between the cells and matrices of the epidermis and mesenchyme. In some instances, communication may be mediated by growth factors, receptors, and similar molecules. We have focused on epidermal growth factor and fibroblast growth factor, since both are expressed in skin, where they are presumed to perform regulatory functions. In sheep, EGF receptors are located on skin epithelia. An EGF-like protein was detected by immunochemistry in fetal epidermis but was not associated with the cells of developing wool follicles. During subsequent development the molecule was associated with the sebaceous glands and the outer root sheath. If the ORS may be considered a source of stem cells for the proliferating matrix, EGF may act as a differentiation factor, determining cell fates by cell contact mechanisms similar to those in invertebrates. FGF was localized in the epidermis and basal lamina and in follicle plugs during morphogenesis. At maturity, FGF was found in the ORS and in the region of the basal lamina of the follicle bulb, suggesting a role in bulb proliferation and fiber growth.

Aging↗
PubMed1991

Construction, expression and characterization of humanized antibodies directed against the human alpha/beta T cell receptor.

Completely humanized antibodies with specificity for the human alpha/beta TCR have been produced by genetic engineering. The L and H chain V region exons encoding the murine mAb BMA 031 CD regions and human EU framework regions were synthesized and replaced into previously isolated genomic fragments. These fragments were inserted into mammalian expression vectors containing the human kappa and gamma 1 C region exons. Two variants were constructed each containing selected BMA 031 amino acids within the human frameworks. The humanized genes were transfected into Sp2/0 hybridoma cells by electroporation and transfectomas secreting humanized antibody were isolated. Levels of antibody expression up to 7 pg/cell/24 h were obtained. The humanized antibody, BMA 031-EUCIV2, competed poorly with murine BMA 031 for binding to T cells. BMA 031-EUCIV3, however, bound specifically to T cells and competed effectively with both the murine BMA 031 antibody and a previously constructed chimeric BMA 031 antibody for binding to these cells. The relative affinity of BMA 031-EUCIV3 was about 2.5 times lower than BMA 031. The ability to promote antibody dependent cell-mediated cytolysis was significantly enhanced with the engineered antibodies as compared to murine BMA 031. Humanized BMA 031 is a clinically relevant, genetically engineered antibody with potential uses in transplantation, graft vs host disease, and autoimmunity.

Amino Acid Sequence↗
PubMed1991

Construction, expression, and biologic activity of murine/human chimeric antibodies with specificity for the human alpha/beta T cell receptor.

Murine/human chimeric antibodies with specificity for the human TCR-alpha/beta have been produced by genetic engineering. The L and H chain V region exons encoding the murine mAb BMA 031 were isolated and inserted into mammalian expression vectors containing the human kappa and gamma 1 or gamma 4 C region exons. The chimeric genes were transfected into murine Sp2/O hybridoma cells by electroporation and transfectomas secreting chimeric antibody were isolated. Secretion levels ranged from 1 to 7 pg/cell/24 h. The chimeric antibodies bound specifically to T cells and competed effectively with the parental murine mAb for binding to these sites. The ability to promote antibody-dependent cell-mediated cytolysis was significantly enhanced in the chimeric antibodies as compared with murine BMA 031. C-dependent cytolysis, however, was not detectable with any of the antibodies. Chimeric BMA 031 is a clinically relevant, genetically engineered antibody with potential uses in transplantation, graft-vs-host disease, autoimmune diseases and other T cell-related disorders.

Animals↗
PubMed1991

Cultivation of mesenchymal cells derived from the skin and hair follicles of the sheep: the involvement of peptide factors in growth regulation.

Mesenchymal components of skin and vibrissa follicles of the sheep have been introduced into culture. Outgrowths of cells were obtained from explants of the dermal papilla, follicular capsule, dermal sheath and the reticular region of the dermis. Following trypsinization, the cells were successfully propagated as monolayers through several passages. As numbers increased, both the papilla and sheath cells displayed aggregative behaviour. Capsular and dermal fibroblasts did not aggregate but became aligned into polarized arrays, the cells appearing to exert tractional forces on each other and the surface of the culture dish. In general, cell proliferation was promoted by fetal bovine serum (FBS), epidermal growth factor (EGF) and fibroblast growth factor (FGF), although the extents of the responses varied amongst the different types. Dermal fibroblasts underwent the greatest increase in numbers in the presence of FBS. The sheath and papilla cells, by contrast, were more responsive to EGF than dermal fibroblasts, with capsular fibroblasts displaying an intermediate response. Intense EGF immunoreactivity was detected in Western immunoblots of freshly isolated capsular tissue. The presence of EGF-like activity in capsular extracts was confirmed by radioreceptor assay, suggesting a specific autocrine or paracrine function for the growth factor in the local follicular environment. Mitogenic responses to FGF were approximately equivalent in all cell types when compared with controls. The similarities in aggregative behaviour and proliferative responses displayed by the dermal sheath and papilla cells suggest that they may be members of a lineage which diverged from that giving rise to the other mesenchymal derivatives during early follicle development.

