Search PubMed⌕ Search

Biomedical subjects

M McLaughlin

Publications and source records attributed to M McLaughlin.

At least 73 records · Page 4Linked to original sources
PubMed1996

Twin sibling differences in parental reports of ADHD, speech, reading and behaviour problems.

Differences between twins and siblings in behaviour problems were investigated in a non-selected sample of 1938 families with children aged 4-12 years. Families were sent a questionnaire based on DSM-III-R criteria for Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD) and Separation Anxiety (SA), which was validated by formal clinical interview. The questionnaire also included measures of speech and reading problems. There were significant differences between twins and siblings for ADHD symptoms, but not for symptoms of ODD, CD or SA. Twins and siblings differed significantly for gestational age, birth weight, speech and reading problems. While there was little evidence for birth weight or gestational age contributing to the difference in ADHD symptoms, there was a strong association between ADHD symptoms and speech and reading problems.

Anxiety, Separation↗
PubMed1996

The use of factor analysis for ascertaining patterns of psychopathology in children with intellectual disability.

The Developmental Behaviour Checklist (DBC) was developed to assess psychopathology in children with intellectual disabilities. A cut-off point between "non-cases' and "cases' was determined by comparison of the total scores with psychiatric clinical assessment. This paper describes a method aimed at determining the types of psychiatric problems in those regarded as "cases'. Factor analysis with varimax rotation carried out on a sample of 1093 subjects extracted six factors. Standardized factor scores were calculated for each subject in a community sample (n = 450), and the only or the dominant positive score was determined for each of the "cases'. Over 80% of "cases' could be allotted to one condition. Only a small number had none, or three or more conditions. The same procedure was replicated on a validation sample (n = 448) with even more satisfactory results. Differences in the prevalence of the six conditions by sex, age and level of mental retardation were ascertained. The validity and clinical relevance of this method are discussed.

Adolescent↗
PubMed1996

Characterization and cell distribution of polycystin, the product of autosomal dominant polycystic kidney disease gene 1.

BACKGROUND: In a majority of cases, autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations within a putative open reading frame of the PKD1 gene. The encoded protein, polycystin, is predicted to span the plasma membrane several times and contains extracellular domains, suggestive of a role in cell adhesion. The cellular distribution and function of polycystin is not known. MATERIALS AND METHODS: We selected as immunogens two conserved 15 amino acid peptides: P1, located in a predicted extracellular region of polycystin, and P2, located in the C-terminal putative cytoplasmic tail. The anti-peptide antibodies from immunized rabbits were affinity purified on peptide-coupled resins and their specificity confirmed by their selective binding to recombinant polycystin fusion proteins. Western blotting and immunohistochemistry were used to characterize the size, tissue, and cell distribution of polycystin. RESULTS: A high-molecular mass protein (about 642 kD) was detected by Western blotting in rat brain tissue. A few additional bands, in the 100- to 400-kD range, probably representing tissue-specific variants and/or proteolytic fragments, were recognized in human and rat tissues. Polycystin was abundantly expressed in fetal kidney epithelia, where it displayed basolateral and apical membrane distribution in epithelial cells of the ureteric buds, collecting ducts, and glomeruli. In normal human adult kidney, polycystin was detected at moderate levels and in a cell surface-associated distribution in cortical collecting ducts and glomerular visceral epithelium. Expression of polycystin was significantly increased in cyst-lining epithelium in ADPKD kidneys, but was primarily intracellular. CONCLUSIONS: Polycystin appears to be a developmentally regulated and membrane-associated glycoprotein. Its intracellular localization in the cyst-lining epithelium of ADPKD kidneys suggests an abnormality in protein sorting in this disease.

Animals↗
PubMed1995

Reduced left ventricular systolic pump performance and depressed myocardial contractile function in patients > 65 years of age with normal ejection fraction and a high relative wall thickness.

