Biomedical subjects

J Lund

Publications and source records attributed to J Lund.

At least 163 records · Page 9Linked to original sources

PubMed1986

Characterization of a binding protein for the PCB metabolite 4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl present in bronchoalveolar lavage from healthy smokers and non-smokers.

Bronchoalveolar lavage (BAL) was performed in a group of healthy subjects (10 smokers and 10 non-smokers) and the recovered fluid was shown to contain specific binding sites for a metabolite of a polychlorinated biphenyl (PCB), 4,4'-bis ([3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl [(3H-MeSO2)2TCB]. The sites seem to reside within a protein-like component and the apparent dissociation constant (Kd) for the binding was approximately 2 X 10(-7) M regardless of the smoking status of the subject. However, the maximum number of binding sites (Bmax) was significantly lower for the smokers (p less than 0.001). Competition studies indicated that some PCB methyl sulfones had similar affinities for the specific binding sites as (MeSO2)2TCB. Physicochemical characterization of the human (3H-MeSO2)2TCB-binding protein indicated a Stokes radius of 22 A and a sedimentation coefficient of 1.9 S, and on the basis of these parameters an apparent molecular weight of 17,700 was calculated. The binding protein had an apparent pI of 4.9. It is suggested that the specific binding protein for certain PCB methyl sulfones in bronchoalveolar lavage fluid from healthy subjects is responsible for the previously observed tendency of PCB metabolites to accumulate in human lung tissue.

Adult↗

PubMed1986

The influence of abdominal surgical trauma on the exchange of blood-borne amino acids in the human leg.

Associated with surgical trauma is an increased release of gluconeogenic substrates from the periphery. The present study was undertaken to investigate the peripheral exchange of blood and plasma amino acids as well as some other gluconeogenic substrates (lactate and glycerol) in connection with abdominal surgery. Measurements of leg blood flow and femoral arterio-venous substrate differences were made before, during and immediately after elective cholecystectomy. Blood and plasma concentrations of most amino acids except alanine decreased during and immediately after surgery. Simultaneously there was an increased release of several of the amino acids as well as lactate and glycerol from the leg. The total release of plasma amino acids from one leg in the immediate postoperative period was about 2.5 times as high as before surgery. The turnover rates of amino acids as well as the changes in turnover rates were comparable whether the calculations were made from plasma or whole blood concentrations. At the end of surgery there was a high peripheral uptake of 3-hydroxybutyrate concomitant with a low release of amino acids.

Journal Article↗

PubMed1986

The exchange of blood-borne amino acids in the leg during abdominal surgical trauma: effects of glucose infusion.

The exchange of plasma amino acids and glucose, lactate, glycerol and 3-hydroxybutyrate in the leg was studied in otherwise healthy patients undergoing elective cholecystectomy. Seven patients were given a constant intravenous infusion of glucose at a rate of 1.1 mmol/min throughout the study. Seven other patients who received normal saline only served as a control group. Measurement of leg blood flow and arterio-femoral venous differences of amino acids and other energy metabolites were made on four occasions: (I) before surgery, (II) 10 min after skin incision, (III) at the end of surgery, and (IV) 30 min after the end of anaesthesia. The release of amino acids from the leg was comparable in the two groups before and during the early part of surgery. At the end of surgery the release of several individual amino acids, as well as the total release of amino acids, from the leg was higher in the patients given glucose infusion compared with the control patients. The infusion of glucose prevented the intraoperative rise in arterial levels and uptake of 3-hydroxybutyrate in the leg. A high release of amino acids at the end of surgery was thus associated with low arterial levels of 3-hydroxybutyrate while the reverse pattern was seen in the control patients. These effects of glucose infusion were qualitatively different from those seen in uninjured postabsorptive man.

3-Hydroxybutyric Acid↗

PubMed1986

Effect of extradural analgesia on glucose metabolism and gluconeogenesis. Studies in association with upper abdominal surgery.

Concentrations of glucose and gluconeogenic substrates across the splanchnic circulation were studied in 20 patients undergoing cholecystectomy with general anaesthesia. In 10 patients, general anaesthesia was administered alone, and in 10 general anaesthesia was combined with thoracic extradural analgesia. All patients received a constant i.v. infusion of glucose. Blood glucose concentration increased markedly in the general anaesthesia group in contrast to a moderate and shortlived increase in the patients given extradural analgesia, in whom the splanchnic release of glucose tended to be lower. The splanchnic uptake of glycerol was lower in the patients given extradural analgesia, while the uptake of lactate and the increase in alanine uptake was similar in both groups. Plasma catecholamine and serum cortisol concentrations were higher in the group receiving general anaesthesia alone, while serum growth hormone concentration was higher after surgery in the extradural group. The addition of extradural blockade to general anaesthesia suppresses the increase in blood glucose concentration--and this may be related to a reduced splanchnic release of glucose combined with an increased peripheral uptake.

