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Biomedical subjects

J Lund

Publications and source records attributed to J Lund.

At least 91 records · Page 5Linked to original sources
PubMed1994

Ontogeny of a human polychlorinated biphenyl-binding protein. Level of expression in tracheal aspirates in bronchopulmonary dysplasia.

A human lung polychlorinated biphenyl binding protein (PCB-BP,M(r) 13 kd) has recently been purified from lavage fluid. Polyclonal monospecific antibodies against PCB-BP were produced and used for immunohistochemical staining in sections of human lung tissue. PCB-BP was found to localize preferentially to the nonciliated (Clara) cells of the lung, whereas the alveolar cells and ciliated cells of the larger airways were devoid of staining. Tracheal aspirates from infants receiving mechanical ventilation were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis separation and Western immunoblotting. The antibodies to human PCB-BP detected a single band of the expected molecular weight, and a quantitative analysis of the ontogeny of PCB-BP in tracheal aspirates was performed by construction of Western immunoblot standard curves. A significant increase in the levels of PCB-BP in late gestation (gestational weeks 39 to 41) was demonstrated. In similar experiments, levels of PCB-BP in tracheal aspirates obtained from infants with bronchopulmonary dysplasia (BPD) at the postconceptional age of less than 38 weeks were found to be significantly elevated as compared with a normal study group of similar gestational age (21.8 +/- 4.8 vs 3.1 +/- 0.8 ng of PCB-BP per microgram of total protein, p < 0.005). It is suggested that the high levels of PCB-BP at the postconceptional age of less than 38 weeks observed in infants with BPD may reflect inflammatory injury and regeneration of airway epithelium, associated with proliferation of Clara cells.

Blotting, Western↗
PubMed1994

Large scale ex vivo expansion and activation of human natural killer cells for autologous therapy.

Immunotherapy with recombinant interleukin-2 (rIL-2) activated natural killer cells (ANK) may be useful in the treatment of malignancies. Difficulties in large scale cultivation of purified ANK have hampered clinical trials. In a first set of experiments designed to characterize ANK precursors in blood we demonstrated that both FACS purified CD56+/CD3- and CD56-/CD3- cultured with rIL-2 give rise to an expanded cell population bearing the CD56+(bright)/CD3- phenotype and having both NK and lymphokine-activated killer (LAK) activity. Cultivation of NK was markedly enhanced by autologous monocytes. We next demonstrated that panning of peripheral blood stem cells on CD5/CD8 coated flasks yielded a starting population enriched for monocytes and NK precursors which after cultivation resulted in production of 4 x 10(10) highly cytotoxic ANK adequate for in vivo clinical trials. Finally, we demonstrated that ANK generated in high dose IL-2 maintain NK and LAK activity for up to 6 days when cultured in as little as 1 U/ml rIL-2. This may allow infusion of ANK with a rIL-2 dose achievable in vivo that does not produce significant systemic toxicity. We plan to test the efficacy of ANK to prevent relapse in a minimal residual disease state following autologous bone marrow transplant.

Adult↗
PubMed1994

Arterial line filtration protects brain microcirculation during cardiopulmonary bypass in the pig.

Microemboli in the brain may inhibit brain function during cardiopulmonary bypass, and in a previous study in pigs of normothermic nonpulsatile bypass we reported a significant decrease in cerebral glucose consumption secondary to interruption of the capillary flow, possibly caused by microemboli. In the present study we measured the regional cerebral glucose consumption and the regional capillary diffusion capacity (that is, the number of perfused capillaries) in 10 different brain regions in two separate groups of animals with and without an arterial filter during normothermic cardiopulmonary bypass. Inclusion of a 40 micron arterial filter in the bypass circuit increased the regional brain glucose consumption 27% (median; range -12% to 145%) and regional capillary diffusion capacity increased 123% (median; range 36% to 829%). No change in brain histologic features, the cerebrovascular permeability to serum proteins, or cerebral water content was observed. The arterial filter probably protects the cerebral microcirculation and prevents the decrease in cerebral glucose consumption otherwise seen during bypass.

Animals↗
PubMed1994

Effector mechanisms activated by human IgG subclass antibodies: clinical and molecular aspects. Review article.