We studied the relation between relative wall thickness, left ventricular systolic pump performance, and myocardial contractile function in 77 older patients with normal ejection fraction who were free of valvular and myocardial ischemic disease. Group 1 comprised 49 patients with relative wall thickness > or = 0.45; group 2 (n = 28) had normal relative wall thickness. Pump performance was characterized by stroke volume index, cardiac index, and stroke work; myocardial function was characterized by midwall shortening and circumferential stress versus shortening relations. Group 1 patients had lower end-diastolic volume (83 +/- 3 vs 124 +/- 5 ml, p < 0.05), cardiac index (2.6 +/- 0.2 vs 3.5 +/- 0.1 L/min/m2, p < 0.05), and stroke work/100 g left ventricular mass (43 +/- 2 vs 53 +/- 3 g-m/100 g, p < 0.005). Although there was no significant difference with regard to ejection fraction or fractional shortening at the endocardium, fractional shortening at the midwall was significantly lower in group 1 than in group 2 (16 +/- 1% vs 19 +/- 1%, p < 0.005). This lower value for midwall shortening was observed despite lower values for endsystolic stress, implying decreased myocardial contractile function. Lower stroke volume index in group 1 patients, likely due to small chamber size, was not offset by increased heart rate, resulting in a low-normal cardiac index; in 33% of group 1 patients, cardiac index was < 2.2 L/min/m2, indicating reduced pump performance. Our data indicate an abnormality in pump performance and myocardial function in patients who have high relative wall thickness and normal ejection fraction.

Age Factors↗
PubMed1995

High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection.

Nevirapine, a potent nonnucleoside reverse transcriptase inhibitor, produces a transient antiviral effect at < or = 200 mg/day due to the selection of resistant virus. To examine if higher levels of nevirapine could produce sustained antiviral activity, its safety, pharmacokinetics, and antiviral activity at 400 mg/day were studied in 21 patients. There was a rapid reduction in immune complex-dissociated p24 antigen and serum human immunodeficiency virus RNA concentration in all patients, and 8 of 10 patients had > 50% reduction at 8 weeks. Nevirapine-resistant virus was isolated from all subjects tested at 12 weeks: The mean plasma trough level (4.0 micrograms/mL [15.8 microM]) exceeded the mean IC50 of resistant virus. Rash developed in 48% of patients and was a dose-limiting toxicity factor in 6. These data suggest that clinical testing of potent antiviral compounds that select for drug-resistant virus is justified to determine if serum levels of drug sufficient to overcome resistant virus can be attained.

Adult↗
PubMed1994

Impact of chamber geometry and gender on left ventricular systolic function in patients > 60 years of age with aortic stenosis.

In aortic stenosis, gender and other differences in the adaptive remodeling of the left ventricle have been described, but the influence of left ventricular (LV) geometry on systolic function is not widely appreciated. This study tested the hypothesis that the increased ejection fraction seen in some elderly women with aortic stenosis is due to changes in LV geometry, not increased myocardial mass or enhanced myocardial function. We therefore investigated gender-related differences in LV and myocardial function by analysis of end-systolic circumferential stress versus shortening relations in 65 patients (29 men and 36 women) with aortic stenosis who underwent cardiac catheterization and echocardiography. Despite similar degrees of aortic stenosis, there were significant differences between men and women with regard to LV geometry and function. When compared with men, women had higher peak LV pressures (205 +/- 27 vs 188 +/- 27 mm Hg, p < 0.01), higher ejection fractions (66 +/- 14% vs 57 +/- 18%, p < 0.05), smaller LV end-diastolic dimensions (43 +/- 8 vs 51 +/- 6 mm, p < 0.01) and higher relative wall thickness (0.66 +/- 0.27 vs 0.50 +/- 0.10, p < 0.01). LV mass was similar in the 2 groups. Mean values for stress were lower in women and there was a predominance of women at extremely low levels of stress; this subgroup had very high values for relative wall thickness and endocardial shortening, but overall stress-shortening relations were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

The direct vascular relaxing action of betaxolol, carteolol and timolol in porcine long posterior ciliary artery.