Abdomen↗

PubMed1986

Behavioural symptoms and autistic psychosis in the mentally retarded adult.

302 mentally retarded (MR) adults, representative of the total Danish MR population, were examined with regard to behavioural symptoms and psychiatric disorder. Deviant behaviour was found in 123 (41%) and was correlated to origin and degree of retardation, epilepsy and place of living. The distribution of the symptoms strongly indicates that organic brain damage is the major etiological cause. By grouping behavioural symptoms on three axes: A: social withdrawal (27%), B: abnormal bodily movements and sensory stimulation (22%) and C: conduct behaviour (17%), different patterns of abnormal behaviour were demonstrated. Behavioural symptoms occurred in 74 (87%) of 85 persons given present state psychiatric diagnoses. Behavioural symptoms are prominent in the group of autistic psychosis (childhood autism), which is classified by the triad of 1) autism, 2) abnormal language, and 3) stereotypic behaviour. This diagnosis was established in 23 (7.6%), and differences in psychopathology are basically determined by degree of intellectual resources, with the subgroup of Kanner's early childhood autism constituting the upper level.

Adult↗

PubMed1986

Treatment of psychiatric morbidity in the mentally retarded adult.

302 mentally retarded (MR) adults, representative of the total Danish MR population were surveyed for present psychiatric treatment and care. The care was generally satisfactory with the majority living under good conditions and provided with a fairly sufficient level of training and occupational therapy. The psychopharmacological treatment was balanced and performed after modern principles. However, more elaborate psychiatric treatment approaches, such as psychotherapy and behavioural therapy, were only used in very few cases, despite the obvious need. A brief review is given and a guide to the literature on psychiatric treatment in the field of mental retardation.

Adult↗

PubMed1986

The influence of abdominal surgery on the splanchnic exchange of amino acids.

The splanchnic exchange of amino acids was studied during and immediately after elective cholecystectomy in 10 patients given a constant infusion of glucose (1.1 mmol/min). Measurements of splanchnic blood flow and arteriohepatic venous differences of plasma amino acids, glucose, lactate and glycerol were made preoperatively, intraoperatively and twice in the immediate postoperative period. The arterial plasma concentration of most amino acids declined during and after surgery but the arterial concentration of alanine was highest in the postoperative period. The total splanchnic uptake of amino acids increased from 140.3 +/- 36.0 mumol/min preoperatively to 338.2 +/- 51.7 mumol/min postoperatively (p less than 0.05). Alanine and glutamine accounted for 65-70% of the total splanchnic uptake of amino acids throughout the investigation. The fractional extraction of methionine increased in the immediate postoperative period, while the fractional extraction of the remaining amino acids was stable. The splanchnic uptake of gluconeogenic substrates exceeded the splanchnic glucose release. The splanchnic uptake of amino acids had already increased intraoperatively and further increased postoperatively despite a net splanchnic glucose uptake in this period.

Abdomen↗

PubMed1985

Further characterisation of the FAD and Fe2S2 redox centres of component C, the NADH:acceptor reductase of the soluble methane monooxygenase of Methylococcus capsulatus (Bath).

The absorbance contributions of the FAD and Fe2S2 redox centres of component C of the soluble methane monooxygenase complex have been resolved, using mersalyl to destroy the Fe2S2 centre. The Fe2S2 seems to be very similar to that of spinach ferredoxin, by its absorbance and electron paramagnetic resonance (EPR) spectra, and the FAD semiquinone is a neutral semiquinone. Spectrophotometry near room temperature and EPR spectroscopy near liquid-helium temperature allow the three redox couples of component C to be ordered. Component C can exist in Oe-1 (oxidised), 1e-1 (semiquinone), 2e-1 (mostly semiquinone and reduced Fe2S2), and 3e-1 forms (dihydroquinone and reduced Fe2S2), under equilibrium conditions. The ability of component C to support odd-electron forms is consistent with its proposed role as a 2e-1/1e-1 transformase, splitting electron pairs from NADH for passage to component A in one-electron steps. (The FAD appears to interact with NADH, and transfers single electrons to the Fe2S2, for donation to component A at a constant redox potential.) The mid-point potentials of component C were found using redox dyes and EPR spectroscopy and were: FAD/FAD., Em = -150 mV; Fe2S2/Fe2.S2,Em = -220 mV; FAD./FAD..,Em = -260 mV. the presence of NADH did not alter these mid-point potentials. These mid-point potentials are consistent with the role of component C as the NADH:component A reductase, passing electrons from NADH (Em = -320 mV) onto component A (Em = +150 mV and Em = -150 mV). The reducing power from NADH appears to be required by component A to activate one atom of oxygen, to insert into methane, and the reducing equivalents derived from NADH end up with the other oxygen atom, as water.

