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Biomedical subjects

U Andersson

Publications and source records attributed to U Andersson.

At least 145 records · Page 8Linked to original sources

An immunofluorescent method for identifying individual IFN-gamma-producing lymphocytes.

An immunofluorescent staining method was developed for detecting human IFN-gamma-producing cells in single cell suspensions. Mononuclear leukocytes, stimulated in vitro to produce IFN-gamma, were fixed and made permeable. The cytoplasmic presence of IFN-gamma was visualized by indirect immunofluorescence using IFN-gamma-specific mouse monoclonal antibodies. The staining was found to be specific for IFN-gamma and allowed the detection of newly synthesized rather than internalized IFN-gamma molecules. The cytoplasmic fluorescence appeared locally in a polar, juxtanuclear position, which overlapped the Golgi apparatus, probably reflecting the glycosylation site of the newly formed IFN-gamma molecules. Two-colour staining experiments showed that the method is useful not only for the detection and enumeration but also for the phenotypic characterization of IFN-gamma-producing cells.

Antibodies, Monoclonal↗

Phenotypic characterization of individual interferon-gamma-producing cells after OKT3 antibody activation.

This is the first study using a direct approach to determine the phenotype of interferon gamma (IFN-gamma)-producing cells after polyclonal T cell activation. Blood mononuclear cells (MNC) were cultured and stimulated by OKT3 antibody to produce IFN-gamma. They were then stained with a panel of monoclonal antibodies with specificity for cell surface antigens, fixed and permeabilized in suspension and stained for cytoplasmic IFN-gamma using monoclonal antibodies and indirect immunofluorescence technique. IFN-gamma appeared mainly as a local, polar accumulation in the cytoplasm in a juxtanuclear position, probably identical to the Golgi apparatus. After a culture period of 20 h, 6-11% and 0.2-0.6% of the OKT3-activated MNC from adults or newborns, respectively, produced IFN-gamma in cultures. Unstimulated cultures contained maximally 0.1% IFN-gamma-positive MNC. The majority of the IFN-gamma-producing MNC were T cells and expressed the T11 antigen and receptors for interleukin 2. To our surprise most of these T cells also carried receptors for complement 3bi (OKM1) but did not express class II molecules. Less than 50% displayed T4 or T8 antigens in three out of the four experiments performed. Natural killer cells, as recognized by Leu 7 or B73.1 antibodies, contributed only marginally to the IFN-gamma synthesis whereas B cells (OKB7) and monocytes (Leu M3) showed no production of IFN-gamma.

Antibodies, Monoclonal↗

Spontaneous chewing movements in rats during acute and chronic antipsychotic drug administration.

Single intraperitoneal doses of various antipsychotic drugs (clozapine 6, 12, 25 mg/kg, sulpiride 100 mg/kg, haloperidol 0.5, 1.0, 2.0 mg/kg, fluphenazine 0.5, 1.0, 2.0 mg/kg) induced a depression of the spontaneous chewing movement (SCM) rate in rats during the first 6-8 hours. Haloperidol and fluphenazine elicited a rebound increase in SCM on day 2-5, while clozapine and sulpiride did not. Atropine (5 mg/kg) reduced the SCM rate. During chronic administration for 10 months clozapine (50 mg/kg/day) caused no changes in the SCM rate. Sulpiride (120 mg/kg/day) gave a marginal rise above control levels, while thioridazine (40 mg/kg/day), chlorpromazine (30 mg/kg/day), fluphenazine (0.6 mg/kg/day) and haloperidol (0.4 mg/kg/day) produced highly significant increases in SCM rates. It is suggested that the present animal model may prove useful for monitoring the risk of tardive dyskinesia with individual drugs.

Animals↗

Effect of acyclovir on infectious mononucleosis: a double-blind, placebo-controlled study.

Thirty-one patients with clinical and laboratory diagnoses of infectious mononucleosis who had had symptoms for seven or fewer days were randomized for intravenous treatment with acyclovir (10 mg/kg) or placebo at 8-hr intervals for seven days in a double-blind trial. Clinical signs and symptoms were registered, and excretion of virus in the saliva as well as antibody responses in sera and saliva were assessed before, during, and at regular intervals in the six months after treatment. Acyclovir significantly (P less than .001), but reversibly, inhibited oropharyngeal shedding of Epstein-Barr virus. The humoral and cellular immune responses, however, did not differ between the two groups; nor did the development of viral latency. There were no significant (P greater than .05) differences in individual clinical symptoms or in laboratory parameters between the two groups; however, when data concerning duration of fever, weight loss, tonsillar swelling, pharyngitis, and self-assessment by the patient were combined, a significant (P less than or equal to .01) effect of treatment with acyclovir was evident.

