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Biomedical subjects

R Matre

Publications and source records attributed to R Matre.

At least 19 recordsLinked to original sources

Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma.

Sera from patients with myasthenia gravis were examined by Western blot for the presence of antibodies to proteins of the sarcoplasmic reticulum from rabbit skeletal muscle. Fourteen of 30 patients with myasthenia gravis and a thymoma had IgG autoantibodies to the calcium release channel of the sarcoplasmic reticulum (the ryanodine receptor), which plays a crucial role in the mechanism of excitation-contraction coupling in striated muscle. Ryanodine receptor autoantibodies were not detected in any of the 45 sera from patients with myasthenia gravis without a thymoma. Ryanodine receptor autoantibodies may have pathogenetic relevance in thymoma-associated myasthenia gravis.

Autoantibodies

The influence of the host on the course of gastric carcinoma.

Immunoglobulins (Ig) and some complement components (C) were quantified in sera from patients with gastric carcinoma before surgery and at regular intervals during a 5-year follow-up. The preoperative concentrations of C1-INH and C4 were higher (P < 0.0005 and P < 0.005) and IgG lower (P < 0.0005) in 50 patients with recurrence than in 46 5-year survivors. The prognostic significant of C1-INH was superior to that of the extent of disease (F-values 37.1 and 26.1). The preoperative immune data classified 76% of the patients correctly as to recurrence and no recurrence. Also, the preoperative C1-INH concentration had a highly significant effect on time to recurrence of cancer (P = 0.0007), adjusting for age and disease extent. After surgery the mean IgG concentrations were within normal range and without difference between the two groups. On the other hand, the concentrations of C1-INH and C4 in the individual patients in both groups remained the same from before to after surgery and throughout the observation period (P = 0.34). Apparently, the serum levels of C1-INH and C4 do not reflect the bearing of cancer. We therefore suggest that these variables represent an independent immune state that is appropriate to the host. A comparison of our variables with those of healthy individuals seems to support this idea. This immune state has a significant influence on whether a resected gastric cancer will recur, and also on how soon recurrence may be manifest.

Adult

Myasthenia gravis muscle antibodies examined by ELISA: IgG and IgM antibodies characterize different patient subgroups.

Sera from 90 myasthenia gravis (MG) patients were examined for antibodies against skeletal muscle citric acid extract (CA) antigens by ELISA and indirect haemagglutination (IHA). 31% (ELISA) and 24% (IHA) of the sera were positive, and the results of the two tests were in good agreement. 18 of 28 patients positive in ELISA had IgG CA-antibodies, 10 had IgM and 3 IgA CA-antibodies. The patients with IgG antibodies had a high mean age of MG disease onset, and 9/14 thymectomized patients had a thymoma. Patients with IgM CA-antibodies had a much lower age of onset and 4/5 thymectomized patients had thymus hyperplasia. IgM antibody positive patients had a long disease duration, indicating that they produce IgM antibodies for an indefinite period of time without switching to IgG antibody production.

Adolescent

Myasthenia gravis with thymoma is not associated with an increased incidence of non-muscle autoimmune disorders.

Three groups of thymectomized patients with myasthenia gravis (MG) were selected for study, 16 with thymoma, 16 with thymic atrophy and 32 with follicular hyperplasia of the thymus. All 16 patients with thymoma, 15/16 with thymus atrophy and 30/32 with follicular hyperplasia had AChR antibodies. Non-receptor muscle (CA) antibodies were found in sera of 15/16 patients with thymoma, 3/16 with thymus atrophy and in none of the sera from patients with follicular hyperplasia. There were 2 patients with thymoma and polymyositis, but none of the thymoma patients had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or other autoimmune disorders. Among the 32 patients with follicular hyperplasia of the thymus were 2 with SLE, 2 with RA and 1 with juvenile diabetes mellitus. In this study, there was an increased incidence of non-muscle autoimmune disorders among MG patients with follicular hyperplasia of the thymus but not among MG patients with thymoma.

Adult

Non-receptor muscle antibodies in myasthenia gravis are of IgG1 and IgG4 subclasses.

The IgG subclass distribution of non-receptor muscle antibodies was examined in 15 myasthenia gravis (MG) sera, employing an indirect haemagglutination-immunofluorescence technique. Four sera contained only IgG1, 4 contained only IgG4 and 7 contained both IgG1 and IgG4 muscle antibodies. IgG2 and IgG3 antibodies were not found. Among 11 patients with a defined thymus pathology 8 had thymoma and 3 had thymic atrophy, but there was no correlation between antibody subclass pattern and thymic pathology. Patients with both IgG1 and IgG4 antibodies tended to have the longest disease duration. We conclude that IgG non-receptor muscle antibodies in MG are of the IgG1 and/or IgG4 subclasses, irrespective of thymic pathology.

