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Biomedical subjects

D McCormick

Publications and source records attributed to D McCormick.

At least 19 recordsLinked to original sources
PubMed1992

A murine model of intracranial invasion: morphological observations on central nervous system invasion by murine melanoma cells.

We describe a model of tumour invasion in which murine melanoma/lymphocyte hybrid cells are injected into the lateral ventricle of neonatal mice. CSF circulation carries cells to the third ventricle where attachment to the ependyma and invasion of the underlying brain may be observed. At this distance from the injection site, invasion can be studied free from trauma or inflammation induced by the injection procedure. Accordingly we restricted our attention to the third ventricle. Our results reveal an unusual form of tumour invasion of the ependyma characterized by progressive attenuation of the ependymal cell layer immediately beneath tumour cell aggregates. Continuity of the ependymal cell layer is ultimately lost at a focal point immediately beneath the tumour, permitting direct contact between tumour cells and the neuropil. Subsequent deep invasion of the brain parenchyma is accomplished by pericapillary infiltration.

Animals↗
PubMed1991

Glial fibrillary acidic protein immunoreactivity in adrenocortical and Leydig cells of the Syrian golden hamster (Mesocricetus auratus).

In an immunocytochemical investigation of the expression of glial fibrillary acidic protein (GFAP) in non-nervous system tissues ten anti-GFAP antibodies were used on a range of normal adult organs from different species. All four polyclonal and six monoclonal antibodies revealed the expression of GFAP in cells of the zona fasciculata and reticularis of the adrenal cortex and Leydig cells of the Syrian hamster. The Chinese hamster, mole, rat, mouse, guinea pig, rabbit, pig, duck and man were negative. Co-expression of immunoreactivity for GFAP and vimentin was observed in adrenocortical and Leydig cells of the Syrian hamster but there were differences in the staining patterns of these intermediate filament proteins. Expression of GFAP in adrenal cortex of Syrian hamster is confirmed by immunoblot and limited proteolysis analysis which reveal a light form which is immunochemically indistinguishable from its counterpart in the central nervous system. The results presented here suggest a new model for the study of the possible role of GFAP expression in cells known to be sites of steroid synthesis.

Adrenal Cortex↗
PubMed1990

The biochemical diagnosis of lysosomal storage diseases--a review of five years experience.

The inherited lysosomal storage diseases are a distinct group of inborn errors of metabolism characterised by deficiencies in specific lysosomal enzymes. As many as 40 such disorders have now been described in man. We have measured the activities of up to 16 lysosomal acid hydrolases in plasma and/or extracts of leucocytes and cultured skin fibroblasts from 198 patients referred from throughout Ireland. These 16 assays allowed the biochemical diagnosis of 20 lysosomal storage diseases. Activities were compared with reference ranges to determine homozygotes and heterozygotes. Of the 44 patients with positive results, 15 were diagnosed as being homozygous for a specific lysosomal enzyme deficiency, 4 were identified as having multiple enzyme deficiencies (mucolipidosis Type II/I-cell disease) and 25 had heterozygote (carrier) enzyme levels. Of the latter, 24 were either parents (obligate heterozygotes) or siblings of homozygotes and one was a heterozygote for the X-linked recessively inherited Fabry's disease.

Biological Assay↗
PubMed1990

Mixed venous oximetry during automatic implantable cardioverter-defibrillator placement.

Mixed venous oxygen saturation (SvO2) monitoring was used to assess tissue and circulatory recovery following induced ventricular tachycardia or fibrillation in 17 patients undergoing surgery for automatic implantable cardioverter-defibrillator (AICD) placement. Return of systemic arterial pressure conventionally determines adequate recovery. The duration of circulatory arrest during defibrillator threshold (DFT) testing, measured from the moment of absent phasic pressure at the radial artery until its return, was 18 +/- 8 seconds (mean +/- SD, n = 118 episodes). The absolute decrease in SvO2 from baseline to nadir for these 118 episodes was 14% +/- 6% absolute, and correlated well with the duration of circulatory arrest (r = 0.757, P = 0.0001). The time from onset of phasic arterial blood pressure to the nadir of SvO2, available for 46 episodes, was 28 +/- 14 seconds, and did not correlate with the duration of arrest. The time from onset of phasic pressure to the return of SvO2 to within 1% (absolute) of baseline saturation, available for 84 episodes, was 52 +/- 32 seconds and, in the aggregate, correlated poorly (r = 0.401) with duration of arrest. Simultaneous recording of arterial pressure and SvO2 (n = 41) showed that arterial recovery (6 +/- 3 seconds) occurred long before SvO2 recovery (48 +/- 16 seconds, P = 0.0001). The authors interpret these data as showing that mixed venous oximetry, compared to arterial blood pressure, provides a more sensitive indicator of tissue recovery following periods of circulatory arrest during DFT testing of AICDs.

Arrhythmias, Cardiac↗
PubMed1990

A study of glutamine synthetase in normal human brain and intracranial tumours.

Glutamine synthetase (GS) activity was measured in selected areas of three normal brains and in 262 biopsies from patients with suspected intracranial tumours. In general, levels were higher in grey matter than in white matter and the highest activities of all were found in the hypothalamus which is consistent with its high glutamatergic activity. In the biopsy material, GS activity was greatest in gliotic brain, in keeping with the predominantly astrocytic localization of the enzyme. High levels were also found in astrocytomas and oligodendrogliomas but there was considerable variation between tumours, suggesting a random loss of GS expression during neoplastic transformation or heterogeneity in their cellular origin. The immunocytochemical demonstration of GS in neoplastic oligodendrocytes and in meningioma cells argues against absolute cell-type specificity for this enzyme.

