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Biomedical subjects

A Phillips

Publications and source records attributed to A Phillips.

At least 199 records · Page 11Linked to original sources
PubMed1985

Identification of adults of the Simulium damnosum complex using hydrocarbon analysis.

Using advanced gas liquid chromatography in association with multivariate statistical analysis, a study of four members of the S. damnosum complex - S. sirbanum, S. damnosum s.str., S. yahense and S. sanctipauli, revealed that both adult male and female flies could be distinguished by quantitative analysis of the cuticular hydrocarbon peaks. Adult flies were obtained from sites which were known to contain a very high proportion of pure cytospecies. The females of the complex were more readily separated from each other than were the males. On the basis of preliminary results, the technique provides for the first time, a reliable method for distinguishing S. sirbanum and S. damnosum s.str., the most important vectors of onchocerciasis in the savanna areas of West Africa, as well as an additional method for identification of adult S. sanctipauli and S. yahense. Analysis of the hydrocarbons by GC/MS showed them to be straight chain and branched saturated hydrocarbons ranging from C22-C35. The technique is simple in respect of field methods of collection, and thus holds considerable promise as a means of identifying S. damnosum complex flies throughout the area of onchocerciasis transmission in Africa.

Africa, Western↗
PubMed1984

Comparative effect of estriol and equine conjugated estrogens on the uterus and the vagina.

Estriol has been reported to act selectively on the vagina and cervix without causing endometrial proliferations. Studies comparing this effect of estriol to that of equine conjugated estrogens after intravaginal administration have not been reported. In this study, intravaginally administered Ortho- Gynest which contains estriol, and Premarin which contains equine conjugated estrogens, were evaluated for their ability to stimulate vaginal maturation and uterine growth in rats. Approximately 15 times more conjugated estrogens than estriol was needed to induce the same degree of vaginal cornification in castrated rats. In contrast, estriol was less potent than the conjugated estrogens in causing uterine growth in immature rats after subcutaneous administration in sesame oil and in mature rats after intravaginal administration in cream preparations. In studies evaluating the vaginal irritation potential of estriol vaginal cream, the irritation exhibited by treated rabbits was found to be comparable to that of sham-treated control rabbits. Estriol was well-tolerated in an oral acute safety study in rats.

Administration, Topical↗
PubMed1984

Inhibin activity and steroid hormone levels in ovarian extracts and ovarian vein plasma of female monkeys during postnatal development.

Inhibin activity, follicle-stimulating hormone (FSH)-suppressing substance, estrogen, progesterone, and androstenedione were measured in charcoal-treated ovarian tissue and ovarian venous and peripheral blood of eight rhesus monkeys ranging from 12 to 48 months of age. All of the monkeys demonstrated inhibin activity in ovarian tissue, which, if expressed per milligram protein, was relatively constant throughout development. However, if the activity was expressed per ovary, the amount of ovarian FSH-suppressing substance increased between 26 and 48 months; it was present in detectable amounts in ovarian venous blood only in one 26-month-old monkey. Detectable levels of estrogen were present in ovarian venous blood of the 26-month-old and the 48-month-old monkeys but not in the younger monkeys. It is possible that the secretion of inhibin activity may be in part responsible for low levels of serum FSH observed prior to puberty, because it has been observed by others that bilateral ovariectomy in the prepubertal monkey can result in a rise in FSH and that administration of charcoal-treated ovarian follicular fluid can suppress serum FSH in castrated prepubertal and adult rhesus monkeys.

Androstenedione↗
PubMed1984

Potency and activity variation of LHRH analogs in different models and species.

The LHRH agonist [D-His(Bzl)6, Pro9-NHEt]LHRH was estimated to be 3.4, 4.4 and 9.2 times more potent than LHRH as a stimulator of ovulation in Nembutal-anesthetized, androgen-sterilized and diestrus rats, respectively; and 57 times more potent than LHRH as a stimulator of uterine growth in immature mice. Higher doses of agonist were required to induce ovulation in diestrus hamsters and mice than were needed in diestrus rats. Rats and hamsters also exhibited different sensitivities to an antagonist of LHRH. The LHRH antagonist [N-Ac delta 3-Pro1, D-pF-Phe2,D-Trp3,6]LHRH was active but higher doses were required to inhibit ovulation in hamsters than were needed in rats. In addition, treatment at 1500 hr on the day of proestrus in rats, in contrast to treatment at 1000 hr in hamsters, caused the greatest inhibition of ovulation. It is clear from these data, that the estimated in vivo potencies of analogs of LHRH are greatly influenced by species and animal model, as well as route of administration and biopharmaceutic factors previously reported.

