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Biomedical subjects

J Lund

Publications and source records attributed to J Lund.

At least 145 records · Page 8Linked to original sources
PubMed1988

Developmental expression of bovine adrenocortical steroid hydroxylases. Regulation of P-450(17 alpha) expression leads to episodic fetal cortisol production.

The developmental expression of adrenocortical steroid hydroxylases was studied in bovine fetuses from 40 to 280 days gestational age. The expression of P-450(17 alpha) is first detected at a gestational age of 50 days and reaches a maximum at 60-70 days. The expression of P-450(17 alpha) then declines and is nondetectable at a gestational age of 100 days. P-450(17 alpha) is not expressed again until about 240 days, i.e. shortly before birth (approximately 280 days). P-450scc, P-450c21, P-450(11 beta) and adrenodoxin were present in fetal adrenals throughout gestation. This "on-off-on" pattern of P-450(17 alpha) expression during fetal development was associated with a corresponding episodic production of cortisol. Immunoreactive corticotropin (ACTH) levels in fetal plasma were elevated in small fetuses (corresponding to less than or equal to 100 days) and in near-term fetuses (corresponding to greater than 250 days) compared with those in mid-gestation fetuses. In primary culture, adrenal cells from mid-gestation fetuses contained no detectable P-450(17 alpha) but rapidly responded to ACTH with an increase in P-450(17 alpha) protein and mRNA. The tissue specificity of the developmental patterns is emphasized by the fact that both P-450(17 alpha) and P-450scc were detectable throughout the development of the fetal testes, whereas only P-450scc was detectable in fetal bovine ovary prior to 200 days. Thus, in fetal bovine adrenal it appears that ACTH is the major regulatory factor effecting the intermittent presence of P-450(17 alpha), whereas the presence of the other steroid hydroxylases is either regulated by additional factors or shows a much different sensitivity to ACTH.

Adrenal Cortex↗
PubMed1988

Partial purification of a binding protein for polychlorinated biphenyls from rat lung cytosol: physicochemical and immunochemical characterization.

A binding protein for certain methyl sulfone metabolites of polychlorinated biphenyls (PCB) was partially purified from lung cytosol of untreated female rats. The protein has an Mr of 13,000 and a pI of 5.3 in the absence of reducing agents. In the presence of dithioerythreitol or beta-mercaptoethanol, the protein is split into subunits with a more basic pI. The 13-kDa protein was electroeluted from SDS-polyacrylamide gels, and an antiserum against the protein was raised in rabbit. The immunoglobulin fraction was shown to contain monospecific antibodies against the 13-kDa protein as determined by Western immunoblots. The antibodies retained partially purified binding protein labeled with radioactive ligand when subjected to protein A-Sepharose chromatography and caused a shift in the elution of the labeled protein from Sephadex G-75 and a shift in its sedimentation behavior on sucrose gradients. Due to striking similarities in physicochemical characteristics of the 13-kDa protein and a protein purified from rabbit lung and uterus, uteroglobin, the anti 13-kDa protein antibodies were tested for cross-reactivity. As judged by Western immunoblots, the anti 13-kDa protein antibodies did not cross-react with uteroglobin and the two proteins, although similar, do not seem to be identical. The 13-kDa protein is proposed to be responsible for the accumulation of certain methylsulfonyl-PCBs in lung tissue of rats. Monospecific antibodies against the 13-kDa protein should constitute immunochemical probes of great value in attempts to elucidate the physiological role of the protein as well as its possible role in PCB-induced respiratory toxicity.

Animals↗
PubMed1988

Changes in the ATPase activity of insect fibrillar flight muscle during sinusoidal length oscillation probed by phosphate-water oxygen exchange.

Extensive phosphate-water oxygen exchange occurs when ATP is hydrolyzed in an [18O]water medium by length oscillated and Ca2+-activated, chemically skinned fibers from the flight muscle of the giant waterbug Lethocerus indicus. For fibers which are length oscillated under conditions not optimal for ATPase activity or oscillatory work, the pattern of exchange shows two pathways for hydrolysis. One pathway has low exchange, because steps controlling Pi release are rapid; the other pathway has high exchange and slow Pi release. Steps controlling Pi release appear rate-limiting for changes in the high-exchange ATPase activity that occur on varying the frequency and amplitude of oscillation. On length oscillation under conditions of optimal ATPase activity or work, only the high-exchange pathway is present. Cross-bridges following the high-exchange pathway are therefore responsible for oscillatory work, the physiological function of the muscle, and behave uniformly with respect to oxygen exchange. The single pathway and the magnitude of the ATPase activity are both similar to results with isometric strained fibers (Lund, J., Webb, M. R., and White, D. C. S. (1987) J. Biol. Chem. 262, 8584-8590). A qualitative model is suggested for oscillatory work by cross-bridges, arising from the common periodicity of the thick and thin filaments in insect flight muscle.