Acyclovir↗

Mumps virus-induced enhancement of the in vitro cytotoxicity of cord blood lymphocytes.

Purified lymphocytes from the umbilical cord of healthy donors (CBL) displayed lower natural cytotoxicity (NK) and antibody-dependent cellular cytotoxicity (ADCC) than peripheral blood (PBL) from adult donors. In contrast, CBL treated with small amounts of UV-inactivated or live mumps virions expressed the same level of enhanced cytotoxicity (virus-dependent cytotoxicity (VDCC)) against non-infected target cells as PBL. For individual CBL donors there was no correlation between the level of NK and VDCC, indicating involvement of partly distinct effector cell populations. The heterogeneity of the effector cells active in VDCC was confirmed by cell fractionation experiments. The major CBL effector cells in NK and ADCC were found in 'non-T' lymphocyte fractions and/or in fractions containing cells with high-avidity receptors for IgG. In contrast, CBL fractions consisting of about 100% lymphocytes bearing T-cell markers and depleted of Fc gamma R+ cells were strongly cytotoxic in VDCC when T24 cells (human bladder carcinoma) were the targets. With two other target cell types of similar susceptibility to VDCC, the cytotoxic activity of T-cell-containing fractions was less pronounced, indicating that the target cells play an active role in effector cell selection. The surface marker profiles of the VDCC effector cells were the same for CBL and adult PBL. Incubation of CBL with UV-inactivated virions usually gave no significant stimulation of DNA synthesis above that seen in virus-free controls. Taken together, our results suggest that neither specific recognition of viral antigen by T cells nor mitogenic effects of viral material are involved in VDCC generation.

Adult↗

Development of B lymphocyte function in childhood.

The capacity of blood lymphocytes of children aged from birth to six years to produce immunoglobulins was studied in vitro at the cell level using a direct B lymphocyte activator (Epstein-Barr virus) or a T lymphocyte dependent B lymphocyte activator (pokeweed mitogen). Umbilical cord blood lymphocytes secreted IgM at adult levels after Epstein-Barr virus stimulation, while the ability to synthesize IgG and IgA increased up to the ages of 1 and 2 years, respectively, but not beyond this period. IgG3 production preceded that of the other IgG subclasses. The T lymphocyte dependent IgM synthesis was low at birth, but approached adult levels at two years of age. T cell dependent IgG and IgA secretion, however, remained reduced even up to 6 years of age.

Adult↗

Acyclovir treatment in primary Epstein-Barr virus infection. A double-blind placebo-controlled study.

Acyclovir (ACV), which effectively inhibits in vitro Epstein-Barr virus (EBV) production, was tested in 31 patients with clinical and laboratory diagnosis of infectious mononucleosis (IM) in a double-blind trial. Patients with symptoms not exceeding 7 days were randomised to intravenous ACV 10 mg/kg or placebo (PLO) treatment every 8 h for 7 days. Clinical, virological and immunological parameters were followed in each patient before, during and after treatment. There were no significant differences (p greater than 0.05) between the treatment groups for any single clinical symptom between the treatment groups. If data concerning duration of fever, weight loss, tonsillar swelling, sore throat and patient self-assessment of general health were combined, a significant effect (p less than or equal to 0.01) favouring ACV treatment was determined. ACV significantly inhibited oropharyngeal EBV shedding (p less than or equal to 0.001), but the salivary EBV titer returned within 3 weeks after cessation of treatment. Specific cellular and humoral immunity was not affected, nor was the development of virus latency.

Acyclovir↗

Secretion of gamma-interferon at the cellular level. Induction by Epstein-Barr virus.

Using a haemolytic plaque assay for gamma-interferon (IFN-gamma) secretion we found that in vitro Epstein-Barr virus (EBV) exposure of peripheral blood mononuclear cells from EBV immune individuals led to IFN-gamma secretion, which was apparent within 6 h after virus contact and peaked 12-24 h after induction. Live, ultraviolet-light-irradiated and heat-inactivated virions all caused IFN-gamma secretion. In contrast, blood mononuclear cells from EBV non-immune adults or neonates could not be activated to IFN-gamma production by EBV.

Cells, Cultured↗

Spontaneous production of interferon-gamma in adult and newborn humans.

By using a hemolytic plaque assay for IFN-gamma secretion by single cells, we found that one to three IFN-gamma secreting cells per 1 X 10(3) mononuclear cells were present in the blood from normal adult and newborn humans, without in vitro culture or stimulation by antigens or mitogens. The frequency of such cells was higher in newborns. These spontaneous IFN-gamma-secreting cells were predominantly T cells of the helper/inducer phenotype, as defined by treatment with monoclonal antibody and complement. By using indirect immunofluorescence staining, it was seen that 1% of blood mononuclear cells from adults and 3.5% from newborns contained cytoplasmic IFN-gamma. These cytoplasmic IFN-gamma-positive cells belonged to a heterogeneous population by morphology and by staining with monoclonal antibody. The majority of these cells were DR-positive T cells. We propose that these IFN-gamma-producing cells were activated in vivo, and that they possibly mediate antiviral or lymphokine activities.