Animals↗
PubMed1983

Steroidogenic and morphological responses of hen granulosa cells to luteinizing hormone in vitro.

We examined in vitro progesterone production in granulosa cells isolated from the first (F1 group, 35 mm diameter) and third (F3 group, 25 mm diameter) largest ovarian follicles and granulosa cells isolated from hens stimulated hormonally to produce multiple follicular maturation (PMSG group). All granulosa cell groups maintained in a 48 hr culture produced progesterone. Luteinizing hormone (LH) significantly increased progesterone production for each group with the PMSG group progesterone levels the highest and F3 group the lowest. Light and scanning electron microscopy revealed that few single granulosa cells were present after 48 hr culture. Instead, granulosa cells were observed as multicellular aggregates, referred to here as clusters, which ranged between 15 and 60 micron in diameter. Regardless of the cell group few clusters attached to a support surface. The surface of F1 and PMSG clusters were irregular due to short folds and formed few surface elaborations. Individual cell boundaries within a cluster could not be discerned. With LH, surface folds became more elaborate, often giving rise to microvilli. Blebs about 1 micron in diameter or less also were more prevalent on clusters from groups cultured with LH. Clusters within the F3 group cultured with and without LH were similar in appearance. Therefore, in the F1 and PMSG groups, the development of surface elaborations in the form of microvilli and blebs was correlated with the LH promoted increase in progesterone production.

Animals↗
PubMed1982

Dystrophic mutation (dy2J) affecting regulation of lactate dehydrogenase (LDH) and pyruvate kinase (PK) in C57BL/6J mice.

The genotype difference (dystrophic vs nondystrophic) in the LDH isozymes is observed in kidney. These differences are evident only at birth and at early developmental stages (before the expression of dystrophic symptoms). The tissue specific genotype differences for PK are limited to the thigh muscle (M form) and heart (L form), after the onset of the condition. These differences may reflect the pleiotropic effect of the dy2J locus during the temporal regulation of these and other enzymes implicated in muscular dystrophy (MD).

Aging↗
PubMed1982

Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: experience in 26 cases.

Purified Fab fragments of digoxin-specific antibodies obtained from sheep were used to treat 26 patients with advanced, life-threatening digoxin (23 cases) or digitoxin (3 cases) toxicity. These patients had advanced cardiac arrhythmias, and in some cases hyperkalemia, which were resistant to conventional treatment. All patients had an initial favorable response to doses of Fab fragments calculated (in most cases) to be equivalent, on a molar basis, to the amount of cardiac glycoside in the patient's body. In four patients treated after prolonged hypotension and low cardiac output, death ensued from cerebral or myocardial hypoperfusion. In one case the available Fab fragment supply was inadequate to reverse a massive suicidal ingestion of digoxin, and the patient died after recurrent ventricular arrhythmias. In the remaining 21 patients, cardiac rhythm disturbances and hyperkalemia were rapidly reversed, and full recovery ensued. There were no adverse reactions to the treatment. We conclude that the use of purified digoxin-specific Fab fragments is a safe and effective means to reverse advanced, life-threatening digitalis intoxication.

Adolescent↗
PubMed1982

The effect of porcine follicular fluid on ovulation, mating and pregnancy in the rat.

