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Biomedical subjects

G Cole

Publications and source records attributed to G Cole.

At least 55 records · Page 3Linked to original sources

Alexander's disease in infancy and childhood: a report of two cases.

Two cases of Alexander's disease are described. One case of infantile onset died at the age of 6 months and the second case was of the juvenile type with onset at 2 years and death at 10 years. A clinical diagnosis of this disease is difficult since signs can vary according to the age of the patient. The severity of the pathological changes can also depend upon the age of onset of this disease, but they are restricted to the central nervous system. The Rosenthal fibre is the characteristic feature of Alexander's disease and we have examined for the first time its ultrastructure and immunocytochemical characteristics at the electron microscopical level and demonstrated coexpression of anti-glial fibrillary acidic protein and anti-ubiquitin antisera.

Astrocytes↗

EEG features and their evolution in the acute phase of haemorrhagic shock and encephalopathy syndrome.

Serial EEGs have been carried out during the acute phase of haemorrhagic shock and encephalopathy syndrome (HS&E) in 22 infants and children aged 3 months to 14 years. Most patients presented with fits and coma and all had shock with bleeding and disseminated intravascular coagulation (DIC). The initial EEG showed prolonged runs of often rhythmic discharges which fluctuated in amount and amplitude with varying distribution and morphology ("electrical storms"). Over a period of days the "electrical storms" gradually decreased leaving only low amplitude EEG activities or evolving to electrocerebral silence (7 cases). Fifteen patients died and all five children with multifocal "electrical storms" who survived showed gross neurological handicap. The rather distinctive EEG pattern is unusual in the context of an acute encephalopathy outside the neonatal period although similar "electrical storms" may be seen in a less extreme form in infants and children with other conditions associated with DIC. This EEG pattern presumably reflects changes in the cerebral microcirculation which in HS&E are usually relentlessly progressive and associated with devastating cortical damage.

Adolescent↗

Neuronal hypertrophy in the pars reticulata of the substantia nigra in Parkinson's disease.

The size of neurons in the pars reticulata of the substantia nigra in patients dying with Parkinson's disease has been compared with that in non-parkinsonian control cases. Parkinson's disease is accompanied by a significant (+53%) hypertrophy of reticulata neurons. This is similar to changes seen in experimental rats with ipsilateral damage of the striatum. It is suggested that the enlargement seen in Parkinson's disease, similar to that in the rat, is indicative of plasticity in the GABA-ergic reticulata neurons, and may be associated with increased inhibitory flux in pathways arising from the pars reticulata to the superior colliculus and thalamus.

Adult↗

Breast-feeding policies and routines among Arizona hospitals and nursery staff: results and implications of a descriptive study.

In 1988, Arizona's 61 hospitals providing obstetrical services were canvased with regard to hospital routines that favor either breast-feeding or bottle-feeding. Forty-five hospitals provided responses that were used in the survey. Practices favoring breast-feeding, which were reported by a majority of the hospitals (more than 50%), were demand feeding, staff assessment for "latch-on" (the action of nipple presentation and sucking initiation) and positioning, "rooming-in" (the practice of minimal mother-infant separation), and information about follow-up support services. Hospital practices suggested to promote bottle-feeding were the provision of pacifiers and supplemental water or glucose, issuance of formula packs at discharge, and a first feed of sterile water. A positive significant relationship was identified for policies advocating breast-feeding and the prevalence of breast-feeding encouragement from professional staff. Of 44 respondents, 41 indicated that their hospital's policies endorse breast-feeding as the ideal method of feeding healthy newborns. Hospital staff perceived that they encourage mothers to breast-feed and offer support to those who initiate breast-feeding. On the basis of this information, we conclude that dietetics practitioners should evaluate current breast-feeding practices and integrate policies supportive of breast-feeding into the health care system.

Arizona↗

Amyloid beta-protein precursor is associated with extracellular matrix.

The ultrastructural distribution of the amyloid beta-protein precursor (ABPP) in cultures of a neuronal cell line is examined. ABPP is associated with the extensive extracellular matrix (ECM) secreted by these cells. The possible role of matrix associated ABPP in the pathogenesis of Alzheimer's disease is discussed.

Amyloid↗

LR White embedding allows a multi-method approach to the analysis of brain tissue from patients with Alzheimer's disease.

