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Biomedical subjects

M McGrath

Publications and source records attributed to M McGrath.

At least 73 records · Page 4Linked to original sources
PubMed1987

Characterization and epitope mapping of a human monoclonal antibody reactive with the envelope glycoprotein of human immunodeficiency virus.

A human monoclonal antibody (IgG2, lambda), 1B8.env, was produced, reactive with the envelope glycoprotein of human immunodeficiency virus (HIV). The antibody specifically stains cells infected with HIV, as assessed by indirect immunofluorescence analysis and reacts with determinants displayed on the surface of infected cells. In Western blot analysis, the antibody reacts with bands of 160 and 41 kD, consistent with the precursor and transmembrane forms of the HIV envelope glycoprotein. The antibody also reacts specifically in immunofluorescence and Western blot analysis with cells infected with the recombinant vaccinia virus VSC-25, which contains the envelope gene of HIV. With the lambda gt11 expression vector, the epitope recognized by 1B8.env was mapped to a region of 11 amino acids in the coding region of gp41. This domain is highly conserved between several otherwise highly variable HIV isolates. In addition, this epitope appears to be recognized by the vast majority of HIV seropositive individuals. Although antibody IB8.env does not neutralize HIV virion infectivity or virally mediated cell fusion, the results presented here demonstrate the feasibility of generating and characterizing human monoclonal antibodies to HIV with these techniques. Additional antibodies produced in this manner will help to further characterize the humoral response to HIV infection, define biologically significant determinants on HIV proteins, and may be useful in clinical applications.

Amino Acid Sequence↗
PubMed1987

Propidium binding to a ribonuclease-DNA complex: X-ray and fluorescence studies.

Propidium iodide, an antitumor compound, was diffused into crystals of a complex between RNase A and deoxytetraadenylate (dpA)4). This complex has four deoxyoligomers bound per protein molecule. A difference Fourier analysis at 2.9 A showed that the principal binding site for the propidium in the crystals was a hydrophobic depression on the side of RNase away from the active site and apparently involves methionine 13 and phenylalanine 8. Binding of propidium at this site produces small conformational changes that effect binding of nucleotides at the active site of the enzyme. Fluorescence titrations in the presence and absence of nucleotide inhibitors suggested that propidium iodide is a competitive inhibitor of the enzyme with a Kl of approximately 1 mM. No significant binding of propidium to the 16 nucleotides of single-stranded DNA associated with each protein molecule was observed.

Fourier Analysis↗
PubMed1986

An experiment regarding crystallization of soluble proteins in the presence of beta-octyl glucoside.

Twenty-one soluble proteins, five tRNAs, and three protein-nucleic acid complexes were studied in a systematic manner with regard to their crystallization behavior from polyethylene glycol and ammonium sulfate solutions in the presence of 0 to 1.5% beta-octyl glucoside. Our observations suggest that this neutral detergent does influence in a very positive way the growth characteristics of the macromolecules included in this experiment. In general, more reproducible and rapid growth was noted with an increased number of large individual crystals at the expense of microcrystals. In several cases, new crystal forms were discovered. Selected x-ray diffraction analyses imply that crystals grown in the presence of beta-octyl glucoside diffract as well or better than those grown in its absence. In addition, a screen of two proteins grown in the presence of 14 different common detergents suggested that a general detergent effect may be beneficial for the growth of crystals of biological macromolecules.

Crystallization↗
PubMed1985

Blood content of broiler chicken carcases prepared by different slaughter methods.

Two trials using broiler chickens were undertaken to determine if variations in commercial slaughter techniques affected either the appearance or the residual blood content of the carcases produced. In the first trial groups of broilers were either stunned (55, 80 or 105 volts), electrocuted (240 volts) or anaesthetised and the subsequent bleed-out volumes after one, two, three and four minutes exsanguination were measured. The method of slaughter made no difference to the amount of blood lost after venesection. Haemoglobin content of the pectoral muscle was used to measure residual blood and was uniformly low in all groups (0.7 to 0.16 mg haemoglobin/g of muscle). In the second trial groups of chickens were either stunned and bled out, electrocuted, electrocuted and bled out, decapitated or halal killed before processing. The edible portions of the carcases were minced and the average haemoglobin content for each group was 0.19, 0.36, 0.22, 0.17 and 0.17 mg/g of soft tissue. The appearance of chickens that were stunned and bled out was the same as that of chickens that were electrocuted and bled out. The authors conclude that killing chickens by electrocution before exsanguination does not adversely affect the carcase appearance. Furthermore, electrocution ensures that broiler chickens are humanely slaughtered.

Abattoirs↗
PubMed1985

Red cell deformability and other haemorheological variables in stable coronary artery disease.

