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Biomedical subjects

M Carlsson

Publications and source records attributed to M Carlsson.

At least 127 records · Page 7Linked to original sources
PubMed1992

Pharmacokinetics of factor VIII in humans. Obtaining clinically relevant data from comparative studies.

The pharmacokinetics of Factor VIII procoagulant activity (FVIII:C) were investigated in 10 patients receiving 2 different high purity concentrates of FVIII. The in vivo recovery of FVIII:C depended on the method of blood volume estimation and on the in vitro assay used to define the potency of the concentrate; more generally, it also depends on the study design. The use of in vivo recovery to compare FVIII preparations should therefore be discouraged and the achieved area under the FVIII activity-time curve (AUC) should be used instead. The volume of distribution at steady-state (Vss) of FVIII:C was significantly greater than the estimated plasma volume of the patients. The mean terminal half-life of FVIII:C was slightly assay-dependent, being 14h by a 1-stage clotting assay and 12h by a chromogenic assay. The calculated apparent clearance (CL) of FVIII:C, as well as the Vss and the in vivo recovery, depended on the measured in vitro potency of the FVIII concentrate. These methodological aspects of pharmacokinetic studies are of direct interest to the clinician, since the routine administration of FVIII is based on the pharmacokinetic properties of the specific preparation.

Chromatography, Affinity↗
PubMed1992

alpha-Interferon inhibits spontaneous and induced DNA synthesis in hairy cell leukemia.

The effect of alpha-interferon (alpha-IFN) on spontaneous or induced proliferation of isolated peripheral blood mononuclear cells from 5 hairy cell leukemia patients was studied. alpha-IFN inhibited the low spontaneous proliferation of B-ly7 positive hairy cells (HCs) and also the proliferation induced by tumour necrosis factor (TNF). Interleukin-2 did not affect HCs, but induced CD4 positive T cells to proliferate, an effect which alpha-IFN antagonized. The stimulatory effect of TNF on the growth of HCs proved to be reversible and was partially blocked with either anti-TNF receptor or anti-lymphotoxin antibodies. Cellular or secreted thymidine kinase levels reflected the proliferative state of HCs in response to different in vitro treatments, as confirmed by thymidine incorporation and cell cycle studies.

Cell Cycle↗
PubMed1992

Increase in interleukin 6 (IL-6) and IL-6 receptor expression in a human multiple myeloma cell line, U-266, during long-term in vitro culture and the development of a possible autocrine IL-6 loop.

A human multiple myeloma (MM) cell line, U-266, has developed the ability to grow independently of exogenous interleukin 6 (IL-6) during long-term cultivation in vitro. The early passage, feeder-cell dependent U-266 cell line (U-266-1970) was compared with the late passage U-266-1984 cell line with respect to response to IL-6, IL-1 beta and tumour necrosis factor alpha and expression of IL-6 and IL-6 receptor (IL-6R) mRNA and protein. The results showed that; (a) only the U-266-1970 cell line was stimulated to growth by IL-6, (b) IL-6 and IL-6R mRNA were expressed in both cell lines, (c) the level of IL-6 mRNA was increased in the U-266-1984 cell line and only this line produced IL-6 and, (d) the level of IL-6R mRNA was highest in the U-266-1984 cell line and the number of IL-6R about ten times higher than in U-266-1970. The growth of the IL-6-producing U-266-1984 cell line was inhibited by 30% by anti-IL-6R antibodies suggesting the possibility that an autocrine IL-6 loop might have developed during the long-term cultivation. In addition to many other phenotypic alterations of the U-266 cell line, having developed as a consequence of tumor progression in vitro, its growth factor requirement seems to have evolved from a dependence on IL-6 as a paracrine growth factor to a capacity for autonomous growth, dependent on autocrine IL-6 stimulation. Whether such a development also may take place in MM clones in vivo remains to be established.

Blotting, Northern↗
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

Synergistic interactions between muscarinic antagonists, adrenergic agonists and NMDA antagonists with respect to locomotor stimulatory effects in monoamine-depleted mice.

The purpose of the present investigation was to study the effects of simultaneous manipulations of central cholinergic, adrenergic and glutamatergic systems on locomotion in an animal model of Parkinson's disease. Mice were deprived of their monoamine stores by pretreatment with the monoamine depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine, given 18 h and 60 min, respectively, before the acute experiment. Traditionally, only dopaminergic agonists have been shown to reverse the akinesia thus produced. However, in the present study it is demonstrated that if a muscarine receptor antagonist (atropine or biperiden) is combined with an alpha-adrenergic agonist/alpha-adrenergic agonist precursor (clonidine or L-alpha-methyl-dopa), a marked locomotor stimulation can be achieved, although either agent given alone is ineffective. Adding an NMDA antagonist (MK-801, ketamine or SDZ EAA 494) to the combination biperiden + clonidine resulted in further potentiation of the locomotor stimulatory effects.