Binding Sites↗

PubMed1985

Electron transfer reactions in the soluble methane monooxygenase of Methylococcus capsulatus (Bath).

Aerobic stopped-flow experiments have confirmed that component C is the methane monooxygenase component responsible for interaction with NADH. Reduction of component C by NADH is not the rate-limiting step for component C in the methane monooxygenase reaction. Removal and reconstitution of the redox centres of component C suggest a correlation between the presence of the FAD and Fe2S2 redox centres and NADH: acceptor reductase activity and methane monooxygenase activity respectively, consistent with the order of electron flow: NADH----FAD----Fe2S2----component A. This order suggests that component C functions as a 2e-1/1e-1 transformase, splitting electron pairs from NADH for transfer to component A via the one-electron-carrying Fe2S2 centre. Electron transfer has been demonstrated between the reductase component, component C and the oxygenase component, component A, of the methane monooxygenase complex from Methylococcus capsulatus (Bath) by three separate methods. This intermolecular electron transfer step is not rate-determining for the methane monooxygenase reaction. Intermolecular electron transfer was independent of component B, the third component of the methane monooxygenase. Component B is required to switch the oxidase activity of component A to methane mono-oxygenase activity, suggesting that the role of component B is to couple substrate oxidation to electron transfer, via the methane monooxygenase components.

Electrochemistry↗

PubMed1985

A hydroxylapatite microassay for receptor binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene in various target tissues.

A "batch" hydroxylapatite assay for the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) receptor that does not require detergents is described. The receptor could be assayed in rat target tissues using either of the cytochrome P1-450 inducers [3H]TCDD or [3H]3-methylcholanthrene as radioligands. A phosphate buffer washing procedure was developed on the basis of chromatographic data and optimized to separate nonspecifically and specifically bound ligand. The assay was characterized with respect to washing efficiency, binding specificity, competition, adsorption time, amount of hydroxylapatite required to bind receptor complexes, sensitivity, and effects of detergents. Equilibrium binding parameters were determined. Receptor extracted with phosphate from hydroxylapatite was analyzed on sucrose gradients and was found to exhibit the same sedimentation properties as the receptor in crude cytosol. Furthermore, the applicability of the assay has been demonstrated in cytosolic preparations from three different target tissues: liver, lung, and thymus.

Animals↗

PubMed1985

Inappropriate emergency department visits.

Guidelines adopted in 1982 by the American College of Emergency Physicians were used to determine appropriate and inappropriate emergency department (ED) utilization patterns at three community hospitals during a two-week period in August 1983. In all, 3,130 visits were examined. There was an overall inappropriate visit rate of 10.8%, although considerable variation was observed among the three hospitals. Subgroups with the highest inappropriate visit rates included the following: 1) persons with Medicaid as the primary payment source (17.3%); 2) children aged 5 years or younger (15.2%); 3) those unable to identify a personal physician (14.1%); 4) unemployed persons (13.1%); 5) patients making visits during regular office hours (12.6%); and 6) those failing to attempt to contact their personal physicians (12.4%). These variations in inappropriate usage were all statistically significant at the P less than .05 level or better. Inability to identify a personal physician emerged as the most pervasive influence on inappropriate ED visit rates (P less than .001).

Adolescent↗

PubMed1985

Mentally retarded admitted to psychiatric hospitals in Denmark.

Computerized register linkage and a questionnaire survey showed that the number of mentally retarded admitted to psychiatric hospitals in Denmark is rapidly increasing. This development is highly deplorable. Diagnosis and treatment are frequently complicated by the nature of the mental handicap and, especially, the often diverging clinical appearance of the psychiatric disorders in these persons. Mentally retarded with a psychiatric disorder should, in general, be treated in special institutions or outpatient clinics, by specially trained social psychiatrists and staffs.

Adolescent↗

PubMed1985

Epilepsy and psychiatric disorder in the mentally retarded adult.