Adenosine Triphosphatases↗
PubMed1988

The binding of methylsulfonyl-polychloro-biphenyls to uteroglobin.

The binding of methylsulfonyl-polychloro-biphenyls (methylsulfonyl-PCBs) to purified uteroglobin was studied by a dextran-coated charcoal assay using 4,4'-bis([ 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl [(3H-MeSO2)2TCB] as radiolabeled ligand. The specific binding of this ligand to uteroglobin was enhanced by the presence of dithiothreitol, and the optimal concentration of dithiothreitol for binding was 20 mM. The specific [(3H-MeSO2)2TCB] binding was inhibited by 4-methylsulfonyl-2,2',4',5,5'-pentachlorobiphenyl in a concentration-dependent manner. The molecular structures of methylsulfonyl-PCBs, and progesterone, were fitted into the X-ray crystallographic structure of uteroglobin using the molecular graphics program TOM. In these simulations the water-accessible surfaces of the ligands appeared quite similar, and fitted nicely in the internal water-accessible surface of uteroglobulin. Moreover, it appeared from the computer-supported ligand-binding studies that the sulfone oxygens of the studied methylsulfonyl-PCBs, as well as the carbonyl (C20) of progesterone, may form hydrogen bonds with the hydroxyl group of TYR 21 of uteroglobulin. These findings may explain why both steroids and methylsulfonyl-PCBs interact with the same protein, although these two types of ligands are structurally dissimilar.

Binding, Competitive↗
PubMed1988

Differences between chick and turkey embryos in sensitivity to 3,3',4,4'-tetrachloro-biphenyl and in concentration/affinity of the hepatic receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin.

1. 3,3',4,4'-Tetrachlorobiphenyl (TCB) was 20-100 times more toxic in chick embryos than in turkey embryos when injected into eggs. 2. The ED50-value for induction of AHH activity by TCB in the liver of early chick and turkey embryos was estimated to be 0.6 and 6 micrograms/kg egg, respectively. 3. In both species alpha-naphthoflavone was more effective than metyrapone at inhibiting basal and TCB-induced AHH activities. 4. The TCDD receptor was detected in the liver of 7-day-old chick embryos, while it was not found in 9-day-old turkey embryo liver.

Animals↗
PubMed1988

Psychiatric aspects of Down's syndrome.

In a survey study of psychiatric morbidity, based on a representative sample from the Danish mental retardation register, 44 adults with Down's syndrome (DS) were compared with 258 other mentally retarded adults. Assessed by the parameters psychiatric disorder, behaviour problems, neurotic traits, and deviant social interaction, the DS group functioned better on all parameters. However, male and female DS patients were very different, the females constituting a superior well-functioning group while the males had major problems in every area. High prevalence rates of dementia and infantile autism were found in the DS group. General function rapidly decreased with age in DS patients.

Adult↗
PubMed1988

Human calpactin II (lipocortin I) messenger ribonucleic acid is not induced by glucocorticoids.

Studies were carried out to examine the effect of glucocorticoids on human calpactin II (lipocortin I) mRNA expression. A cRNA probe for human calpactin II (hCPII) was used in a solution hybridization assay to study the effect of dexamethasone on hCPII mRNA levels in human skin fibroblasts, peripheral lymphocytes, pulmonary alveolar macrophages, and HeLa S3 cells. As a positive control, human metallothionein II (hMTII) mRNA levels were measured since hMTII is known to be regulated by glucocorticoids and heavy metals, both of which induce transcriptional activity of the gene. Dexamethasone treatment of these human cell types caused a dose-dependent increase in hMTII mRNA levels, whereas no effect on hCPII mRNA levels was observed. These findings were confirmed in time course studies, where 10(-6) M dexamethasone treatment caused a maximal 2- to 5-fold increase in hMTII mRNA levels after 6-8 h of treatment but no increase in hCPII mRNA levels was observed at any time point up to 24 h. A human glucocorticoid sensitive lymphoid cell line, CEM C7, and a glucocorticoid resistant mutant, ICR-27, isolated from CEM C7, were included in order to confirm the requirement of a functional glucocorticoid receptor (GR) in the induction of glucocorticoid-regulated genes. Dexamethasone (10(-6) M) induced hMTII but not hCPII mRNA in CEM C7 cells, whereas neither hMTII nor hCPII mRNA was induced in ICR-27 cells. In conclusion, our data suggest that glucocorticoids do not induce calpactin II (lipocortin I) mRNA in the human cell types studied.

Annexins↗
PubMed1988

Cross-bridge kinetics in asynchronous insect flight muscle.

