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Biomedical subjects

F Kristensen

Publications and source records attributed to F Kristensen.

At least 19 recordsLinked to original sources
PubMed1995

Diagnostic importance of urothelial cells of the dog and cat.

The cells lining the canine and feline urinary tract and their role in the diagnosis of urological diseases in small animals is assessed. The urothelium was found to consist of transitional epithelial cells ranging from the calyces to the urethra. Caudate cells were found lining the ureter, renal pelvis and the calyces. There was no feature that could be used to distinguish the transitional cells from different parts of the urothelium. Squamous cells were found lining the urinary tract from the trigone to the vagina in females and to the urethra in male animals. Hydropic degeneration in the form of vacuolation of the cytoplasm, granulation and total loss of cytoplasm was one of the urine-induced degenerative changes recorded in the transitional cells. The significance of the degenerative changes in the management of urological problems is discussed.

Animals↗
PubMed1993

[Prioritizing in hospital departments].

A framework for decision-making is introduced in which two out of five patients will be denied treatment. Certain resource constraints are accepted in this hypothetical example. The authors' own ranking of five patients from a department of internal medicine are presented. It was not difficult to select the highest prioritized patients. However, ranking of the remaining patients revealed considerable controversy. Emphasis is therefore laid on the reasons given for each ranking. An interesting finding is that variations in awarding priority to some cases are clearly based on disagreement about facts, not values. The article concludes by suggesting a classification of selection criteria for priority setting based on a distinction between necessary, controversial and unacceptable criteria. The article is presented in an attempt to stimulate a debate about priority setting in everyday hospital work.

Decision Making↗
PubMed1991

Enhanced granulocyte function in a case of chronic granulocytic leukemia in a dog.

Chronic granulocytic leukemia is a rare myeloproliferative disorder in dogs. The present study investigated various functions of leukemic granulocytes in a dog that presented with thrombocytopenic purpura, anaemia and a classical leukemic hemogram. All analyses were performed in parallel with a control dog. Purification of the leukemic granulocytes by density gradient centrifugation revealed three neutrophil and neutrophil precursor populations with different densities. Comparison of cell morphology and density showed that cell density increased with increasing maturity. The control dog possessed only one neutrophil population, with a density greater than 1.077. Analysis of cellular contents of the granular enzymes, elastase, myeloperoxidase and lysozyme showed that leukemic neutrophils were quantitatively markedly different from normal neutrophils with respect to enzyme activities. There were no major differences between leukemic and normal cells as regards aggregatory and migratory responses to different stimuli. The phagocytic capacity of the leukemic cells, however, was dramatically increased compared with the control, and exceeded all previously encountered responses in the assay employed. In a similar fashion, superoxide generation and secretion of elastase and lysozyme in response to zymosan and phorbol myristate acetate were substantially higher than in the control dog. Priming of cell function to a level exceeding that normally attainable in neutrophils appears to have taken place in peripheral blood of the leukemic dog. The only endogenous mediator known to prime neutrophil functions to the extent seen in the present case is the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is intimately involved in regulation of myelopoiesis in mammals. On the basis of the enzymological and functional findings in the leukemic dog, we hypothesize that a lactoferrin deficiency in leukemic neutrophils leads to enhanced GM-CSF synthesis, which is ultimately the cause of the observed cellular hyperresponsiveness and contributes to the monocytosis seen in the patient.

Animals↗
PubMed1991

Impairment of neutrophil functions in a dog with an eosinophilic dermatosis.

An eosinophilic dermatosis was diagnosed in a dog with a multifocal distribution of pruritic, pustular and erosive lesions on the trunk. Ectoparasites, fungi and bacteria were not detected in the skin of the dog. At a subsequent admission to the university clinic, bacterial conjunctivitis and superficial pyoderma had developed. At a time when the dog received no medical therapy, evaluation of phagocytosis and chemotactic migration towards a variety of chemotactic factors revealed a general suppression of patient neutrophil responsiveness, as compared to a control dog. Viability of the patient's neutrophils was normal. It was proposed that deactivation of neutrophil functions occurred following exposure to suppressive factors from mast cells, or as a consequence of surface receptor down-regulation due to prolonged cell activation by as yet unknown stimulants. The observed susceptibility to infections in the dog suffering from a primary, sterile eosinophilic dermatosis may be related to impaired host defence against opportunistic microorganisms.

Animals↗
PubMed1990

Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets.

Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum and tablets (p greater than 0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts.

Adult↗
PubMed1986

Interference of a C3-fragment preparation with IL 2-dependent proliferation.

A C3-fragment preparation (C3-FP) was studied for its ability to regulate human peripheral blood lymphocyte activation. It was found that very low concentrations of this low m.w. fraction, which was free of C3a, inhibited the PHA-induced lymphocyte proliferation without any cytotoxicity. Cytofluorometric analysis showed that C3-FP did not influence the transition of T cells from the G0 to the G1a phase of the cell cycle. However, the IL 2-dependent transition from the G1a to the G1b phase of the cell cycle was effectively blocked. Addition of exogenous IL 2 did not release cells arrested in the G1a phase. Furthermore, neither IL 2 production nor IL 2 receptor formation was inhibited by C3-FP, and binding of IL 2 to its receptor was unaltered. It was found that only IL 2-dependent cell lines were inhibited in their proliferation; all other tested cell lines were unaffected by C3-FP. Our findings suggest that cleaved products of C3 may inhibit IL 2-dependent lymphocyte proliferation at a stage where the IL 2 signal is required for initiation of proliferation.

