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Biomedical subjects

K Nilsson

Publications and source records attributed to K Nilsson.

At least 253 records · Page 14Linked to original sources
PubMed1988

Phorbol ester and B cell-stimulatory factor synergize to induce B-chronic lymphocytic leukemia cells to simultaneous immunoglobulin secretion and DNA synthesis.

This paper discusses the response of two B cell-type chronic lymphocytic leukemia (B-CLL) clones, 173 and 183, to the phorbol ester TPA combined with a B cell-stimulatory factor (BSF) derived from a T helper cell hybridoma (MP6). Previous studies with 173 and 183 cells have consistently shown that TPA alone induces differentiation but no proliferation. However, when the two clones were exposed to TPA plus BSF-MP6, not only differentiation but also DNA synthesis was observed. Compared with TPA exposure alone, the fraction of cells with induced lymphoblastoid-plasmacytoid morphology increased and Ig secretion was enhanced. By a 1-hr TPA pulse followed by BSF-MP6, the DNA synthesis was further augmented, but less maturation was observed. T cell and monocyte removal, using cell sorting, showed that the DNA synthesis induced was independent of these cell types, also under serum-free conditions. Quantitation of several cell cycle-associated surface Ags showed that the 4F2, Ba, Bac-1, and cD23 Ags increased while the CD37 decreased in expression upon addition of BSF-MP6. We conclude that B-CLLs are inducible by TPA and BSF-MP6 not only to differentiation, but also to DNA synthesis even under serum-free conditions in vitro. The results furthermore suggest that the very low proliferation activity in B-CLL tumors in vivo may reflect a relative deficiency of proper growth and differentiation factors or a subnormal response of B-CLL cells to such factors.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Chronic B-lymphocytic leukemia--expression of B cell activation markers in relation to activity of the disease.

Two-color FACS analysis was used to study phenotypic subset and activation markers on circulating B (tumor) cells of 21 patients with chronic B-lymphocytic leukemia (B-CLL). Patients with clinically active (progressive) disease differed from patients with stable disease: B cells from the former patient category showed a significantly increased expression of the activation antigen 1D11 and FN99(CD9), and a decreased expression of the FN1 B subset marker. No clinical associations were observed using the CD23, CD25, 4F2, Ba, Bac-1 or FN50 markers. Functional studies showed that the B cells from both clinical categories of patients responded equally well with DNA synthesis when optimally triggered and supplied with T cell factors. However, B-CLL cells from patients with progressive disease secreted significantly higher levels of IgM in response to phorbol ester. The present experiments thus show that differences exist in the activation of B-CLL cells in vivo and that these patterns are correlated with disease activity. Further, the maximal in vitro proliferative capacity of individual tumor cells is similar, whereas differences in accessory T cell functions may exist between patients.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1987

Cytogenetic studies on human myeloma cell lines.

Cell lines (U-266, U-1957, U-1996 and U-2030) established from 4 patients with multiple myeloma (MM) were analyzed cytogenetically. The cell lines represent different stages in B-cell differentiation as evidenced by ultrastructural and functional characteristics. The karyotypic pattern in 3 newly established myeloma lines was studied after a few months in culture and compared to the old myeloma cell line U-266, which was examined after 6, 7 and 8 years of continuous cultivation. Frequency of progressive numerical and structural aberrations during long-term cultivation and their correlation with alterations in growth properties were addressed. We describe the presence of a high frequency of both numerical and structural chromosomal abnormalities in the cells of all 4 myeloma lines studied. Chromosomes often associated with structural abnormalities were 1, 3, 6, 12 and 14. A 14q + marker chromosome was detected in 2 of the 4 cell lines. The breakpoints on the chromosomes participating in structural aberrations in myeloma exhibit some correlation to chromosome sites at or close to locations of mapped oncogenes. No translocations of c-myc were found. These data were further supported by Southern blot analysis (unpublished data). The extent of numerical, but not structural, aberrations correlates with the differentiation stage of the myeloma lines in that the 2 mature lines U-266 and U-1957 were both near-diploid. Multiple progressive chromosomal changes have emerged in U-266 during a period of 8 years with development of independence of feeder cells and increased growth rate. However, capacity for production of complete Ig molecules has remained stable.

