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Biomedical subjects

G Nilsson

Publications and source records attributed to G Nilsson.

At least 163 records · Page 9Linked to original sources

Characterization of human mast cells developed in vitro from fetal liver cells cocultured with murine 3T3 fibroblasts.

Cocultures of dispersed human fetal liver cells with murine Swiss 3T3 fibroblasts resulted in the development of human mast cells after 1 to 4 weeks of culture. Mast cells were detected by immunohistochemistry using a murine monoclonal anti-tryptase antibody, before metachromasia appeared with toluidine blue. When subjected to double immunohistochemistry using murine monoclonal anti-chymase and anti-tryptase antibodies, 94% +/- 10% (SD) of the mast cells seen at day 30 of culture were of the MCT type. These results contrast with those obtained with human mast cells derived from cord blood mononuclear cells cocultured with murine 3T3 fibroblasts which are comprised of substantially greater numbers of MCTC cells, averaging 48% +/- 31% (SD) at day 30 of culture. Mast cells developed in vitro from fetal liver cells or cord blood mononuclear cells contained similar amounts (+/- SD) of histamine (0.9 +/- 0.5 pg/cell and 1.1 +/- 1 pg/cell, respectively) and tryptase (1.7 +/- 0.4 pg/cell and 1.9 +/- 1.2 pg/cell, respectively) on day 30 of culture. Fetal-liver-derived mast cells from a 30-day-old culture were identified by immunoelectron microscopy using gold-labelled antitryptase antibody. Typically, these mast cells appeared immature as they had large nuclear to cytoplasmic ratio and a small number of ill-formed cytoplasmic granules. For both fetal-liver- and cord-blood-derived mast cells, there was no evidence of conversion of the MCT type into the MCTC type provided by this study. These results suggest that commitment to develop as an MCT or MCTC type of mast cell may have occurred in mast cell precursors present in fetal liver and cord blood mononuclear cells, prior to granulation.

Animals↗

Studies of a proposed mechanism regulating parietal cell emptying.

We have proposed and provided experimental evidence for the existence of a mechanism controlling the output of hydrochloric acid from the parietal cells. On stimulation of the cells, histamine not only activates the H+/K-pump but also prevents acid from leaving the cell. The delay may be caused by cAMP activation. When the appropriate conditions have been obtained, the acid leaves the cell and enters the gastric lumen. A delay in onset of acid secretion is convenient from several points of view. For example, salivary amylase, which is responsible for approximately 50% of the carbohydrate digestion, will have time to exert its digesting effect in the stomach before the pH decreases and the enzyme becomes inactivated. Also, bicarbonate secretion will be started before high concentrations of acid have been obtained in the stomach and thereby contributes to protection of gastric mucosa.

Aminopyrine↗

Distribution patterns of ventricular premature complexes in long-term electrocardiographic recordings and their usefulness in disclosing modulated parasystole.

Long-term electrocardiographic recordings from 25 patients with abundant ventricular premature complexes (VPCs) were screened with a computer program for sequences of interectopic intervals with the number of sinus beats consistent with manifest or concealed bigeminy/trigeminy. On average, 19.0% of VPCs in this patient series were followed by an uninterrupted sequence of greater than or equal to 10 interectopic intervals with concealed bigeminy. The corresponding figure for concealed trigeminy was 2.2%, for manifest bigeminy 9.6%, and for manifest trigeminy 0.8%. The longest sequence with concealed bigeminy comprised 149 interectopic intervals. The corresponding figure for concealed trigeminy was 135 interectopic intervals. The sequences of concealed bigeminy occurred at significantly lower heart rates than those of concealed trigeminy. These findings can be explained by the entrainment phenomena described in experimental models of modulation of a ventricular parasystolic focus across a zone of impaired conduction.

Adult↗

M-component with reactivity against actin associated with thrombotic thrombocytopenic purpura.

A patient with a monoclonal B-cell disorder producing an M-component with antiactin activity is described. After more than 3 years of observations, the final diagnosis is not completely established, but a malignant lymphoproliferative process is evidently under evolution. On three occasions, she has presented with symptoms compatible with a thrombotic thrombocytopenic purpura-like syndrome, concomitant with an increase in paraprotein. A relationship between this autoantibody and the patient's symptoms is proposed. Steroids have so far had a beneficial effect on the symptoms.

Actins↗

Effects on immune responses in rats after neuromanipulation with capsaicin.

