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Biomedical subjects

G Berlin

Publications and source records attributed to G Berlin.

At least 37 records · Page 2Linked to original sources

Autoantibodies versus clinical symptoms in blood donors.

A group of 255 blood donors was analyzed for the presence of serum autoantibodies, e.g., antinuclear antibodies, smooth muscle antibodies, antimitochondrial antibodies, antiparietal cell antibodies and antireticulin antibodies by indirect immunofluorescence microscopy. The 37 (15%) who had autoantibodies underwent examination and extended laboratory investigation. We found no strong evidence of disease in any of the blood donors with autoantibodies.

Adult↗

Antibodies to peripheral nerve myelin may occur without clinical neuropathy in healthy persons.

To study the role of autoantibodies against peripheral nerve myelin (PNM), sera from 255 healthy blood donors were investigated by enzyme-linked immunosorbent assay (ELISA), and persons with anti-PNM antibodies were further studied clinically and by neurography, 25 blood donors (10%) had anti-PNM antibodies of IgM, IgG or IgA isotype. The 12 blood donors with anti-PNM antibodies of IgM isotype showed only slightly decreased nerve conduction velocities compared to 12 blood donors without anti-PNM antibodies. Two blood donors with anti-PNM antibodies of IgM and IgG isotype respectively showed a clinical, previously undiagnosed polyneuropathy (PN), verified by neurography. However, also one blood donor without anti-PNM antibodies had a clinical and neurography-verified PN. We conclude that antibodies against PNM may occur in healthy persons without evidence of a clinical or subclinical PN.

Adult↗

Effect of hemodilution on maximal oxygen consumption, blood lactate response to exercise and cerebral blood flow in subjects with a high-affinity hemoglobin.

10 subjects with Hb Linköping (beta 36 Pro greater than Thr), a high-affinity hemoglobin variant, with a P50 of 2.2 kPa (16.5 mm Hg) were investigated before and 3-4 days after normovolemic hemodilution. Blood hemoglobin concentration decreased from 176 +/- 13 (SD) to 146 +/- 15 g l-1 and the red cell volume from 2.77 +/- 0.83 to 2.23 +/- 0.67 l. Maximal oxygen consumption decreased slightly by 2.7 +/- 3.8 ml min-1 kg-1 and maximal exercise power by 11 +/- 23 W; these changes were, however, not statistically significant. Maximal heart rate was unchanged (-1.1 +/- 6.4 beats min-1) while submaximal heart rate was consistently increased on comparable loads after hemodilution compared to before. The exercise ECG was normal both before and after hemodilution. Capillary lactate levels at exercise were always higher after hemodilution than before. Cerebral blood flow was normal both before and after hemodilution in all subjects but one who had a high flow. The grey matter blood flow increased slightly but significantly by 8.6 +/- 10.3 ml min-1 100 g-1 from before to after hemodilution. The results indicate that subjects with Hb Linköping have only limited benefit from their increased blood hemoglobin concentration.

Adult↗

Plasma exchange in endocrine ophthalmopathy.

We studied the effects of intensive plasma exchange on endocrine ophthalmopathy in 12 patients with Graves' disease and one with Hashimoto's thyroiditis. All patients were euthyroid at the time of plasma exchange. All but five had concomitant treatment with azathioprine. Each patient had a treatment period consisting of six plasma exchanges performed in 2-3 weeks; two patients were treated in two periods. Each time a mean of 2.4 liters plasma was exchanged. There was a prompt reduction in the concentration of circulating immune complexes and/or thyrotropin receptor antibodies following plasma exchange. Six of the 13 patients improved their proptosis; their median duration of eye symptoms before treatment was less than 8 months. In patients suffering from eye symptoms for more than 1 year improvement was rare. Overall the Hertel values were 24.1 +/- 4.4 (SD) before and 22.8 +/- 3.4 after plasma exchange for the left eyes (P = 0.07) and 23.8 +/- 4.0 before and 23.0 +/- 3.8 after for the right eyes (P = 0.09). Nine patients altogether improved their ophthalmopathy index and periorbital oedema. In patients with disabling endocrine ophthalmopathy plasma exchange may sometimes be of value to induce a relief of the ophthalmopathy; when it is used it should be instituted before fibrotic changes occur. We suggest that concomitant immunosuppressive drugs should be given to prevent rebound phenomenon induced by plasma exchange. To establish the role of plasma exchange in the treatment of endocrine ophthalmopathy controlled studies should be performed.

Adult↗

No increased relapse frequency in acute Guillain-Barré syndrome after plasma exchange.

Relapse frequency in 23 patients with acute Guillain-Barré syndrome (GBS) treated with plasma exchange (PE) was studied. Fifteen patients showed clear improvement, and 4 patients some improvement during the PE period, whereas 4 patients did not improve in immediate connection to the PE treatment. During the follow up time of 6-96 months (mean 36 months), only one of the 23 patients had a relapse, which appeared after 3 months. This relapse frequency is similar to that reported as the natural history of GBS, and thus, we can not verify the recently reported increased relapse frequency of GBS after PE.