Aneuploidy↗
PubMed1987

Establishment of a new human myeloma cell line (U-2030) and selection of a hat-sensitive subline.

We have established a new human myeloma cell line from the pleural effusion of a patient with an IgA lambda myeloma, using special tissue culture conditions and selection procedures to prevent the outgrowth of contaminating Epstein-Barr virus (EBV)-carrying normal B-lymphoblastoid cells present in the explant. The myeloma cell line, U-2030, is aneuploid and EBNA-negative and has morphological features, reactivity with cytochemical markers and cell-surface antigen expression typical of plasmablasts. The cell line thus appears to be representative of the malignant clone in vivo. However, functionally the line is a non-Ig-producer and must therefore be derived from a non-secretory variant cell present within the highly aneuploid myeloma cell clone in vivo. The U-2030 differs from previously established human myeloma cell lines in that it has a comparatively high growth rate, is clonable and can be made HAT-sensitive relatively easily. This, together with the facts that it is a non-Ig-producer and mycoplasma-free, suggests that the 6-thioguanine-resistant, HAT-sensitive subline, U-2030 TG, derived from this cell line may be used as a malignant fusion partner for the production of human-human hybridomas. An EBV-carrying lymphoblastoid cell line (U-2031) was also established. This line was diploid and had all the phenotypic properties of lymphoblastoid lines established from normal individuals.

Aminopterin↗
PubMed1987

Induction of platelet-derived growth factor gene expression during megakaryoblastic and monocytic differentiation of human leukemia cell lines.

Platelet-derived growth factor (PDGF) is one of the most important polypeptide growth factors in human serum. It is composed of two polypeptide chains linked by disulfide bonds. The B-chain is encoded by the c-sis proto-oncogene, which is expressed in several malignant and non-malignant cells including K562 cells differentiating towards megakaryoblasts. Expression of the A-chain has been reported to occur in human solid tumor cell lines independently of c-sis expression. We report here the non-coordinate expression of the A- and B-chains in human leukemia cell lines. The PDGF-A and B-chain (c-sis) RNA expression as well as secretion of PDGF polypeptides are induced in the K562 cell line upon induction of megakaryoblastic differentiation with 12-O-tetradecanoyl phorbol-13-acetate (TPA) whereas erythroid differentiation induced with sodium butyrate is accompanied by c-sis expression only. Simultaneously with megakaryoblastic differentiation the RNA level for another platelet protein, the transforming growth factor-beta was also increased, but in a complex manner. The promyelocytic leukemia cell line HL-60 does not express PDGF-A RNA, whereas the promonocytic cell line U937 does. Preferential induction of the A-chain RNA is obtained in both cell lines after treatment with TPA which causes monocytic differentiation. PDGF-A expression in HL-60 cells is also observed after treatment with the tumor necrosis factor-alpha but granulocytic differentiation of HL-60 cells induced with dimethyl sulfoxide or the granulocyte colony-stimulating factor is not associated with PDGF gene expression.

Cell Differentiation↗
PubMed1987

TPA induces cytoplasmic alkalinization in human monoblastic U-937 cells without activation of Na+/H+ exchange.

The effect of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on cytoplasmic pH (pHi) and H+ extrusion was studied in the human monoblastic cell line U-937. About 2 min after addition of TPA, pHi started to increase and reached a steady state 10-15 min later. The resulting alkalinization corresponded to 0.03 and 0.09 pH units at 10(-10) and 10(-7) M TPA, respectively. The TPA-induced increase in pHi was independent of the presence of extracellular Na+. Moreover, TPA did not affect the H+ extrusion from the U-937 cells. Together these observations indicate the presence of a novel mechanism for TPA-induced cytoplasmic alkalinization. This mechanism is independent of Na+/H+ exchange across the plasma membrane, but may involve organelle sequestration of H+.

Carrier Proteins↗
PubMed1987

Susceptibility to infection by the human immunodeficiency virus (HIV) correlates with T4 expression in a parental monocytoid cell line and its subclones.