The effect of capsaicin treatment on the immune response, assessed as antibody formation in vivo and in vitro, was studied in ovalbumin (OA)-immunized rates. Rats were treated with capsaicin at 1-2 days of life or at adult age, before or after immunization. The levels of IgA, IgE and IgG antibodies as well as immunoglobulins were measured in serum and supernatants from cultured lymph node cells, spleen cells and peripheral blood lymphocytes. Capsaicin treatment affected the antibody levels depending on the timing of capsaicin treatment in relation to immunization. Different effects of capsaicin treatment were also observed on the different immunoglobulin isotypes. One of the most striking effects by capsaicin treatment was the reduction of IgA and IgG synthesis in cultured lymphoid cells from aerosol immunized animals treated with capsaicin after immunization. In contrast, in vivo the level of total serum IgA was increased in similarly treated animals. In this study we show that capsaicin treatment, which is known to decrease the levels of neuropeptides of sensory origin, has a time-dependent effect on both antibody levels in vivo as well as the formation of immunoglobulin in vitro. Although the mechanisms responsible for this are not obvious, we conclude a link between depletion of neuropeptides in sensory nerves and the antibody synthesis.

Animals↗

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↗

Local immune response and bronchial reactivity in rats after capsaicin treatment.

The interaction between the nervous system, immune system and bronchial reactivity was studied in rats by using the neurotoxin capsaicin. Rats were treated with capsaicin at 1-2 days of age or at adult age, before or after sensitization by subcutaneous injections with ovalbumin (OA). The levels of the neuropeptides neurokinin A and calcitonin gene-related peptide were decreased in the lung after capsaicin treatment, as determined with radioimmunoassay, whereas the levels of neuropeptide Y were unaffected. The levels of IgA, IgE and IgG in bronchial lavage were also affected by capsaicin treatment; however, the results were heterogeneous. Capsaicin treatment after sensitization reduced the bronchial reactivity to challenge with OA aerosol and serotonin iv. The results demonstrated that reduction of neuropeptide levels with capsaicin affected both bronchial reactivity and the levels of antibodies in bronchial lavage fluid. However, no correlation between these two parameters was seen, demonstrating the complexity of the system.

Animals↗

Sensory neuropeptide involvement in animal models of airway irritation and of allergen-evoked asthma.

C-fiber afferents in the airways are in close contact with mast cells and are activated both upon allergic reactions and by inhalation of irritants such as capsaicin and cigarette smoke. This evokes both protective reflexes such as cough as well as local release of tachykinins and calcitonin gene-related peptide (CGRP) with subsequent actions on blood vessels (vasodilatation and plasma protein extravasation) and bronchial smooth muscle (bronchoconstriction). After capsaicin pretreatment when peptides have been depleted from the sensory nerves, there is a marked reduction of the vasodilatatory response upon allergen challenge and the protein extravasation evoked by cigarette smoke. Conversely, chronic cigarette smoke exposure is accompanied by increased coughing to capsaicin challenge. Furthermore, aerosol immunization and chronic smoke exposure are both associated with elevated tissue levels of CGRP, suggesting upregulation of C-fiber function and peptide synthesis, which may contribute to airway hyperreactivity.

Aerosols↗

Time course of inhibition of gastric acid secretion by omeprazole and ranitidine in gastric fistula rats.

Basal, pentagastrin- and histamine-stimulated acid secretion were measured in gastric fistula rats treated with the H+/K(+)-ATPase inhibitor, omeprazole, and the H2-receptor antagonist, ranitidine. All doses of omeprazole (20, 30, 40, 80, 400 mumol/kg) and ranitidine (125, 187.5, 250, 375 mumol/kg) essentially abolished the basal acid output for various periods of time. Omeprazole, 80 mumol/kg, administered twice daily, reduced the 24-h basal acid secretion more effectively than did 400 mumol/kg given once daily. Four daily administrations of ranitidine reduced the 24-h basal acid output to a similar extent as omeprazole administered twice. Omeprazole (20, 80 mumol/kg) was more effective than ranitidine (125, 375 mumol/kg) in inhibiting acid secretion evoked by maximal doses of pentagastrin (650 nmol/kg per h) and histamine dihydrochloride (136 mumol/kg), whereas this difference was less pronounced for the inhibition of acid responses induced by a threshold dose (1.1 mumol/kg) of histamine. The inhibition evoked by omeprazole (80 mumol/kg x 2) and ranitidine (375 mumol/kg x 4) of basal and histamine (1.1 and 136 mumol/kg)-induced acid secretion was similar after 1 and 4 weeks of treatment. After the end of drug administration, the acid secretion induced by threshold doses of histamine was significantly elevated in the omeprazole-treated rats, whereas no significant hypersecretion of acid was seen during the recovery period in rats treated with ranitidine. Plasma gastrin concentrations were significantly elevated after 4 weeks of treatment with omeprazole but returned to pretreatment levels after 4 weeks of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Peptidergic innervation of rat lymphoid tissue and lung: relation to mast cells and sensitivity to capsaicin and immunization.

