Biomedical subjects
D McCormick
Publications and source records attributed to D McCormick.
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.
Langerhan's cell histiocytosis in the sphenoid sinus: a case of diabetes insipidus.
We present a case of diabetes insipidus in a young man caused by Langerhan's cell histiocytosis of the sphenoid sinus with involvement of the pituitary gland. Diagnosis and management of this rare condition is discussed, along with a brief view of the literature.
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.
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.
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.
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.
The importance of pre-fixation orientation of duodenal biopsies.
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Right heart obstruction due to intracavitary prolymphocytic leukemia.
A 52-year-old woman with prolymphocytic leukemia in whom right heart failure developed from leukemic infiltration of the heart with right ventricular outflow tract obstruction is described. Two-dimensional echocardiography helped guide successful treatment of this complication with radiation and chemotherapy.
School re-entry program for oncology patients.
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Studies on the secretion, metabolism and action of atrial natriuretic peptide in man.
Radio-immunoassay of atrial natriuretic peptide (ANP) and infusions of alpha-human ANP (alpha-hANP) have been used to study the secretion, metabolism, regulation and actions of ANP in man. Plasma immunoreactive ANP (irANP) was twice as high in arterial blood as in simultaneously sampled venous plasma from the femoral, hepatic and renal vein, but no arteriovenous difference was found across the lung. Analysis of plasma extracts by high performance liquid chromatography confirmed that alpha-hANP-like material was a major component in coronary sinus and peripheral arterial and venous plasma. In normal subjects, venous plasma irANP was increased by both acute and chronic sodium loads, and by exercise. The cardiac secretion of irANP, and peripheral venous levels, were markedly increased by atrial pacing in four patients investigated for arrhythmia. Plasma irANP concentrations were elevated in many patients with circulatory disorders, including chronic renal failure, congestive heart failure and during spontaneous tachyarrhythmias. Constant 60-min intravenous infusions of alpha-hANP increased urinary sodium excretion in normal subjects, under conditions of both high- and low-sodium intake, and selectively reduced plasma aldosterone concentrations. These effects were observed at the venous levels of plasma irANP found in some patients with circulatory disease. Taken together, the present studies suggest that ANP has important endocrine functions in human health and disease.
Production of glial fibrillary acidic protein (GFAP) by neoplastic cells: adaptation to the microenvironment.
In 80 specimens of human glioma the production of glial fibrillary acidic protein (GFAP) by tumour cells invading meninges or connective tissue was studied immuno-cytochemically by the PAP technique. In 38 of 55 cases of astrocytoma, glioblastoma, gliosarcoma, and oligoastrocytoma, GFAP immunoreactivity was greater in the invading cells as compared with the main part of the neoplasm. Fifty-eight percent of the astroglial tumours invading the leptomeninges, all astroglial tumours invading connective tissue and all gliosarcomas showed enhanced GFAP immuno-reactivity of tumour cells getting in contact with collagenous tissue, whereas meningeal infiltrates of 25 non-astroglial tumours (oligodendroglioma, ependymoma, medulloblastoma) remained GFAP-negative like the main part of the respective tumours. In the majority of astroglial tumours an increase of GFAP immunoreactivity was found also in perivascular cells of the main part of the tumour. It is concluded that glioma cells are capable of adapting their cytoskeleton to their micro-environment. Contact with dense collagenous tissue appears as an important factor able to induce an increased production of GFAP by adjacent glial cells.
The establishment and characterization of a cell line and mouse xenografts from a human malignant melanoma.
A permanent cell line has been established from a human intracranial secondary melanoma. During 3 years of continuous growth in vitro the cells have maintained their characteristic phenotypic properties including melanin production. The cultured cells are highly tumorigenic in the athymic mouse and the tumours produced are histologically identical to the human tumour of origin.
The use of hypercapnia in the study of regional cerebral blood flow abnormalities with 133Xe.
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An investigation in vitro of the exocytosis of lysosomal enzymes from C6 glioma cells.
The rates of exocytosis on the lysosomal hydrolase n-acetyl-beta D-glucosaminidase and beta-glucuronidase were measured in monolayer cultures of the C-6 glioma cell line. A comparison of the kinetics of release of the enzymes and the effects of cytochalasin B suggest that either intralysosomal localisation or the mechanism of release may be different for each enzyme. Evidence was obtained that exocytosis is accompanied by receptor-mediated endocytosis of hydrolases and the importance of the microtubular system in the maintenance of the exocytosis equilibrium was indicated by the effect of colchicine on the rate of extracellular accumulation of the enzymes.
Heel deformity in hereditary spastic paraplegia.
The association of pes cavus deformity and neurological disorder is well known. Varus deformity of the heel is often associated with, and may even precede the development of pes cavus. Clinical and radiographic examinations of the feet of members of three kindreds of hereditary spastic paraplegia, a rare neurologic disorder, suggested that the autosomal dominant form manifests a significantly higher incidence and degree of heel varus deformity than the autosomal recessive form of the disease. Therefore, heel varus deformity may be a sign suggestive of autosomal dominant inheritance of hereditary spastic paraplegia.
A biochemical, histological and electronmicroscopical study of possible carriers in Duchenne muscular dystrophy.
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Clinicopathological study of Refsum's disease with particular reference to fatal complications.
The clinical and pathological findings in two brothers with biochemically diagnosed Refsum's disease are given. The pathology, in general, was that already described in this condition. An unusual complication in one case was the development of renal failure. Death was caused in the other by heart failure.