Adult↗

Bromocriptine in tardive dyskinesia.

Five schizophrenics and one alcoholic with tardive dyskinesia were given bromocriptine for two 8-week periods. The first trial was made during neuroleptic treatment and the second following a 3 weeks' wash-out of neuroleptics. When neuroleptics were given bromocriptine was essentially without effects, but after the neuroleptics had been discontinued the same bromocriptine treatment caused amelioration of dyskinesia in three and aggravation in two subjects. During the second bromocriptine trial all schizophrenic patients showed deterioration of psychotic symptoms followed by a reduction of symptoms when bromocriptine was discontinued.

Aged↗

Serum concentrations of thioridazine, its major metabolites and serum neuroleptic-like activities in schizophrenics with and without tardive dyskinesia.

Two groups of elderly chronic schizophrenic patients, one with and one without tardive dyskinesia (TD), were studied. In addition to estimation of the neuroleptic-like radioreceptor activity (RRA) of the serum, serum concentrations of thioridazine (THD) and its major metabolites, THD-2-sulfoxide, THD-2-sulfone and THD-5-oxide, were measured with high performance liquid chromatography. Blood samples were collected at two different occasions when the patients were considered to be in a pharmacological "steady state". The concentrations of THD and its metabolites, as well as RRA values, were similar at both occasions. In general, THD-2-sulfoxide and THD-5-oxide were present in higher concentrations than the parent compounds, and the serum concentrations of THD, its metabolites and the RRA values were positively correlated with the administered daily dose of THD. However, no significant difference in serum levels of THD, its metabolites, or significant difference in serum levels of THD, its metabolites, or RRA values existed between the patients with and without TD. These data suggest that pharmacodynamic rather than pharmacokinetic differences may be more important in producing high risk for TD in patients on long-term neuroleptic treatment.

Aged↗

Angiography and computed tomography in the diagnosis of primary lymphoma of the brain.

Three patients with primary lymphomas of the brain are presented. The angiographic and computed tomographic (CT) appearances resembled the few cases reported previously. In all three cases angiography showed avascular tumours with little vessel displacement or involvement whereas the CT scans showed large strongly and homogeneously enhancing tumour masses. Neither method alone gives pathognomonic appearances, but taken together angiography and CT should suggest the diagnosis of this rare tumour.

Adult↗

A sequential study of human B lymphocyte function from birth to two years of age.

The immunoglobulin synthesizing capacity of individual lymphocytes from newborns and infants aged 2, 6, 12 and 24 months respectively has been studied. The technique has been to expose purified lymphocytes to a T lymphocyte dependent (pokeweed mitogen) or a T lymphocyte independent (Epstein-Barr virus) activator of B lymphocytes. Activation has been measured as immunoglobulin secretion of individual B lymphocytes using a hemolytic plaque assay. B lymphocytes from newborns can be made to synthesize IgM at adult levels, but not IgG and IgA. Within 24 months from birth the secretion of IgG has reached adult capacity whereas IgA formation is still diminished. Lymphocytes synthesizing IgG subclasses appear at different times insofar as IgG1 and IgG3 are well demonstrable within 12 months from birth whereas IgG2 and IgG4 has not at all reached adult levels even 24 months after birth. The T lymphocyte dependent activator (pokeweed mitogen) fails to induce immunoglobulin synthesis in peripheral blood lymphocytes from newborns because of a defect helper T cell function. Such T cell capacity appears at the age of 6 months. The data unequivocally demonstrate restricted but definite B lymphocyte functional capacity already at birth and a gradual but partial acquisition of adult competence until the age of 2 years.

Age Factors↗

Gingival recession in 15-year old pupils.

In a clinical examination of 174 15-year old pupils approximately 62 per cent showed some degree of gingival recession on the labial surfaces of maxillary teeth. The number of affected teeth per individual was low, one tooth in about 35 per cent and teeth in 25 per cent of the individuals. First molars and first premolars were the teeth most often affected. The majority of the defects were not extensive, i.e. the gingival margin was situated at the cemento-enamel junction. The number of cases affected by recession was lower in individuals using an "unspecific" toothbrushing technique compared with those using roll or vibratory technique. This difference may not be due to the technique but rather to a minor interest in oral hygiene measures in the "unspecific" groups. No statistically significant correlation was found between frequencies of recession and the stiffness of the toothbrushes used.

Adolescent↗