Complement C3↗
PubMed1985

Age-related changes in the formation of glucocorticoid and insulin receptors during lectin-induced activation of human peripheral blood lymphocytes.

The influence of age on the number of receptors for insulin and glucocorticoids on human T cells was examined. The specific binding of 125I-insulin and 3H-dexamethasone to phytohemagglutinin-(PHA)-stimulated T cells was found to decrease with age. Populations of PHA-stimulated T cells, however, are heterogeneous with respect to cell cycle phases, and cells in different cell cycle phases have been shown to bear different numbers of receptors. Therefore, it was not clear whether the measured decrease in specific binding in cultures from aged donors was due to a decreased number of activated cells or to a decreased number of binding sites per cell. In parallel to measurements of receptors, performed at different times following stimulation (20 and 44 h), numbers of cells in the different early cell cycle phases G0, G1a and G1b were quantitated by flow cytometry. In this way the receptor number per cell in each phase of the cell cycle could be determined. Receptor numbers on resting cells and in the earliest phase of activation (G1a) were found not to be influenced by age. A decreased receptor density, however, was apparent on G1b cells from aged donors.

Adult↗
PubMed1984

Mechanisms of serotonin-induced lymphocyte proliferation inhibition.

When human peripheral blood lymphocytes were stimulated with phytohemagglutinin in the presence of serotonin, inhibition of [3H]thymidine incorporation occurred, the most marked inhibition occurring at high (10(-3)M) serotonin concentrations. This effect could not be reversed by the addition of Interleukin 2 (IL-2)-containing supernatants. Cytofluorometric analysis showed that virtually all of the cells remained in the G0 phase (unactivated) at 24 hr while some of the cells entered the G1a and G1b phases of the cell cycle by 42 hr. The cellular production of IL-2 was not affected by serotonin, as supernatants of treated cultures contained essentially the same IL-2 titers as did control cultures. Serotonin seemed to primarily affect cell activation and had little or no effect on proliferating cells. This was further confirmed by the lack of effects of serotonin on a variety of established proliferating lymphocyte, macrophage, and fibroblast cell lines. By contrast, dose-dependent inhibition of IL-2-dependent CTLL cells occurred. Serotonin was not toxic even at 10(-3) M concentrations. A marked decrease in IL-2 receptors and a change in their distribution on responder cells was seen when treated cultures were examined with the anti-Tac monoclonal antibody. At 24 hr this effect was contrastingly not seen for the OKT-8 marker, although a slight decrease in OKT-4-positive cells was seen. Serotonin thus produced an inhibition of lectin-stimulated lymphocyte proliferation via a mechanism independent of IL-2 production, and caused a decrease in the expression and distribution of IL-2 receptors on the surface of responder cells.

Adult↗
PubMed1984

Interleukin 2-independent stimulation of rabbit chondrocyte collagenase and prostaglandin E2 production by an interleukin 1-like factor.

In the present study, interleukin 1 (IL 1)-containing media from different sources, namely a murine macrophage cell line (P388D1), rabbit peritoneal macrophages, and human peripheral blood mononuclear cells, were compared for their effect on thymocyte proliferation and on collagenase and PGE2 secretion by chondrocytes. A high correlation was found between the enhancement of thymocyte proliferation and the induction of collagenase and PGE2 secretion by chondrocytes. Furthermore, a highly purified IL 1-like factor, namely mononuclear cell factor (MCF) was also active on chondrocytes. The addition of highly purified IL 2 to rabbit chondrocytes had no effect on collagenase and PGE2 secretion induced by IL 1-containing media. Our findings suggest that the factor which induced collagenase and PGE2 secretion by rabbit chondrocytes was an IL 1-like factor. Thus, collagenase secretion by chondrocytes may be used as an IL 2-insensitive assay for the detection of IL 1-like factors.

Animals↗
PubMed1984

Lymphokine regulation of human lymphocyte proliferation: formation of resting G0 cells by removal of interleukin 2 in cultures of proliferating T lymphocytes.

