Search PubMed⌕ Search

Biomedical subjects

J Lund

Publications and source records attributed to J Lund.

At least 127 records · Page 7Linked to original sources
PubMed1991

Glucocorticoid receptor mRNA expression in pulmonary alveolar macrophages in sarcoidosis.

The presence of the glucocorticoid receptor was demonstrated by immunocytochemistry in pulmonary alveolar macrophages obtained by bronchoalveolar lavage. Also, GR mRNA content was determined by solution hybridization in PAM from 12 healthy volunteers and in 6 patients with sarcoidosis. No significant differences with regard to GR mRNA expression was detected between the two groups examined. For comparison, lung tissue from three patients undergoing thoracic surgery was examined and found to contain GR mRNA levels in the same range. As an indication of GR function, we also determined the mRNA levels of a glucocorticoid-regulated gene, metallothionein IIA, during basal conditions and after in vitro incubation of PAM with dexamethasone. Neither the control sample nor the dexamethasone-stimulated MTII mRNA values in PAMs differed significantly between the two groups. Solution hybridization is a rapid, sensitive and convenient assay which enables accurate and specific quantitation of GR mRNA in PAM. The GR mRNA content and basal as well as dexamethasone-induced MTII mRNA levels in PAM from patients with sarcoidosis is not significantly different from those in healthy volunteers.

Adult↗
PubMed1990

[Spirapril and nitrendipine in arterial hypertension. A comparison of therapeutic effects and tolerance].

In a double-blind, randomized parallel-group investigation, a new angiotensin-converting enzyme-inhibitor, spirapril, was compared with a calcium antagonist, nitrendipine, in 266 patients with mild to moderate hypertension (diastolic blood pressure 96-119 mmHg). The object was to reduce the diastolic blood pressure measured 24 hours after intake of medicine to less than or equal to 90 mmHg. After monotherapy for four weeks with either 20 mg nitrendipine once daily or 12 mg spirapril once daily, the dosages were doubled in the patients in whom the desired blood pressure had not been obtained. After treatment for eight weeks, 12.5 mg hydrochlorthiazide daily was employed as a supplement in patients who had not yet obtained satisfactory blood pressures. Both methods of treatment resulted a lower number of patients who responded and lesser decreases in blood pressure than anticipated. No differences were found in the decreases in blood pressure resulting from the two therapeutic methods. The effect of supplementary hydrochlorthiazide to spirapril treatment was as anticipated while the combination with nitrendipine only resulted in a marginally extra decrease in blood pressure. Nitrendipine resulted in significantly more side effects and more patients defected from the investigation on account of side effects in the nitrendipine group (27%) than in the spirapril group (7%). This investigation had documented the abilities of nitrendipine and spirapril to reduce blood pressure and the side effects associated with this but does not predict whether the preparations can be employed to prevent the complications of hypertension which constitute the indications for treatment. Supplementing nitrendipine therapy with hydrochlorthiazide is not recommended.

Double-Blind Method↗
PubMed1990

Cloning, structure, and expression of a rat binding protein for polychlorinated biphenyls. Homology to the hormonally regulated progesterone-binding protein uteroglobin.

Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. Here, we report the isolation of a cDNA encoding the rat lung PCB-binding protein. The identity of the PCB-binding protein is supported by expression of the cDNA in Cos-1 cells where the homogenates from transfected cells show specific binding of 4,4'-bis([ 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, a high affinity ligand for the PCB-binding protein. Also a monospecific antiserum to the PCB-binding protein recognizes a 13-kDa protein in the homogenates of transfected cells but not in the corresponding fraction of mock-transfected cells. Northern blot analysis of total RNA from different rat tissues demonstrates that the cDNA detects a approximately 600-base pair mRNA which appears to be solely expressed in lung. Interestingly, DNA sequence analysis and prediction of the amino acid sequence reveals that the PCB-binding protein shares 53% positional amino acid identity with uteroglobin, a progesterone-binding protein found in rabbit uterus and lung. Furthermore, amino acids shown by x-ray crystallography to delineate the central cavity of uteroglobin, which fits progesterone, are highly conserved in the two proteins.

Amino Acid Sequence↗
PubMed1990

A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins.

Quantitative oligosaccharide profiles were determined for each of 18 human IgG paraproteins representing the four subclasses. Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined.

