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Biomedical subjects

P McDermott

Publications and source records attributed to P McDermott.

At least 19 recordsLinked to original sources
PubMed1994

Dexamethasone therapy for isosexual precocious pseudopuberty caused by generalized glucocorticoid resistance.

Generalized glucocorticoid resistance presents with clinical features secondary to excess production of mineralocorticoids and adrenal androgens. It is our hypothesis that these clinical and biochemical features will respond to glucocorticoid therapy. We tested this hypothesis in a boy with generalized glucocorticoid resistance and increased adrenal androgens. Dexamethasone was administered from age 7 6/12 yr until the onset of true puberty at 11 0/12 yr. Serum concentrations of cortisol and adrenal androgens decreased to the normal or near normal range. The accelerated precocity improved. Secondary sex characteristics did not progress; the difference between bone age and chronological age decreased from 3 1/2 yr to 2 yr, and the difference between height age and bone age decreased from 2 yr to 1/2 yr. We conclude that dexamethasone is effective and safe therapy for the sexual precocity of generalized glucocorticoid resistance.

Age Determination by Skeleton↗
PubMed1993

Locomotion of aged rats: relationship to neurochemical but not morphological changes in nigrostriatal dopaminergic neurons.

Spontaneous locomotion and motor coordination was evaluated in young (5-6 month old) and aged (24-25 month old) rats. Animals were tested for spontaneous locomotor activity in Digiscan Animal Activity Monitors during the nocturnal cycle. Aged animals exhibited a significant hypoactivity compared to their young counterparts. Evaluation of the time course of activity revealed that the young animals had a cyclical pattern of activity during the 12-hour testing period with clear peaks at 2-4 hours after the initiation of testing and at 8- to 10-hour intervals thereafter. In contrast, the aged animals exhibited a blunted initial activity peak. During the remainder of the test period the aged animals activity was stable with no further peaks in activity. Compared to the young animals the aged animals also (a) remained suspended from a horizontal wire for less time, (b) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (c) fell more rapidly from a rotating rod and (d) were unable to maintain their balance on a series of wooden beams with either a square or rounded top of varying widths. Histological analysis demonstrated that there was no reduction in the number, area, or length of tyrosine hydroxylase-immunoreactive neurons within the A8, A9, or A10 region of the aged animals. Neurochemical analysis revealed that while DA and HVA levels were not decreased in the aged rats, DOPAC levels, as well as the ratios of DA/DOPAC and DA/HVA, were decreased. These results indicate that neurochemical but not morphological changes within the nigrostriatal dopaminergic system underlie the deficits in motor behavior observed in aged rats.

Aging↗
PubMed1993

A mutation of the glucocorticoid receptor in primary cortisol resistance.

The precise molecular abnormalities that cause primary cortisol resistance have not been completely described. In a subject with primary cortisol resistance we have observed glucocorticoid receptors (hGR) with a decreased affinity for dexamethasone. We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance. Total RNA isolated from the index subject's mononuclear leukocytes was used to produce first strand hGR cDNAs, and the entire hGR cDNA was amplified in segments and sequenced. At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GTT) substitution at amino acid 729. When the wild-type hGR and hGR-Ile 729 were expressed in COS-1 cells and assayed for [3H]-Dexamethasone binding, the dissociation constants were 0.799 +/- 0.068 and 1.54 +/- 0.06 nM (mean +/- SEM) (P < 0.01), respectively. When the wild-type hGR and hGR-Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase (CAT) gene, the hGR-Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity. The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject.

Adult↗
PubMed1990

Characterization of the Fc gamma receptor on human platelets.

IgG-containing immune complexes may play a role in the immune destruction of human platelets by interacting with an Fc gamma receptor on the platelet surface. We studied the platelet Fc gamma receptor and characterized its interaction with IgG ligand and anti-Fc gamma receptor monoclonal antibodies. Oligomers of IgG, but not monomeric IgG, bound to platelets and the number of binding sites was significantly increased at low ionic strength. Ligand-binding studies indicated that normal human platelets express a single Fc gamma receptor (Fc gamma RII) with 8559 +/- 852 sites per cell, Kd = 12.5 +/- 1.7 X 10(-8) M using trimeric IgG. Results of studies with bivalent and Fab monoclonal anti-Fc gamma RII were consistent with each Fc gamma receptor expressing two epitopes recognized by the antibody. The number of Fc gamma binding sites and affinity of binding were unchanged by the presence of 2.0 mM Mg2+ or 10 micrograms/ml cytochalasin B. Platelet stimulation with thrombin or ADP in the presence of fibrinogen also did not alter the number of Fc gamma binding sites or the affinity of binding. However, platelets preincubated with 5 microM dexamethasone expressed a decreased number of Fc gamma binding sites as well as decreased IgG-dependent platelet aggregation. Platelets from patients with Glanzmann's thrombasthenia and from patients with the Bernard Soulier syndrome expressed a normal number and affinity of Fc gamma binding sites. The data suggest that platelet Fc gamma RII binding of trimeric IgG occurs independent of actin filament interaction, Mg2+, ADP, or thrombin and does not require GPIIb/IIIa or GPIIb/IIIa-fibrinogen interaction. Furthermore, this receptor appears to be normally expressed on GPIb-deficient platelets and susceptible to modulation by glucocorticoids. Finally, the Fc gamma-binding protein was isolated from whole platelets as a 220-kDa protein which upon reduction dissociates into 50,000 Mr subunits.

