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Biomedical subjects

M McGuinness

Publications and source records attributed to M McGuinness.

12 recordsLinked to original sources
PubMed2002

The effect of nutrient intake on bone mineral status in young adults: the Northern Ireland young hearts project.

Optimizing peak bone mass in early life may reduce osteoporosis risk in later life. Such optimization may be partly dependent upon diet. In the present study, nutrient intakes and selected lifestyle parameters were assessed in adolescent subjects (238 males, 205 females; aged 15 y) and again, in the same subjects, on one occasion in young adulthood (aged between 20 and 25 y). The extent of the relationships between these parameters and bone mineral density (BMD), dual energy X-ray absorptiometry (DXA), lumbar spine (L2-L4), and femoral neck measured concurrently with diet in young adulthood only, was assessed. Adjusted linear regression models were constructed. Variables included a measure of pubertal status (at age 15 y), age (at young adulthood), height, weight, physical activity, smoking, and mean daily intakes of energy, calcium, protein, vitamin D, phosphorus, total fat, and alcohol. In both sexes, body weight at adolescence and young adulthood was the only factor consistently positively associated with BMD at both measurement sites. Effects of nutrient intake on BMD were inconsistent. Vitamin D and calcium intakes reported by female adolescents showed significant positive relationships with BMD measured in young adulthood (vitamin D measured at the lumbar spine; calcium measured at the femoral neck). The positive relationship between vitamin D and BMD remained significant at young adulthood, but at the femoral neck rather than at the lumbar spine. Also in females, intakes of phosphorus and the calcium:phosphorus ratio (Ca:P) at adolescence were strongly negatively related to femoral neck BMD measured at young adulthood. In males, however, Ca:P reported at young adulthood had a significant positive relationship with lumbar spine BMD, whereas Ca:protein was negatively associated with BMD at the lumbar spine. Intakes of Ca reported by adolescent males also had a strong negative effect on lumbar spine BMD measured at young adulthood.

Adolescent↗
PubMed2001

STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity.

Activating mutations of c-kit at codon 816 (Asp(816)) have been identified in variety of malignancies, including acute myeloid leukemia (AML), mastocytosis and germ cell tumors. The mutant c-Kit receptor confers cytokine independence and induces tumorigenicity. However, the molecular mechanisms, particularly the changes in the signal transduction pathways, responsible for these biological effects induced by mutant c-Kit are largely undefined. Using the human embryonic kidney cell line, 293, we show in the current report that constitutive activation of STAT3 and STAT1 is associated with D816H mutant c-Kit. Transfection of dominant negative STAT3, but not STAT1 inhibits mutant c-Kit mediated anchorage-independent growth in vitro and tumor formation in vivo. Expression of constitutively activated STAT3 restores the mutant c-Kit receptor's transforming ability in 293 cells. These results demonstrate that activation of STAT3 by Asp(816) mutant c-Kit is required for the anchorage-independent growth and tumorigenicity induced by Asp(816) mutant c-Kit.

Amino Acid Substitution↗
PubMed2000

Team management in community mental health.

The community mental health team is now the established model for mental health service delivery in the community. Managing CMHTs requires a diverse range of managerial skills, role clarity and authority. More research needs to be undertaken on the role and effectiveness of the CMHT manager.

Community Mental Health Services↗
PubMed1995

Phenotype of patients with peroxisomal disorders subdivided into sixteen complementation groups.

OBJECTIVE: To use the technique of complementation analysis to help define genotype and classify patients with clinical manifestations consistent with those of the disorders of peroxisome assembly, namely the Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). STUDY DESIGN: Clinical findings, peroxisomal function, and complementation groups were examined in 173 patients with the clinical manifestations of these disorders. RESULTS: In 37 patients (21%), peroxisome assembly was intact and isolated deficiencies of one of five peroxisomal enzymes involved in the beta-oxidation of fatty acids or plasmalogen biosynthesis were demonstrated. Ten complementation groups were identified among 93 patients (54%) with impaired peroxisome assembly and one of three phenotypes (ZS, NALD, or IRD) without correlation between complementation group and phenotype. Forty-three patients (25%) had impaired peroxisome assembly associated with the RCDP phenotype and belonged to a single complementation group. Of the 173 patients, 10 had unusually mild clinical manifestations, including survival to the fifth decade or deficits limited to congenital cataracts. CONCLUSIONS: At least 16 complementation groups, and hence genotypes, are associated with clinical manifestations of disorders of peroxisome assembly. The range of phenotype is wide, and some patients have mild involvement.

Acyltransferases↗
PubMed1991

Purification and characterization of peroxisomal L-pipecolic acid oxidase from monkey liver.