In this study, red cell deformability and other haemorheological variables were measured in 40 patients who underwent cardiac catheterization for the investigation of chest pain. The patients were divided into two groups - those with extensive disease and those with less extensive or no disease. Deformability was assessed by a filtration method. There were no significant differences in filterability, haematocrit, plasma viscosity or plasma fibrinogen between the two groups of patients. However, those with extensive disease had significantly higher blood viscosity than those with less extensive disease. Thus the study was able to demonstrate an association between blood viscosity and extent of coronary artery disease but not between the individual determinants of blood viscosity (red cell deformability, plasma fibrinogen and haematocrit) and extent of disease.

Adult↗
PubMed1985

Differential response of normal rat mammary epithelial cells to mammogenic hormones and EGF.

A simple dissociation procedure and the collagen gel culture system have been utilized to determine the effects of mammogenic hormones and epidermal growth factor (EGF) on the proliferation of normal rat mammary epithelial (RME) cells in serum-free culture. Epithelial fragments, isolated from normal virgin F344 rat mammary glands by enzyme digestion followed by Percoll density gradient centrifugation, were embedded within a rat tail collagen matrix. A three- to four-fold increase in cell number was observed when ovine prolactin (PRL) and progesterone (P) were present in the basal medium during 7 days of culture. Mouse EGF stimulated one cell doubling during the same culture period. Isolated mammary organoids produced a 'stellate' type colony when PRL + P were present in the culture medium. These colonies were composed of small, tightly packed cuboidal cells. The addition of EGF to the basal medium produced a diffuse 'basket' type colony which was composed of large, elongate cells. When the complete hormonal and growth factor combination (PRL + P + EGF) was present, a 'mixed' type colony was observed which contained both the large and small epithelial cell types. Immunocytochemical analysis revealed that both the cuboidal and elongate cells present in the two colony types stained with antibodies to keratin indicating that these cells were epithelial in nature. The small cuboidal cells also expressed thioesterase II and alpha-lactalbumin, both specific for secretory mammary epithelial cells. The large, elongate cell type, however, was positive for actin but did not stain for either secretory epithelial specific marker. The results reported here suggest that normal rat mammary tissue may contain two epithelial populations, one which responds to PRL + P and the other which responds to EGF.

Animals↗
PubMed1985

Protection of recently shorn sheep against adverse weather using plastic coats.

Sheep cold stressed for 10.5 h had plastic coats applied then the cold stress was continued. In 9 of 10 sheep (test group) showing hypothermia at the time coats were applied, body temperatures had returned to near normal 2.5 h later and to normal in 13.5 h. One sheep severely hypothermic before the coat was applied did not improve and was killed after 2.5 h. Sheep that were cold stressed without coats (wet controls) developed marked hypothermia and were killed between 10.5 h and 21 h. Rectal temperatures remained normal in controls that were cold stressed with coats on (coated wet controls) and in the controls not subjected to wetting (dry controls). Plasma cortisol increased markedly in the cold stressed sheep until plastic coats were applied, but the levels had fallen to normal levels 20 h later. Serum thyroxine levels increased at a faster rate in the test group and in wet controls than in the dry controls and coated wet controls during the first 9 h of cold stress. In 4 sheep of the test group energy utilisation increased markedly and remained high for a variable time after coats were applied then gradually returned to pre-cold stress levels. Liver tyrosine aminotransferase levels of the wet controls were markedly elevated compared to levels found in the test group sheep killed 79.5 h after coats were applied. Histological changes in the spleen and liver of wet controls was absent or only mildly present in the test group sheep. There was severe depletion of muscle and liver glycogen in the wet controls compared with the test group sheep, which were similar to the dry controls and coated wet controls.

Animals↗
PubMed1985

Intermodal timing relations and audio-visual speech recognition by normal-hearing adults.

Audio-visual identification of sentences was measured as a function of audio delay in untrained observers with normal hearing; the soundtrack was replaced by rectangular pulses originally synchronized to the closing of the talker's vocal folds and then subjected to delay. When the soundtrack was delayed by 160 ms, identification scores were no better than when no acoustical information at all was provided. Delays of up to 80 ms had little effect on group-mean performance, but a separate analysis of a subgroup of better lipreaders showed a significant trend of reduced scores with increased delay in the range from 0-80 ms. A second experiment tested the interpretation that, although the main disruptive effect of the delay occurred on a syllabic time scale, better lipreaders might be attempting to use intermodal timing cues at a phonemic level. Normal-hearing observers determined whether a 120-Hz complex tone started before or after the opening of a pair of liplike Lissajou figures. Group-mean difference limens (70.7% correct DLs) were - 79 ms (sound leading) and + 138 ms (sound lagging), with no significant correlation between DLs and sentence lipreading scores. It was concluded that most observers, whether good lipreaders or not, possess insufficient sensitivity to intermodal timing cues in audio-visual speech for them to be used analogously to voice onset time in auditory speech perception. The results of both experiments imply that delays of up to about 40 ms introduced by signal-processing algorithms in aids to lipreading should not materially affect audio-visual speech understanding.

Adult↗
PubMed1984

Correlation between in vitro growth and regulation of estrogen and progesterone receptors in rat mammary epithelial cells.