Adult↗
PubMed1990

Measurement of blood flow to the adrenal capsule, cortex and medulla in dogs after hemorrhage by fluorescent microspheres.

Changes in adrenal medullary and total cortical blood flow after hemorrhage have been described using radioactive microspheres. To assess changes in adrenal capsular and in intracortical adrenal blood flow, a method was used based on microscopic detection of non-radioactive microspheres. Injection of microspheres labelled with fluorescent dyes permitted multiple determinations of blood flow. Pentobarbital anesthetized dogs (n = 6) were prepared acutely with left ventricular and aortic catheters for injection and collection of microspheres, respectively. Adrenal denervation was done unilaterally by cutting the thoracic splanchnic nerve. Injections of 16-microns spheres were made prior to and immediately after 18 ml/kg hemorrhage done over 6 min. Dogs were killed with KCl and adrenals were removed, fixed and sectioned at 80 microns. Using fluorescence microscopy, microspheres were counted in the adrenal capsule, zona glomerulosa, inner cortex (zona facsiculata and reticularis), and the medulla. The majority (95%) of microspheres in the adrenal cortex were trapped in the zona glomerulosa, precluding an independent estimate of blood flow to the inner cortex. Thus, total cortical blood flow was determined by summing the number of 16-microns microspheres in the zona glomerulosa and inner cortex. Prior to hemorrhage, blood flow was greater in the capsule (5.4 +/- 1.6 ml/min/g) compared to the cortex (1.8 +/- 0.9 ml/min/g) and the medulla (2.9 +/- 1.8 ml/min/g). Splanchnicotomy did not change blood flow in the resting state. Following hemorrhage, in innervated glands, medullary blood flow increased to 8.6 +/- 3.1 ml/min/g, whereas blood flow to other zones was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1989

Monocyte Fc gamma receptor recognition of cell-bound and aggregated IgG.

Monocyte and macrophage Fc gamma receptors are important components in the recognition of IgG-coated cells and IgG-containing immune complexes. Two proteins have been identified on human peripheral blood monocytes that can function as Fc gamma receptors, Fc gamma RI (70 Kd) and Fc gamma RII (40 Kd). We studied the role of Fc gamma RI and Fc gamma RII on human monocytes by examining their binding of IgG-sensitized cells (human IgG anti-D-coated RBCs and rabbit IgG-sensitized sheep RBCs) and their binding of human trimeric IgG. To examine the function of monocyte Fc gamma RII, we used an anti-Fc gamma RII monoclonal antibody (MoAb) that competes for the Fc gamma RII ligand binding site. Preincubation of monocytes with saturating concentrations of anti-Fc gamma RII MoAb did not alter the recognition of IgG (anti-D)-sensitized human RBCs by monocytes. Furthermore, ligand-binding studies demonstrated that anti-Fc gamma RII antibody altered neither the number nor the affinity of monocyte-binding sites for human IgG trimer. Anti-Fc gamma RII inhibited monocyte binding of rabbit IgG-sensitized sheep RBCs, but only at low ionic strength or temperature when increased numbers of monocyte Fc gamma RII were expressed. At low ionic strength and 4 degrees C, anti-Fc gamma RII also partially inhibited monocyte binding of human trimeric IgG. Thus, monocyte Fc gamma RII does not appear to recognize IgG-sensitized RBCs or trimeric IgG at physiologic temperatures and ionic strength. The data suggest that Fc gamma RI is the primary Fc gamma receptor on monocytes involved in the binding of IgG (anti-D)-sensitized erythrocytes and low mol wt complexes of IgG.

Animals↗
PubMed1987

Regulation of cardiac myosin synthesis: studies of RNA content in cultured heart cells.

