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Biomedical subjects

J McMahon

Publications and source records attributed to J McMahon.

At least 55 records · Page 3Linked to original sources

Microwave antigen retrieval for immunocytochemistry on formalin-fixed, paraffin-embedded post-mortem CNS tissue.

Microwave antigen retrieval methods were assessed for a panel of antibodies on formalin-fixed, paraffin-embedded sections from a range of human central nervous system (CNS) tissues taken at post-mortem. The immunoreactivity of a number of antigens (synaptophysin, PGP9.5, GFAP, carbonic anhydrase II, CD68, ferritin, HLA-DR, alpha beta-crystallin, measles and herpes viruses) was markedly enhanced by this procedure compared with other methods of antigen unmasking, such as trypsinization. Enhancement was noted both by an increased number of positive cells and by the intensity of reactions within individual cells and their processes. Furthermore, the microwave method produced uniform immunostaining over large surface area sections with no loss of morphological detail. Large cryostat sections of CNS tissue can be difficult to obtain with good morphology. The ability to retrieve a wide range of antigen in formalin-fixed, paraffin-embedded CNS tissue will greatly increase the range of investigations that can be carried out on this type of stored material.

Antigens↗

beta-Endorphin enhances the replication of neurotropic human immunodeficiency virus in fetal perivascular microglia.

The effect of an endogenous opiate, beta-endorphin, on the replication of HIV was investigated in brain perivascular microglia. Beta-endorphin enhanced the synthesis of p-24 antigen and transactivation of HIV promoter. Dialysed culture supernatants of endorphin-treated microglia re-activated latent HIV infection. These culture supernatants showed elevated levels of interleukin-1 beta, IL-6 and tumor necrosis factor alpha. Sub-optimal concentration of beta-endorphin potentiated GP-120-induced synthesis of these cytokines. Nalaxone reversed beta-endorphin-induced, but not GP-120-induced, cytokine production and enhanced HIV replication. These results suggest that endogenous opiates may contribute to the progression of AIDS dementia complex.

Cytokines↗

A comparison of digoxigenin and biotin labelled DNA and RNA probes for in situ hybridization.

A number of in situ hybridization protocols using digoxigenin or biotin labelled probes were assessed for viral nucleic acid detection in formalin fixed, paraffin embedded tissue. Single-step detection protocols for biotin labelled probes produced low sensitivity; however, enzyme based one-step detection protocols for digoxigenin probes produced high sensitivity for both RNA and DNA systems. For both probe types, multistep detection protocols produced equally high sensitivity. Use of an enhanced APAAP procedure for digoxigenin labelled probes achieved maximal sensitivity without use of biotin-strep-tavidin reactions. The sensitivity of nucleic acid detection obtained with a digoxigenin labelled probe is comparable to that obtained using biotin. Digoxigenin labelled probes for nucleic acid detection are recommended for tissues with endogenous biotin.

Animals↗

Mineralizing pulmonary elastosis in chronic cardiac failure. "Endogenous pneumoconiosis" revisited.

The histopathology, ultrastructure, and clinicopathologic correlations in six patients with cardiac failure and iron encrustation of lung elastic tissue were examined at autopsy. Transmission electron microscopy (TEM) and energy dispersive x-ray analysis were applied to two cases. Of the group, five patients had cardiac failure due to systemic hypertension (4 patients), valvular disease (4 patients), or coronary atherosclerosis (4 patients). Biventricular failure in one patient was associated with sleep apnea. Both iron and calcium, identified by histochemical stains, impregnated degenerated alveolar and vascular elastic fibers and were associated with a foreign body reaction and focal interstitial fibrosis. Energy dispersive x-ray analysis and TEM demonstrated iron and calcium on the microfibrillar portion of elastin. Morphometry indicated vascular changes of pulmonary venous hypertension. The authors concluded that mineral deposition probably represents nonspecific precipitation of metallic ions on altered elastic fibers in patients with cardiac failure. "Mineralizing elastosis" potentially contributes to lung restriction and, occasionally, can be a source of diagnostic confusion.

Adult↗

Molecular and phenotypic mapping of the short arm of chromosome 5: sublocalization of the critical region for the cri-du-chat syndrome.

Forty-nine individuals have been identified with deletions or translocations involving the short arm of chromosome 5. While most display the classical phenotype of the cri-du-chat syndrome, several of the patients do not have the syndrome or have only a subset of the clinical features. Somatic cell hybrids containing the deleted chromosome 5 were derived from each patient. Each somatic cell hybrid was analyzed at the DNA level using 136 chromosome 5p-specific DNA fragments. It was possible to unambiguously order most of the chromosomal breakpoints present in the somatic cell hybrids based on the hybridization patterns of Southern blots. Further comparisons between the deletions present in the patients and their clinical features identified several chromosomal regions that were involved in specific clinical features. A critical chromosomal region involved the high-pitched cry mapped to 5p15.3, while the chromosomal region involved in the remaining features of the cri-du-chat syndrome mapped to a small region within 5p15.2. Deletions that did not include these two chromosomal regions presented varying clinical phenotypes from severe mental retardation and microcephaly to a clinically normal phenotype. These results demonstrate the need for careful characterization of a 5p deletion in prenatal cases before clinical predictions are made.

