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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 19 recordsLinked to original sources
PubMed1992

Increased numbers of T cells recognizing multiple myelin basic protein epitopes in multiple sclerosis.

Myelin basic protein (MBP)-autoreactive T cells have a crucial pathogenetic role in experimental allergic encephalomyelitis (EAE) and certain MBP epitopes may be immunodominantly recognized. The heterogeneity and quantity of the T cell response to different epitopes of MBP in multiple sclerosis (MS) and non-MS controls is not so clearly defined. We now study T cell reactivity to six different peptides of MBP in MS compared to controls in short-term cultures of blood mononuclear cells by measuring numbers of T cells that secrete interferon-gamma in response to antigen. In comparison with controls, MS patients showed dramatically increased numbers of MBP peptide-reactive T cells with mean values varying between 10.4 and 22.5 per 10(5) blood mononuclear cells. Among those MBP peptides examined (amino acid 1-20, 63-88, 89-101, 96-118, 110-128 and 148-165), no single peptide is preferentially recognized. Neither is any preferential response apparent after subdivision of the MS patients according to their HLA-DR genotype. Our findings suggest that a quantitative increase of a broad repertoire of myelin-autoreactive T cells with capacity to secrete IFN-gamma can be important for the pathogenesis of MS.

Adult↗
PubMed1992

Spread of synaptic activity along parallel fibres in cat cerebellar anterior lobe.

1. Mossy fibre evoked activity in the cerebellar cortex elicited by peripheral electrical stimulation was studied in chloralose anesthetized cats. The distribution of intracortical field potentials in the C3 and D zones was mapped in order to determine if there is a spread of synaptic activity outside the mossy fibre termination area. This area was identified by the presence of short latency synaptic field potentials in the granular layer. 2. Molecular layer field potentials were recorded up to 1.5 mm outside the mossy fibre termination area. The latencies of these potentials increased with increasing distance from the mossy fibre termination area, corresponding to a conduction velocity of about 0.4 m/s. 3. Recordings from Purkinje cells, within and outside the mossy fibre termination area, revealed an increase of simple spike activity at latencies corresponding to those of the field potentials in the same location. 4. From the spatial and temporal characteristics of the evoked activity, it is concluded that a mossy fibre input results in spread of synaptic activity along the parallel fibres. 5. The findings are discussed in relation to the recently discovered microzonal organization of the C3 zone. It is proposed that the organization of this zone offers a possibility for the control of muscle synergies, each synergy being represented by a mossy fibre input and the specific set of microzones activated by this input via the parallel fibres.

Animals↗
PubMed1992

RGD-directed attachment of isolated rat osteoclasts to osteopontin, bone sialoprotein, and fibronectin.

Osteoclasts isolated from the long bones of 5-day-old rats were seeded onto glass surfaces coated with osteopontin, bone sialoprotein, or fibronectin. Cell binding was promoted by all three proteins and inhibited in a dose-dependent manner by an RGD-containing peptide, while an RGE-containing peptide was ineffective. Immunocytochemistry of bone tissue showed enhanced concentration of osteopontin in bone opposite the clear zone of the osteoclasts, whereas immunolocalization of bone sialoprotein and fibronectin showed no accumulation on bone surfaces facing cells. The observations corroborate previous findings that the osteoclast is attached via an integrin to osteopontin on the bone surface. Although bone sialoprotein and fibronectin can mediate osteoclast binding in vitro, such a role in vivo is not supported by the immunocytochemical observations.

Amino Acid Sequence↗
PubMed1992

The effect of amperozide, a new antipsychotic drug, on plasma corticosterone concentration in the rat.

Amperozide is an atypical antipsychotic drug with high affinity for the serotonin 5-HT2 receptor but with low affinity for the dopamine D1 and D2 receptors. Amperozide dose-dependently increased the level of plasma corticocorticosterone in the rat. The effect of amperozide on plasma corticosterone was not inhibited by pretreatment with the 5-HT1A receptor antagonist pindolol or the 5-HT2 receptor antagonist ritanserin. Nor was it inhibited by the dopamine D2 receptor antagonist haloperidol. In contrast to ritanserin, amperozide did not antagonize plasma corticosterone elevation elicited by the serotonin receptor agonist MK-212. Similar to the serotonin uptake inhibitor fluoxetine, amperozide (0.5 mg/kg) significantly (p < 0.05) blocked p-chloroamphetamine (PCA) induced corticosterone release 4 and 16 hrs after amperozide administration. However, amperozide significantly increased the plasma corticosterone concentration also in rats pretreated with parachlorophenylalanine (PCPA). These data suggest that other mechanisms than a 5-HT uptake inhibitory effect are involved in the acute stimulation of corticosterone by amperozide.