The vascular relaxing properties of three beta adrenoceptor antagonists, betaxolol, carteolol and timolol, currently used in the treatment of glaucoma, were characterized, compared and contrasted in the porcine long posterior ciliary artery. Isolated arterial ring segments precontracted with increased extracellular KCl (plus 40 mM) or the thromboxane analog, U-46619 (3 x 10(-7) M), were relaxed in a concentration-dependent fashion by betaxolol, carteolol, timolol or nitroprusside. In vessel segments depolarized with increased extracellular KCl, EC50 values indicated that the intrinsic relaxant sensitivity to betaxolol was equal to that of nitroprusside, six-fold greater than that of carteolol, and ten-fold greater than that of timolol. Similarly, the maximum relaxation occurring at equimolar concentrations (10(-4) M) for the beta adrenoceptor antagonists was betaxolol > carteolol = timolol. Qualitatively similar results were noted in ring segments of the rabbit external iliac artery precontracted with increased extracellular KCl (plus 30 mM). Under conditions in which specific receptor-linked events are absent and voltage-gated Ca++ entry is maximized, the Ca++ concentration response relationship in porcine long posterior ciliary artery was shifted to the right in an apparent competitive manner by betaxolol, reflecting a 5.6-fold reduction in the sensitivity to Ca++. Conversely, nitroprusside reduced the Ca++ sensitivity three-fold in a noncompetitive fashion; not only shifting the Ca++ concentration response relationship to the right, but also depressing the maximum by 57%. Porcine long posterior ciliary arterial segments precontracted to a similar degree with U-46619, in which voltage-gated Ca++ entry is only one component of many specific cell signalling transduction mechanisms contributing to the precontraction, exhibited a sensitivity to betaxolol that was six-fold less than to nitroprusside, but two-fold greater than to timolol and 20-fold greater than to carteolol. These results are consistent with an obvious direct vascular relaxing capacity for beta adrenoceptor antagonists that primarily represents a capacity for inhibiting voltage-gated Ca++ entry in vascular smooth muscle. Additionally, the differential potencies of these three beta adrenoceptor antagonists characterized in this study suggests that this property is much more likely to contribute to any potentially beneficial effects of betaxolol than carteolol or timolol.

Animals↗
PubMed1994

Quality of life, appetite, and weight change in patients receiving dose-intensive chemotherapy.

Quality of life was assessed by self-report questionnaires in 30 patients receiving dose-intensive chemotherapy for either non-small-cell lung cancer (20 patients) or recurrent head and neck cancer (10 patients). Megestrol acetate was given daily to try to improve appetite and prevent the weight loss usually associated with this chemotherapy. Appetite did not change significantly overall during the first 4 weeks of chemotherapy, but it did improve in those patients still receiving chemotherapy at 8 weeks. Changes in global quality of life were significantly correlated with changes in appetite, fatigue, energy level, and physical function. Thus, these parameters may have more relevance to patients' perceptions of quality of life than does weight change, and should be used more frequently as endpoints in studies of supportive care and palliative treatment of patients with cancer.

Antineoplastic Agents↗
PubMed1993

Alterations in the activity of adenylate cyclase and high affinity GTPase in Alzheimer's disease.

The aim of this study was to assess the effect of Alzheimer's disease has on the functional integrity of several signal transduction proteins. The relative levels of the G-protein alpha subunits Gs alpha-L, Gs alpha-S, Gi alpha-2 and G(o) alpha were measured by western blotting and found to be unchanged in membranes prepared from Alzheimer-diseased frontal cortex or hippocampus compared to control brains. However the activity of the G-protein associated enzyme, high affinity GTPase, was found to be reduced in the frontal cortex (reduced by 25%) and by a similar magnitude in the hippocampus (reduced by 27%) of Alzheimer subjects. The same membrane preparations were also assayed for the activity of adenylate cyclase. Basal enzyme activity was not significantly altered in Alzheimer diseased hippocampus, but was markedly reduced (by 45%) in the frontal cortex. The ability of fluoride and aluminium ions to stimulate adenylate cyclase was not significantly changed in either brain region. This suggests that G-proteins, especially Gs, are still able to interact with this enzyme. These results indicate that although the presence of Alzheimer's disease does not significantly alter G-protein levels, changes have taken place in the overall activity of these proteins. However this alteration does not affect their ability to stimulate adenylate cyclase activity.

Adenylyl Cyclases↗
PubMed1993

VACTERL with hydrocephalus: spontaneous chromosome breakage and rearrangement in a family showing apparent sex-linked recessive inheritance.