Calcium-activated insect flight muscle is further activated by small applied strain. We have investigated the mechanism of strain activation by measuring the extent of oxygen exchange between phosphate and water during ATP hydrolysis by Ca2+ -activated, chemically skinned fibers from the flight muscle of the giant waterbug Lethocerus indicus at different degrees of strain. The maximally activated insect fibres show a pattern of oxygen exchange which is well fitted by a single pathway of ATP hydrolysis. This differs from results with rabbit muscle, which show a more complicated form of oxygen exchange. We ascribe this difference to the different pattern of distribution of myosin heads on the thick filament. Calcium-activated, but unstrained, insect fibres also require more than a simple pathway of ATP hydrolysis to account for the pattern of oxygen exchange. The transition between the more complex pathway and the simple pathway occurs over a very narrow range of strain, centred at zero strain (rest length in the relaxed fibres). We describe how the experimental results of strain activation might occur, based upon Wray's description of filament geometries, but taking into account likely sarcomere mechanics. The pattern of oxygen exchange found in fully activated insect fibres suggests that the process of phosphate release from the actomyosin is rate limiting, implying that the main tension-generating state is an AM.ADP.Pi complex.

Actomyosin↗
PubMed1987

Changes in the ATPase activity of insect fibrillar flight muscle during calcium and strain activation probed by phosphate-water oxygen exchange.

During ATP hydrolysis by Ca2+-activated chemically skinned fibers from the flight muscle of the giant waterbug Lethocerus indicus, there is extensive phosphate-water oxygen exchange. For unstrained fibers the pattern of exchange shows that there is more than one pathway for hydrolysis, due to the ATPase activity of cross-bridges. Multiple pathways are an established property of both vertebrate actomyosin and fibers. The pattern of exchange can be fitted by two pathways: one with low exchange because the step(s) controlling Pi release are rapid, the other with high exchange and slow Pi release. The high-exchange pathway is responsible for most of the increase in ATPase activity on Ca2+ activation. On strain activation, only the high-exchange pathway is present, accounting for all the ATPase increase and responsible for force generation. In fully activated fibers, the cross-bridges which hydrolyze ATP and generate force behave uniformly with respect to oxygen exchange. The exchange pattern shows that the rate of Pi release changes dramatically over a very narrow strain increase. Step(s) controlling Pi release are at least partially rate-limiting for the overall ATPase reaction. The results are discussed in relation to models for strain activation and the identity of force-generating states.

Adenosine Triphosphatases↗
PubMed1987

The influence of epidural analgesia on the splanchnic exchange of amino acids during upper abdominal surgery.

Splanchnic turnover of plasma amino acids was studied in 10 patients given thoracic epidural analgesia combined with general anaesthesia for elective cholecystectomy. Ten other patients given only general anaesthesia for cholecystectomy served as a control group. All patients received an infusion of glucose during the investigation. The total concentration of amino acids in arterial plasma did not change in the patients given epidural analgesia but decreased by approximately 15% in the non-epidural group. In both groups splanchnic uptake of amino acids increased during surgery and was found to be more than doubled in the early postoperative period. The addition of epidural analgesia to general anaesthesia did not modify the splanchnic uptake of amino acids during surgery and in the immediate (2 h) postoperative period.

Abdomen↗
PubMed1987

Epithelial membrane antigen expression in benign and malignant squamous epithelium of the head and neck.

A distinction between benign, preneoplastic, and malignant tissue, based upon the expression of surface antigens, would provide useful clinical information. Epithelial membrane antigen (EMA) has been reported in squamous cell carcinomas, but not in normal squamous epithelium. Twenty-nine specimens from 15 patients, representative of the spectra of changes seen in squamous cell epithelium from normal through dysplasia to squamous cell carcinoma, were fixed in B-5 and examined with anti-EMA monoclonal antibody in an immunoperoxidase technique. Normal squamous epithelium does express EMA. Squamous cell carcinoma also expresses EMA. Well-differentiated tumors stain more intensely and in greater numbers of cells than less-differentiated tumors. The presence or absence of EMA expression does not distinguish normal squamous epithelium from carcinoma. Investigations of membrane antigen content in fixed tissue must use methods of fixation that preserve antigenicity. While strict quantitation of immunoperoxidase preparations is not possible, quantitative differences in expression may be important.

Carcinoma, Squamous Cell↗
PubMed1986

Characterization of the DNA-binding properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The DNA-binding properties of the receptor for 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) were investigated using chromatography on DNA-cellulose columns. A maximal binding of about 40% of the total receptor complex to DNA-cellulose was observed. In order to interact with DNA, the receptor must first bind TCDD. A heat-activation step followed by gel permeation chromatography using Sephadex G-25 increased the binding of the cytosolic receptor to DNA. The DNA-binding ability of the receptor was almost lost following mild proteolysis using trypsin or alpha-chymotrypsin, although these treatments did not reduce its ligand binding capacity and had no apparent effect on its size. Furthermore, pre-treatment of the DNA-cellulose column with an intercalating drug, ethidium bromide, resulted in inhibition of the binding of the TCDD-receptor complex to DNA, indicating that not only electrostatic interactions but also the configuration of DNA are of importance in receptor-DNA interactions.

Animals↗