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Biomedical subjects

K Nilsson

Publications and source records attributed to K Nilsson.

At least 199 records · Page 11Linked to original sources
PubMed1991

Expression of the c-myc protein is down-regulated at the terminal stages during in vitro differentiation of B-type chronic lymphocytic leukemia cells.

The translocated c-myc oncogene in Burkitt's lymphoma (BL) and murine plasmacytoma (MPC) has been proposed to be expressed at a stage of differentiation at which the gene is normally silent, resulting in a continuous proliferation and an inhibited terminal differentiation. To determine whether c-myc is differently expressed at the various stages of the differentiation pathway, we used B-type chronic lymphocytic leukemia (B-CLL) cells, representing resting B lymphocytes, inducible to proliferation and/or differentiation in vitro. The c-myc protein, and Ig lambda-light chain and PCA-1 antigen as markers of B-cell maturation, were analyzed in single, morphologically defined cells by immunocytochemical double-staining. The proliferation of individual cells was determined by 3H-thymidine incorporation and by analysis of Ki-67 antigen expression. The results show that the level of c-myc expression correlates to the stage of differentiation and to the proliferative activity. Uninduced resting cells did not express c-myc. The c-myc protein was observed in the highest amount at the proliferative B-lymphoblast stage of maturation and was reduced in plasmablasts and undetectable in plasma cells. The results suggest that maturation of B cells into nonproliferative, terminally differentiated plasma cells is associated with a downregulated c-myc expression and thus support the view that the deregulated c-myc gene in BL and MPC is expressed at an inappropriate stage of maturation and thereby inhibits terminal differentiation.

Antigens, Surface↗
PubMed1991

Enhancement of IgE synthesis in the human myeloma cell line U-266 with an IgE binding factor from a human T-cell line.

An IgE-binding factor(s) (IgE-BF(s] was partially purified from the supernatant of human HTLV-II carrying T-cell line MO. This IgE-BF(s) was shown to increase the IgE synthesis in the human myeloma cell line U-266, but did not affect its viability or growth. The effect of the IgE-BF(s) was dose-dependent and selective for IgE protein synthesis as beta 2-microglobulin synthesis in the U-266 and the immunoglobulin production in the U-1958 IgG-secreting human myeloma cell line were unaffected. The IgE-BF(s) increased the production of the epsilon heavy chain but not the lambda light chain production. The IgE-BF(s) was distinct from IL-1 beta, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, -beta, -gamma, M-CSF, and fragments of CD23.

Cytokines↗
PubMed1991

Long-term use of central venous catheters in paediatric oncology treatment.

During a 26-month period, 158 central venous catheters were inserted in 114 children (median age: 4.5 years) with malignant diseases. Polyurethane catheters were used, inserted either using a cut-down procedure or percutaneously in the external or internal jugular vein. All catheters were tunnelled from the point of insertion to the midpoint of the manubrium or upper sternum. The catheter tip reached the superior caval vein or the right atrium in 94% of the cases. The catheters were used for all infusions, including total parenteral nutrition, and for blood sampling. The median catheter duration was 104 days (range 5-835 days). Sixty-eight (43%) of the catheters were removed as they were no longer needed, and 31 (20%) were removed due to local infection or septicaemia. During a total of 23,486 catheter days (64.4 years), 110 episodes of septicaemia occurred. This represents one episode per 214 catheter days. In 43 of the 110 episodes of septicaemia, blood cultures showed growth of bacteria of the kind usually found in the gastrointestinal and respiratory tracts. All septicaemias were treated with intravenous broad-spectrum antibiotics and in 21 cases the catheters were removed due to septicaemia. Thirty-four (22%) catheters were removed accidentally. There were two cases of subclavian vein thrombosis.

Adolescent↗
PubMed1991

Recombinant interferon-gamma inhibits the growth of IL-6-dependent human multiple myeloma cell lines in vitro.