Secondary systemic immune responses are predominantly of the IgG class and passive administration of intravenous IgG, from pooled normal serum, is an effective prophylactic and/or therapeutic treatment for patients with defined immunodeficiencies. However, the proportions of each IgG subclass present within a specific antibody response may differ dramatically from that of the total IgG pool. For some antigens the response may be essentially restricted to a single subclass and it may be presumed that the antibody isotype produced has an optimal protective role. The clinical consequences of selective IgG subclass deficiency appears to validate this presumption. In this review we emphasize the differences in effector functions activated by the IgG subclasses and hence the mechanisms responsible for the removal and destruction of antigen/antibody complexes. These studies are relevant to diagnosis and treatment of patients with recurrent infection; the IgG isotype of monoclonal antibodies selected for passive in vivo therapy; the generation of customized antibodies having a pre-determined profile of effector functions and 'immuno-direction' with new vaccines to provoke an antibody response having an isotype profile optimal for the proposed application.

Complement Activation↗
PubMed1993

[Asthma as immediate cause of death].

In 1987 the Danish National Health Board registered 223 deaths from asthma, and even after correction for errors this is an increase during the last decade. The increase is remarkable, because the antiinflammatory treatment during the same period has been intensified, and a reduction in lethal asthma was expected. Available records of the terminal courses are studied and referred, and it is concluded that well-known risk factors such as severe asthma, previous attacks of acute severe asthma and undertreatment can only explain half of the cases. The onset of maximal asthma treatment is delayed from three to 24 hours, averagely five hours from the first warning sign. The onset of treatment is dependent on the patients' own estimation of their actual state, and it is therefore concluded that better education of asthmatics in objectivizing their lung function is desirable. It is estimated that some asthma deaths might be avoided if the patients are given better and more frequent antiinflammatory treatment, if they use peak-flow meters regularly and if they cooperate with their doctor in working out a personal, specific plan of action in case of warning signs.

Adolescent↗
PubMed1993

[Cardiac arrhythmias after transmediastinal resection of the esophagus].

A study of 45 patients who underwent blunt transmediastinal resection of the esophagus without thoracotomy is presented. Sixteen patients (38%) developed a cardiac arrhythmia. The most common arrhythmia was atrial fibrillation/flutter. Even though 14 of the arrhythmias (88%) converted to sinus rhythm, a significantly higher death-rate was seen in this group of patients (p < 0.0014). As we suspect a relation between cardiac arrhythmia and increased mortality after this type of operation, we propose that a double-blind study should be carried out in order to determine the value of an antiarrhythmic treatment.

Aged↗
PubMed1993

Cooperating nonconsensus cAMP-responsive elements are mediators of adrenocorticotropin-induced VL30 transcription in steroidogenic adrenal cells.

Pituitary-derived trophic hormones regulate cell-type-specific expression of VL30 retrotransposons in tissues that are engaged in steroidogenesis. We show that adrenocorticotropic hormone and forskolin induced VL30 transcription in the steroidogenic adrenal cell line Y1 and that the transcriptional activation was cell type- and protein kinase A-dependent. Three novel cAMP-responsive elements (CREs), within the VL30 long terminal repeat, were identified and shown to activate transcription synergistically when templates bearing multiple sites were compared with templates bearing a single site. This type of regulation was evident only in forskolin-treated cells, and the response elements were found to be inactive as mediators of constitutive transcription. In vitro binding analyses indicated that a consensus CRE and the nonconsensus VL30 CREs differ with respect to binding affinity and specificity to a number of nuclear factors that were identified to be related to proteins within the CREB, Jun, and C/EBP families of transcription factors. The relatively low affinity and/or a restricted binding specificity of the VL30 CREs made it possible to detect forskolin-induced binding of CREB- and Jun-related proteins to these sequences. We suggest that cAMP-induced transcription, specific for steroidogenic cells, can be mediated by a novel type of nonconsensus CREs and that the mechanism for this type of gene regulation is distinct from that mediated through a consensus CRE. We also report the identification of a novel factor, distinct from previously characterized CRE-binding proteins, that constitutively binds to the identified CREs.

Adrenal Glands↗
PubMed1993

[Food allergy].

Explore the source record for details and available documents.

Food Hypersensitivity↗
PubMed1993

Aglycosylated chimaeric human IgG3 can trigger the human phagocyte respiratory burst.

This study investigates the capacity of a complexed aglycosylated chimaeric human IgG3 antibody to induce the respiratory burst in human monocyte-like U937 cells. It demonstrates that the aglycosylated antibody, prepared by cell culture in tunicamycin, retains significant capacity to trigger this effector function which was assayed as superoxide generation. Erythrocytes sensitized with near maximal levels of aglycosylated IgG3 were able to trigger > 80% of the superoxide generation triggered by the glycosylated antibody from U937 cells induced to differentiate by interferon gamma and the aglycosylated IgG3 gave half maximal responses at sensitization levels only 72% higher than those required by the glycosylated form. Aglycosylated IgG3 was, however, much less effective in triggering superoxide generation by interferon gamma treated U937 cells at low sensitization levels as threshold responses required only 60 glycosylated IgG3 molecules per erythrocyte compared with 16,000 aglycosylated molecules. In addition, these studies indicate significant differences between the target cell to effector cell ratios which permit IgG sensitized erythrocytes to stimulate the respiratory burst and those which stimulate ADCC in the same effector cell type.

