[The regulation of anti-acetylcholine receptor antibody production by T cells responding in autologous mixed lymphocyte reaction in patients with myasthenia gravis].
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Adolescent↗
Biomedical subjects
H C Chiu
Publications and source records attributed to H C Chiu.
[Clinical and electrophysiological studies of diabetic neuropathy].
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Adult↗
[Thymectomy in Chinese myasthenia gravis].
From 1972 to 1986, 80 Chinese myasthenia gravis patients with thymectomy were studied. There were 25 males, aged from 21 to 70 years old (mean age 44) and 55 females aged from 12 to 56 years old (mean age 34). According to Osserman's criteria 10 patients belonged to grade I, 28 to IIa, 31 to IIb, 4 to III, 2 to IV and 5 to V. The postoperative follow ups ranged from 1 month to 13 years. The thymic pathology showed: hyperplasia in 44 cases, atrophy in 17 cases and presence of thymoma in 19 cases. The postoperative improvement occurred in 50% in thymomatous patients, 81% in non-thymomatous patients. There was no relationship between the duration of illness before operation and the postoperative status. However the patients with age onset after 40 had higher incidence of thymoma, and a higher rate of death from myasthenia gravis despite short duration of illness before surgery. All of 18 patients in whom serum was examined, the antiacetylcholine receptor antibody was detectable. The mean titres of this antibody in 8 hyperplasia patients, 3 atrophy patients and 7 thymoma patients were all higher than the mean value of 67 myasthenia gravis patients who did not received any treatment except anticholinesterase. Seven cases had postthymectomy followups of the antibody titres, 3 cases showed decreased antibody titre after thymectomy. Ten ocular myasthenic patients received thymectomy, 3 had thymoma, 5 had hyperplasia and 2 had atrophic thymus. The improvement rate in this group was around 71%.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Biology of human megakaryocyte factor V.
To learn more about human megakaryocyte coagulation cofactor V (FV), we studied the expression of this protein in normal bone marrow megakaryocytes and in megakaryocytes cloned from their colony-forming unit in FV-depleted plasma clot cultures. Mouse monoclonal antibodies directed against either the light chain or an activation peptide of human FV and a rabbit polyclonal, monospecific FV antiserum were used as probes for these experiments in conjunction with a variety of immunochemical detection techniques. All morphologically recognizable megakaryocytes were shown to contain FV. The origin of this protein appeared to be both from FV bound to the cell as well as from endogenous FV in the majority of cells examined. The existence of a population of small bone marrow mononuclear cells that simultaneously expressed platelet glycoproteins and FV was also noted. Such cells represented approximately 70% of all small cells positive for platelet glycoproteins. In contrast, only about 40% of megakaryocyte colonies cloned in FV-deficient medium contained cells with immunochemically detectable FV. FV expression was most clearly demonstrated in large cells in the colonies, whereas smaller, presumably less mature cells labeled weakly or not at all. Synthesis of FV by human megakaryocytes was documented using elutriation-enriched cells incubated in 35S-methionine-containing medium. Megakaryocyte lysates and medium conditioned by these cells were subjected to immunoaffinity column purification. Column eluates analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed radioactive bands comigrating with the heavy and light chains of thrombin-activated FV. These studies suggest that human megakaryocytes both bind and synthesize FV. Expression of these traits appears to be related to cell maturation, with binding ability appearing earlier than the ability to synthesize this protein. Finally, although the ability to bind FV appears to be universal among megakaryocytes, our culture data suggest that synthesis may be a restricted, or constitutively expressed property of these cells.
Animals↗
Diagnostic values of IgG-albumin index and agarose gel electrophoresis in neurologic diseases.
Sixty cerebrospinal fluids (CSFs) with paired serum samples from a variety of patients with neurologic diseases were studied using rate nephelometry to measure IgG-albumin index, and also agarose gel electrophoresis (EP) with protein blotting technique to characterize discrete IgG bands. The patients included: A) 16 cases of multiple sclerosis (MS); B) 23 cases of inflammatory diseases of the central nervous system (CNS); C) 21 cases of other non-inflammatory neurologic disorders. The average IgG-albumin index was 0.65 +/- 0.25 in Group A, 1.10 +/- 0.78 in B, and 0.50 +/- 0.12 in C. If 0.72 is taken as the upper normal limit, an increased index was found in 31%, 43% and 5% of Groups A, B and C, respectively. Discrete IgG bands were detected in 69%, 9% and 5% of Groups A, B and C, respectively. Gamma globulin bands were not always IgG, and true oligoclonal myeloma proteins were not encountered. It is concluded that both IgG-albumin index measurement and agarose gel EP are useful for diagnostic differentiation in neurologic diseases: the former, for inflammatory diseases of CNS; and the latter, for MS.