Recombinant human IFN-gamma (100-1000 U/ml) inhibited the IL-6-induced growth of 2 human IL-6-dependent multiple myeloma (MM) cell lines U-1958 and U-266-1970 in vitro. In contrast, the U-1996 line, independent of IL-6 for maintenance at a slow growth rate but responding to IL-6 by increased proliferation, and the IL-6-independent U-266-1984 were refractory to the anti-proliferative effect of IFN-gamma. The effect of IFN-gamma in the sensitive MM cell lines was cytostatic in U-266-1970, and cytostatic and cytotoxic in U-1958. Northern blot analysis revealed that the growth inhibition of the IL-6-dependent MM cell line U-1958 was not due to down-regulation of IL-6 receptor mRNA expression and that the differential sensitivity to IFN-gamma was not due to differences in IFN-gamma receptor expression. The growth inhibition was not a consequence of an IFN-gamma-induced terminal differentiation as flow cytometric analyses demonstrated an arrest in all phases of the cell cycle. IFN-alpha inhibited the growth in 3 of the 4 cell lines tested. The results thus suggest that the particular MM phenotype, which includes IL-6 dependency for survival and growth, may also be characterized by IFN-gamma sensitivity. Furthermore, the study demonstrates that MM cell lines are not simultaneously sensitive to IFN-gamma and alpha, indicating that the mechanisms of action of the two types of IFN are distinct.

Cell Division↗
PubMed1991

Investigation of the possible dopaminergic toxicity of 1-methyl-3-phenyl-1,2,3,6-tetrahydropyridine, an isomer to the neurotoxin MPTP.

1-Methyl-3-phenyl-1,2,3,6-tetrahydropyridine (M-3-PTP) is an analogue to the Parkinson-producing dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), M-3-PTP, and simple analogues thereof, are versatile intermediates in organic synthesis. The present study was undertaken to investigate the possible dopaminergic toxicity of M-3-PTP. Male albino mice were injected with 50 mg/kg of either MPTP or M-3-PTP and dopamine (DA) and its metabolites were determined 2 hr and 7 days after the administration. Two hr after MPTP profound acute changes in brain DA metabolism were found, i.e. an approximately 50% reduction in the concentration of DA together with a 10-fold increase in the level of 3-methoxytyramine. Seven days after MPTP, DA and metabolites were markedly reduced which is consistent with a degeneration of the dopaminergic neurones. In contrast M-3-PTP produced no acute or long-term alterations in the concentrations of DA and its metabolites in mouse brain. Furthermore, in vitro experiments show that M-3-PTP does not inhibit monoamine oxidase B. Thus, the present data show that M-3-PTP is devoid of dopaminergic toxicity in mouse brain and is not likely to produce Parkinson's disease in humans. The lack of toxicity is probably explained by the low affinity of M-3-PTP for monoamino oxidase B.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Heterogeneity in response to interleukin 6 (IL-6), expression of IL-6 and IL-6 receptor mRNA in a panel of established human multiple myeloma cell lines.

The controversial role of interleukin-6 (IL-6) as an auto- or paracrine growth factor for human multiple myeloma (MM) cells was studied using a panel of six well characterized feeder-cell dependent and independent MM cell lines as models. With respect to the effect of IL-6 on growth and survival, three types of lines were found: (1) U-1958, dependent on IL-6 both for growth and survival; (2) U-1996, dependent on IL-6 for growth but not survival; and (3) U-266-1984, Fravel, L363, and Karpas 707, independent of IL-6. Feeder-cell supernatants were as efficient as feeder-cell monolayers in stimulating growth and contained IL-6 as the only growth promoting activity. IL-6 was growth stimulatory and sustained the growth of U-1958 only when the medium contained fetal calf serum. The nature of the serum factor(s) is unknown, but it was excluded to be the IL-6 carrier protein a2-macroglobulin. IL-1, IL-2, IL-3, TNF-alpha, GM-CSF, IGF-1, and insulin were neither co-stimulatory with IL-6 nor stimulated growth on their own. Only U-266-1984 expressed IL-6 mRNA. IL-6 receptor mRNA was expressed in all lines except the L363 and Fravel. We conclude that the response to IL-6 is heterogeneous among the MM lines and that IL-6 acts as a paracrine growth factor for two of six lines. In a third line, U-266-1984, the IL-6 mRNA expression suggests the possibility of an autocrine growth stimulation.

Antibodies↗
PubMed1991

In vitro maturation of mononuclear phagocytes and susceptibility to HIV-1 infection.