Dose-Response Relationship, Immunologic↗
PubMed1993

Human Fc gamma RI triggering of the mononuclear phagocyte respiratory burst.

This study investigates the role played by Fc gamma RI and Fc gamma RII in triggering the respiratory burst induced in human monocyte-like U937 cells by monoclonal chimaeric anti-NIP antibodies expressing the human IgG subclass and mouse IgG2b heavy chains. Respiratory burst activity was measured as superoxide generation. Four separate lines of evidence indicate a predominant role for Fc gamma RI in triggering superoxide generation induced by erythrocytes sensitized with up to the maximum of 100,000 IgG molecules per cell. Firstly, erythrocytes sensitized with mouse IgG2b anti-NIP antibodies which are not recognized by human Fc gamma RI, did not induce a response but when residue Glu-235 was replaced by Leu to give the lower hinge sequence of mouse IgG2a which is recognized by Fc gamma RI, the mutant bound to Fc gamma RI and induced a response equal to 80% of that given by chimaeric human IgG3. Chimaeric human IgG3 antibodies with amino acid substitutions in the lower hinge showed reduced activity and the greatest reductions (< 32% of wild type antibody activity) were associated with changes at Leu-235 which is critical for recognition by Fc gamma RI. Secondly, chimaeric human IgG4 antibodies which are not recognized by Fc gamma RII, were able to induce superoxide generation. The rank order of abilities of chimaeric human IgG subclass antibodies to induce responses was IgG3 > IgG1 > IgG4 > > IgG2. Thirdly, responses induced by chimaeric human IgG were inhibited by concns of monomeric human IgG3 in the nM range. Finally, chimaeric human IgG3 induced responses were inhibited by anti-Fc gamma RI, but not anti-Fc gamma RII monoclonal antibodies. Consistent with a major role for Fc gamma RI in triggering the responses of U937 cells, erythrocytes sensitized with chimaeric human IgG3 did not induce superoxide generation by neutrophils which express Fc gamma RII and Fc gamma RIII, or eosinophils which express Fc gamma RII, but neither of which expresses Fc gamma RI.

Antibodies, Monoclonal↗
PubMed1993

Control of IgG/Fc glycosylation: a comparison of oligosaccharides from chimeric human/mouse and mouse subclass immunoglobulin Gs.

Oligosaccharide profiles were obtained for chimeric mouse-human antibodies corresponding to each of the human IgG subclasses 1-4, and mouse IgG2b antibodies each expressed in the mouse J558L cell line. These antibodies have specificity for the NIP hapten and form a matched set of IgGs. An IgG4 chimeric antibody (B72.3) produced in the chinese hamster ovary (CHO-K1) cell line was also analysed for carbohydrate. Additionally aglycosylated mutants of this IgG4 (B72.3) and anti-NIP mouse IgG2b were analysed. The total lack of carbohydrate found in the aglycosylated site-directed mutants human chimeric IgG4 B72.3 (Asn 297-->Gln) and mouse IgG2b (Asn 297-->Ala) demonstrates that there are no N-glycosylation sites other than Asn 297. Therefore glycosylation profiles for all the IgGs analysed reflect carbohydrate attached to this site. Factors such as cell type (A), template direction by the IgG heavy chains (B) and culture conditions (C) are shown to influence IgG glycosylation profiles. (A) The anti-NIP IgG antibodies expressed by the J558L cell line may have one or two Gal (alpha 1-->3) Gal residues per oligosaccharide unit, indicative of the presence of (alpha 1-->3) galactosyl transferase in the J558L mouse cell line. (B) The galactosylation profiles obtained for the IgG heavy chains, in particular the preference for galactosylation of the Man (alpha 1-->6) arm rather than the Man (alpha 1-->3) arm, contrary to the beta-galactosyltransferase specificity, suggest that the polypeptide chain may act as a template to influence the extent of galactosylation and hence the proportions of each oligosaccharide incorporated. The IgG2 antibody does not display this galactosylation preference. (C) The extent of galactosylation appears to be influenced by the growth conditions, with the highest levels of galactosylation being found for IgG produced by cells grown in still cultures, rather than cells grown as ascites or in hollow fibre bioreactors. It is concluded that though the profile of glycosylation is controlled predominantly by the glycosylation activity of the cell in which the IgG is expressed, differences between the IgG heavy chain templates of the various subclasses and culture conditions can also influence glycosylation.