Adult

The influence of age on the growth and spread of gastric carcinoma.

A twelve year series of 375 patients with gastric carcinoma has been studied. Patients were divided into TNM Groups. Tumours were classified as intestinal-type and diffuse. The patients with T1-3NOMO diffuse tumour were ten years younger than the patients with T1-3NOMO intestinal-type tumour. The mean age increased from T1 through T2 to those with T3 tumour. The age differences between the T-stages were the same in both groups, which indicate that once started, the diffuse and the intestinal-type tumours infiltrate the gastric wall at about the same rate. Among the patients with intestinal-type tumour, those with lymph node or distant metastases were three to seven years younger than the patients without metastases. On the other hand, the patients with diffuse tumour and metastases were as many years older than the patients without metastases. Apparently, tumour spread is age dependent and different between the two types of gastric carcinoma. The ill repute of the diffuse gastric carcinoma may therefore be explained by the advanced stage of that tumour at the time of treatment as compared to the intestinal-type tumour. The diffuse tumour seems to be clinically more silent and to give symptoms at a later stage than the intestinal-type tumour.

Adult

Neonatal tetanus despite protective serum antitoxin concentration.

Using the ELISA technique to estimate serum antibodies against tetanus toxin, seven neonates with clinical tetanus were found to have antibody levels 4-13 times higher than the presumed minimum protective level of 0.01 IU/ml. All but one of their mothers had been vaccinated with tetanus toxoid in pregnancy. In two other neonates, whose mothers had received multiple booster doses of toxoid during pregnancy, the anti-toxin concentrations were 100- and 400-times the presumed protective level. Therefore the toxin dose may overwhelm the pre-existing anti-toxin level and produce disease. Furthermore, multiple booster injections of tetanus toxoid may not only enhance serum anti-toxin titres, but could also lead to an ineffective immune response.

Enzyme-Linked Immunosorbent Assay

IgG Fc receptor heterogeneity in human peripheral nerves.

The presence of Fc-receptors for IgG, FcRI (CD64), FcRII (CD32) and FcRIII (CD16) in human peripheral nerves was studied by indirect immunofluorescence staining of cryostat sections with monoclonal antibodies (mabs). The mabs 32.2 against FcRI, IV.3 and C1KM5 against FcRII, B1D6 against a 40 kD FcR with low affinity for IgG, and Leu-11b and 3G8 against FcRIII stained a few scattered cells in the endoneurium, apparently monocytes/macrophages. In addition, B1D6 and Leu11b gave a membranous staining of Schwann cells, endothelial cells and perineurial cells. Axons and fibroblasts were not stained by any of the mabs. The FcR may be important in binding immune complexes, in phagocytosis, in the release of lymphokines as well as cytotoxic and inflammatory mediators and in local immunoregulation.

Antibodies, Monoclonal

Age and sex distribution of intestinal type and diffuse gastric carcinoma.

A twelve-year series of 375 patients with gastric carcinoma has been studied. Primary tumours were classified as intestinal type (58%) or diffuse (26%), whereas 16% were unclassifiable. The relative age and sex incidence rates of intestinal type and diffuse gastric carcinoma were estimated using the age and sex distribution of individuals in Norway as the basis for calculation. There was no difference in the rates of diffuse gastric carcinoma between the sexes. On the other hand, the rate of men with intestinal type carcinoma was more than twice as high as that of women. This difference was consistent within each age group from adolescence to senescence. The findings indicate that Laurén's two types of gastric carcinoma are aetiologically different. The rates of both types increased with age up to the 70-79 age group, whereas the rates in octogenarians tended to be lower than in septuagenarians. A comparison of our data with the data of incidence of gastric cancer in Norway indicates that some of the older patients do not come for surgery.

Adult

Acute effect of passive Heymann nephritis on renal blood flow and glomerular filtration rate in rat: the effect of infusion of F(ab')2 fraction of anti-FX1(A) antibody.