Analysis of Variance↗
PubMed1992

Intracerebroventricular 5,7-DHT alters the in vitro function of rat cortical GABAA/benzodiazepine chloride ionophore receptor complexes.

We have earlier presented data indicating that the anxiolytic-like effect obtained in rats after depletion of brain 5-HT by means of PCPA or 5,7-DHT treatment is indirect and appears to involve the GABAA/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC), and that it is abolished by adrenalectomy. In the present series of experiments we have therefore investigated the 36Cl(-)-uptake in rat synaptoneurosomal preparations of central cortices from 5,7-DHT- and SHAM-lesioned animals. The GABA as well as the 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (THDOC) induced picrotoxin-sensitive increase in 36Cl(-)-uptake was significantly lower than that observed in the SHAM-lesioned animals, indicating that the 5,7-DHT lesion has rendered the GABAA/BDZ-RC subsensitive to two of its tentative endogenous ligands. This effect of the 5,7-DHT lesion on the function on the GABAA/BDZ-RC was reversed by adrenalectomy, indicating that an intact adrenocortical function is required for the development of GABAA/BDZ-RC subsensitivity in 5,7-DHT-lesioned rats. A tentative conclusion of these findings is that the 5,7-DHT lesion induces an increase in release of GABA and/or barbiturate-like steroids and that this increase is reversed by adrenalectomy. The findings from these in vitro studies parallel those from our previous behavioral experiments and provide further support for the notion that a decreased serotonergic influence in the central nervous system may, possibly via the adrenocortical system, enhance the function of the GABAA/BDZ-RC.

5,7-Dihydroxytryptamine↗
PubMed1992

Oral mucosal findings associated with chewing tobacco in Sweden--a clinical and histological study.

Twenty men of mean age 51,9 years who used Swedish chewing tobacco as their only tobacco habit were examined for clinical and histological changes. On average they had been chewing tobacco for 10,7 hours daily for 11,3 years. The most common clinical finding was a leukoedema-like change of the buccal mucosa at the site where the quid was held after chewing. Ten subjects showed changes similar to mild snuff-induced ones. Histological findings corresponded well with the clinical ones. It appears that oral mucosal changes associated with chewing tobacco in Sweden are discrete.

Adult↗
PubMed1991

Cloning, sequence, and developmental expression of a type 5, tartrate-resistant, acid phosphatase of rat bone.

Tartrate-resistant acid phosphatase (TRAP) is a characteristic constituent of osteoclasts and some mononuclear preosteoclasts and, therefore, used as a histochemical and biochemical marker for osteoclasts and bone resorption. We now report the isolation of a 1397-base pair (bp) full-length TRAP/tartrate-resistant acid ATPase (TrATPase) cDNA clone from a neonatal rat calvaria lambda gt11 cDNA library. The cDNA clone consists of a 92-bp untranslated 5'-flank, an open reading frame of 981 bp and a 324-bp untranslated 3'-poly(A)-containing region. The deduced protein sequence of 327 amino acids contains a putative cleavable signal sequence of 21 amino acids. The mature polypeptide of 306 amino acids has a calculated Mr of 34,350 Da and a pI of 9.18, and it contains two potential N-glycosylation sites and the lysosomal targeting sequence DKRFQ. At the protein level, the sequence displays 89-94% homology to TRAP enzymes from human placenta, beef spleen, and uteroferrin and identity to the N terminus of purified rat bone TRAP/TrATPase. An N-terminal amino acid segment is strikingly homologous to the corresponding region in lysosomal and prostatic acid phosphatases. The cDNA recognized a 1.5-kilobase mRNA in long bones and calvaria, and in vitro translation using, as template, mRNA transcribed from the full-length insert yielded an immunoprecipitated product of 34 kDa. In neonatal rats, TRAP/TrATPase mRNA was highly expressed in skeletal tissues, with much lower (less than 10%) levels detected in spleen, thymus, liver, skin, brain, kidney, brain, lung, and heart. In situ hybridization demonstrated specific labeling of osteoclasts at endostal surfaces and bone trabeculae of long bones. Thus, despite the apparent similarity of this osteoclastic TRAP/TrATPase with type 5, tartrate-resistant and purple, acid phosphatases expressed in other mammalian tissues, this gene appears to be preferentially expressed at skeletal sites.