Carbohydrate Sequence↗
PubMed1990

Transcriptional regulation of the bovine CYP17 (P-450(17)alpha) gene. Identification of two cAMP regulatory regions lacking the consensus cAMP-responsive element (CRE).

Regions within the 5'-flanking sequence of the bovine CYP17 (P-450(17)alpha) gene which are required for cAMP-dependent regulation of transcription have been localized by transient transfection of chimeric reporter gene constructs into mouse adrenal tumor Y1 cells. Two sequences have been found which individually confer cAMP responsiveness to reporter genes; they are located at -243/-225 and -80/-40 base pairs (bp). Obvious sequence homology between these two regions is not apparent. Gel shift competition analysis indicates that nuclear protein(s) binding to the -243/-225-bp region can be competed for by the addition of a double-stranded oligonucleotide containing a consensus cAMP-responsive element (CRE) from the human chorionic gonadotropin alpha gene, whereas addition of this CRE does not abolish protein-DNA complexes formed with fragments containing the -80/-40-bp sequence. Gel shift and Southwestern analysis indicate that the -243/-225-bp region of the P-450(17)alpha gene and the CRE both bind a 47-kDa protein and that the CRE binds additional proteins (43 and 68 kDa) not apparently recognized by the -243/-225-bp sequence. Thus cAMP-dependent regulation of the bovine P-450(17)alpha gene appears to involve two independent cis-regulatory regions, neither of which contains a consensus CRE. Based on protein binding analysis, one of these regions (that including -80/-40 bp) is distinct from the consensus CRE while the other (that containing -243/-225 bp) may be related to the consensus CRE.

Adrenal Gland Neoplasms↗
PubMed1990

Characterization of the promoter/regulatory region of the bovine CYP11A (P-450scc) gene. Basal and cAMP-dependent expression.

The promoter/regulatory region of the bovine CYP11A (P-450scc) gene was cloned from a bovine genomic library. One major start site of transcription was identified by primer extension analysis with a minor start site four nucleotides further upstream. A putative TATA box is located at position -31, and at position -68 resides a putative binding site for the transcription factor Sp1. Transient transfection of chimeric reporter gene constructs into mouse adrenal tumor Y1 cells was used to locate regions within the P-450scc 5'-flanking sequences that are important for basal and cAMP-dependent transcription of the reporter genes. While cAMP-dependent accumulation of mRNA derived from expression of the endogenous bovine P-450scc gene can be inhibited by protein synthesis inhibitors, transcription of reporter gene constructs containing the promoter/regulatory region of the P-450scc gene is not affected by cycloheximide following transient transfection of Y1 cells or primary bovine adrenocortical cells. Basal expression of these constructs as well as cAMP responsiveness is reduced upon deletion of sequences between -186 and -101, further deletion to -50 leading to loss of virtually all the remaining cAMP responsiveness. The sequence between -183 and -83 alone will direct both basal and cAMP-enhanced transcription when fused to a heterologous promoter and is equally active in either the correct or reverse orientation. No homology to the consensus cAMP-responsive element (CRE) or AP-2 binding site is found in this region whereas an activator protein 1-like sequence is found at position -116. It is concluded that the cAMP responsiveness of P-450scc gene expression is mediated by sequences different from canonical consensus regulatory elements. Whether or not there are sequences conferring cAMP responsiveness which are common both to P-450scc and the other steroidogenic P-450 genes remains to be established.

Adrenal Gland Neoplasms↗
PubMed1990

Molecular definition of interaction sites on human IgG for Fc receptors (huFc gamma R).

Evidence from several experimental approaches allows us to conclude that the primary amino acid sequence of the lower hinge region (residues 234-237) of human IgG molecules determines recognition by human Fc gamma RI, Fc gamma RII and Fc gamma RIII. Glycosylation of the CH2 domain is also essential, although the carbohydrate is not accessible for direct interaction with ligands. The role of the carbohydrate moiety may be to maintain a protein conformation that allows accessibility to amino acid side chains essential for ligand recognition and binding. It appears logical that the evolutionarily-related Fc gamma R molecules should interact with overlapping non-identical sites on the IgG molecule.

Amino Acids↗
PubMed1990

A protein structural change in aglycosylated IgG3 correlates with loss of huFc gamma R1 and huFc gamma R111 binding and/or activation.