The peptidergic innervation of lymphoid tissue and the lung in relation to mast cells was studied in rat. The sensitivity of neuropeptide-containing nerves to capsaicin treatment and immunization was also examined. Measurements of the content of neurokinin A and calcitonin gene-related peptide revealed that the lung contained the highest content of both neuropeptides; lymph nodes had intermediate levels, whereas the spleen had the lowest content. Immunohistochemistry showed that the calcitonin gene-related peptide- and neurokinin A-immunoreactive nerves in lymph nodes were mainly found around blood vessels, whereas in the lung the nerves were present within the lining respiratory epithelium, bronchial smooth muscle, around blood vessels and close to lymphoid aggregates. Combined immunohistochemistry for serotonin (5-hydroxytryptamine), as a marker for mast cells, and tachykinins or calcitonin gene-related peptide revealed that a close association was often present between the nerves and 5-hydroxytryptamine-positive cells in the bronchi of the lung, while 5-hydroxytryptamine-positive cells were not observed in lymph nodes. The neurokinin A and calcitonin gene-related peptide content in lymph nodes, spleen and lung, but not the content of neuropeptide Y, was markedly decreased by capsaicin treatment, suggesting a sensory origin for the two former peptides. Aerosol immunization increased the levels of calcitonin gene-related peptide in the lung, whereas the content in mediastinal lymph nodes was not affected. These data demonstrate a peptidergic innervation mainly of blood vessels in lymphoid tissue and a close relation between sensory nerves and mast cells as well as lymphoid aggregates in the bronchi of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Accumulation of CD8+ cells after immunization with soluble antigen.

Rats were immunized with ovalbumin, either subcutaneously or by aerosol inhalation. The lymphocyte distribution in lymph nodes, peripheral blood, and spleen was investigated by flow cytometry after labelling with T pan (OX19 and W3/13), T helper lymphocytes (W3/25), T cytotoxic/suppressor lymphocytes (OX8), kappa light chain (MAR 18-5), or MHC class II (OX6) monoclonal antibodies. The influence of the neurotoxic agent capsaicin on the lymphocyte distribution was also analysed. Subcutaneous immunization resulted in an increased number of OX8+ cells in mesenteric lymph nodes, spleen, and peripheral blood but not in the draining lymph nodes, axillary, brachial, and mediastinal lymph nodes. The number of positive cells for the other cell markers used were not affected by immunization. The neuromodulatory effect of capsaicin had no effect on the lymphocyte distribution. The results showed that the type of immunization used, low amounts of antigen without adjuvant given during a prolonged period, selectively induced OX8+ cells. The patterns were unaffected by neuromodulation using capsaicin.

Animals↗

Observations on biochemical and haematological parameters in healthy people above 80 years of age.

Ninety-five apparently healthy people, aged 80 years or above, living in the Stockholm County Council of Sweden, participated in a pilot study in 1984. Reference values were obtained for routine haematological and biochemical analyses. Deviations from expected levels were confined to thyroid-stimulating hormone (TSH), vitamin B12 and calcium. It is noteworthy that a low-risk cholesterol level characterized this elderly population. It is suggested that in order to evaluate the influence of age, a dynamic aspect should be added using functional tests of various organs.

Aged↗

Pharmacokinetics of terlipressin after single i.v. doses to healthy volunteers.

The pharmacokinetics of triglycyl-lysine-vasopressin (TGLVP) were studied in healthy male volunteers after single i.v. injections of 5, 10 and 20 micrograms/kg b. wt. The half-life of distribution and elimination was 8 and 50 min, respectively. The volume of distribution was 0.7 l/kg b.wt. and the plasma clearance 9 ml/kg b.wt./min. These values are different from those for arginine-vasopressin and lysine-vasopressin (LVP) but confirm to some extent earlier results on TGLVP. No dose-dependent changes of the pharmacokinetics of TGLVP were evident. The LVP formation after TGLVP is described in principle using a combination of pharmacokinetic and pharmacodynamic data. Therapeutically the results in this study suggest a 4-hour interval between injections.

Adult↗

Effects of long-term hypergastrinaemia on the ultrastructure of enterochromaffin-like cells in the stomach of the rat, hamster and guinea pig.