The present studies examine 1) the effect of enzymatic cell dissociation on the level of cytosolic estrogen receptor (ER) and progesterone receptor (PR) for normal rat mammary tissue, 2) the concentrations of ER and PR in rat mammary epithelial (RME) cells cultured within collagen gel, and 3) correlations that may exist between receptor concentration and cultured RME cell proliferation after hormonal stimulation in vitro. After cell dissociation, ER was present in mammary cells at higher concentrations than those found in the whole gland, whereas PR concentrations were similar to those in the whole gland. As characterized by Scatchard analysis, PR and, to a lesser extent, ER can be maintained in cells cultured in serum-free medium within a collagen gel matrix. ER is apparently functional at relatively low levels, since estradiol did induce PR synthesis, and cytosolic ER was reduced by estrogen administration. However, estradiol had no mitogenic effect on RME cells in this system, supporting the hypothesis that there may be a dichotomy between estrogen's effect on growth and progesterone receptor synthesis. PRL plus progesterone act synergistically to induce cell proliferation in our system, and this correlates with increased concentrations of progesterone receptors. Thus, the collagen gel system appears to provide a useful in vitro model for the study of receptor regulation and cell proliferation.

Animals↗
PubMed1984

Issues in fertility control for mentally retarded female adolescents: I. Sexual activity, sexual abuse, and contraception.

Little information is available about sexual activity, sexual assault, and contraceptive use among mentally retarded adolescents. The experience in these areas among 87 mentally retarded females is reviewed. (A companion paper focuses on these patients' parental attitudes toward sterilization.) All subjects attended a multiservice adolescent clinic with a large developmentally disabled patient group. Charts were reviewed and 69 parents were interviewed. The patients had an age range from 11 to 23 years (mean 16.7). Forty-one subjects were mildly retarded (IQ 55 to 69), 23 were moderately retarded (IQ 41 to 54), and 23 were severely retarded (IQ less than 41). Half of the mildly retarded had had sexual intercourse, a proportion comparable to the general adolescent population. Thirty-two percent of the moderately retarded and nine percent of the severely retarded adolescents had had intercourse. One third of the mildly retarded and one fourth of the moderately retarded adolescents had been victims of rape or incest. Continued sexual activity correlated with sexual abuse, but the majority of victims had no prior or subsequent evidence of intercourse. Forty-two subjects (48%) had used contraception at some time; intrauterine devices and injectable medroxyprogesterone acetate were preferred to oral contraceptives. Six of the 14 patients (43%) who continued sexual activity became pregnant, suggesting that currently available contraception is not providing sufficient protection.

Adolescent↗
PubMed1984

Issues in fertility control for mentally retarded female adolescents: II. Parental attitudes toward sterilization.

Knowledge of the issues involving sterilization for mentally retarded adolescents is limited. Data were obtained from 69 interviewed parents whose mentally retarded daughters were attending the Cincinnati Adolescent Clinic. (A companion paper focuses on the experience of these girls with sexual activity, sexual abuse, and contraceptive use.) Forty-six percent of the parents had considered sterilization for their daughters. Twenty-six percent were still seeking the operation. Interest in sterilization especially correlated with increased severity of retardation (P less than .005) and with difficulty teaching menstrual hygiene (P less than .005). Parents of mildly retarded females sought tubal ligation, and those with severely retarded daughters chose hysterectomy and stressed their concern about menstrual management. Eighty-five percent of the parents favored a state statute that would enable sterilization under certain conditions and limitations. In general, few parents supported either an extremely restrictive or permissive position about sterilization.

Adolescent↗
PubMed1983

Disposition of ethanol in human maternal venous blood and amniotic fluid.

The disposition of ethanol and acetaldehyde in maternal venous blood and amniotic fluid was studied over 3.5 hours following the ingestion of 0.3 gm/kg of ethanol by six healthy pregnant women at 16 to 18 weeks' gestation. There was a time lag in the appearance of ethanol in amniotic fluid compared with its appearance in maternal venous blood. The maximum maternal venous blood ethanol concentration was twice the maximum amniotic fluid ethanol concentration and occurred at an earlier time. At 3.5 hours, ethanol was present in amniotic fluid, whereas there was virtually no measurable ethanol in maternal venous blood. The rate of ethanol elimination from amniotic fluid was about half the elimination rate from maternal venous blood. Acetaldehyde was present in the maternal venous blood of four subjects, and the maximum acetaldehyde concentration occurred at about the same time as the maximum maternal venous blood ethanol concentration. Acetaldehyde was found in the amniotic fluid of one of these four subjects, and the acetaldehyde concentration was greater in amniotic fluid than in maternal venous blood. It is proposed that the amniotic fluid may act as a reservoir for ethanol following maternal ingestion such that the fetus would be exposed to ethanol for a longer time period than would be predicted by the maternal venous blood ethanol concentration.

Acetaldehyde↗