Brain↗
PubMed1989

Androgens affect the processing of secretory protein precursors in the guinea pig seminal vesicle. II. Identification of conserved sites for protein processing.

The guinea pig seminal vesicle epithelium is an androgen-dependent tissue that synthesizes and secretes four major secretory proteins (SVP-1, SVP-2, SVP-3, and SVP-4). Sequencing of near full-length cDNA clones corresponding to the two most abundant mRNAs produced by the seminal vesicle reveals that all four secretory proteins are cleaved from two secretory protein precursors. Amino acid sequences from purified SVP-2 match the central region of the predicted amino acid sequences from the smaller cDNA clone, GP2 (581 nucleotides). Similar analysis demonstrates that the predicted amino acid sequence from the longer cDNA clone, GP1 (1368 nucleotides), codes for the related proteins SVP-3 and SVP-4 as well as SVP-1. The 43.2 kilodalton polyprotein precursor coded by GP1 contains two different sets of 24 amino acid tandemly repeated sequences. The two secretory protein precursors have extensive regions of peptide sequence homology, particularly in regions where protein processing must occur to produce the mature secretory proteins. Analysis of the predicted secondary structure of the two precursor polypeptides revealed a strong correlation between structural features and sites of protein processing.

Amino Acid Sequence↗
PubMed1988

The use and interaction of permanent pacemakers and the automatic implantable cardioverter defibrillator.

The adverse interactions of permanent pacemakers and automatic implantable cardioverter defibrillators (AICD) were studied in nine patients in whom both devices were implanted. Both unipolar and bipolar pacemakers were evaluated. The permanent pacemakers were also used to do noninvasive electrophysiological studies and to induce ventricular fibrillation. Undersensing of ventricular fibrillation by the permanent pacemakers caused inappropriate pacemaker stimuli, which caused undersensing of ventricular fibrillation by the AICD in three of four patients with unipolar pacemakers. After an AICD discharge, pacemaker noncapture was seen in eight of 22 episodes for an average 4.9 seconds and inability to sense was seen in 11 of 20 episodes for an average 9.0 seconds. Counting of pacemaker stimuli and QRS by the AICD caused inappropriate discharges. Noninvasive electrophysiological testing by the pacemakers correlated with invasive testing. Furthermore, induction of ventricular fibrillation was successful in four of five patients attempted, though requiring long bursts at high outputs at the shortest cycle lengths obtainable by these pacemakers. Operation of the AICD and permanent pacemakers must be clearly understood to avoid adverse interactions of these devices.

Electric Countershock↗
PubMed1987

An in-vitro study of irradiated vitreo-retinal membranes.

Standard perforating injuries were created in the right eye of 30 rabbits. Twenty of these had the site of injury irradiated using the radioactive ophthalmic 60Cobalt applicator. Vitreo-retinal membranes obtained from non-irradiated and irradiated eyes were propagated in vitro. The morphology and viability of the cells that grew as a monolayer was studied using phase, light and electron microscopy. The proportions of the different cell types that constituted the monolayer was determined using immunofluorescent staining techniques. Non-irradiated membranes elaborated an abundant outgrowth of healthy cells that were predominantly fibroblasts. Irradiated membranes developed a sparse outgrowth of cells with vacuolated cytoplasm and pyknotic nuclei indicating cell destruction. The majority of the surviving cells were glial, with fibroblasts and retinal pigment epithelial cells forming the remainder.

Animals↗
PubMed1987

Structure of the glycosaminoglycan domain in the type IX collagen-proteoglycan.

Type IX collagen represents 5-20% of the total collagen in hyaline cartilage. The molecules of this collagen are composed of three genetically distinct polypeptide subunits. One of these subunits, alpha 2(IX), contains covalently bound glycosaminoglycan (chondroitin sulfate or dermatan sulfate). We report here on the structure of the glycosaminoglycan attachment site of type IX collagen-proteoglycan. We show, by a combination of cDNA and peptide sequencing, that the attachment region contains the sequence Gly-Ser-Ala-Asp, located within the noncollagenous domain NC3 of the alpha 2(IX) chain. By comparing the exons encoding the NC3 domain in the alpha 2(IX) and alpha 1(IX) genes, we find that the exon coding for the glycosaminoglycan attachment site in the alpha 2(IX) gene is 48 base pairs long, whereas the homologous alpha 1(IX) exon is 33 base pairs. The NC3 domain is, therefore, five amino acid residues longer in alpha 2(IX) than in alpha 1(IX). The extra sequence in alpha 2(IX), Val-Glu-Gly-Ser-Ala, provides a simple explanation for the kink observed at the NC3 domain of type IX molecules when examined by electron microscopy. The inserted block of amino acid residues also provides the NC3 domain of alpha 2(IX) chains with a serine residue, not present in alpha 1(IX) that serves as attachment site for a glycosaminoglycan side chain. Our data show that the amino acid sequence that surrounds the glycosylated serine residue in type IX collagen-proteoglycan differs from glycosylated sequences in noncollagenous core proteins. The data also provide strong evidence that glycosylation of type IX collagen is not a chance glycosylation of a serine residue in a noncollagenous domain, but is a specific post-translational modification of this unusual collagen molecule.

Amino Acid Sequence↗