We have earlier shown that there is an immediate fall in renal blood flow (RBF) and glomerular filtration rate (GFR) during induction of passive Heymann nephritis (PHN) by infusion of rabbit antibodies towards rat renal brush-border antigens (anti-Fx1A). To investigate the role of complement activation in this stage of the disease, we infused the F(ab')2 fraction of anti-Fx1A (aFFab) in one group of rats and the F(ab')2 fraction of normal rabbit IgG in another group (controls). aFFab produced no hemodynamic changes when compared to controls. Sixty minutes after infusion of aFFab, RBF was 5.7 +/- 0.4 ml/min/g kidney weight (control 7.3 +/- 1.0, NS), after anti-Fx1A RBF was 3.2 +/- 0.7, p less than 0.05 compared to control. GFR after infusion of aFFab was 1.0 +/- 0.1 ml/min/g (control 0.8 +/- 0.1, NS), after infusion of anti-Fx1A 0.2 +/- 0.1 (p less than 0.02 compared to control). The blood pressure was unaffected by aFFab infusion, while there was a temporary fall in blood pressure to a minimal value of 76 +/- 4 mm Hg 10-20 min after infusion of anti-Fx1A (p less than 0.01 compared to control). Immunofluorescence studies showed granular immune deposits in the subepithelial region of the glomerular basement membrane as shown after infusion of anti-Fx1A antibodies. In addition, fluorescence was seen in the brush-border of proximal tubuli. The results indicate that the immediate fall in RBF and GFR during induction of PHN in mediated via activation of the complement system.

Animals

IgG Fc receptors on epithelial cells of distal tubuli and on endothelial cells in human kidney.

IgG Fc receptors (FcR) in cryostat sections of human kidney were studied using functional assays and monoclonal antibodies (MoAbs). Using functional assays, FcR were detected on cells in glomeruli and distal convoluted tubuli, on endothelial cells and on interstitial cells. These cells were also stained with B1D6, a MoAb reactive with a 40-kD molecule with low affinity FcR activity. Using MoAbs against leukocyte FcR, a different pattern of reactivity was obtained. MoAbs against FcR I (32.2), FcR II (IV.3 and C1KM5) and FcR III (3G8 and Leu11b) stained interstitial macrophages only. The data confirm the presence of FcR on renal glomeruli and interstitial cells and also indicate that epithelial cells of distal tubuli and endothelial cells express FcR. Furthermore, renal FcR appear to be structurally different from the FcR I, II and III defined on leukocytes.

Antibodies, Monoclonal

Fc gamma-receptors on Langerhans' cells and keratinocytes in suspension from normal skin characterized using soluble immune complexes and monoclonal antibodies.

Fc-receptors for IgG (FcR) on epidermal cells in suspension were studied using soluble immune complexes and monoclonal antibodies (MoAbs) against FcR I, FcR II and FcR III using an indirect immunofluorescence technique. The binding of immune complexes demonstrated that most Langerhans' cells (greater than 95%) and a proportion of keratinocytes (25 +/- 6%) expressed functional FcR activity. The reactivity with MoAbs showed that epidermal cells possess different types of FcR. Langerhans' cells reacted only with IV.3 (anti-FcR II/-CDw32). A varying percentage of keratinocytes reacted with 32.2 (anti-FcR I/-CD64) (18 +/- 10%), Leu 11b (anti-FcR III/-CD16) (19 +/- 6%) and B1D6 (against a placental FcR) (35 +/- 8%). Both with immune complexes and MoAbs the staining was strongest along the cell surface, but cytoplasmic staining was also regularly present. The data add further support to the contention that keratinocytes have an immune function. FcR on epidermal cells may play an immunoregulatory role interacting with isotypes and cytokines in the skin. Keratinocyte-produced soluble FcR could also be an immunological mediator.

Antibodies, Monoclonal

The ontogenesis of Fc gamma receptors and complement receptors CR1 in human peripheral nerve.

The ontogenesis of Fc gamma receptors (FcR) and C3b/C4b receptors (CR1) was studied in peripheral nerves from ten fetuses aged from 20 to 38 weeks using immunohistochemical and functional assays. Monoclonal antibodies (mAbs) against FcR and CR1 stained nerve fibers at 10 weeks of gestation and the staining intensity increased during nerve maturation. FcR and CR1 are probably expressed on Schwann cells and are early markers during the development of peripheral nerves. Functional FcR activity was detected in nerve sections before initiation of myelination, which occurs at approximately 18-19 weeks, whereas functional CR1 activity was found in the sections after myelination. Functional CR1 activity may, therefore, be related to myelin. The ontogenesis of FcR and CR1 was also studied on Schwann cells in culture from three fetuses aged 14, 16 and 19 weeks, using immunofluorescence technique with mAbs. The FcR and CR1 are lost on cultured Schwann cells. This suggests that the receptors are not intrinsic to the cells or that Schwann cells require axonal contact for the expression of FcR and CR1.