The rate of spontaneous and mitomycin C induced chromosome breakage and sister chromatid exchange (SCE) was studied in three related cases diagnosed with VACTERL-H syndrome. There have been recent reports of sporadic patients with VACTERL-H in whom high rates of chromosome breakage were observed. This has led to the suggestion that some of these patients may represent the severe expression of Fanconi anemia. The pattern of inheritance in our family is highly suggestive of X-linked recessive inheritance supporting the hypothesis that VACTERL-H is, at least in some cases, a syndrome and not an association.

Abnormalities, Multiple↗
PubMed1993

Use of fluorescence in situ hybridization to confirm the interpretation of a balanced complex chromosome rearrangement ascertained through prenatal diagnosis.

A balanced complex chromosome rearrangement (BCCR) involving 3 chromosomes with 4 breakpoints, was identified in a 36-yr-old woman who was studied because her fetus was discovered to have an unbalanced reciprocal translocation (7q;10q). Analysis of high resolution bands and the application of fluorescence in situ hybridization has identified the BCCR as der(7)t(7;10)(q21.13;q23.33)ins(21;7)(q21.3;q11.22q21.13), der(10)t(7;10)(q21.13; q23.33), der(21)ins(21;7)(q21.3;q11.22q21.13). Alternate segregation of the BCCR appears to be favoured, and has resulted in two pregnancies with an unbalanced chromosome constitution.

Abnormalities, Multiple↗
PubMed1993

Location of gp330/alpha 2-m receptor-associated protein (alpha 2-MRAP) and its binding sites in kidney: distribution of endogenous alpha 2-MRAP is modified by tissue processing.

The alpha 2-macroglobulin receptor-associated protein (alpha 2-MRAP) is a 39 to 44 kDa protein that copurifies with the alpha 2-macroglobulin receptor (alpha 2-MR/LRP) and also with gp330, a highly glycosylated protein located within kidney proximal tubules and glomerular podocytes. Both gp330 and the alpha 2-macroglobulin receptor are members of the low density lipoprotein receptor family but the physiological ligands for gp330 are unknown. In order to understand potential functions of the alpha 2-MRAP, specific anti-alpha 2-MRAP antibodies were used for immunocytochemical studies on paraformaldehyde lysine periodate (PLP)-fixed rat kidneys and on snap-frozen/acetone-fixed tissue. Conflicting results were obtained. After PLP fixation, alpha 2-MRAP was detected almost exclusively in rough endoplasmic reticulum (RER) cisternae; cell surface staining was virtually absent. In snap-frozen tissue, intense staining of the proximal tubule brush border was found, with little or no cytoplasmic staining. A series of experiments showed that during incubation of snap-frozen tissues, endogenous alpha 2-MRAP is released in soluble form from its intracellular location (i.e., the RER) and binds to gp330 on the brush border of proximal tubules. The location of binding sites for alpha 2-MRAP in rat kidney was also examined, using an alpha 2-MRAP-IgG fusion protein. In both snap-frozen and PLP-fixed tissues, this probe bound exclusively to brush borders, and not to intracellular sites. Our results demonstrate: a) that in renal proximal tubule cells, alpha 2-MRAP is located predominantly in the RER, b) that alpha 2-MRAP-binding sites are present on gp330, which is on the proximal tubule brush border, and c) that the apparent brush border localization of alpha 2-MRAP detected in snap-frozen sections is due to an artifactual redistribution of endogenous alpha 2-MRAP that occurs during tissue processing.

Animals↗
PubMed1993

Detection of two forms of GP330. Their role in Heymann nephritis.