L-Pipecolic acid oxidase has been purified to near homogeneity from Rhesus monkey liver. The protein, a yellow monomer, has a molecular weight of 46,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a pI of 8.9. It contains a covalently bound flavin with absorption maxima at 457 and 383 nm and a shoulder at 480 nm. The purified enzyme is most reactive toward L-pipecolic acid, with lesser reactivities toward L-proline and sarcosine. The enzyme has no significant reactivity toward the D-enantiomer of pipecolic acid or toward any other amino acid tested. Benzoic acid is a competitive inhibitor of the enzyme with a Ki of 750 microM. The Km of the purified enzyme is 3.7 mM for L-pipecolic acid. With less purified preparations, the reaction product is alpha-aminodipic acid. The purified enzyme, however, produces an intermediate which reacts with ortho-aminobenzaldehyde to form an alpha-aminoadipic acid semialdehyde adduct. Thus, the formation of alpha-aminoadipic acid requires at least two enzymes.

Animals↗
PubMed1987

Release of malignancy-related fucopeptides from ascites tumour cells in association with membrane vesicles.

Membrane vesicles were found to be released from Landschütz ascites cells in vivo and in vitro. Vesicle fractions were highly enriched in the large fucopeptides which are a known feature of malignant cell membranes. Incubation with trypsin in vitro is commonly used to release these fucopeptides from tumour cells. The present results show that the enzyme acts by increasing the release of lipid vesicles enriched in these components, rather than by liberating soluble tryptic products. Thus, the parent molecules in the cell would appear to be integral membrane proteins which are insensitive to direct cleavage by trypsin.

Animals↗
PubMed1980

Interaction of Streptococcus mutans glucosyltransferases with teichoic acids.

The Streptococcus mutans GS5 glucosyltransferase activities (both water-soluble and -insoluble glucan-synthesizing fractions) were inhibited by purified lipoteichoic acid. In vitro sucrose-dependent colonization of smooth surfaces by strain GS5 was also markedly reduced in the presence of the amphipathic molecules. The inhibition of soluble glucan synthesis by lipoteichoic acid appeared to be competitive with respect to both sucrose and primer dextran T10. These inhibitory effects were dependent on the presence of the fatty acid components of lipoteichoic acid since deacylated lipoteichoic acids did not inhibit glucosyltransferase activity. However, the deacylated molecules did interact with the enzymes since deacylated lipoteichoic acid partially protected the enzyme activity against heat inactivation and also induced the formation of high-molecular-weight enzyme complexes from the soluble glucan-synthesizing fraction. The presence of teichoic acid in high-molecular-weight aggregates of glucosyltransferase isolated from the culture fluids of strain GS5 was suggested by the detection of polyglycerophosphate in these fractions. In addition to strain GS5, two other organisms containing polyglycerophosphate teichoic acids, Lactobacillus casei and Lactobacillus fermentum, were demonstrated to bind glucosyltransferase activity. These results are discussed relative to the potential role of teichoic acid-glucosyltransferase interactions in enzyme binding to the cell surface of S. mutans and the formation of high-molecular-weight enzyme aggregates in the culture fluids of the organism.

Acylation↗
PubMedDate not supplied

Comparison between different perineal outcomes on tissue healing.

Perineal healing was compared between 181 women with episiotomies and 186 women without episiotomies at one to two weeks after delivery. Subjects were medically indigent low-risk women who had normal spontaneous vaginal deliveries at the same tertiary-care hospital. Maternal age, race, parity, and birth weight did not have an independent effect on perineal healing. Perineal outcome at delivery and length of second stage exhibited a significant relationship with perineal healing. Overall, there was a 4.9% incidence of delayed perineal healing due to wound separation or clinical infection. In the episiotomy group, 7.7% of the subjects experienced delayed perineal healing compared with 2.2% in the no-episiotomy group. This was statistically significant using Pearson chi-square analysis. These results suggest that women without episiotomies exhibit better perineal healing than women with episiotomies.

Adult↗
PubMedDate not supplied

Insulin-like growth factors.

The insulin-like growth factors (IGF-I and IGF-II) play important roles in the regulation of growth and metabolism. While the liver is the main source of circulating IGFs, their production by numerous extrahepatic tissues suggests the existence of autocrine and paracrine modes of action in addition to typical endocrine mechanisms. The actions of the IGFs are mediated through their activation of specific cell surface receptors, primarily the IGF-I receptor, although some effects may be mediated through the IGF-II receptor and the insulin receptor. The stability of the IGFs and their interaction with their receptors are mediated by specific IGF binding proteins (IGF-BPs) which are found in the circulation and in extracellular fluids. Thus, the overall biological actions of the IGFs can be regulated by control of ligand biosynthesis, modulation of receptor levels and postreceptor signalling pathways, and changes in the levels and activity of IGF-BPs.

Animals↗