Animals↗

Negative alcohol expectancy predicts post-treatment abstinence survivorship: the whether, when and why of relapse to a first drink.

Using survival analysis, the association was explored between positive and negative alcohol expectancies measured on admission to a non-residential alcohol dependence treatment unit and post-treatment relapse to a first drink (first slip). A reliable association between negative alcohol expectancy (but not positive) and relapse was found. The active negative alcohol expectancies were distal rather than proximal: proximal expectancies surround consumption ('same day' expectancies) and distal expectancies relate to the 'next-day' following consumption or those longer term expectancies coming from 'continued drinking'. Only the 'next day' component of distal expectancies formed a reliable association with relapse. The use to which negative alcohol expectancy as measured by the Negative Alcohol Expectancy Questionnaire might be put is discussed in terms of (i) a bottom-up representation of motivation for recovery to help treatment match and (ii) a provisor of detailed, client-specific information for structuring motivational interventions.

Adult↗

Association of measles virus with neurofibrillary tangles in subacute sclerosing panencephalitis: a combined in situ hybridization and immunocytochemical investigation.

Neurofibrillary tangle formation, a cardinal characteristic of Alzheimer's disease, is also a feature of several other neurodegenerative disorders, including subacute sclerosing panencephalitis (SSPE). In the present study the association of measles virus genome with neurofibrillary tangle formation has been studied in five cases of SSPE, using in situ hybridization (measles genome) and immunocytochemistry (tau, ubiquitin and beta/A4 amyloid). In two cases with duration of disease less than one year, neurofibrillary tangle formation was not observed. However, in those cases in which the disease was of several years duration, numerous tau- and ubiquitin-positive neurofibrillary tangles were demonstrated. In the two cases of longest duration, double-labelling techniques demonstrated the frequent association of neurofibrillary tangle formation with neuronal measles virus genome positivity. Immunocytochemistry for beta/A4 amyloid failed to demonstrate amyloid in any of the five cases. These findings support the hypothesis that neurofibrillary tangle formation can occur independently of amyloid formation and that this mechanism may operate in both Alzheimer's disease and in virally-induced disease.

Adolescent↗

Negative and positive alcohol expectancies as predictors of abstinence after discharge from a residential treatment program: a one-month and three-month follow-up study in men.

Male alcohol dependent clients (N = 53), who were given the Alcohol Expectancy Questionnaire and the Negative Alcohol Expectancy Questionnaire upon admission to a residential alcohol treatment program, were successfully followed-up 1 month and 3 months after discharge to assess their compliance with the treatment goal of total abstinence. At 1 month, neither demographic variables nor alcohol expectancies were associated with outcome consumption. At 3 months, however, the demographic variable, age, total negative expectancy (but not total positive) and the two subscales, global positive expectancy and continued-drinking negative expectancy (representing longer term expected negative consequences), were. The potential importance of negative alcohol expectancy in drinking decisions and the limitations of the study were identified.

Adult↗

Mutations in the gyrB domain of eukaryotic topoisomerase II can lead to partially dominant resistance to etoposide and amsacrine.

Anti-topoisomerase II agents represent a major class of anticancer therapeutic agents. Resistance to this class of agents can be mediated by several possible mechanisms. One mechanism may involve mutations in the structural gene(s) for topoisomerases, altering the drug sensitivity of the enzymes. Several mutations have been described in mammalian cell lines that were selected for resistance to topoisomerase II-targeting drugs such as Adriamycin, etoposide, or amsacrine. The difficulty of performing genetic analysis in mammalian cell lines has complicated the determination of whether the observed mutations are responsible for drug resistance. We have reconstructed, in the yeast topoisomerase II gene, the arginine to glutamine mutation at position 450 of human topoisomerase II alpha that was originally identified by Bugg et al. [Proc. Natl. Acad. Sci. USA 88:7654-7658 (1991)]. Mutation of Lys439, the equivalent amino acid in the yeast protein, to either glutamine or glutamic acid confers resistance to etoposide and amsacrine. Interestingly, in diploid yeast cells the heterozygous mutation can still confer partial drug resistance, compared with a diploid strain that is homozygous for wild-type topoisomerase II. Because mutations in the topoisomerase II gene that can confer dominant resistance to anti-topoisomerase II agents are relatively rare, mutations in the gyrB region may be important in the development of clinical drug resistance.

Amino Acid Sequence↗

The human myelin basic protein gene is included within a 179-kilobase transcription unit: expression in the immune and central nervous systems.

Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs have been isolated from a human oligodendroglioma cell line. Analysis of these cDNAs has enabled us to determine the entire structure of the human Golli-MBP gene. The Golli-MBP gene, which encompasses the MBP transcription unit, is approximately 179 kb in length and consists of 10 exons, seven of which constitute the MBP gene. The human Golli-MBP gene contains two transcription start sites, each of which gives rise to a family of alternatively spliced transcripts. At least two Golli-MBP transcripts, containing the first three exons of the gene and one or more MBP exons, are produced from the first transcription start site. The second family of transcripts contains only MBP exons and produces the well-known MBPs. In humans, RNA blot analysis revealed that Golli-MBP transcripts were expressed in fetal thymus, spleen, and human B-cell and macrophage cell lines, as well as in fetal spinal cord. These findings clearly link the expression of exons encoding the autoimmunogen/encephalitogen MBP in the central nervous system to cells and tissues of the immune system through normal expression of the Golli-MBP gene. They also establish that this genetic locus, which includes the MBP gene, is conserved among species, providing further evidence that the MBP transcription unit is an integral part of the Golli transcription unit and suggest that this structural arrangement is important for the genetic function and/or regulation of these genes.

Alternative Splicing↗

Diet and dental caries in preschool children.

A study was carried out in two New Zealand cities with a fluoridated water supply, to look at the dietary habits of preschool children and to investigate whether any dietary factors or other variables are associated with dental decay in the deciduous teeth of these children. From a final study of 355 (a 59% response rate), demographic data, a dental examination, a series of three 24 h recalls over a period of 1 year, and a food frequency questionnaire to cover the same 1 year interval were collected. The sample included 93 children with dental decay and 262 caries-free children, matched for age, sex and sociodemographic variables. The energy and nutrient intakes of the preschool children were sufficient to support normal growth. The main sources of dietary energy in the diets of this study group came from bakery and dairy products. Boys had slightly higher mean intakes of most nutrients than girls. No significant differences were found in the food patterns or intakes of macronutrients between the children of this study group with caries and those without. There was an inverse relationship between social background and dental health, with increasing social advantage being associated with decreasing dental health problems. Syrup medicines and, in particular, antibiotic syrups independently increased the risk that a child would have a number of carious lesions, especially if taken frequently.

Anthropometry↗

Congenital oesophageal respiratory tract fistula presenting in adult life.

Congenital oesophageal respiratory tract fistula presenting in adult life is rare. A tracheo-oesophageal and a broncho-oesophageal fistula presenting in a 22 year old female and 68 year male, respectively, are described. In both, symptoms of chronic recurrent pulmonary suppuration were initially attributed to alternative aetiologies, resulting in diagnostic delay and inappropriate management. Correct diagnosis was established by flexible bronchoscopy and oesophageal contrast studies. Surgical division of fistulae resulted in complete symptom resolution.

Adult↗

FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter.

The receptors for at least two hematopoietic growth factors, namely the stem cell factor and colony-stimulating factor 1, belong to class III receptor tyrosine kinases. Here we describe cloning of a partial complementary DNA for FLT4, an additional member of this gene family from human leukemia cells. The FLT4 tyrosine kinase domain is 79% homologous with the previously cloned FLT1 (M. Shibuya et al., Oncogene, 5: 519-524, 1990) tyrosine kinase and maps to the chromosomal region 5q33-qter. We have found FLT4 expression in human placenta, lung, heart, and kidney, whereas the pancreas and brain appeared to contain very little if any FLT4 RNA. The results suggest that FLT4 functions in multiple adult tissues.

Adult↗

Negative and positive expectancies in lone and group problem drinkers.

In this experiment we show that measuring positive expectancy of alcohol use does not discriminate between lone and group problem drinkers whereas measuring negative expectancy does. Reliably, lower measures in group drinkers is consistent with: (i) our view that negative expectancy provides the motivation for problem drinkers to quit and that anything which inhibits the translation of negative experience into negative expectancy will correspondingly inhibit motivation; and with (ii) the observations of others that social (or group) support can, indeed, often inhibit recovery.

Alcohol Drinking↗

The change process in alcoholics: client motivation and denial in the treatment of alcoholism within the context of contemporary nursing.

Despite being constantly cited as a critical intervening variable in the recovery from alcohol problems, there is a paucity of literature on client motivation. This paper reviews the current literature which impacts on motivation and its importance in treatment and develops in a stepwise manner the revised expectancy/motivation hypothesis, tentatively explaining both motivation and denial as a natural process in behavioural change. Because of the revised expectancy/motivation hypothesis' distinctly defined stages which closely relate to the process of nursing and the qualitative and quantitative measurement it entails which the nursing process demands, it offers a particularly appropriate model for treatment within nurse practice.

Adaptation, Psychological↗