Glycosylated chimeric mouse-human anti-NIP IgG3 antibody produced by growth of the J558L mouse B cell plasmacytoma is characterised with respect to the single carbohydrate chain at Asn-297 in the CH2 domain indicating that the mouse cell glycosyl transferases dictate the pattern of glycosylation rather than the human CH region of the heavy chain. Additionally, three unusual alpha-galactose-containing oligosaccharides are reported. Only the Fc region has detectable carbohydrate. Aglycosylated anti-NIP IgG3 antibody has been produced by cell growth in the presence of the antibiotic tunicamycin. Functionally, whilst the glycosylated intact IgG3 interacts with human Fc gamma R111 expressed on human killer (K) cells to trigger antibody-dependent cellular cytotoxicity the aglycosylated intact IgG3 fails to trigger cell lysis, localising the site on IgG for triggering human Fc gamma R111 mediated functions to the CH2 domain. The monomeric aglycosylated trypsin Fc fragment inhibits human Fc gamma R1 recognition by U937 cells 115-fold less well (K50 = 2 microM) than does glycosylated Fc (K50 = 17 nM), confirming that aglycosylation disrupts the site for human Fc gamma R1 within the CH2 domain and indicating that the trypsin Fc fragments reflect the functional properties of the intact IgG glycoforms. Structurally, 1H NMR shows that the absence of carbohydrate at Asn-297 results in a small and localised protein structural change in the vicinity of the reporter group His-268 within the CH2 domain. The site on IgG for triggering human Fc gamma R111 mediated functions is then localised to the vicinity of His-268. The profound impact of aglycosylation on human Fc gamma R1 recognition implies structural disruption of the proposed site for human Fc gamma R1 in the lower hinge region of IgG (residues 234-239), proximal to His-268.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Mentally retarded criminal offenders in Denmark.

Based on data from the Danish Central Criminal Register, the total number of mentally retarded offenders serving statutory care orders on a census day decreased from 290 in 1973 to 91 in 1984. The reduction was caused by shorter sentences and a dramatic decrease in the number of sentenced borderline retarded offenders: the total number of sentences per year slightly decreased, and the number of first-time sentences was stable. Crimes of property are decreasing among this population, while violence, arson, and sexual offences are increasing. Behaviour disorder was found in 87.5% of 91 offenders serving care orders in 1984. Offensive behaviour was significantly predicted by early institutionalisation, having retarded or divorced parents of low socio-economic status, and behaviour disorder of social-aggressive type. Independent significant effects were attributed to behaviour disorder and low socioeconomic background. All predictors were closely correlated. Biological factors did not have any significant predictive value.

Adolescent↗
PubMed1989

Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing Fc gamma RI and/or Fc gamma RII receptors.

Aglycosylated human IgG1 and IgG3 monoclonal anti-D (Rh) and human IgG1 and IgG3 chimaeric anti-5-iodo-4-hydroxy-3-nitrophenacetyl (anti-NIP) monoclonal antibodies produced in the presence of tunicamycin have been compared with the native glycosylated proteins with respect to recognition by human Fc gamma RI and/or Fc gamma RII receptors on U937, Daudi or K562 cells. Human red cells sensitized with glycosylated IgG3 form rosettes via Fc gamma RI with 60% of U937 cells. Inhibition of rosette formation required greater than 35-fold concentrated more aglycosylated than glycosylated human monoclonal anti-D (Rh) antibody. Unlabelled polyclonal human IgG and glycosylated monoclonal IgG1 and anti-D (Rh) antibody inhibited the binding of 125I-labelled monomeric human IgG binding by U937 Fc gamma RI at concentrations greater than 50-fold lower than the aglycosylated monoclonal IgG1 anti-D (Rh) (K50 approximately 3 x 10(-9) M and approximately 6 x 10(-7) M respectively). Similar results were obtained using glycosylated and aglycosylated monoclonal human IgG1 or IgG3 chimaeric anti-NIP antibody-sensitized red cells rosetting with Fc gamma RI-/Fc gamma RII+ Daudi and K562 cells. Rosette formation could be inhibited by the glycosylated form (at greater than 10(-6) M) but not by the aglycosylated form. Haemagglutination analysis using a panel of murine monoclonal antibodies specific for epitopes located on C gamma 2, C gamma 3 or C gamma 2/C gamma 3 interface regions did not demonstrate differences in Fc conformation between the glycosylated or aglycosylated human monoclonal antibodies. These data suggest that the Fc gamma RI and Fc gamma RII sites on human IgG are highly conformation-dependent and that the carbohydrate moiety serves to stabilize the Fc structure rather than interacting directly with Fc receptors.