The monocytoid tumor cell line U-937 and five derived subclones were infected with the HTLV-IIIB isolate of the human immunodeficiency virus (HIV). Susceptibility to infection and sensitivity to the cytopathic effects correlated with the expression of the T4 antigen on the cell surface. On the basis of these characteristics the lines could be divided into three groups. Less than 10% T4 positive cells were present in the parental line and clone 4; hence productive infection could only be established after a long latency or with a high virus inoculum. These lines showed no or only marginal cytopathic effect. Clone 16 contained more than 95% T4 positive cells and was the most sensitive line to infection with HTLV-IIIB and its cytopathic effect. Cell death was so extensive following infection that no continuous virus producer line could ever be established from clone 16 cells. Cultures with intermediate T4 expression (50-70% T4+ cells) also had intermediate susceptibility to virus infection. Cytopathic changes, even if pronounced, could be overcome in the infected cultures by the addition of uninfected cells and, in each case, a producer line could be established. HTLV-IIIB infection of clone 16 cells could be blocked by preincubation with monoclonal anti-T4 antibodies indicating a close similarity between the HTLV-IIIB receptor on T4 positive T cells and monocytoid cells. The results thus show that T4 positive monocytoid cells can function as target cells for the HIV.

Antibodies, Monoclonal↗
PubMed1987

Drastically increased expression of MYC and FOS protooncogenes during in vitro differentiation of chronic lymphocytic leukemia cells.

Chronic lymphocytic leukemia cells, representing a clonal population of resting B lymphocytes, were induced to differentiate into immunoglobulin-secreting lymphoblasts and plasmablasts by phorbol 12-myristate 13-acetate. The induction resulted in a rapid increase in the molar ratio of secreted/membrane-bound mu-chain mRNA. Immunoglobulin secretion was preceded by a transition of the cells from the G0 to G1 phase of the cell cycle, as indicated by an increase in RNA and protein synthesis, and an overall increase in cellular RNA. The cells, however, became blocked in G1 and did not enter S phase. The expression of MYC and FOS was rapidly induced by the phorbol 12-myristate 13-acetate treatment. The induction of FOS preceded the shift in secreted/membrane-bound mu-chain mRNA molar ratio, while that of MYC occurred concomitantly with the shift, but prior to induction of total RNA synthesis and immunoglobulin secretion. MYC expression remained at a relatively high level during the whole differentiation process. It is thus concluded that a decline of MYC expression is not a prerequisite for differentiation of the chronic lymphocytic leukemia cells. This suggests that MYC expression may play a different role during differentiation of nonproliferating B cells than in the myelomonocytic cell lines HL-60 and U-937, where MYC expression has been reported to decrease during induced differentiation. The results also show that the expression of the MYC and FOS genes does not result in the transition of these cells into the S phase of the cell cycle.

Actins↗
PubMed1987

Radial arterial catheters in children and neonates: a prospective study.

Over a 3-yr period (1982 to 1984), 533 arterial catheters were inserted in 476 patients admitted to the pediatric ICU or the operating room. Radial arterial catheterization with small-bore, 0.8-mm, 22-ga Teflon cannulas was the most common method (376 of 533 cannulations), and 296 of these catheters were inserted in patients less than 1 yr of age. All catheters were flushed intermittently with heparin (12.5 U/ml) in isotonic saline. The mean catheter duration was 2.6 days, and only minor complications were noted. The main reason for catheter removal was malfunction of the arterial line. There was no difference in duration or complication rate between catheters inserted percutaneously or by cutdown. Over a 6-month period (1985 to 1986), 42 0.8-mm, 22-ga radial arterial catheters were inserted in 39 patients less than 1 yr of age; all catheters were maintained by a continuous flushing system using heparin (5 U/ml) in isotonic saline. The mean duration was 6.3 days. No complications were noted, and the proportion of catheter malfunction decreased. This study confirms the safety of radial arterial catheterization in children and neonates. The continuous flushing system considerably improved catheter patency compared to a method using intermittent flushing.

Adolescent↗
PubMed1987

Effects of rectal thiopentone and methohexitone on carbon dioxide tension in infant anaesthesia with spontaneous ventilation.