Adrenergic alpha-Agonists↗
PubMed1991

Synergistic interactions between the NMDA antagonist dizocilpine and the preferential dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 with regard to locomotor stimulation in monoamine-depleted mice.

When administered to mice pretreated with the monoamine-depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine, the preferential autoreceptor antagonists (+)-AJ76 and (+)-UH 232 induced weak locomotor stimulation. When either (+)-AJ 76 or (+)-UH 232 was combined with a subthreshold dose of the selective NMDA antagonist dizocilpine (MK-801), a marked locomotor stimulation was produced in monoamine-depleted mice. The mechanism of this stimulation, although reduced by dopamine antagonists, remains to be clarified.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

A comparison between the non-competitive NMDA antagonist dizocilpine (MK-801) and the competitive NMDA antagonist D-CPPene with regard to dopamine turnover and locomotor-stimulatory properties in mice.

Following intraperitoneal administration of the non-competitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801), levels of the dopamine (DA) metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in mouse striatum and limbic forebrain. When dizocilpine was given to animals treated with NSD 1015, an inhibitor of 3,4-dihydroxyphenylalanine (DOPA) decarboxylase and monoamine oxidase, there was an increase in levels of DOPA and 3-methoxytyramine (3-MT). These findings suggest that dizocilpine stimulates DA synthesis and release in mouse brain. Following dizocilpine treatment a clear-cut increase in spontaneous locomotor activity was observed, probably partly due to enhanced dopaminergic tone. The competitive NMDA antagonist D-CPPene produced locomotor stimulation as well, but in contrast to following dizocilpine treatment levels of 3-MT decreased. Thus the stimulation of locomotor activity following D-CPPene treatment does not seem to be mediated through activation of central dopaminergic systems. However, haloperidol pretreatment antagonized this locomotor response, indicating that the dopaminergic system plays a permissive role in this context.

Animals↗
PubMed1991

The oldest old: patterns of adjustment and dependence.

The aim of the present study was to investigate how dependence was experienced by 129 non-institutionalized 85-year-old persons, who previously had been categorized into seven different patterns of adjustment. The participants' subjective experiences of dependence were expressed in in-depth interviews and additionally, mobility, self-maintenance and need of help in daily living was conventionally assessed. When the results from these two methods were compared, it was found that subjectively experienced dependence did not generally correspond with the scorings on dependence. The in-depth interviews revealed that subjects with poorer adjustment could be most affected by minor impairments, while physical impairments were of a subordinate importance to those who were better adjusted. For appropriate caring interventions, it is therefore suggested that conventionally assessed dependence needs to be supplemented with documented subjective experiences of dependence.

Activities of Daily Living↗
PubMed1991

The oldest old: patterns of adjustment and life experiences.

A qualitative method was used to study the life experiences and the adjustment to very old age of a non-institutionalized population of 129 85-year-olds living in Gothenburg, Sweden. In-depth interviews were analyzed and categorized and seven patterns of adjustment emerged: Self-Realizing, Mature Aging, Adapting, Dependent, Resignedly Accepting, Despairing and Withdrawing. Additionally, a coping strategy--ritualization of time and occupations--was revealed in the interviews. These results reflect the heterogeneity among this age group and indicate that the subjective reality should be seriously considered both in further research and in the care of the elderly.

Adaptation, Psychological↗
PubMed1990

The non-competitive NMDA antagonists MK-801 and PCP, as well as the competitive NMDA antagonist SDZ EAA494 (D-CPPene), interact synergistically with clonidine to promote locomotion in monoamine-depleted mice.

The present study shows that high doses of the non-competitive NMDA antagonist phencyclidine (PCP) as well as of the competitive NMDA antagonist SDZ EAA494 (D-CPPene) increase locomotion in monoamine-depleted mice. The pattern of movement produced following treatment with these agents is very similar to that previously observed following MK-801 administration to monamine-depleted mice. When subthreshold doses of MK-801, PCP and SDZ EAA494 were combined with the alpha-adrenergic agonist clonidine, a dramatic stimulation of locomotion was observed in monoamine-depleted mice; the gross appearance of the animals was similar with the three drug combinations. These results support our previous conclusion that suppression of glutamatergic neurotransmission promotes the locomotor stimulatory potential of other (e.g. adrenergic) transmitter systems. The present findings may be of relevance for future treatment strategies in (L-DOPA-resistant) Parkinson's disease.

Animals↗
PubMed1990

Interfering with glutamatergic neurotransmission by means of NMDA antagonist administration discloses the locomotor stimulatory potential of other transmitter systems.

