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Biomedical subjects

J McLean

Publications and source records attributed to J McLean.

At least 91 records · Page 5Linked to original sources
PubMed1985

Clonal T lymphocyte recognition of the fine structure of the HLA-A2 molecule.

A human alloimmune cytotoxic T lymphocyte (CTL) clone (4E4) was generated against the HLA-A2 molecule. Lysis of 51Cr-labeled HLA-A2 target cells was blocked by monoclonal antibodies (mAb), including mAb PA2.1 (anti-HLA-A2), mAb BB7.2 (anti-HLA-A2), mAb 4B (anti-HLA-A2-plus-A28), mAb MA2.1 (anti-HLA-A2-plus-B17), and mAb W6/32 (anti-HLA-A,B,C), which are directed against different serologic epitopes on the HLA-A2 molecule. However, HLA-A2 mutant lines lacking the serologic epitope recognized by mAb BB7.2 (anti-HLA-A2) were efficiently lysed by CTL 4E4. Thus, although mAb may block cytolysis, the HLA-A2 epitope recognized the 4E4 CTL clone is distinct from the HLA-A2-specific epitope recognized by serologic reagents. Moreover, analysis of HLA-A2 population variants revealed that only the predominant HLA-A2.1 subtype molecule was recognized by CTL 4E4. No cross-reactivity on other, biochemically related HLA-A2 population subtypes was observed, including HLA-A2.2 cells (Hill, CVE, ZYL, M7), HLA-A2.3 cells (TENJ, DK1), or HLA-A2.4 cells (CLA, KNE). This CTL clone appears to recognize a single epitope and, like monoclonal antibody counterparts, can be used to discriminate among immunogenic cellular and serologic epitopes on closely related HLA-A2 molecules. On the basis of the known sequence changes in mutant and subtype HLA-A2 molecules, it appears that the sequence spanning residues 147 to 157 may be critical for cellular recognition of this Class I MHC molecule.

Amino Acid Sequence↗
PubMed1984

Identification of shared antigenic determinants of the putative human T lymphocyte antigen receptor.

A mouse antiserum, anti-gp40,49 was obtained by immunizing BALB/c mice with the putative T cell antigen receptor isolated from HPB-MLT cells. This antiserum reacted with peripheral blood lymphocyte (PBL) and a panel of immunocompetent T cell lines and clones in each case precipitating from lysates of cells labeled by surface iodination, a disulfide-linked dimer consisting of an alpha subunit Mr (46,000-49,000) and a beta subunit Mr (40,000-45,000). Variability in Mr of the two subunits, particularly of the beta (light) subunit, was observed when the receptors of immunocompetent T cell lines with different antigen specificities were compared. Anti-gp40,49 serum reacted selectively with the alpha subunit after reduction and alkylation of the protein complex. These results confirm the relationship between the gp40,49 protein complex of HPB-MLT cells and the putative T cell antigen receptor on normal immunocompetent T cells and indicate that the alpha subunit of the human receptor expressed shared determinant(s) that are immunogenic in the mouse. Some features of the T cell antigen receptor appear to be unusual in that even with a xenoantiserum against the purified molecule, only antibodies against clonotypic determinants could be detected at the cell surface by quantitative immunofluorescence analysis.

Animals↗
PubMed1984

Neurological injuries in South Australia: the influence of distance on management and outcome.

It has been shown that in at least two Australian states (New South Wales and South Australia), there is a disproportionately high incidence of lethal neurological injuries in country areas. To determine whether any of this increased rural mortality results from geographical remoteness from specialized hospital services, we have studied prospectively a consecutive series of 153 patients with head injuries (140) or spinal injuries (13), who were transferred to Adelaide, South Australia from country centres during a six month period. Distance appeared to be an occasional cause of delay in instituting expert primary treatment. Of 13 deaths, three resulted from potentially remediable causes (intracranial bleeding, airway obstruction), and in two others difficulties in early supportive care may have contributed to death. First aid sometimes had to be administered by lay persons, and appeared to have been occasionally inadequate. Undesirable delay in transfer from accident site to country hospital was recorded in a few cases; in some of these, private transport was used. Distance was an important cause of delay in transferring patients to Adelaide, since 77% of patients had to travel in excess of 50 km. Thirty patients were brought to Adelaide by medical retrieval teams. These teams, which are centrally co-ordinated, have been useful in extending to country areas the specialized techniques of emergency intensive care and less frequently of operative neurosurgery.