Animals↗
PubMed1991

Lack of effect of epidermal growth factor treatment in late-pregnant ewes on subsequent lactation.

Twin-bearing ewes were treated with epidermal growth factor (EGF) to determine its effect on mammogenesis and resultant milk production and composition. The EGF was infused intravenously at a dose rate of 0.5 mg/d in 300 ml saline between days 117 and 139 of gestation; control animals received placebo infusions of saline. All animals then received continuous infusions of 300 ml/d saline on days 139-144. Following parturition 1-5 d later, ewes were milked by hand for 10 d and thereafter were machine-milked until day 16 of lactation. At this level of treatment, EGF was not detected in the circulation during infusion and feed intake was not affected. All ewes gave birth to healthy twin lambs. There were no effects of EGF on birth weights of lambs, live weights of ewes or lengths of gestation. An EGF-immunoreactive material was detected in the mammary secretions of control ewes at a mean concentration of 2 micrograms/l on day 1 of lactation. Two ewes had detectable levels on day 2, but none was found in the milk thereafter. In the EGF-infused group, concentrations of EGF in colostrum were approximately 10 times higher than in the control ewes on day 1 of lactation and EGF was detected in mammary secretions on day 2 but not in subsequent milk samples. A range of 0.3-0.5% of the EGF infused appeared in mammary secretions over the first 2 d of lactation. No other differences were observed for colostrum composition, subsequent milk yield or composition between the two groups of ewes indicating that mammary gland development and function were unaffected. The levels of EGF observed in the mammary secretions of treated and control ewes indicate that the mammary glands accumulate and store EGF in the pre partum period.

Animals↗
PubMed1991

Management of the violent patient. Therapeutic and legal considerations.

1. Express consent is desirable in caring for patients. However, in an emergency, when the patient is incapable of giving valid consent and harm from failure to treat is potentially imminent, care must be provided. 2. Presentation of a combative patient to an Emergency Department implies a duty of the emergency physician to render assistance according to standards of emergency medical care. 3. Third-party interests must be considered when other patients, coworkers, or potential victims of harm or violence are foreseeably recognized.

Antipsychotic Agents↗
PubMed1990

Cultivation of keratinocytes derived from epidermal explants of sheep skin and the roles of growth factors in the regulation of proliferation.

Procedures to promote the growth of primary cultures of keratinocytes derived from sheep epidermis through several passages are described. Rapid epithelial outgrowth was obtained from explants of epidermis isolated from trypsinized inguinal skin biopsy specimens. Following initiation and attachment, cells displayed the polygonal morphology typical of keratinocytes in culture and survived a number of passages before terminally differentiating and sloughing from the surface of the culture vessel. Proliferation occurred in the absence of a feeder layer and was attained in a medium supplemented with foetal bovine serum and hydrocortisone or cholera toxin. Growth was stimulated by the addition of epidermal growth factor or fibroblast growth factor (FGF) to the culture medium. The detection of basic-FGF immunoreactivity in Western immunoblots of extracts of fresh tissues suggests a role for this factor in autocrine or paracrine growth regulation of skin cell populations in vivo.

Animals↗
PubMed1990

Construction, expression and characterization of a murine/human chimeric antibody with specificity for hepatitis B surface antigen.

A murine/human chimeric antibody with specificity for Hepatitis B surface antigen has been produced by genetic engineering. The light and heavy chain variable region exons encoding the murine monoclonal antibody 2H1 were isolated and inserted into mammalian expression vectors containing the human kappa and gamma 1 constant region exons. The chimeric genes were transfected into murine Sp2/0 hybridoma cells by electroporation and transfectomas secreting chimeric antibody were isolated. Secretion levels ranged from 1-7 pg/cell/24 hr. The chimeric antibody bound specifically to Hepatitis B surface antigen and competed effectively with the parental murine monoclonal antibody for binding to these sites. Chimeric 2H1 is the first clinically relevant, genetically engineered anti-viral antibody and may represent an improved agent for the prevention of hepatitis B virus transmission.