The present report describes the ultrastructure of the enterochromaffin-like (ECL) cells in the stomach of the rat, hamster and guinea pig, and the ultrastructural consequences of long-term hypergastrinaemia evoked either by continuous infusion of synthetic human (Leu15)-gastrin-17 for 4 weeks (rats) or by daily treatment with large doses of the antisecretory agent omeprazole for 2-10 weeks (rats, hamsters and guinea pigs). As a result, the ECL cells increased greatly in size (maximal effect after 2 weeks of omeprazole treatment, no further gain in size after 4 or 10 weeks). Also the endoplasmic reticulum and Golgi area were enlarged. The most conspicuous feature of the ECL cells is the cytoplasmic vesicles, which are of varying size and either devoid of a dense core or with a small, often eccentrically located dense core. The vesicles probably represent the main storage site of the secretory products of the ECL cell. In addition, the cytoplasm contains granules, which differ from the vesicles in that they possess a more or less electron-dense core, surrounded by a narrow halo. The size of the vesicles ranged from small to very large, while the granules were uniformly small. Many vesicles were seen to lie very close together, some displaying an irregular outline (vacuole-like vesicles), at times giving the impression that they were undergoing fusion. The profile size (median value) of the vesicles was unaffected by gastrin infusion for 4 weeks. However, there was a tendency to a relative increase in the number of very small vesicles. In contrast, the vesicles became larger during the omeprazole treatment. Also, the number of vesicles that seemed to be engaged in fusion increased after omeprazole treatment but not after gastrin infusion. The observations support the view that ECL cells are influenced by gastrin. The effects of gastrin infusion and of omeprazole treatment on ECL cell ultrastructure were not completely identical. It cannot be excluded that the omeprazole-evoked achlorhydria evokes effects unrelated to those of hypergastrinaemia on the ECL cells, or that endogenous gastrins may evoke effects that are in some ways distinct from those of synthetic human (Leu15)-gastrin-17. Alternatively, the additional effects seen after long-term omeprazole treatment may reflect simply the duration of the hypergastrinaemic stimulus.

Animals↗

Chlorhexidine for prevention of neonatal colonization with group B streptococci. V. Chlorhexidine concentrations in blood following vaginal washing during delivery.

Chlorhexidine 2 g/l was applied to the vagina of 96 women during delivery, whereas 28 served as controls. Both groups were given a shower using a chlorhexidine soap, and outer washing of the outer anogenital tract was also performed in all patients using chlorhexidine 2 g/l. Using a gas chromatographic method with a detection limit of 10 ng chlorhexidine per ml blood, 10-83 ng/ml was demonstrated in 34 (35%) of the study group patients, whereas the remaining study group patients and controls showed no detectable chlorhexidine. Performing the washing a second time after 6 hours in 14 patients and a third time in 3 patients after a further 6 hours did not result in increased serum levels. It was concluded that small amounts of chlorhexidine are absorbed through the vaginal mucosa and that chlorhexidine is not accumulated in the blood on repeated usage with 6 hour intervals during delivery.

Administration, Intravaginal↗

Validity of a postal questionnaire with regard to the prevalence of myocardial infarction in a general population sample.

In order to evaluate the possibility of finding persons who have suffered a myocardial infarction (MI) by postal questionnaire, a self-administered questionnaire was sent to a random sample of 4400 men aged 45-64 years, drawn from the general population. The response rate was 95%. 176 men indicated that they had been hospitalized for MI, out of which 124 cases could be verified from medical records. Of the remaining men, 33 had evidence of cardiovascular disease (CVD) in their records but no MI, and 19 men had no evidence of CVD. The sensitivity (estimated from a subsample) was 100% and the specificity 98.7%. The predictive value was 100% for a negative response and 70.5% for a positive response. The 33 positive responders whose MI could not be verified but who had evidence of CVD had characteristics fairly similar to the responders with verified MIs. However, the 19 positive responders whose MI could not be verified and who had no evidence of CVD had characteristics that were dissimilar from the MI group as well as from the negative responders. The questionnaire thus identified all the MI cases. The need for validation can be limited to the relatively small group of positive responders.

Cardiovascular Diseases↗

Diagnostic value of longterm ambulatory ECG in patients with syncope, dizziness or palpitations.

The diagnostic value of longterm ambulatory ECG recording (LTER) was determined in 63 patients referred for investigation of syncope, in 32 with dizziness and in 89 with palpitations. Among patients referred for syncope, dizziness or palpitations 8, 13 and 54%, respectively, had typical symptoms during the recording with concomitant arrhythmia explaining the symptom, and 6, 50 and 11% had a typical symptom without concomitant arrhythmia. In 12 and 3% of the patients referred for syncope or dizziness, respectively, arrhythmia was observed and probably explained their previous complaint, but no symptoms occurred during LTER. LTER was found to be of diagnostic value in 24% of the patients with syncope, in 66% of those with dizziness and in 65% of those with palpitations. In the latter two groups the presence of symptoms the week before the start of these recordings predicted the occurrence of symptoms during LTER. Only occasionally was there a higher yield of typical symptoms beyond 48 h of recording.

Aged↗