The influence of rectal administration of barbiturates on PCO2 during mask anaesthesia with spontaneous ventilation was studied in 72 infants. The age of the patients ranged between 6 and 24 months and they were all subjected to minor paediatric surgery. The patients were divided into four equally large groups: a control group receiving no premedication, a group receiving rectal thiopentone 30 mg X kg-1 and two groups receiving methohexitone either 20 or 30 mg X kg-1. In all patients PCO2 was measured in an arterialized capillary blood sample obtained during stable anaesthesia with oxygen, nitrous oxide and halothane before and after surgery. After rectal induction with barbiturates, the mean PCO2 was significantly higher in the different barbiturate groups than in the control group (P less than 0.05). The mean PCO2 value +/- s.d. in kPa for the control group was 5.6 +/- 0.7, for the group receiving thiopentone 30 mg X kg-1 6.5 +/- 1.6, for the groups receiving methohexitone 20 or 30 mg X kg-1 6.1 +/- 1.2 and 6.3 +/- 1.1, respectively. It is concluded that the combination of rectal induction with barbiturates and mask anaesthesia with oxygen, nitrous oxide and halothane carries an increased risk of hypoventilation in infants under 2 years of age.

Administration, Rectal↗
PubMed1987

Carbon dioxide tensions in infants during mask anaesthesia with spontaneous ventilation.

Carbon dioxide tensions (PCO2) in arterialized capillary blood samples were measured in 39 infants anaesthetized for minor paediatric surgery. Anaesthesia was induced and maintained with oxygen, nitrous oxide and halothane, using a Mapleson-D system with spontaneous ventilation and a Rendell-Baker face mask. The duration of anaesthesia was between 15 and 95 min. Two capillary blood samples were obtained during stable anaesthesia before and after surgery. The PCO2 values varied between 3.7 and 8.0 kPa. The highest values were found in infants aged 15-30 days, 6.6 +/- 0.7 kPa (mean +/- s.d.), compared to 5.9 +/- 0.7 in infants aged 31-60 days, 5.6 +/- 0.8 in infants aged 61-180 days and 5.5 +/- 0.7 in infants aged 181-300 days. Comparison between measurements before and after surgery did not in any group indicate a progressive hypoventilation or a correlation between the length of the anaesthesia and the PCO2. It is concluded that anaesthesia with oxygen, nitrous oxide and halothane with spontaneous mask ventilation is a satisfactory method for minor procedures in infants over 1 month of age, while in younger infants controlled ventilation with intubation may be a safer choice of method.

Anesthesia, Inhalation↗
PubMed1987

Mortality in severe depression. A prospective study including 103 suicides.

Twelve hundred and six psychiatric in-patients, 506 men and 700 women, with severe depression/melancholia were rated at discharge with a multi-dimensional diagnostic schedule during 1956-1969. The sample was followed up until December 31, 1983. A total of 476 deaths were recorded including 103 suicides. Suicides and to a small proportion diseases of the nervous system constituted the total excess mortality in unipolar disorders. In bipolar disorders there was also an increased mortality from physical disorders, while the suicide frequency was lower (9% versus 4%). Male suicides had higher initial ratings for the items brittle, sensitive, marital problems, acute onset and lower ratings for psychomotor retardation than other men. Female suicides had a higher frequency of attempted suicides than other women. Acute onset and attempted suicide were associated with suicides early in the course contrary to the other differentiating items. The suicide frequency was similar in admissions during 1956-1962 compared with those during 1963-1969.

Adult↗
PubMed1987

Serum deoxythymidine kinase correlates with peripheral lymphocyte thymidine uptake in chronic lymphocytic leukemia.

The serum thymidine kinase (S-TK) and proliferative activity of the leukemic cells were determined in 27 untreated patients with chronic lymphocytic leukemia (CLL). A significant positive correlation between S-TK and proliferation expressed as a proliferative index (PI) was found (r = 0.70, p less than 0.001). Additionally, PI (r = 0.59, p less than 0.01) and S-TK (r = 0.47, p less than 0.05) correlated to peripheral blood lymphocyte count. When different variables and combinations of variables were studied in order to define their capacity for discriminating between progressive and indolent CLL, S-TK activity and PI proved to be powerful indications. In longitudinal studies, both S-TK and PI paralleled disease activity. A model where a combination of S-TK and PI gives information of the degree of localized disease is proposed.

Adult↗