Light (LM) and electron (EM) microscope comparisons of the cytochemistry and immunocytochemistry of neuritic plaques and neurofibrillary tangles, the main histopathological changes in the brains of Alzheimer's disease sufferers, have been almost impossible because of the disparity between the two technologies. By embedding unosmicated brain tissue in the acrylic resin LR White, direct comparisons can be made between techniques applied at the LM level with those at the EM level. After partial dehydration in 70% ethanol, the tissue is embedded by rapid infiltration and polymerization at 0 degrees C, which has been shown to maximally preserve tissue immunoreactivity. Semithin sections are then receptive to routine LM stains, silver stains e.g. Gomori's methenamine silver, and immunocytochemistry with immunoperoxidase or immunocolloidal gold. Serial thin sections are stable in the EM and can be immunolabelled and directly compared with their LM counterparts. Results from the use of a mouse monoclonal antibody against beta-amyloid and a rabbit polyclonal antibody against ubiquitin are presented. LR White resin includes no elements other than carbon, oxygen and nitrogen, of which it is composed, so that sections of it are valuable for sensitive X-ray energy dispersive microanalysis.

Acrylic Resins↗

X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci.

We have studied the inheritance of several polymorphic Xq27/28 DNA marker loci in two three generation families with the X linked neonatal lethal form of centronuclear/myotubular myopathy (XL MTM). We found complete linkage of XLMTM to all four informative Xq28 markers analysed, with GCP/RCP (Z = 3.876, theta = 0.00), with DXS15 (Z = 3.737, theta = 0.00), with DXS52 (Z = 2.709, theta = 0.00), and with F8C (Z = 1.020, theta = 0.00). In the absence of any observable recombination, we are unable to sublocalise the XLMTM locus further within the Xq28 region. This evidence for an Xq28 localisation may allow us to carry out useful genetic counselling within such families.

Cell Nucleus↗

Relationships among measures of alcohol drinking behavior, life-events and perceived stress.

Two measures of stress (life-events and perceived stress) and a measure of alcohol-drinking behavior were administered to 6,747 adult males. Analysis was carried out to examine the extent to which subjects classified into drinking-behavior groups differed on stress measures while controlling for age, income, and race. Significant differences held up under age, race, and income controls for life-events and perceived stress between the abstinence, common-use, and problem-drinking groups. Stress scores increased sequentially across the drinking-behavior groups. Apparently, men who are life-long abstainers (teetotallers) experience fewer life-events and perceive less stress than moderate drinkers, while moderate drinkers experience less stress than heavy drinkers.

Adaptation, Psychological↗

Differential involvement of protein kinase C isozymes in Alzheimer's disease.

Decreased levels of protein kinase C (PKC) and a reduction in the in vitro phosphorylation of a Mr 86,000 protein (P86), the major PKC substrate, are biochemical characteristics of brain tissue from patients with Alzheimer's disease (AD) (Cole et al., 1988). In the current study, we utilized antibodies against individual isozymes of PKC to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC(beta II) was lower in particulate fractions prepared from AD hippocampal and cortical tissue than in controls and higher in AD cytosol fractions from the cortex than in controls. Immunohistochemical studies in AD neocortex revealed reduced numbers of anti-PKC(beta II)-immunopositive neurons and diminished staining intensity. In contrast, AD hippocampal neurons in CA3-CA4 were more intensely stained with anti-PKC(beta II) antiserum than were controls. The concentration of PKC(beta I) was lower in particulate fractions prepared from AD hippocampus than in controls and was higher in soluble fractions prepared from AD cortex than in controls. The concentration of PKC(alpha) was lower in AD particulate fractions than in controls in the hippocampus. Immunohistochemistry with PKC(alpha) antiserum revealed moderately intense neuron staining and an intense staining of glial cells in AD neocortex. The concentrations and histochemical distributions of PKC(gamma) were not altered in the disease. PKC immunoreactivity was also found in neuritic plaques. The staining patterns of neuritic plaques with different isoform antibodies varied considerably. Anti-PKC(alpha) faintly stained entire plaques and surrounding glial cells; anti-PKC(beta I) stained dystrophic plaque neurites; and anti-PKC(beta II) stained the amyloid-containing portions of plaques.

Aged↗

Secreted form of amyloid beta protein precursor is involved in the growth regulation of fibroblasts.