We have examined the effects of charcoal-treated, greater than 10,000 MW porcine follicular fluid (PFF retentate) treatment on ovulation, cyclicity, mating and pregnancy in the rat. Rats treated i.p. with PFF retentate twice on the day of metestrus and once on the day of diestrus exhibited a dose-related reduction in the mean number of ova when oviducts were checked on the afternoon of expected estrus. However, oviducts checked on the morning of expected metestrus contained a normal number of ova. To study the effects of PFF retentate on cyclicity, mating and subsequent pregnancy, rats were treated (0.2 ml, i.p.) two, three or four times a day beginning on the day of metestrus until proestrus cytology was exhibited. PFF retentate treatment resulted in a dose-related delay in the appearance of proestrus cytology and a reduction in the number of embryonic implants following cohabitation with males on the night of proestrus. However, PFF retentate had no effect on the number of implants, when given post-coitally. These results show that administration of PFF retentate to female rats delays ovulation, alters the estrous cycle and reduces the mean number of embryonic implants in a dose-related manner.

Animals↗
PubMed1982

Flat small intestinal mucosa and autoantibodies against the gut epithelium.

A male infant, aged 1 year 3 months, was admitted to the hospital with protracted diarrhoea, vomiting, and weight loss. The diarrhoea and vomiting coincided with an outbreak of acute diarrhoea and vomiting affecting other family members. Biopsy showed a flat small intestinal mucosa which did not respond to a diet free of gluten, cow's milk, and eggs, or during 8 weeks of intravenous alimentation. Steroids were given, and courses of nalcrom and later cimetidine, but these did not produce any significant improvement. A rare IgG autoantibody specific for gut epithelium was found, which, when present, was associated with a cytological abnormality of crypt enteroblasts. The autoantibody disappeared after treatment with cyclophosphamide, and the cytological abnormality subsequently diminished. However, the mucosa remained severely abnormal and has been so for 23 months. It is possible that an autoimmune reaction against the patient's small intestinal mucosa has led to persistence of the enteropathy.

Animals↗
PubMed1982

Traveller's diarrhoea with a vengeance in children of UK immigrants visiting their parental homeland.

Six healthy children, born in the UK, travelled to their parental homeland and developed a severe form of traveller's diarrhoea. This was characterised by rapid loss of weight and chronic diarrhoea. On return to this country, investigation in 5 of them showed an abnormal, small intestinal mucosa. There was a high incidence of pathogens and potential pathogens found in stools and duodenal juice. Immunodeficiency was found in 2 of them. Small intestinal mucosal damage related to gut infection in previously well children appears to be of cardinal importance in the interaction between chronic diarrhoea and malnutrition. This observation may point the way to future research into the primary role of gut infection in the initiation of the cycle of malnutrition and chronic diarrhoea in developing communities.

Body Weight↗
PubMed1982

Analysis of phosphate in serum with the phosphate redox electrode system.

A phosphate redox electrode system (PRES) was designed, constructed, and evaluated for analysis of inorganic phosphate in serum. This system is based on the observed phosphate ion potential of a chemically treated iron wire in a turbulent flow-through cell at constant oxygen tension. We analyzed 110 clinical samples by this technique and with the Technicon SMAC. Of the specimens analyzed, 32% contained abnormal phosphate concentrations. Each was assayed two to four times with the PRES and once with the SMAC. The PRES assay rate was 60 samples/h. Mean phosphorus concentrations (and SEM) were: PRES, range of values for replicate data sets, 30.5-31.0 (0.5-1.1) mg/L; SMAC, 30.8 (1.0) mg/L. Results for the PRES (y) correlated well with those by the SMAC: r = 0.968 to 0.980, estimated slope = 0.99 to 1.03, and estimated intercept = -1.1 to 0.1 mg/L. Differences in results by the two methods were not statistically significant.

Electrochemistry↗
PubMed1978

Cows' milk-sensitive enteropathy.

Serial small intestinal biopsies related to withdrawal and challenge with cows' milk are described in 5 infants with cows' milk protein intolerenace. On the basis of these serial observations the existence of a cows' milk-sensitive enteropathy in infancy is clearly established. The cows' milk-sensitive mucosal lesion varied in its severity ranging from a partly flat mucosa to a mild degree of partial villous atrophy. Intraepithelial lymphocyte counts rose after a positive milk challenge, but on only one occasion to a level outside the normal range. The technique of serial biopsies related to dietary milk enables a firm diagnosis of cows' milk intolerance to be made upon the basis of a single milk challenge. Clinically this appears to be a temporary condition which disappears by the age of 2 years.