Acid Phosphatase↗
PubMed1991

T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) is believed to involve an autoimmune component directed against the myelin sheath. One potential target Ag for such autoimmune attack is the myelin-oligodendrocyte glycoprotein (MOG) because an anti-MOG mAb has profound influence on the course of experimental autoimmune encephalomyelitis, which to some extent represents an experimental model of MS. Using single cell assays, we have evaluated T and B cell reactivities to MOG in MS patients and controls. T cell reactivity was estimated by counting the number of cells that secreted IFN-gamma in response to MOG, whereas B cell reactivity was estimated by enumerating cells secreting antibodies that bound to MOG. MOG reactive T cells were detected in the peripheral blood of the majority of the 16 MS patients examined (mean 1/7299 mononuclear cells), but infrequently and at lower numbers in samples from neurologic controls. MOG-reactive T cells were more frequent among MS patients' cerebrospinal fluid (CSF) mononuclear cells (mean 1/450 cells). The T cell response to MOG was evidently MHC class II restricted, because Fab fragments of a rabbit polyclonal anti HLA-DR antibodies abrogated the Ag-induced increase in number of cells that secreted IFN-gamma, as analyzed on CSF and PBMC from three patients with MS. Anti-MOG IgG antibody-secreting cells were detected in blood in 8 of 16 MS patients (mean 1/25,641 cells), but they were also strongly accumulated in CSF, being detected in 8 of 10 MS patients examined (mean 1/265 cells), while rarely found in controls. The findings imply that MOG may represent a pathogenetically important target Ag in MS.

Adult↗
PubMed1991

Characterization of a tartrate-resistant acid phosphatase (ATPase) from rat bone: hydrodynamic properties and N-terminal amino acid sequence.

Certain physicochemical properties of rat bone tartrate-resistant acid ATPase (TrATPase), including the size and shape of the enzyme, potential subunit composition, and detergent binding, have been elucidated. SDS-polyacrylamide gel electrophoresis in combination with immunoblot analysis showed that the bone TrATPase has a molecular weight of 33,000 D and is composed of disulfide-linked polypeptides of 20,000 and 16,000 D. The enzyme contains 1.7 mol Fe per mol enzyme. Hydrodynamic studies allowed calculation of the Stokes radius (24 A), the sedimentation coefficient (3.19S), the partial specific volume (0.748 ml/g), the frictional ratio (0.995), and the axial ratio (1.0). The amount of detergent bound to the protein was determined to 4 mol of Triton X-100 per mol enzyme. The molecular weight of bone TrATPase derived from these parameters was 31,900 D. N-terminal amino acid sequence analysis of the Mr 20,000 subunit indicated a high degree of similarity with TRAP enzymes from spleen, uterus, placenta, hairy cell leukemia, and osteoclastoma. It is concluded that rat bone TrATPase belongs to the type 5 (tartrate-resistant and purple) acid phosphatase family. The similarities in the N-terminal amino acid sequences, iron content, and physicochemical properties of TRAP enzymes indicate a close structural relationship between type 5 acid phosphatases expressed in different tissues. The findings that TrATPase has a spherical shape and binds low amounts of detergent suggest that the enzyme is a soluble protein, compatible with the view that TrATPase is secreted by the osteoclast.

Acid Phosphatase↗
PubMed1991

Enalaprilat in acute myocardial infarction: tolerability and effects on the renin-angiotensin system.

We treated 48 patients with intravenous enalaprilat within 24 hours from the onset of acute myocardial infarction. Concomitant therapy included thrombolytic treatment (29), intravenous metoprolol (34), intravenous nitroglycerin (16) and intravenous furosemide (15). The first 40 patients included had systolic blood pressure at baseline greater than or equal to 110 mmHg. Intravenous bolus injections of 0.2-1.2 mg (mean 1.0 mg) enalaprilat in one hour were given to 20 patients and an intravenous infusion of 1 mg over two hours was administered to another 20 patients, as well as to a separate group of 8 patients with systolic blood pressure between 100-109 mmHg at baseline. The infusion was stopped in five cases when the systolic blood pressure fell below 100 and 90 mmHg, respectively, in the two infusion groups. No hypotensive reactions were symptomatic. Blood pressure decreased from a mean of 134/82, 131/79 and 106/72 mmHg to a minimum of 117/71, 118/73 and 97/63 mmHg, respectively, in the three groups. Almost complete suppression of plasma angiotensin converting enzyme activity was achieved within 30 minutes. No significant changes were found in plasma levels of angiotensin II, renin activity or atrial natriuretic peptide between baseline and 24 hours. Treatment was continued with oral enalapril 2.5-10 mg/day, which was generally well tolerated. We conclude that intravenous and oral enalapril added to conventional therapy in the early phase of acute myocardial infarction is well tolerated in selected patients, but should be carefully titrated.

Aged↗
PubMed1991

Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures.

Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition of the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity.

Adsorption↗
PubMed1991

Short-term stability of depressive symptoms and suicide attempts in Swedish adolescents.