In the present report, we have studied the in vitro transition of normal blood monocytes to macrophages by changes in cell morphology, and the expression of surface antigens with a panel of monoclonal antibodies. The maturation process was accompanied by notable changes in cell-surface markers in a time-dependent manner. The percentage of cells expressing CD11c, ICAM-1, HLA-DR, and Fc receptor class III increased while the CD4 and CD35 expression was markedly decreased. After demonstrating that in vitro monocytes mature to macrophages in a recognizable manner, we studied the susceptibility to HIV-1 infection at time points representing different stages of cell maturation. The results show that monocyte/macrophages are susceptible to HIV-1 infection at all stages of differentiation. However, the kinetics of virus replication depends on the degree of maturation at the time of infection. Two major patterns of replication were observed: Infection of monocytes resulted in efficient virus production measurable by reverse transcriptase activity in culture supernatant, whereas infection of fully differentiated macrophages yielded low but sustained virus release only demonstrable by p24 antigen assay. We were not able to detect differences in the capacity of the virus to infect and replicate in monocyte/macrophages with respect to cellular origin of the virus isolate and whether the viruses were laboratory-adapted strains or low-passaged patient isolates.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effects of smoking and irradiated volume on inflammatory response in the lung of irradiated breast cancer patients evaluated with bronchoalveolar lavage.

Quantitative measurements of the effects of irradiation on normal tissues in humans have been hard to obtain because most tissues are inaccessible and/or direct responses are difficult to quantify in a nondestructive manner. Pneumonitis and fibrotic lung disease are adverse effects seen in varying intensity in patients treated with radiotherapy for carcinomas of the thorax, e.g., breast cancer. In the present study the aim was to evaluate the inflammatory reaction in the underlying parenchyma following postoperative irradiation with bronchoalveolar lavage technique. Twenty-one patients (11 smokers, 10 nonsmokers) with breast cancer stage T1N0M0 received radiotherapy with photons to a target dose of 56 Gy following breast conservative surgery. Nineteen healthy controls were also included. The results showed a clear elevation of neutrophils, mast cells, eosinophils, and lymphocytes in the total irradiated groups, compared to controls. When subclassifying the material according to smoking habit, it was obvious that the smokers displayed a significantly decreased inflammatory reaction, i.e., reduced levels of mast cells and lymphocytes, compared to both nonsmoking controls and patients. Eosinophils were seen in an elevated number in all irradiated patients. Radiological signs of pneumonitis were observed in three patients, all in the nonsmoking group. No correlation was found between the volume of lung irradiated and the inflammatory response. It is concluded that bronchoalveolar lavage is a suitable and sensitive method for investigating radiotherapy-induced reactions in the human lung. Furthermore, ongoing smoking during the treatment depressed the inflammatory response in the lung parenchyma induced by irradiation. The present study as well as earlier observations justify further studies concerning the possibility of interaction of smoking with cancer treatment, both from the view of therapeutic failures and reduced adverse effects.

Breast Neoplasms↗
PubMed1990

Neuron-specific enolase as a follow-up marker in small cell bronchial carcinoma. A prospective study in an unselected series.

The value of measurement of serum neuron-specific enolase (NSE) as a follow-up marker was investigated in 88 patients with small cell bronchial carcinoma. Of these, 42 had extensive disease and 46 had limited disease. The mean NSE levels before treatment, at response, and at recurrence in extensive disease were 107, 10, and 52 ng/ml, respectively, and the corresponding levels in limited disease were 35, 10, and 19 ng/ml, respectively. All differences were statistically clearly significant. However, the sensitivity of NSE in serum at response was 66% and at recurrence, 38%. The predictive value of an NSE decrease at response was 88%, and at recurrence, 72%. It is concluded that NSE changes during follow-up support the evaluation of the outcome but cannot be used as a monitoring agent in an individual patient.

Adult↗
PubMed1990

The use of macroporous gelatin carriers for the cultivation of mammalian cells in fluidised bed reactors.

A fluidised bed system for the cultivation of mammalian cells on a new type of macroporous gelatin microcarrier is described. The volumetric cell densities achieved under controlled conditions for two 'standard cell lines' (VERO, CHO) were one order of magnitude higher compared to conventional techniques using spherical microcarriers. The system can be potentially used for both anchorage dependent and independent cells.

Animals↗
PubMed1990

Hyaluronan reflects the pre-fibrotic inflammation in irradiated rat lung: concomitant analysis of parenchymal tissues and bronchoalveolar lavage.