Animals↗
PubMed1975

Purification and properties of Escherichia coli dihydrofolate reductase.

Dihydrofolate reductase has been purified 40-fold to apparent homogeneity from a trimethoprim-resistant strain of Escherichia coli (RT 500) using a procedure that includes methotrexate affinity column chromatography. Determinations of the molecular weight of the enzyme based on its amino acid composition, sedimentation velocity, and sodium dodecyl sulfate gel electrophoresis gave values of 17680, 17470 and 18300, respectively. An aggregated form of the enzyme with a low specific activity can be separated from the monomer by gel filtration; treatment of the aggregate with mercaptoethanol or dithiothreitol results in an increase in enzymic activity and a regeneration of the monomer. Also, multiple molecular forms of the monomer have been detected by polyacrylamide gel electrophoresis. The unresolved enzyme exhibits two pH optima (pH 4.5 and pH 7.0) with dihydrofolate as a substrate. Highest activities are observed in buffers containing large organic cations. In 100 mM imidazolium chloride (pH 7), the specific activity is 47 mumol of dihydrofolate reduced per min per mg at 30 degrees. Folic acid also serves as a substrate with a single pH optimum of pH 4.5. At this pH the Km for folate is 16 muM, and the Vmax is 1/1000 of the rate observed with dihydrofolate as the substrate. Monovalent cations (Na+, K+, Rb+, and Cs+) inhibit dihydrofolate reductase; at a given ionic strength the degree of inhibition is a function of the ionic radius of the cation. Divalent cations are more potent inhibitors; the I50 of BaCl2 is 250 muM, as compared to 125 mM for KCl. Anions neither inhibit nor activate the enzyme.

Amino Acids↗
PubMed1973

Mechanics of sphincter action. Studies on the lower esophageal sphincter.

The purpose of this study was to evaluate the mechanical factors involved in the genesis of lower esophageal sphincter pressure. We determined the relationship between intraluminal pressure and inside diameter, estimated the ratio between the wall thickness to inside radius, and calculated the tension in the wall of the lower esophageal sphincter as a function of the inside diameter. Various degrees of circumferential stretch were applied by introducing probes of different diameters in the rat lower esophageal sphincter in vivo. The intraluminal pressure produced by the lower esophageal sphincter around each probe was measured and pressure-diameter curves were constructed during (a) resting state, (b) contraction produced by electrical stimulation, and (c) relaxation produced by esophageal distension. The intraluminal pressure at an inside diameter of 0.5 mm was similar to that at inside diameter of 3.2 mm. This was true for the sphincter at rest as well as upon electrical stimulation. The pressure diameter curve, however, was sigmoid in shape; at first it showed a decline and then an increase followed by decline in pressure again with increasing diameters. The ratio of wall thickness to inside radius or the magnification factor varied with inside diameters as expected and this ratio increased steeply at small inside diameters. The tension diameter curves of the sphincter muscle showed that optimal tension development occurred not near sphincter closure but at a much wider diameter of 3.2 mm and that this muscle developed tension even at small luminal diameters. This behavior of the sphincter muscle ensures effective intraluminal pressure over a wide range of luminal diameters.

Animals↗
PubMed1971

Mechanical properties of the esophageal wall.

Pressure-diameter curves of the esophagus were obtained to define its mechanical properties. The mucosal contribution to the strength of the esophagus was negligible until the outer diameter almost doubled, suggesting that small intraluminal pressures are held by the muscle layer alone. For larger deformations mucosal contribution increased and at failure the mucosa held over one-half of the failure pressure of the esophagus. The paths followed during loading and unloading are different and exhibit hysteresis. They are influenced by the rate of pressure change, being more compliant for low rates of pressure change. They are influenced by the history of loading, being different for successive loading-unloading cycles. If enough loading-unloading cycles are repeated a stable loop is reached, which does not change thereafter. Both the mucosa and the whole esophagus show increasing stiffness with increasing pressure. This behavior can be represented by a simple exponential relationship. However, at rapid rates of pressure increases, the esophageal muscles produce sigmoid loading curves, which gradually become exponential when repeating loading.

Animals↗