Animals↗
PubMed1990

Comparison of intraosseous versus intravenous loading of phenytoin in pigs and effect on bone marrow.

Much recent literature supports the resurgence of the intraosseous route of access in pediatrics. Intraosseous lines provide a timely noncollapsable route to the circulation in medical or traumatic emergencies when intravenous access is not possible. There has been no controlled study comparing intravenous and intraosseous loading of phenytoin. A 15 mg/kg dose of phenytoin was administered over 15 minutes to pigs by either the intravenous (n = 6) or tibial intraosseous route (n = 6). Femoral artery blood samples were drawn every 5 minutes for 35 minutes after initiation of infusion to determine phenytoin levels. There was no statistical difference between the two groups using analysis of variance repeated measures (P = .160). Microscopic examination of the cortex and marrow at the intraosseous site in these pigs was normal 5 weeks postinfusion. The authors conclude that the intraosseous route is an effective alternative to intravenous loading of phenytoin without permanent damage to the marrow.

Animals↗
PubMed1990

Comparison of cimetidine and diphenhydramine in the treatment of acute urticaria.

Recent case reports have suggested that H2-antihistamines used alone may be effective in the treatment of acute urticaria, a common complaint of patients presenting to the emergency department. This contradicts accepted doctrine on the treatment of acute urticaria. Based on theories of H1- and H2-receptor interaction at the cellular level, it has been stated that H2-blockade before H1-blockade may exacerbate symptoms. The purpose of our study was to compare diphenhydramine, an H1-blocker, with cimetidine, an H2-blocker, in a randomized, prospective, double-blind clinical trial. Ninety-three patients presenting to the ED with clinical evidence of acute urticaria were treated with either 50 mg diphenhydramine IM or 300 mg cimetidine IM. Patients' signs and symptoms were quantitated on a numeric scale before receiving medications and 30 minutes after treatment. Parameters measured included degree of itching, intensity and extent of wheals, degree of sedation, and perception of overall improvement. Each medication provided significant relief of itching and wheal intensity (P less than .0001). Sedation was caused by both diphenhydramine (P less than .0001) and cimetidine (P less than .0006). However, the degree of sedation caused by diphenhydramine was significantly greater than that caused by cimetidine (P = .0001). The perception of overall improvement was greater with cimetidine, with 87% of patients reporting improvement, whereas 76% of diphenhydramine-treated patients reported improvement. Our results indicate that cimetidine is efficacious as the initial treatment of acute urticaria and has less tendency toward sedation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Electroglottography and vocal fold physiology.

The electroglottogram (EGG) is known to be related to vocal fold motion. A major hypothesis undergoing examination in several research centers is that the EGG is related to the area of contact of the vocal folds. This hypothesis is difficult to substantiate with direct measurements using human subjects. However, other supporting evidence can be offered. For this study we made measurements from synchronized ultra high-speed laryngeal films and from EGG waveforms collected from subjects with normal larynges and patients with vocal disorders. We compare certain features of the EGG waveform to (a) the instant of the opening of the glottis, (b) the instant of the closing of the glottis, and (c) the instant of the maximum opening of the glottis. In addition, we compare both the open quotient and the relative average perturbation measured from the glottal area to that estimated from the EGG. All of these comparisons indicate that vocal fold vibratory characteristics are reflected by features of the EGG waveform. This makes the EGG useful for speech analysis and synthesis as well as for modeling laryngeal behavior. The limitations of the EGG are discussed.

Electrodiagnosis↗
PubMed1990

Postnatal development of the hair cycle in the domestic pig.

The postnatal patterns of hair follicle activity have been quantified in pigs born in summer and winter. Animals were skin sampled monthly during the first year of life and the stages of the hair cycle were identified from follicles in histological sections. Percentages of active follicles were used to determine hair cycle patterns and as a measure of how the hair cycle became synchronised with that of the adult. At birth, in excess of 95% of follicles were active in fibre production. Within the first 12 weeks of life, the proportions of active follicles were found to approach those found in adult skin, and thereafter the hair follicle population of the growing pig displayed cycles of activity and rest reminiscent of those of the mature animal.

Aging↗