Antibodies, Monoclonal↗
PubMed1989

Recurrent stenosis by duplex scan following carotid endarterectomy.

Between June 1984 and January 1986, 155 carotid endarterectomies were performed with routine shunting. Serial duplex scanning was performed during an 18-month period on 124 vessels. The results of this duplex scan review revealed the following data: A normal scan was obtained in 87/124 (70.1%). Recurrent stenosis was identified in 35/124 (28.1%), and an occluded vessel was identified in 2/124 (1.6%). Of the total recurrent stenosis group, recurrent stenosis was graded mild in 22/124 (17.7%), moderate in 7/124 (5.6%), and severe in 6/124 (4.8%). Of the 35 vessels with recurrent stenosis by duplex scanning, 22/35 (62.8%) were in female patients, and 13/35 (37.2%) were in male patients. Of the vessels with severe recurrent stenosis, 5/6 (83%) were in female patients. Recurrent stenosis following carotid endarterectomy is more common than appreciated clinically, and female patients in particular may be more prone to recurrent stenosis.

Adult↗
PubMed1989

Developmental regulation of P-45017 alpha gene expression in fetal bovine adrenal.

Among the multifactorial aspects of regulation of steroid hydroxylase gene expression, it is the developmental process which leads to imprinting of expression of particular steroid hydroxylases in specific cell types. We have begun to investigate the ontogeny of steroidogenesis in fetal bovine tissues. Expression of most steroid hydroxylases and related enzymes is detectable in adrenals of the smallest fetuses studied and continues throughout fetal life. Like the other steroid hydroxylases, P-450(17)alpha is detectable in the earliest fetal adrenals studied. However, following an increase in expression, P-450(17)alpha disappears from the fetal adrenal by 100 days gestational age and remains absent until about 230 days gestational age. The absence of P-450(17)alpha is correlated with the absence of cortisol in the fetal adrenal and the absence of ACTH in fetal plasma. Thus expression of P-450(17)alpha in bovine fetal adrenal appears to be strictly dependent on cAMP while expression of other steroid hydroxylases appears to involve both cAMP-dependent and cAMP-independent mechanisms. Furthermore, P-450(17)alpha is expressed in fetal testis at gestational times when it is absent in fetal adrenal. We have begun to examine binding of nuclear proteins from adrenals of various gestational ages to the 5'-flanking region of the bovine P-450(17)alpha gene. Preliminary evidence indicates the presence of a protein in nuclei of fetal adrenals not expressing P-450(17)alpha that is not present in fetal adrenals of other gestational ages.

Adrenal Glands↗
PubMed1989

Dimensional approach to infantile autism in mentally retarded adults.

By use of latent trait models, a 7-item autism rating scale was established, based on the Medical Research Council's Schedule of Handicaps, Behaviours and Skills. Data from a community-based sample of 302 mentally retarded adults were assigning good internal validity to the autism scale, and revealing a distribution of symptoms consistent with dimensional, rather than categorical, distribution of infantile autism. A total of 23 (7.6%) of the sample were earlier diagnosed as suffering from infantile autism. Using this clinical diagnosis as a reference, the autism rating scale, with a cut-off point at greater than or equal to 2, established diagnoses with a sensitivity of 0.83 and specificity of 0.89.

Adult↗
PubMed1989

Measuring behaviour disorder in mental handicap.

By use of latent-trait item analysis (the Rasch model), the internal validity of the behaviour section of the MRC-HBS schedule was analysed. The set of behavioural symptoms in this rating scale was found to measure a one-dimensional structure. Thus addition of item scores provides a meaningful index. Such a numerical measure for the degree of behaviour disorder facilitates comparison between different patients or groups, and furthermore, forms the basis for quantitative description of the outcome of therapeutic intervention. A diagnosis of behaviour disorder was established in 17.2% of 302 mentally-handicapped adults. However, some kind of deviant behaviour was found in 41%, and was correlated with origin and degree of retardation, epilepsy, and place of living. The distribution of the symptoms strongly indicates that organic brain damage is a major aetiological cause.

Adult↗