302 mentally retarded adults, sampled by epidemiological criteria, were examined with regard to epilepsy and psychiatric disorder. Each of the complications was frequent and related to degree and origin of mental retardation. In 55 (18.2%) epilepsy had occurred at some time during their lives, in 25 (8.3%) of these in the past year. In 52% of persons with seizures in the past year a present state psychiatric diagnosis was established, compared to 26% in those without seizures. The nature of the combination of epilepsy and psychiatric disorder is complex, but in the mentally retarded most often reflecting underlying brain pathology in the form of widespread cortical and subcortical cerebral damage causing epilepsy of generalised or mixed type, and predominantly interictal psychiatric disorders unrelated in time to seizures and dominated by behaviour problems.

Adult↗

PubMed1985

The prevalence of psychiatric morbidity in mentally retarded adults.

302 mentally retarded adults, sampled by epidemiological criteria, were examined with regard to handicaps, behaviour, skills and psychopathology by use of the MRC HBS-schedule and a list of psychiatric items. Based on research criteria, a computerized psychiatric diagnosis was made on a hierarchial scale. A psychiatric disorder was diagnosed in 85 (27.1%), which is a smaller prevalence rate than found in other studies. Next to behaviour disorder (10.9%), psychosis of uncertain type (5%) was the most common disorder. Dementia and early childhood autism were found equally often (3.6% each). Neurosis was seldom (2%), while schizophrenia (1.3%) and affective disorder (1.7%) occurred at about the same rates as found in similar investigations. No cases of alcohol or drug abuse were found.

Adolescent↗

PubMed1985

Target cells for the polychlorinated biphenyl metabolite 4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl. Characterization of high affinity binding in rat and mouse lung cytosol.

When a tritium-labeled metabolite of polychlorinated biphenyls (PCB), 4,4'-bis[( 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl [(3H-MeSO2)2TCB] is administered intraperitoneally to rats, a selective labeling is registered in the apical cytoplasm of the nonciliated bronchiolar (Clara) cells of the lung as determined by microautoradiography of sections of methacrylate-embedded tissue. In vitro, (3H-MeSO2)2TCB binds with high affinity (Kd = 2.5-15 nM) and high capacity (Bmax = 30-70 pmol/mg of protein) to rat lung cytosol. Binding of (3H-MeSO2)2TCB to the high affinity sites is temperature dependent, reversible, and saturable. The sites seem to reside within a protein-like component, since proteolytic enzymes significantly reduce the binding. Physiochemical characterization of the (3H-MeSO2)2TCB-binding protein indicates a Stokes radius of 22 A and a sedimentation coefficient of 1.7 S and, on the basis of these parameters, an apparent molecular weight of 16,000 may be calculated. The binding entity has an apparent pI of 5.3 and elutes as a single radioactive peak from CM-Sepharose at 75 mM acetate. Binding with similar affinities (IC50 values, 4-65 nM) is shown to occur also with other PCB methyl sulfones, whereas only one PCB, 2,2',4,4'5,5'-hexachlorobiphenyl, competes for (3H-MeSO2)2TCB binding, but with a lower affinity (IC50 = 3 microM). Among other compounds tested, only progesterone and some derivatives thereof display an affinity for the (3H-MeSO2)2TCB-binding protein (IC50 values ranging from 1 to 10 microM). Lung cytosol shows by far the highest amount of specific (3H-MeSO2)2TCB binding. However, low but detectable amounts are also found in cytosolic preparations from prostate, kidney, and large intestine. Finally, (3H-MeSO2)2TCB also binds to an entity in mouse lung cytosol with the same physicochemical characteristics as that in rat lung cytosol and to a progesterone-binding protein purified from rabbit uterus (uteroglobin). It is concluded that rat lung contains a uteroglobin-like macromolecule with a pronounced affinity for at least certain PCB methyl sulfones, and it is suggested that this binding entity is responsible for the striking accumulation of such metabolites in lung tissue following administration of PCB to rats and mice.

Animals↗

PubMed1984

The murine T cell antigen receptor and associated structures.