Antibodies, Monoclonal

Properties of solubilized Fc gamma-receptors from psoriatic scales.

Extracts from psoriatic scales, prepared using Tris-HCl buffer containing ethylenediaminetetraacetatic acid (EDTA) and 2-mercaptoethanol (ME), agglutinated erythrocytes (E) sensitized with IgG antibodies (A) (EA), but not E or E sensitized with F(ab')2-fragments of IgG. The agglutination was inhibited by IgG and Fc fragments of IgG, but not by IgA, IgM or F(ab')2-fragments of IgG. Partially reduced and alkylated IgG did not inhibit the agglutination, indicating that an inter-heavy-chain disulphide-linked Fc region is required for binding of FcR. The extracts inhibited EA, but not E or EAC rosette formation with mononuclear cells. The results strongly indicated that the extract contained functionally active FcR. The agglutinating activity of the extract was not affected by treatment with periodic acid or formaldehyde, whereas heat reduced the activity. Using a monoclonal antibody (B1D6) a functionally active 40 kDa FcR with low affinity for native IgG was purified from the scale extract. The extracts also contained FcR activity not recognized by B1D6.

Antigens, Differentiation

Peripheral nerve CR1 limit complement-mediated haemolysis.

CR1 were purified from sciatic nerve extracts by monoclonal antibody affinity chromatography. The effect of CR1 on complement-mediated haemolysis was studied by adding purified CR1 to a mixture of human serum as source of complement and sheep erythrocytes sensitized with rabbit IgG. A dose-dependent inhibition of the haemolysis occurred. There was no effect on the haemolysis when phosphate-buffered saline, elution buffer or run-through fraction not containing CR1 was added. Addition of a polyclonal anti-CR1 antibody to purified CR1 suppressed the inhibiting activity, strongly indicating that peripheral nerve CR1 inhibit complement-mediated haemolysis. This may be of great importance in vivo since CR1 present on the Schwann cell membrane may prevent the formation of terminal lytic complexes.

Complement System Proteins

Peripheral nerve CR1 express in situ cofactor activity for degradation of C3b.

Adsorption of sheep erythrocytes (E) sensitized with IgM antibodies (A) and C3b (EAC3b) to C3b/C4b receptors (CR1) in cryostat sections of human myelinated nerves was studied using the closed chamber technique. The adsorption was stable for at least 3 h at 37 degrees C. In the presence of purified factor I, the indicator cells detached from the sections after 40 min at 37 degrees C. Factor H was not required. The release was not due to loss of CR1 activity in the sections. The detached indicator cells were negative in the immune adherence test and were agglutinated by antibody to C3d, but not by antibody to C3c. Western blot of the detached indicator cells revealed the presence of C3d and C3c was found in the chamber fluid. Accordingly, detachment of the indicator cells was due to degradation of C3b to C3d with the release of C3c into the chamber fluid. Protease inhibitors did not prevent the detachment of the indicator cells. EAC3b incubated with sections of myelinated nerves pre-incubated with anti-CR1 antibody or with sections of unmyelinated nerves which contain functionally inactive CR1 were not degraded. The results therefore indicate that CR1 in situ in myelinated nerves can provide the necessary cofactor activity for factor I-mediated degradation of C3b to C3d and C3c.

Animals

Fc gamma receptor heterogeneity in the human placenta.

Fc receptors for IgG, FcRI (CD64), FcRII (CD32), and FcRIII (CD16) in human placenta were studied by indirect immunohistochemistry using avidin-biotin peroxidase complexes for the staining of cryostat sections. The MoAb 32.2 against FcRI stained cells in the loose connective tissue of the placental villi. The MoAb IV3 (FcRII) and C1KM5 (FcRII) also stained stromal cells and in addition stained the endothelium of the placental villi. The MoAb anti-Leu-11b against FcRIII and B1D6 against a 40-kDa FcR from placenta stained both stromal cells and endothelium as well as the fetal trophoblasts lining the villi. The MoAb 3G8 (FcRIII) also stained trophoblasts and stromal cells but did not stain the endothelium. The heterogeneity of FcR expression on human placenta is established. The function of the different receptors is still unclear.

Antibodies, Monoclonal