Adolescent↗
PubMed1984

Thymic and body weight during first syngeneic and allogeneic pregnancy in the rat, and the effects of strain difference.

Two hundred female rats, 91-101 days of age, were used in this investigation which provided data on thymic weight, body weight and where appropriate the number of progeny. The observations began in oestrus phase virgin females from the two highly inbred strains AO (RT1u/AgB2) and DA (RT1a/AgB4), continued at five day intervals throughout syngeneic and allogeneic pregnancy in both strains and were completed in the immediate post-partum period. This experimental protocol permitted sequential observations throughout gestation and allowed syngeneic:allogeneic and interstrain comparisons to be made. The syngeneic:allogeneic comparisons demonstrated significant differences in the body weight response and the number of progeny while the AO:DA comparisons demonstrated significant differences in the thymic weight and body weight responses.

Animals↗
PubMed1984

Mental retardation and inspection time: a two-stage model for sensory registration and central processing.

Mildly mentally retarded and nonretarded young adults were compared in simple visual discrimination tasks from which can be derived an estimate of inspection time (lambda), assumed to reflect the time taken by some basic component in the decision process. In the first experiment retarded and nonretarded subjects' performance showed improvement in a condition employing a backward mask to limit the duration of sensory information available to subsequent central processes, but substantial group differences in lambda remain unchanged. When target stimuli were presented for short durations, but without interruption by masking, retarded subjects performed less effectively than did nonretarded subjects and, despite extensive practice, did not achieve nonretarded subjects' levels. These results suggested a two-stage serial model of discrimination that was tested in the second experiment. Concurrent manipulation of two factors confirmed that (a) lambda involves initial sensory registration followed by central processing, (b) for both groups these stages are independent, and (c) poorer performance among retarded subjects is the consequence of deficiencies at both stages.

Adolescent↗
PubMed1983

Mechanisms of action of neurotensin on motility of canine gastric corpus in vitro.

Increasing concentrations of neurotensin produced a biphasic contractile response, inhibition followed by excitation, when added to full-thickness circular strips of canine gastric corpus muscle cut in a circular orientation and incubated at 37 degrees C in vitro. The inhibitory response (mean effective concentration (EC50) 7 x 10(-9)M) was not altered by addition of concentrations of tetrodotoxin or scorpion venom sufficient to block field-stimulated neural responses nor by any other antagonist tested. Therefore, it would appear that inhibition is due to an excitation of the smooth muscle receptor. The excitatory response (EC50 4 x 10(-7)M) was only present in full-thickness strips, i.e., was absent in strips of circular muscle, and was reduced by mepyramine or histamine tachyphylaxis. Pretreatment with disodium cromoglycate or repeated doses of 48/80 to extinction of the response completely eliminated the excitatory response as did repeated doses of substance P to tachyphylaxis. Since 48/80 and substance P have been shown to degranulate mast cells and disodium cromoglycate to stabilize mast cell membranes, neurotensin would appear to produce excitation by releasing histamine and other material from mast cells. In contrast to in vivo studies, where two classes of receptors producing inhibition were found, i.e., a high-affinity receptor on adrenergic nerves and a lower affinity receptor on smooth muscles, in vitro there appears to be only one class of receptor producing inhibition on the smooth muscle itself as no neural receptors were found. The neurotensin receptor responsible for excitation appeared to be on mast cells. The action of neurotensin thus depends upon the locus and the affinity of the receptor and the presence of the receptor on the method of study, i.e., in vivo vs. in vitro.