The pathogenesis of pulmonary fibrosis is a complicated chain of interactions between cells and molecules. During recent years bronchoalveolar lavage (BAL) in patients with various interstitial lung disorders has increased our knowledge of the fibrosis process and focused on new interesting interactions. Here we present an animal model which makes it possible to apply both morphological and immunohistochemical tissue staining to perform bronchoalveolar lavage in the same animal. Irradiation is an established method for experimentally evoking lung fibrosis in animals. Rats received irradiation (30 Gy) to the lower parts of both lungs. Bronchoalveolar lavage was performed in the right lung. The biochemical determination of lavage concentration of hyaluronan (HA) and cellular differential counts were compared with interstitial morphology. Animals were sacrificed and analysed 2, 4, 6, 8 and 10 weeks after irradiation. After 6 weeks a massive increase in connective tissue mast cells was seen in the peribronchial and alveolar-interstitial tissue. This mastocytosis was closely related to a marked increase in HA. It became obvious that, in this model, cellular analysis of BAL fluid did not correctly reflect the cellular changes in the lung interstitium. While BAL revealed a pronounced increase of neutrophils with no--or only very few--mast cells, a concomitant increase in mononuclear cells and mast cells was seen in the lung interstitium. In contrast an increase in HA in BAL correlated well with an increase in HA-deposition in the lung interstitium, indicating that measurement of a non-cellular component, such as HA, may better reflect the tissue inflammation.

Animals↗
PubMed1990

Influence of fluid regimens on perioperative blood-glucose concentrations in neonates.

Blood concentrations of glucose were measured during surgery and during the first 8 h after operation in 30 neonates undergoing major surgery during the first week of life. Fifteen of the neonates were given Ringer-acetate as the only crystalloid peroperative fluid; to the other 15, 10% glucose i.v. was administered during surgery. In the Ringer-acetate group, mean (SD) blood concentration of glucose increased from 3.1 (2.0) to 4.3 (2.4) mmol litre-1 during surgery. The corresponding increase in the glucose-supplemented group was 3.4 (1.5) to 6.3 (2.2) mmol litre-1. In the Ringer-acetate group, peroperative blood concentrations of glucose were found to be low if a preoperative glucose infusion was interrupted at the start of anaesthesia. Hypoglycaemia occurred in both groups, but more often in the group given Ringer-acetate only (3/15 vs 1/15). Hypoglycaemia was found only in neonates less than 48 h of age and during the first 1 h of anaesthesia only. Monitoring of blood concentrations of glucose and adjustment of the glucose infusion appears to be desirable during and after surgery in neonates.

Blood Glucose↗
PubMed1990

Postanaesthetic nausea in children.

The incidence of emetic episodes during the first 24 h after anaesthesia was studied prospectively in 485 children aged 0-16 years in relation to age, premedication, type of induction, type and duration of anaesthesia, type of surgery and use of postoperative analgesics. The incidence of emetic episodes was 25% in the whole material. The majority of the emetic episodes were recorded after the immediate recovery period. In children under 2 years of age, vomiting was only recorded in 5%. Nausea and vomiting was most common after squint surgery (75%) and least common after endoscopies (17%). Neither premedication with diazepam nor the method of induction (thiopentone, i.v., thiopentone rectally, inhalation with halothane) influenced the incidence of nausea. For the same type of surgery, maintenance of anaesthesia with halothane resulted in a lower incidence of nausea than anaesthesia with fentanyl-pancuronium.

Adolescent↗
PubMed1990

A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation.

Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Phorbol ester treatment down-regulates immunoglobulin RNA steady-state levels in B type chronic lymphocytic leukemia and non-Hodgkin's lymphoma cells.

The human B-lymphoma cell lines BJAB and Daudi, as well as the human pre-B cell line KM3, were found to down-regulate steady-state immunoglobulin RNA levels 2- to 4-fold after stimulation with phorbol 12-myristate-13-acetate (PMA) for 24 hr. No down-regulation of the transcriptional rate of a kappa promoter could be observed in any of these cell lines upon transient expression transfection. The observed down-regulation of steady-state immunoglobulin RNA affected both the secretory and the membrane form of the mu transcript equally. When freshly isolated chronic lymphocytic leukemia (CLL) cells where tested for their response to PMA, three of four isolates responded by down-regulating their steady-state immunoglobulin RNA levels.

Animals↗