In the present paper it is shown that when either of the noncompetitive NMDA antagonists MK-801 or ketamine are combined with the alpha-adrenergic agonist clonidine, a pronounced stimulation of locomotion is produced in monoamine-depleted mice. Likewise, when a subthreshold dose of MK-801 is combined with the muscarinic antagonist atropine, a forceful synergism with regard to locomotor activity in monoamine-depleted mice is observed. Furthermore, the present study shows that also in monoamine-depleted rats MK-801, as well as the competitive NMDA antagonist AP-5 (DL-2-amino-5-phosphonovaleric acid), interact synergistically with clonidine to enhance locomotor activity. Taken together, our findings suggest that central glutamatergic systems exert a powerful inhibitory influence on locomotion. Interfering with this inhibitory force by administration of an NMDA antagonist promotes locomotion and discloses the activational potential of other transmitter systems. The results are discussed in relation to 1) the pathophysiology of schizophrenia, with emphasis on the glutamate hypothesis of schizophrenia, and 2) implications for the treatment of Parkinson's disease.

Animals↗
PubMed1990

Interactions between glutamatergic and monoaminergic systems within the basal ganglia--implications for schizophrenia and Parkinson's disease.

Recent animal experiments suggest that dopamine plays a less crucial role than formerly supposed in the regulation of psychomotor functions. This is illustrated by the finding that even in the almost complete absence of brain dopamine, a pronounced behavioural activation is produced in mice following suppression of glutamatergic neurotransmission. This paper discusses the possibility that a deficient activity within the corticostriatal glutamatergic/aspartergic pathway may be an important pathophysiological component in schizophrenia, and that glutamatergic agonists may be beneficial in the treatment of this disease. In addition, it is suggested that glutamatergic antagonists may be valuable supplements in the treatment of Parkinson's disease.

Animals↗
PubMed1990

Liquid chromatographic separation and stereoselective detection of L- and D-amino acids with catalytic reaction detection using immobilized enzymes.

A post-column LC detection system is described for the stereoselective detection of L- and D-amino acids. The effluent of the LC column passes an immobilized enzyme reactor (IMER) containing either L- or D-amino acid oxidase. The hydrogen peroxide formed in this reactor by the oxidation of the amino acids is then transported to a second IMER containing horse-radish peroxidase. With the addition of 4-aminophenazone and dichlorophenosulphonyl chloride to the carrier, the hydrogen peroxide is reacted to form a red-coloured complex which is detected in a flow-through photometric cell at 514 nm. Applications to the analysis of amino acids in bovine and human sera are described.

Amino Acid Oxidoreductases↗
PubMed1990

Schizophrenia: a subcortical neurotransmitter imbalance syndrome?

Recent animal experiments suggest that glutamate plays a fundamental role in the control of psychomotor activity. This is illustrated by the finding that even in the virtually complete absence of dopamine, a marked behavioral activation is produced in mice following suppression of glutamatergic neurotransmission. This article discusses the possibility that a deficient activity within the cortico-striatal glutamatergic pathway is an important pathophysiological component in some cases of schizophrenia and that glutamatergic agonists may prove beneficial in this disorder. In a broader perspective, schizophrenia may be looked upon as a syndrome induced by a neurotransmitter imbalance in a feedback-regulated system, where dopamine and glutamate play a crucial role in controlling arousal and the processing of signals from the outer world to the cerebral cortex via the thalamus.

Animals↗
PubMed1990

Decreased mitogenic activity in hypercholesterolaemic plasma.

The mitogenic activity on rat aortic smooth muscle cells of plasma from patients with hypercholesterolaemia was compared to that of plasma from a normocholesterolaemic control group and to that obtained after lowering plasma cholesterol levels in the hypercholesterolaemic groups with simvastatin. Mean plasma total and low density lipoprotein cholesterol and apolipoprotein B concentrations in the two groups were 8.62 +/- 0.62 mmol l-1, 7.03 +/- 0.56 mmol l-1 and 1.96 +/- 0.14 g l-1, respectively, and 5.05 +/- 0.20 mmol l-1, 3.42 +/- 0.18 mmol l-1 and 0.80 +/- 0.04 g l-1, respectively, all differences significant at P less than 0.001. During simvastatin treatment these parameters decreased to 5.70 +/- 0.35, 4.15 +/- 0.33 mmol l-1 and 1.33 +/- 0.08 g l-1, all changes being significantly (P less than 0.001) lower than before treatment. Hyperlipidaemic plasma in untreated patients had a significantly lower mitogenic activity than normolipidaemic control plasma as measured by autoradiographic labelling of DNA after 3H-thymidine incorporation, 25.7 +/- 1.8% vs. 32.0 +/- 1.9%, P less than 0.05. Lowering plasma cholesterol levels in the hyperlipidaemic patients 'normalized' the mitogenic activity to 32.3 +/- 1.6%, P less than 0.05. The reason for this unexpected finding is not known.

Adult↗
PubMed1989

T-cell activation and subset patterns are altered in B-CLL and correlate with the stage of the disease.

Two-color FACS analysis was used to study activated and "functional" T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T-suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T-cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.

Antigen-Presenting Cells↗