Fibroblasts that harbor an antisense construct of amyloid beta protein precursor (ABPP) cDNA, A-1, produced less ABPP mRNA and ABPP and grew poorly. Normal growth was restored when either parent cell conditioned medium (CM) or purified ABPP was provided. The capacity of the CM to restore cell growth was abolished by passage through an anti-ABPP immunoaffinity column; the activity was in the bound fraction. A Mr 90,000 protein recognized by the anti-ABPP antibody was diminished in the CM of A-1. CM from ABPP cDNA-transfected cells expressing high levels of ABPP was more potent than that from non-transfected parent cells in restoring A-1 growth. These results indicate that ABPP is released from cells into the medium and has an autocrine function in growth regulation.

Amyloid↗

Amyloid beta protein precursor is a mitogen.

The form of the secreted amyloid beta-protein precursor which contains the protease inhibitor sequence is mitogenic for Swiss 3T3 cells, while the precursor molecule lacking the protease inhibitor domain is not. A ten-fold stimulation of DNA synthesis occurs at 8 x 10(-9) M protein.

Alzheimer Disease↗

An antiserum against amyloid beta-protein precursor detects a unique peptide in Alzheimer brain.

An antiserum was raised against an amino acid sequence predicted from the DNA sequence of amyloid beta-protein precursor (ABPP), and it was then affinity-purified. This affinity-purified antibody (anti-GID) intensely stained neurons and dystrophic neurites in plaques of Alzheimer's disease (AD) patients, but marginally stained neurons of age-matched normal individuals. Anti-GID antibody detected a series of protein bands with a molecular weight centered at 100,000 and a second band at 55,000 on a blot of the human brain particulate fraction. It also stained a set of bands with a molecular weight around 95,000 and a doublet of Mr 16,000 in the soluble fraction. A band at Mr 35,000 was detected in the soluble fraction prepared from brain tissue of AD patients but not from control brain tissue. A strong immunostaining of AD sections with anti-GID and the presence of a Mr 35,000 band unique to AD might reflect an altered processing of ABPP in AD brains.

Alzheimer Disease↗

Reduced protein kinase C immunoreactivity and altered protein phosphorylation in Alzheimer's disease fibroblasts.

Abnormal protein kinase C levels and protein kinase C-dependent phosphorylation are biochemical alterations in brain tissue obtained from patients with Alzheimer's disease. Because many biochemical and biophysical abnormalities are found in peripheral tissues of patients with Alzheimer's disease, we studied protein kinase C levels and the in vitro phosphorylation of proteins under protein kinase C-activating conditions in fibroblasts derived from patients with Alzheimer's disease. The concentration of protein kinase C-like immunoreactivity was reduced in Alzheimer's disease samples, although the protein kinase C activity determined by the phosphorylation of exogenous histone was not. The degree of in vitro phosphorylation of an Mr 79,000 protein in the presence of protein kinase C activators was less in Alzheimer's disease than in control fibroblast cytosol, and a reduction was more prominent in cases of familial Alzheimer's disease than in sporadic Alzheimer's disease. Therefore, the aberrant phosphorylation mediated by protein kinase C is found not only in the brain but also in fibroblasts.

Alzheimer Disease↗

Decreased adhesiveness of Alzheimer's disease fibroblasts: is amyloid beta-protein precursor involved?

The adhesiveness of fibroblasts derived from Alzheimer's disease (AD) patients to a plastic substratum was assessed as the proportion of cells attached to a plastic dish bottom after a 30-minute incubation in culture medium of cells dissociated in ethylenediaminetetraacetic acid and was compared with the adhesiveness of normal fibroblasts from non-AD controls. It was found that the normal fibroblasts adhered better to plastic than did AD cells. This reduced adhesiveness was observed in fibroblasts derived from both sporadic and familial AD patients. Because of the possible involvement of amyloid beta-protein precursor (ABPP) in the process of cellular adhesion, the amount of ABPP messenger RNA was measured in these fibroblasts and was found to be decreased in the familial AD fibroblasts, although not in cells from sporadic AD patients. Furthermore, there were fewer molecules detected by an anti-ABPP antibody in conditioned media from familial AD fibroblasts as compared with media from control fibroblasts. Therefore, although it is possible that the reduced adhesiveness of familial AD fibroblasts may result from genetic deficits in ABPP gene expression, the reduced adhesiveness of sporadic AD fibroblasts most likely results from certain deficits in molecules other than the ABPP.

Alzheimer Disease↗