The question of whether lymphocytes which have once been activated and have completed one or several cell cycle(s) can return to the G0 phase and stay ready for a new activation (G0-G1 transition), rather than simply die, was investigated. To do so interleukin 2 (IL-2) was removed from cultures of continuously proliferating human T lymphocytes and the formation of resting (G0) cells was measured. Kinetic analyses in freshly prepared peripheral blood lymphocytes (PBL) revealed that the onset of detectable RNA synthesis and the appearance of structures binding the anti-Tac antibody occurred simultaneously. This allowed the expansion of the definition of G0 T lymphocytes as cells having a low RNA (and DNA) content, and no Tac antigen. When cultured human T cells proliferating continuously by means of IL-2 were characterized in terms of their distribution in the cell cycle, 7 days after the initial PHA stimulation, it could be demonstrated that very few cells were in the G0 phase, supporting the concept of direct S/G2/M-G1 transition. However, when IL-2 was removed from the cultures, the [3H]thymidine incorporation per 10(4) cells and correspondingly the number of cells in the S/G2/M and G1 phases were reduced drastically and during the following 72-hr period, the number of G0 cells increased markedly. Restimulation of such in vitro formed G0 cells, under conditions permitting observation of their shift from the G0 to G0 phase, demonstrated that most cells could respond normally. Based on these observations, it was concluded that IL-2 not only ensures T-lymphocyte survival and proliferation, but IL-2 starvation induces many continuously proliferating T lymphocytes to stop cycling and to return to the G0 phase of the cell cycle where they remain functional.

Antibodies, Monoclonal↗
PubMed1984

Interleukin 1- and 2-like activities in the dog.

Canine adherent and non-adherent peripheral blood leukocytes and spleen cells were examined for their ability to produce soluble factors with Interleukin 1- and 2- (IL-1 and IL-2) like activities. For this purpose, three conventional assay systems were used: (a) proliferation on an IL-2-dependent murine cytotoxic T-lymphocyte cell line, (b) enhancement of PHA-induced murine thymocyte proliferation and (c) proliferation of lectin-primed canine peripheral blood lymphocytes (PBL). Only the latter two types of cells respond to IL-1, whereas all three types respond to IL-2. Both types of factors were produced and the kinetics of their release/production were found to be identical to those of human PBL. Results suggested that species-related differences existed. Canine interleukin-containing supernatants had higher titers than murine interleukin-containing supernatants when analyzed on canine lymphocytes, and the reverse was found if murine target cells were used.

Animals↗
PubMed1984

Cell cycle-related changes in number of T-lymphocyte receptors for glucocorticoids and insulin.

Enriched human peripheral T-lymphocytes were stimulated with PHA and examined for variations in insulin and glucocorticoid (dexamethasone) receptor numbers during the early phases of the cell cycle. Cells in G0, G1a and G1b phases, where the G1a - G1b transition is an Interleukin 2 dependent event, were quantitated by flow cytometry. Few but significant numbers of glucocorticoid receptors (2700/cell) and no insulin receptors (-1/cell) were found in the resting (G0) phase. As cells entered the G1a phase the specific binding of dexamethasone increased and of insulin took place. Although the specific binding further increased as T-cells entered the G1b phase (as measured at 44 h of incubation and using hydroxyurea-treated cells), the major changes in the specific binding of dexamethasone took place during the period 16 - 20 h after stimulation. Based on these findings, it is concluded that both receptor types (cell membrane and cytoplasmic receptors) are being formed and increased at G1 phase prior to cell proliferation, indicating the importance of G1 phase in immunoregulation.

Adult↗
PubMed1984

Lymphokine regulation of activated (G1) lymphocytes. II. Glucocorticoid and anti-Tac-induced inhibition of human T lymphocyte proliferation.

The regulation of the first cell cycle of human, activated (G1) PBL was analyzed by flow cytometry and [3H]thymidine incorporation. Endogenous IL 2 production was blocked in situ by pharmacologic concentration of DEX (100 to 1000 nM), resulting in an 80 to 90% reduction of thymidine uptake. Although T lymphocyte activation (G0-G1a transition) by PHA was unaltered, cells remained in the G1a phase of the cell cycle due to insufficient RNA synthesis for proliferation. The addition of IL 2-containing supernatants reversed this inhibitory effect of DEX by allowing the cells to synthesize more RNA (G1a-G1b transition). Such cells could enter the S phase and proliferate. Similar studies were performed on cells treated with a monoclonal antibody (anti-Tac) against the IL 2 receptor. In these studies, IL 2-induced RNA synthesis, and subsequent proliferation of DEX-treated and PHA-stimulated cells was inhibited by anti-Tac. Anti-Tac did not, however, inhibit the effect of endogenous IL 2 (PHA-stimulated PBL without DEX treatment), although it did bind equally well to such cells. Thus, IL 2 directly or indirectly regulates human T cell proliferation at the level of RNA synthesis. Furthermore, anti-Tac can inhibit the mitogenic signal given by endogenous IL 2, but not by in situ produced IL 2, an observation of importance to further investigations of the mechanisms by which IL 2 interacts with specific receptors to elicit proliferation.

Adult↗
PubMed1983

A simple and rapid flow cytometric method for routine assessment of baker's yeast uptake by human polymorphonuclear leukocytes.

A new method for measuring uptake of baker's yeast (BY) by human polymorphonuclear leukocytes (PMN) using flow cytometry is described. The method correlates excellently with the visual method, is reproducible and provides a means for investigating the early phases of the phagocytic process as well as the phagocytic capacity of PMN. This quick and accurate method allows the counting of large numbers of cells, and monitoring of the process of particle uptake and has a considerable potential in the routine assessment of polymorph function in various clinical situations.

Acridine Orange↗