Contraction regulates the myosin content and the rate of myosin synthesis in cultured neonatal rat heart cells. To further explore the mechanism for this regulation we examined various parameters of RNA content and RNA synthesis in contacting versus noncontracting myocytes. While contraction stimulated myosin heavy chain (MHC) synthesis by 72% compared to that of KCl-arrested cells, simultaneous analyses of polysome profiles were no different under the two culture conditions. Incorporation of [3H]uridine monophosphate into cellular RNA revealed no change in the rate of total RNA or ribosomal subunits synthesis. In vitro translation of cellular RNA yielded similar incorporation of [35S]methionine into trichloroacetic acid precipitable protein. Specific transcription of the MHC gene was examined by dot-blot analysis and was unaltered by contraction. Northern blot analysis of the MHC sequences detected by a cDNA probe revealed an mRNA sequence corresponding to a molecular weight of approximately 30 S. These data suggest that RNA synthesis and RNA content are unaltered by contraction in cultured heart cells and therefore the changes in myosin synthesis may be mediated at a post-transcriptional control level.

Animals↗
PubMed1985

Human monocyte recognition of complement-coated lymphoblastoid cells.

The macrophage system in man plays a significant role in the detection of foreign cells. The mechanisms by which macrophages recognize malignant cells, however, are not well understood. We used human monocytes and four lymphoblastoid cell (LC) lines derived from human acute lymphocytic leukemia to investigate the initial recognition of tumor cells by monocytes. IgM antibody mediated the binding of these cells to monocytes only in the presence of complement. The stepwise addition of complement components to IgM-coated LC indicated that C3 was necessary to monocyte binding. Similarly, monocyte recognition of IgM-coated LC was maximal in the presence of sera from patients with congenital C5 or C6 deficiency, but absent in the presence of sera deficient C4 or from a patient with congenital C2 deficiency. Complement activation was associated with C3 consumption and the deposition of substantial amounts of C3 on to LC. Although 3H-C3 bound to LC appeared stable for 2 hours, approximately 4.0 +/- 2 X 10(5) 3H-C3 per LC was necessary for monocyte recognition, compared to approximately 2.7 +/- 0.5 X 10(3) 3H-C3 per RBC. The data indicate that LC can be recognized by monocytes through complement by mechanisms similar to nonmalignant target cells. However, substantial amounts of C3 are necessary to induce monocyte recognition of IgM-coated LC and, thus, such complement mediated recognition may be inefficient.

Cell Communication↗
PubMed1985

Measurement of myosin adenosinetriphosphatase and myosin content in cultured heart cells.

An assay specific for myosin ATPase in whole-cell extracts of cultured heart cells has been developed. Myosin ATPase is measured by the production of Pi from ATP in the presence of high ionic strength (0.5 M KCl) at pH 9.1. Enzyme activity is maximal with 10 mM CaCl2 and completely inhibited with 5 mM MgCl2. Spontaneously beating myocytes grown in the presence of 10% newborn calf serum and 0.1 mM 5-bromo-2'-deoxyuridine show a significant rise in myosin ATPase between Days 1 and 4 in culture. The measurement of myosin ATPase allows for the quantitation of cellular myosin content, and can be used to assess changes in myosin content that occur during growth, development, and cellular repair.

Adenosine Triphosphatases↗
PubMed1985

Contraction regulates myosin synthesis and myosin content of cultured heart cells.

Cultured neonatal rat heart cells are a useful model for studying the regulation of myocyte growth. The myosin content of heart cells increases between days 1 and 4 in culture. To determine if contraction per se can regulate myocyte growth, myosin content and protein synthesis were compared in spontaneously contracting and noncontracting cultured heart cells. Myosin content, assayed as the total myosin ATPase activity per culture dish, was significantly increased in contracting cells after 3, 4, and 5 days in culture. Protein synthesis was measured by incorporation of [14C]lysine into total cell protein and into sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved myosin. Contraction stimulated both total cell protein content and protein synthesis by day 3 in culture. Compared with heart cells arrested with 50 mM KCl, myosin synthesis was significantly increased by 96, 112, and 46% at days 2, 3, and 4, respectively. Similar results were observed when myosin content and protein synthesis in contracting myocytes were compared with cells arrested with either 25 mM KCl or 10(-5) M verapamil. The present studies suggest that contraction increases the myosin content in cultured heart cells and that this increase is mediated via a stimulation of myosin synthesis in association with cell growth.

Adenosine Triphosphatases↗
PubMed1983

Reciprocal relationship between the levels of the hepatic nuclear binding sites for T3 and DNA replication in the liver of the rat: a possible unifying concept.