Heymann nephritis is characterized by glomerular immune deposits that contain a glycoprotein called gp330. The deposits are believed to result from shedding of immune complexes formed on podocytes. Complexes are also shed from proximal tubule cells, when antibodies combine with gp330 on the cell surface. We performed the present study to investigate what portion of the gp330 molecule is shed, using a rabbit antiserum against a peptide deduced to be in the cytoplasmic domain of gp330, as well as a rabbit antiserum and two monoclonal antibodies that recognize extracellular epitopes of gp330. The anti-cytoplasmic peptide antiserum precipitated from Fx1A (a crude renal cortical membrane preparation), a protein with a mass of about 440 kd that was reactive with two monoclonal anti-gp330 antibodies. (In our experiments, the protein called gp330 generally has a mass estimated to be about 440 kd.) The anti-cytoplasmic peptide antiserum also reacted with a truncated gp330 protein produced in transfected COS cells. Immunohistochemical studies showed that all the antibodies recognized the same group of epithelial cells. However, as seen in immunoultrastructural studies of proximal tubules, the anti-cytoplasmic peptide antiserum reacted only with components at the base of microvilli, whereas the anti-gp330 ectodomain antibodies identified material not only at the base, but over the surface of microvilli as well. In rats with Heymann nephritis, glomerular deposits and material shed into tubule lumens reacted with antibodies against extracellular epitopes of gp330, but not with the anti-cytoplasmic peptide antiserum. We propose that there are two forms of gp330 on the cell surface of proximal renal tubules. One form is restricted to coated pit regions at the base of microvilli and has a cytoplasmic domain containing a sequence deduced from a partial complementary DNA encoding gp330. The other form is present over microvilli (and possibly at the base of microvilli as well) and lacks the cytoplasmic domain deduced from the complementary DNA. The complexes that are shed in Heymann nephritis contain either a portion of gp330 cleaved from the full-length molecule or a form of gp330 that lacks the cytoplasmic domain.

Amino Acid Sequence↗
PubMed1992

Which newborns in New York City are at risk for special education placement?

In this study of 162 third graders in New York City public schools, we found that slightly over half of the children in special education were males who had Medicaid coverage at birth and mothers with medical conditions or adverse health habits noted on the birth certificate; two thirds of the children with this combination of characteristics actually were placed in special education. These findings suggest that newborns at risk for later learning disabilities can be targeted to receive preventive interventions.

Birth Certificates↗
PubMed1991

Robustness of G proteins in Alzheimer's disease: an immunoblot study.

Many of the neurotransmitter systems that are altered in senile dementia of the Alzheimer type are known to mediate their effects via G proteins, yet the integrity of guanine nucleotide-binding proteins (G proteins) in Alzheimer's diseased brains has received minimal investigation. The aim of this study was to establish whether the level of G alpha subunits of five G proteins was altered in Alzheimer's disease. We used immunoblotting (Western blotting) to compare the amounts of Gi1, Gi2, GsH (heavy molecular weight), GsL (light molecular weight), and Go in the frontal cortex and hippocampus, two regions severely affected by the disease, and the cerebellum, which is less severely affected. The number of senile plaques was also quantified. We report that there was no significant difference in the level of these G alpha subunits between Alzheimer's diseased and age-matched postmortem brains. These results suggest that alterations in the amount of G protein alpha subunits are not a feature of Alzheimer's disease.

Alzheimer Disease↗
PubMed1991

Expression in non-lens tissues of an enzyme activity related to the 'lens-specific' protein, delta crystallin.

When chick embryo neutral retina (NR) cells are cultured for long periods in vitro, they undergo extensive transdifferentiation into lens and express the lens protein, delta crystallin. We now demonstrate that this process is accompanied by a change in the chromatin conformation of the delta-gene locus from DNAase1-resistant to DNAase1-sensitive in the nuclei of most cells. Transcripts hybridising to a delta probe are also much more prevalent among the in vitro transcription products from lens or transdifferentiated NR culture nuclei, as compared to nuclei from fresh NR tissue. Published evidence indicates that the chick delta 1 crystallin gene encodes the major structural protein of embryonic lens fibres, whereas the closely related delta 2 gene may encode the urea-cycle enzyme argininosuccinate lyase (ASL). Our present data lends further support to this view. Both immunodetectable delta-related protein(s) and ASL activity are present in fresh embryonic NR tissue, as well as in mouse and Rana liver, and in Rana lens. Our polyclonal anti-delta antibody also cross-reacts with a major constituent of commercial bovine ASL, of the same molecular size as chick delta crystallin. Immunoselection studies suggest that the ASL activity in chick embryonic NR is conferred mainly by the delta-related protein band. So-called 'ectopic' expression of delta crystallin in embryonic NR (and other tissues) may thus involve the delta 2/ASL gene, and could reflect some metabolic requirement for ASL activity.

Animals↗