Adolescent↗

Cerebrospinal fluid immunoglobulins and beta 2-microglobulin in lymphoproliferative and other neoplastic diseases of the central nervous system.

Humoral immune aberrations may occur in the cerebrospinal fluid (CSF) of patients with lymphoproliferative and other neoplastic diseases infiltrating the central nervous system (CNS). Such aberrations may be of diagnostic importance. We therefore studied CSF and serum from 47 patients with lymphoproliferative diseases and from 16 patients with various nonlymphoid neoplasias; 17 patients and 12 patients, respectively, had neoplastic CNS involvement. Elevated CSF IgM index and oligoclonal IgG bands in CSF and serum were commonly found, especially in patients with CNS involvement. Cerebrospinal fluid IgG and IgA indexes were usually normal. Increased CSF to serum albumin ratio, reflecting blood-brain barrier dysfunction, and increased CSF beta 2-microglobulin concentration were most common in patients with CNS involvement. The results indicate that neoplastic CNS disease should be borne in mind when CSF humoral immune aberrations are found.

Brain Neoplasms↗

Hb Linköping (beta 36 Pro----Thr): a new high oxygen affinity hemoglobin variant found in two families of Finnish origin.

Several members representing three generations of two families with erythrocytosis due to a newly described hemoglobinopathy (Hb Linköping, beta 36 Pro----Thr) were studied. All affected family members had a pronounced left-shift of the oxygen dissociation curve, indicating an increased oxygen affinity leading to compensatory erythrocytosis. The proband of each family was found by a simple method determining the oxygen pressure at half hemoglobin saturation (P50), which was used as a screening test evaluating patients with polycythemia. In both cases the hemoglobinopathy was missed by routine hemoglobin electrophoresis. The abnormal hemoglobin was confirmed by isoelectric focusing and the altered amino acid sequence was identified by reversed-phase high-performance liquid chromatography (HPLC). The importance of a correct diagnosis in patients with erythrocytosis due to high-affinity hemoglobin variants is discussed.

Adult↗

Cell surface markers for diagnosis of central nervous system involvement in lymphoproliferative diseases.

To diagnose lymphoproliferative central nervous system (CNS) involvement we have used monoclonal antibodies in an immunocytochemical method for differentiation of cells in cerebrospinal fluid (CSF) and peripheral blood. The cell distribution in 9 patients with B-cell lymphoma and 7 patients with chronic lymphatic leukemia was compared to that in a group of patients with aseptic meningitis. Most patients with neoplastic CNS involvement showed a high proportion of CSF B cells (OKB2+ and/or OKB7+) and a concurrently low proportion of CSF T cells (anti-Leu 1+). Proliferating cells expressing transferrin receptor (OKT9 labeled) were increased in the CSF of 2 patients with neoplastic CNS involvement. In 2 patients with infectious CNS complications, the cell distribution in CSF did not differ from that in patients with aseptic meningitis. Patients with leukemia who had no CNS symptoms, and also 1 patient with meningitis and blood-brain barrier damage, showed a normal cell distribution in CSF despite high B-cell numbers in the peripheral blood. This indicates a selective passage of leukocytes into the CNS and/or local proliferation.

Adult↗

Non-differential inhibition of histamine and serotonin release from mast cells by amitriptyline.

A differential amine release from mast cells induced by an inhibitory effect of the antidepressant drug amitriptyline on the release of histamine but not on that of serotonin has recently been reported. In view of the potential biological importance of a differential release of mast cell amines we have studied the effect of amitriptyline on the dynamics of the secretory process using a combination of vital berberine staining (demonstrating intracellular granules that have released amines) and measurement of histamine, serotonin (5-HT), and heparin release. The results show a non-differential inhibition of the release of histamine and 5-HT by amitriptyline. The basic pattern of the secretory process, studied in terms of granule extrusion and amine release from intracellular granules, was unaffected by the drug.

Amitriptyline↗

Peripheral neuropathy and monoclonal IgM with antibody activity against peripheral nerve myelin; effect of plasma exchange.

Serum IgM antibodies directed against peripheral nerve myelin were demonstrated using enzyme-linked immunosorbent assay, mixed haemagglutination and indirect immunofluorescence in 3 patients with chronic polyneuropathy and monoclonal serum IgM. Isoelectric focusing followed by antigen immunofixation and autoradiography showed that the antimyelin antibodies co-migrated with the monoclonal IgM. Plasma exchange alone, without chemotherapy, proved beneficial in 2 patients. In one patient, plasma exchange was discontinued because of low IgG levels. Serum IgM and antimyelin antibodies decreased during plasma exchange and no increase beyond initial levels was noted after cessation of treatment.