Animals↗
PubMed1982

Chromosome localization and gene synteny of the major histocompatibility complex in the owl monkey, Aotus.

Rodent cells were hybridized with owl monkey (Aotus) cells of karyotypes II, III, V, and VI. Aotus-rodent somatic hybrid lines preferentially segregating Aotus chromosomes were selected to determine the chromosomal location of the major histocompatibility complex and other genes with which it is synthetic in man. Based on correlation between concordant segregation of the chromosome as visualized by G-banding and expression of the Aotus antigens or enzymes in independent Aotus-rodent hybrid clones, we have assigned Aotus gene loci for the MHC, GLO, ME1, SOD2, and PGM3 to Aotus chromosome 9 of karyotype VI (2n = 49/50), chromosome 10 of karyotype V (2n = 46), and chromosome 7 of karyotype II and III (2n = 54 and 53). On the basis of banding patterns we previously postulated that these chromosomes of the different karyotypes were homologous. The gene assignments reported here provide independent evidence for that hypothesis. Aotus chromosomes 9 (K-VI), 10 (K-V), and 7 (K-II, III) are homologous to human chromosome 6 in that they all code for the MHC, GLO, ME1, SOD2, and PGM3. The structural differences between these homologous chromosomes probably resulted from a pericentric inversion.

Animals↗
PubMed1982

A technique for the in vitro measurement of principal strains in the human tibia.

An experimental technique employing strain-gauge rosettes is described for the in vitro study of principal strains in the tibia as they are affected by various modes of loading on the knee joint. The experimental procedure, based around a Hewlett-Packard 9830A desk-top computer and an HP 3495A 80-channel scanner, is described in detail. The linearity of strain versus load up to 150 kg is shown in the "normally" loaded knee-joint. In these studies, the angle between the principal compressive strain and the vertical axis of the left tibia is reported to vary between 2.2 degrees and -60.2 degrees (Mean -16.5 degrees +/- 16.2 degrees), depending upon the position on the bone. Due to the gross variation of strain at a given point with respect to the angle of measurement, it is essential that strain-gauge rosettes be used to obtain meaningful data in any study of the strain distribution in the tibia.

Adult↗
PubMed1981

Isolation and characterization of subcellular membranes from canine stomach smooth muscle.

Subcellular membrane fractions were isolated from the circular muscle of the corpus of canine stomach by differential and isopycnic sucrose density gradient centrifugation. Differential centrifugation gave a mitochondrial fraction enriched (fourfold) in cytochrome c oxidase and a microsomal fraction enriched (fourfold) in 5'-nucleotidase and NADPH-cytochrome c reductase over postnuclear supernatant. On the basis of a study using continuous gradient, a discontinuous sucrose density gradient was prepared to yield F1 to F5 fractions. The F3 fraction at the interface of 18-32% (w/w) sucrose was maximally enriched (13-fold) in 5'-nucleotidase. The fraction contained very low levels of cytochrome c oxidase but did contain NADPH-cytochrome c reductase (eightfold enrichment). The F4 fraction, at the interface of 32-40% (w/w) sucrose, was maximally enriched in NADPH-cytochrome c reductase (12-fold) and cytochrome c oxidase (6-fold). The distribution of the azide-insensitive. ATP-dependent Ca2+ uptake correlated very well with that of 5'-nucleotidase but less well with NADPH-cytochrome c reductase and not at all with cytochrome c oxidase. Sodium azide and ruthenium red inhibited the ATP-dependent Ca2+ uptake by the mitochondrial fraction and postnuclear supernatant, but not by the F3 fraction. ATP-dependent Ca2+ uptake by the F3 fraction was inhibited by calcium ionophores A23187 and ionomycin, but not by the sodium ionophore, monensin. These results are consistent with the hypothesis that the plasma membrane plays a major role ih regulating intracellular Ca2+ concentration in canine corpus circular muscle.