Animals↗
PubMed1993

Dopamine, dobutamine, and dopexamine. A comparison of renal effects in unanesthetized human volunteers.

BACKGROUND: Recently, dopexamine (DX), which acts via adrenergic beta 2 and dopaminergic DA1 receptors, has been introduced in the treatment of low cardiac output states. However, the renal effects of DX have not been compared to those produced by equipotent inotropic doses of dopamine (DA), which predominantly stimulates DA1 and DA2 receptors, and of dobutamine (DB), which stimulates beta 1 but not DA receptors. The current study tested the null hypothesis that, with equal increases in cardiac output, DX, DA, and DB would have similar effects on renal function. METHODS: Each drug was given for 2 h on three different occasions to eight normal subjects in doses adjusted to produce a similar 30-35% increase in cardiac output. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured as renal clearances of 131I-hippuran and 99mTc-DTPA, respectively. Lithium clearance (CLi) was used as an index of proximal tubular outflow. RESULTS: Doses of DA, DX, and DB were 2.90 +/- 0.19, 1.00 +/- 0.02, and 4.92 +/- 0.40 microgram.kg-1.min-1, respectively. Dopamine and DX increased ERPF by 23% and 10%, respectively, whereas ERPF remained unchanged during DB. The increase in ERPF was smaller during DX compared with DA. The GFR remained unchanged during DA and DB, but increased during DX (7%). The CLi increased by 35% and 30% during DA and DX, respectively, but was not changed by DB. Calculated absolute proximal reabsorption rate (APR = GFR--CLi) decreased by 13% during DA, but remained unchanged during DB and DX. Dopamine increased sodium clearance (CNa) by 103%, but the changes during DX and DB were not significant. Only DA decreased fractional distal reabsorption (FDRNa = 1--CNa/CLi). CONCLUSIONS: The findings are consistent with a specific, renal-vasodilating effect of DA and DX. However, in the current doses, this effect of DX was of lesser magnitude compared with that of DA. Only DA significantly increased CNa, and the decreases in APR and FDRNa indicate that an effect on tubular reabsorption rate contributed to the natriuresis.

Adult↗
PubMed1993

Mortality in Danish psychiatric long-stay patients, 1972-1982.

By use of the computerized, nationwide psychiatric case register in Denmark, 3 cohorts of psychiatric patients hospitalized for at least one year in 1972, 1977 and 1982, respectively, were identified and followed until April 1, 1988, regarding cause of death. A decline in overall excess mortality compared with the general population was seen from the 1972 cohort to the 1982 cohort irrespective of sex, age group and diagnosis. To analyse cause of death, 298 long-stay patients at Aarhus Psychiatric Hospital were followed for 5.5 years. Lung diseases caused the highest excess mortality. The authors emphasize that risk of death in long-stay patients below 50 years of age is still fourfold compared with the general population and point to the necessity of improving medical care.

Adult↗
PubMed1993

Varicella zoster virus in the health care setting: risk and management.

1. Varicella zoster poses a threat to clients and staff in health care settings because of its ease of transmission and incidence of complications in those over age 20, neonates, and the immunocompromised. 2. Risk surveillance of personnel via a comprehensive screening program will establish the pool of seronegative (or "at risk") health care workers. 3. Clear policies on restricting client admission or visitors, and work restrictions for health care workers related to varicella will aid in preventing outbreaks in the health care setting. 4. Prompt follow up of exposures is best accomplished using an established protocol for loss control.

Herpes Zoster↗
PubMed1993

Glycosylation of human IgG subclass and mouse IgG2b heavy chains secreted by mouse J558L transfectoma cell lines as chimeric antibodies.

Oligosaccharide profiles for monoclonal chimeric mouse-human and mouse IgG2b antibodies produced in the mouse J558L cell line have been determined. These chimeric antibodies share the same mouse light chain and VH region and have a single, complex, oligosaccharide moiety attached to residue 297 of the heavy chain. Since the panel of chimeric antibodies included each of the human IgG subclasses and a set of IgG3 proteins having single residue differences, it was possible to evaluate the contributions of the protein template, the cell line, and the culture conditions to glycosylation. The study shows that the J558L cell line glycosylates human heavy chains with oligosaccharides characteristic of mouse immunoglobulins. This includes a galactose alpha 1-->3 galactose structure not found in human IgG and for which most humans have naturally occurring "anti-Gal" antibodies. The extent of galactosylation was very dependent on the culture conditions and was maximal for still culture. The findings have significance for the production of antibodies for in vivo administration.

Animals↗