The prevalence of depressive symptoms, suicidal ideation and their relationship to perceived health problems and social relations were examined in a sample of 605 Swedish adolescents aged 13-18 years. Short-term stability of depressive symptoms and the turnover rate from a nondepressed to a depressed state were examined for subsamples of 36 depressed and 71 nondepressed subjects, respectively, who were retested after 4 to 6 weeks. Using Beck's criteria for clinical depression, 9% of the adolescents experienced moderate to severe depressive symptom levels. However, a more conservative estimate, 4%, was obtained when DSM-III criteria for major depressive disorder were applied. Approximately 3% of the adolescents had pronounced suicidal ideation and had made at least one previous suicide attempt. There was a tendency for boys to show more stable depressive symptoms and suicidal ideation than girls. Furthermore, a set of 5 psychosocial variables concerning the students' satisfaction with their school and leisure time, conflictual level at home and number of close friends predicted 31% of the variance of the subjects' total depressive symptom scores. Although a 32% decrease of depressive symptoms was noted for the depressed subsample of adolescents, 44% of these subjects continued to experience moderate to severe depression at follow-up.

Adolescent↗
PubMed1991

Clinical classification of Swedish snuff dippers' lesions supported by histology.

From a total material of 184 Swedish users of loose packed moist snuff and 68 users of portion-bag packed moist snuff, cases were selected from subgroups based on a four-point clinical grading scale. The selected material for the study comprised 70 cases (ten from each clinical grade group, no Degree 4 lesion was found among portion-bag users). Features recognized in biopsies from these cases together with findings in previous studies correlated well with the use of a four-point scale for the grading of clinical changes, especially in the context of discriminating lesions for which special efforts should be undertaken to make the patient stop or change the snuff dipping habit and for selecting patients in whom regular clinical follow-up including a biopsy should be carried out. In this article is also discussed the labeling of the clinical oral mucosal changes seen at the site where a quid of snuff is regularly placed. The conceptual use of "snuff dippers' lesions" is recommended instead of e.g. snuff-induced leukoplakia.

Adult↗
PubMed1991

Reversibility of snuff dippers' lesion in Swedish moist snuff users: a clinical and histologic follow-up study.

The purpose of this study was to assess possible reversibility of oral mucosal changes, associated with the use of Swedish moist snuff, after change of habit. Biopsies from a total material of 252 regular snuff users, 184 using loose snuff and 68 using portion-bag packed snuff, were screened microscopically to identify histopathologic epithelial changes in addition to, or differing from, those generally seen as a result of snuff use. The main basis for selection of these variables were the criteria of epithelial dysplasia as defined by WHO and the eight histologic features, which have been reported to be the most important discriminators to separate cases with leukoplakia that subsequently developed carcinoma, from those that did not. Twenty-nine subjects, 3 showing Degree 2 lesions, 21 Degree 3 lesions and 5 Degree 4 lesions, all of them loose snuff users were identified. All the 29 users were re-examined clinically and histologically after 3-6 months. The rebiopsy was always secured from the same mucosal area as the original biopsy. At follow-up, 20 subjects had either stopped their snuff habit or changed to portion-bags and changed placement of the quid. All of them showed a healthy mucosa at the previous biopsy site and normal tissue in the histologic examination of the rebiopsies. Seven subjects had changed to portion-bags and variably reduced their daily exposure to snuff. At follow-up they presented with less pronounced clinical changes and the rebiopsies showed evidence of reduced epithelial changes. One major conclusion from this study is that tissue changes, clinically as well as histologically, are reversible following cessation of snuff habit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings.

Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T-cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-gamma) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN-gamma secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF-alpha) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-alpha was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-alpha response and the negative IL-4 finding may speak for the importance of the Th1-like pattern in immunity to F. tularensis.

Adult↗
PubMed1991

Acetylcholine receptor-reactive T and B cells in myasthenia gravis and controls.

Myasthenia gravis (MG) is strongly associated with antibodies to acetylcholine receptor (AChR), whereas the extent of T cell involvement is not settled. The number of cells secreting interferon-gamma (IFN-gamma) in response to AChR during 48 h culture of blood mononuclear cells (PBL) may reflect AChR-reactive T cells. Using an immunospot assay, we detected such cells in 23 of 30 patients with MG at a mean number of 1 per 33.333 PBL. AChR-reactive T cells were also found in patients with other neurological diseases (OND) and in healthy subjects but at lower frequencies and numbers. The T cell response to purified protein derivative and to PHA, and also to two major myelin proteins (basic protein and proteolipid protein) did not differ between MG and the two control groups, underlining the specificity of an augmented T cell reactivity to AChR in MG. Evaluation of the B cell response by enumerating anti-AChR IgG antibody secreting cells revealed such cells in 27 of 28 patients with MG at a mean value of 1 per 14,085 PBL. Cells secreting anti-AChR antibodies of the IgA and IgM isotypes were also detected in MG, but less frequently, at lower numbers, and only in conjunction with IgG antibody secreting cells. Anti-AChR antibody secreting cells were also found among patient with OND and in healthy controls, but at lower frequencies and numbers. These data confirm that AChR is a major target for autoimmune response in MG.

B-Lymphocytes↗