Adult↗

Long-term remission of pure red cell aplasia after plasma exchange and lymphocytapheresis.

A 57-year-old man with idiopathic pure red cell aplasia went into remission after plasma exchange. He relapsed after 5 months and then failed to respond to treatment with intensive plasma exchange and immunosuppressive agents. Because of a high proportion of T-suppressor cells in the peripheral blood he was treated with lymphocytapheresis in addition to the previous treatment. The patient achieved a long-term haematological remission which has now persisted for more than 3 yr.

Cyclophosphamide↗

The dynamics of mast cell secretion mediated by IgE or polyamines.

Mast cell secretion can be mediated not only by IgE but also by a number of secretagogues of various chemical structure. In the present study the dynamics of the mast cell secretory process induced by different polyamines and anti-IgE were compared using a combination of vital berberine binding (demonstrating intracellular granules that have released amines) and measurement of histamine and heparin release. The results suggest that the basic secretory pattern is the same no matter whether the secretion is induced by polymyxin B, polylysine, compound 48/80, or an IgE-anti-IgE reaction. Histamine can be released from intracellular granules which, according to previous results, may be reincorporated into the cytoplasm, but which are to a large extent expelled from the cell by exocytosis.

Animals↗

The dynamics of mast cell secretion studied by vital berberine staining.

The fluorescent cationic dye berberine in combination with histamine release studies have been used to explore the different steps of the mast cell secretory process. We have previously shown that quantitation of heparin release by the binding of berberine to fixed mast cells can be used as a direct measure of release of granules. This report summarizes recent work using berberine as a vital stain demonstrating the secretory activity of mast cells. After membrane stabilization with polyethylene glycol (PEG) normal mast cells exclude the dye while mast cells stimulated to secretion with polymyxin B show a strongly fluorescent dye binding to individual cytoplasmic granules. The mean fluorescence intensity of the cell populations after vital berberine staining was compared both to heparin and histamine release. The results strongly suggest that berberine, under the vital staining conditions used, is a marker of intracellular granules that have released histamine. The vital staining method was also used to study membrane events following a polymyxin B-induced secretion. The mean fluorescence intensity decreased by 75% during the first hour after the termination of a polymyxin B stimulation while the mast cell content of histamine and heparin remained constant. The findings support the idea that the membranes are rapidly restored after mast cell secretion, permitting a selective amine release without accompanying release of heparin or other matrix components of the granules.

Animals↗

Mast cell secretion. Rapid sealing of exocytotic cavities demonstrated by cytofluorometry.

Mast cell secretion is closely associated with extrusion of granules from the cell, and results in rapid release of both amines and heparin. Amines may also be released from intracellular granules communicating with the extracellular environment through channels formed by membrane fusions. We have recently reported the use of the fluorescent, cationic dye berberine as a vital stain marking amine-releasing granules located within the domains of the cell. The present report concerns early membrane events and the fate of such granules after termination of the secretory process. Purified mast cells were stimulated to a moderate secretory response by a low concentration of polymyxin B. The cells were then kept in a medium without the secretagogue. The fluorescence intensity of individual cells after vital berberine staining (reflecting the number of intracellular granules in contact with the extracellular environment) decreased rapidly after terminated mast cell secretion. The heparin content (reflecting the total number of intracellular granules) and the histamine content of the cells, both reduced by the secretory process, remained constant over a period of 1 h after terminated mast cell secretion. These findings suggest that mast cell membranes are rapidly restored after secretion, permitting selective amine release without accompanying release of heparin or other matrix components.

Animals↗

Fluorescent berberine binding as a marker of secretory activity in mast cells.

We have previously shown that the weakly fluorescent cationic dye, berberine, forms a strongly fluorescent complex with the heparin of fixed mast cells and can be used for cytofluorometric measurement of heparin in both mast cells and individual mast cell granules. Now, we report on the use of berberine as a vital stain, demonstrating the secretory activity of mast cells. At a dye concentration of 0.025%, and after membrane stabilization with polyethylene glycol, normal mast cells exclude the dye while mast cells stimulated to secretion with polymyxin B show a strongly fluorescent dye binding to individual cytoplasmic granules. The mean fluorescence intensity (reflecting the number of stained granules) of the cell populations increased with increasing polymyxin B concentrations up to 2.0 micrograms/ml, thereafter remaining constant up to 10 micrograms/ml. Fluorescence intensity after vital staining with berberine was compared both to release of heparin measured by berberine binding to fixed cells (reflecting exocytosis of mast cell granules) and also to histamine release. The results strongly suggest that berberine specifically stains secreting granules that are located within the domains of the cells but may have released histamine. Vital berberine staining combined with histamine assays and cytofluorometric measurements of heparin is therefore of great potential interest for analyzing the dynamics of mast cell secretion.

Animals↗