The immunochemical approach described in this review has led to the identification of a new component of the T cell surface, the disulfide-linked heterodimer, which has many of the properties expected of a molecule with antigen-specific receptor activity: 1) Expression of the heterodimer is restricted to T cells. 2) The molecule expresses clonotypic epitopes presumably related to the specific antigen recognition site, as well as crossreactive epitopes associated with the molecular framework. 3) At the primary sequence level, the molecule has regions of constant as well as variable structure. The numerous observations from other laboratories that clonotypic antibodies which inhibit antigen-specific reactions are directed against similar disulfide-linked heterodimers provide compelling evidence that this structure is in fact the T cell antigen receptor. Two important conclusions can be drawn from the results of peptide analysis of the receptor subunits. First, the molecular fingerprints of the alpha and beta chains are very different, indicating that the subunits are encoded by different genes. Second, both subunits have constant and variable regions, suggesting that both subunits play a role in producing the antigen combining site. A crucial question that remains to be answered is whether the same or different combining sites are responsible for recognition of antigen and the MHC restricting element. The recent report by Marrack et al. (1983b) that the receptors of two independent T cell hybridomas with the same antigen and MHC specificities expressed the same clonotypic determinant and yielded identical peptide maps (Kappler et al. 1983) provides strong evidence that the heterodimer is responsible for both antigen and MHC recognition. If this is the case, it remains to be determined whether a single site contributed by both subunits recognizes antigen and MHC, or whether one subunit contributes a site for MHC recognition and the other a site for antigen recognition. If, however, as Parham (1984) has recently proposed, conserved rather than polymorphic regions of the MHC product are recognized in MHC restriction, it is possible that the heterodimer functions solely in recognition of antigen, and the restriction may be provided by accessory proteins in a receptor complex. Definitive conclusions as to the role of the individual chains will probably require construction of functional T cells using molecular clones of the genes encoding the receptor and accessory proteins. Recently, the molecular cloning of cDNA encoding putative T cell receptors has been reported from murine (Hedrick et al. 1984) and human (Yanagi et al. 1984) cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

Femoxetine clearance in patients with liver cirrhosis.

The pharmacokinetics of femoxetine (a 5-HT uptake inhibitor with antidepressive effect) was studied in 12 patients with liver cirrhosis and in 6 healthy controls after a single oral dose of femoxetine HC1. The average blood concentration of femoxetine, as assessed by the values of AUC (area under the plasma concentration/time curve), was significantly higher in the patients with liver cirrhosis than in the healthy controls in spite of dose reduction in the patients. The elimination half-life of femoxetine was within the normal limits in most of the patients. The oral clearance of femoxetine was considerably lower in patients, (0.65-4.02 1/hr/kg) than in the controls (8.13- greater than 50 1/hr/kg). It was not directly related to the metabolic function of the liver, measured as the galactose elimination capacity being 0.015-0.024 mmol/min./kg and 0.033-0.041 mmol/min./kg, respectively. When treating patients with reduced liver function, it is recommended to reduce the doses and to monitor closely the plasma levels.

Adult↗

PubMed1983

Physicochemical characterization of specific and nonspecific polyaromatic hydrocarbon binders in rat and mouse liver cytosol.

The aryl hydrocarbon hydroxylase inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene, and benzo(a)pyrene were all shown to bind in a saturable manner to a distinct component in cytosol from both rat and C57BL/6J mouse liver. This component was analyzed by gel permeation chromatography on Sephacryl S-300 and by sucrose density gradient centrifugation and was found to have a Stokes radius of 61 +/- 1.5 A and a sedimentation coefficient of 4.4 S under high salt conditions. Based on these parameters, which were identical for the rat and mouse receptor, a molecular weight of 111,000 was calculated. The same Stokes radius and sedimentation coefficient were observed regardless of the ligand used for labeling of the receptor protein [(3H]TCDD, 3-[3H]methylcholanthrene or [3H]benzo(a)pyrene). On the other hand, 3-[3H]methylcholanthrene and [3H]benzo(a)-pyrene exhibited much more nonspecific binding than [3H]TCDD, at least partially due to contaminating serum components, and it cannot be excluded that some previous findings on low molecular weight hepatic "receptors" for these polyaromatic hydrocarbons may actually be explained in this way. Clearly, use of thoroughly perfused livers would seem to be a prerequisite for investigations on specific binding of aryl hydrocarbon hydroxylase inducers to liver cytosol. The rat hepatic TCDD receptor was also shown to be retained on DEAE-Sepharose (eluted at 0.2-0.3 M NaCl), hydroxylapatite (eluted at 0.15-0.17 M phosphate), and heparin-Sepharose (eluted at 0.3-0.4 M NaCl). In conclusion, the TCDD receptor showed similar physicochemical and chromatographic characteristics to those previously reported for the androgen and glucocorticoid receptors. However, ligand competition experiments indicated that the TCDD receptor is not identical to any steroid receptor. In line with this, monoclonal anti-glucocorticoid receptor-IgG antibodies did not react with the TCDD receptor.

Animals↗