Administration of low levels of thyroid hormone (T3), subsequent to adrenalectomy, cause a pronounced proliferative response in rat liver, as judged by enhanced DNA replication. Adrenalectomy of the rat causes a reduction in the maximal nuclear binding capacity for T3 in the liver, similar to that produced by 70% hepatectomy of the rat, the former decrease lagging approximately 12 h after the latter. Similar kinetics are reported for the enhancement of hepatic nuclear DNA synthesis in these two groups of animals. Both of these effects in either group of surgically-treated animals are obviated by the injection of dexamethasone. Other reports are cited indicating that a reciprocal cause-and-effect relationship may exist between the lowering of the hepatic nuclear maximal binding capacity for T3 and subsequent enhanced hepatic DNA replication in a number of other rat model systems. It is suggested that enhanced hepatic cell proliferation in the rat may be effected by either raising the circulating levels of the thyroid hormones or by lowering the levels of the hepatic nuclear binding sites for these agents.

Adrenalectomy↗
PubMed1982

Double-contrast examination of the oesophagus: the radiological changes of peptic oesophagitis.

A simple method for obtaining double-contrast views of the oesophagus as part of the routine double contrast examination of the upper gastrointestinal tract using high-density low-viscosity barium is described. The typical radiological changes of early peptic oesophagitis (confirmed by endoscopy) which can be readily demonstrated with this technique are illustrated as an example of its practical value. These consist of 'smudged' or 'cobble-stone' mucosa with thickened and distorted longitudinal folds. Superficial erosions and deep ulcers may also be seen. It is suggested that endoscopic confirmation of these characteristic radiological signs of peptic oesophagitis is unnecessary.

Barium↗
PubMed1981

Intravenous cholangiography by bolus injection of meglumine iotroxamate and meglumine iodoxamate: a comparative trial of two new contrast media.

The meglumine salts of iodoxamic and iotroxamic acids are recently developed intravenous cholangiographic media. In several studies these two media have been shown to be significantly better than meglumine iodipamide and meglumine ioglycamate for opacification of the biliary tree and incidence of adverse effects. As part of a multi-centre double-blind trial 100 patients were given iodoxamate or iotroxamate. Comparisons of opacification, side effects and renal excretion of contrast were made. The results showed no statistically significant difference in biliary tree opacification; more frequent renal excretion of contrast with iodoxamate; and contrary to previous reports a slightly higher incidence of side effects with iotroxamate.

Biliary Tract↗
PubMed1975

Effect of corticosteroids on the human monocyte IgG and complement receptors.

A quantitative in vitro assay was employed to directly assess the effect of corticosteroids on the IgG and complement receptor function of human mononuclear phagocytic cells. In this system corticosteroids were solubilized with cholesterol-phospholipid sonicated dispersions before exposure to mononuclear cells. Solubilized corticosteroids at concentrations between 10(-4) and 10(-3) M inhibited both IgG and complement receptor activity in a dose-response fashion. Inhibition was dependent upon the time of interaction of the mononuclear cells with corticosteroids and was half-maximal by 15 min. The inhibitory effect at all concentrations of hydrocortisone was partially overcome by increasing the number of IgG molecules per erythrocyte. Hydrocortisone also inhibited the binding of erythrocytes coated with both IgG and C3, despite the fact that when both were on the erythrocyte surface a synergistic effect on binding to mononuclear cells was observed. At the steroid concentrations employed, the capacity of mononuclear cells to exclude trypan blue and to take up latex particles and neutral red was unaffected. Mineralocorticoids also inhibited receptor activity, but the sex hormones were less effective. These studies demonstrate an effect of steroid hormones on cell membrane receptor function, and they suggest that an inhibition of the recognition system for IgG and C3 in vivo may explain, in part, the effect of corticosteroids in man.

Adrenal Cortex Hormones↗
PubMed1967

A Mössbauer study of ferri- and ferrocytochrome c.

The Mössbauer spectra of horse heart ferri- and ferrocytochrome c were obtained at room temperature using lyophilized powders. The Mössbauer data indicate that the iron in both lyophilized samples is in a low-spin state. The high quadrupole splittings suggest that the iron atom is in an asymmetric ligand field. Upon reduction the asymmetry increases, suggesting a change in the bonding between the protein moieties and the iron atom.

Chemical Phenomena↗
PubMedDate not supplied

The use of allograft bone in revision of total hip arthroplasty.

Fifty-two frozen bone allografts have been used on 44 patients undergoing revision hip arthroplasties. The average follow-up time on these patients has been 17 months, with a range of six to 72 months. Both proximal femoral allografts and the allografts for the reconstruction of acetabular deficiencies have been used. To date, most patients experience marked pain relief and improvement in function. Though the results attained to date are short-term, the use of allografts in the revision hip arthroplasties represents a natural progression of the tumor work. However, while the early results are encouraging, it remains to be seen how the proximal femur allografts and the large acetabular allografts will behave over a long period of time.

Acetabulum↗