Adenosine Triphosphate↗
PubMed1980

Characterization, evolution, and molecular basis of a polymorphic antigenic determinant shared by HLA-A and B products.

In our search for monoclonal antibodies defining specific HLA-A,B antigens we have found a significant number of antibodies with polymorphic reactions that are not explicable with our current picture of HLA-A,B interrelationships. Analysis of one antibody (MB40.1) in some detail shows that it recognizes subsets of both A and B antigens and that it is able to split highly cross-reactive pairs of A or B antigens. These results address an outstanding difference in the serological interpretation of H-2, where these types of public reactions have been well established, from HLA, where they have been poorly characterized. Comparison of these types of serological reactions with amino acid sequence data and the apparent evolutionary stability of these broad cross-reacting determinants suggests a simple model for the molecular nature based upon limited amino acid variability and convergent evolution.

Amino Acid Sequence↗
PubMed1979

The echocardiographic association of mitral valve prolapse and mitral anulus calcification.

Mitral anulus calcification (MAC) and mitral valve prolapse (MVP) are frequently diagnosed conditions. We studied two patients with mild or moderate mitral regurgitation who demonstrated both MAC and MVP on angiography and echocardiography. M-mode echocardiography is probably the definitive test for confirming the presence of MVP. Echocardiography is moderately sensitive in the diagnosis of cardiac calcification, such as MAC, but M-mode echocardiography may not detect the MAC in the majority of patients with both MVP and MAC demonstrated by angiography.

Calcinosis↗
PubMed1979

Coronary vasoactivity of adenosine in the conscious dog.

Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.

Adenine Nucleotides↗
PubMed1978

Technical aids as an economic alternative.

Interest in technical aids is growing. Occupational therapists are beginning to play a role in this area. Four programs in which occupational therapists are involved in Canada are described. The programs are: 1. a province-wide, private agency supported program 2. a university based research project funded by a provincial government 3. a technical aids component of the rehabilitation program at a Regional Rehabilitation Centre. 4. a private consulting business. The economic implications of each program are examined to determine whether the program can be justified economically and whether the occupational therapist can justify economically, adding involvement with technical aids to their existing role.

Adolescent↗
PubMed1978

Attention to compounds by retarded adults.

Severely retarded adults were presented with a matching task in which each of the alternatives to the stimulus that was identical to the target stimulus differed from it on one dimension only. Matching performance was found to be good both when the target stimulus had two relevant dimensions and when it had three relevant dimensions. The findings were consistent with those of Tighe and Tighe (1972) and other (Cole, 1973; Tighe, 1973) that the salience of compounds is higher than that of components for persons of lower developmental level.

Adolescent↗
PubMed1976

Extraneuronal effects of 6-hydroxydopamine. Tissue culture studies on adrenocortical cells of rats.

The effects of various concentrations of 6-hydroxydopamine (6-OHDA) on rat adrenocortical cells in tissue culture were studied with phase contrast and electron microscopy. With 40 mg/l of 6-OHDA the first signs of alteration as revealed by microcinematography appeared in isolated cortical cells as early as 15 min after addition of the drug. There was a cessation of movement of cell organelles and an immobilisation of membrane undulations followed by the development of dark inclusion bodies. The cells underwent increasing shrinkage and collapsed by 1 1/2 h. Chromaffin cells were not affected until 45 min after exposure to the drug and neurons were the most resistant population. However 6 1/2 h after application of the drug most cells in the culture were dead. 6-OHDA applied in different doses and to adrenal explants did not alter the sequence of events. Ultrastructurally cortex cells underwent damage alone two lines: they either showed lytic changes or developed various types of dense bodies before reaching the lytic stage. Treatment of cortical cells with 40 mg/l 5-or 6-OHDA followed by exposure to buffered 2% glyoxylic acid and heat did not produce a fluorescence within the cells. Microspectrofluorimetry on amine models with noradrenaline, 5- and 6-OHDA revealed that neither 5-nor 6-OHDA are capable to form a fluorophore with glyoxylic acid.

Adrenal Cortex↗