Brain Diseases↗
[Clinical and immunological observations in myotonia].
Nine patients of myotonia, 5 being myotonia dystrophica and others being myotonia congenita, were studied for their clinical manifestations and immunological function. In the cases of myotonia dystrophica, they were inherited as autosomal dominant trait; the mean age onset was 17 years. Myotonia dystrophica was a diffuse systemic disorder. In addition to myotonia, there were muscle wasting, hatchet face, frontal baldness, pseudohypertrophy, etc. In the cases of myotonia congenita, none of the parents of the patients has clinical symptoms. The mean age onset was 8 years. The disease involved mainly the skeletal muscle. The immunological functions were studied in 7 patients, including 5 myotonia dystrophica and 2 myotonia congenita. In either myotonia dystrophica or myotonia congenita, the immunological functions were impaired widely, both humoral and cellular immunity. The level of serum IgG was lowered in both diseases.
Adult↗
[Measurements of IgG and albumin in CSF and serum in various neurological diseases].
Many neurological diseases may cause increase of protein in the cerebrospinal fluid (CSF), especially IgG. Breakdown of blood brain barrier (BBB) as well as increased de novo central nervous system (CNS) IgG synthesis may result in an elevation of IgG in the CSF. To assume that the increase of CSF IgG was due to local synthesis but not to BBB damage, Link and others suggested using a more refined quotient, i.e. the IgG index. However, for evaluating local IgG synthesis, the following equation was used (modified from Tourtellotte) de novo CNS IgG synthesis II = [(C. IgG-S.IgG/278.7)-(C.Alb-S.Alb/143.1) X (S. IgG/S. Alb) X 0.43] X 5. In this study we collected 62 cases of various neurological diseases and used the nephelometer to measure their IgG and albumin level in both sera and CSF. There were 4 cases of encephalitis, 17 cases of meningitis, 16 cases of multiple sclerosis, 11 cases of other neurological diseases and 14 cases of control group. The mean value of CSF IgG was 4.1 mg/dl in control group, 21.1 in encephalitis, 11.3 in meningitis, 4.7 in multiple sclerosis and 12.9 in other neurological diseases. The mean value of IgG index was 0.52 in control group, 1.43 in encephalitis, 1.07 in meningitis, 0.68 in multiple sclerosis and 1.11 in other neurological diseases. The mean value of modified de novo CNS IgG synthesis was -0.35 mg/day in control group, 48.79 in encephalitis, 25.48 in meningitis, 6.59 in multiple sclerosis and 15.01 in other neurological diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood-Brain Barrier↗
Biosynthesis of factor V in isolated guinea pig megakaryocytes.
Although platelets contain Factor V, localized primarily in the alpha-granules, the origin of this coagulation cofactor in these cells is not known. We therefore explored whether isolated megakaryocytes could biosynthesize Factor V. Guinea pig plasma Factor V coagulant activity was demonstrated to be neutralized by human monoclonal and rabbit polyclonal antibodies directed monospecifically against human Factor V. These antibodies had been used earlier to purify human Factor V. These antibodies had been used earlier to purify human Factor V and to quantify Factor V antigen concentration, respectively (1983. Chiu, H. C., E. Whitaker, and R. W. Colman. J. Clin. Invest. 72:493-503). As determined by a competitive enzyme-linked immunosorbent assay with guinea pig plasma as a standard, Factor V solubilized from guinea pig megakaryocytes was present at 0.098 +/- 0.018 micrograms/10(5) cells. Each megakaryocyte contained about 500 times as much Factor V as is in a platelet (0.234 +/- 0.180 micrograms/10(8) platelets). The content of Factor V antigen in guinea pig plasma was greater (27.0 +/- 3.0 micrograms/ml) than that of Factor V antigen in human plasma (11.1 +/- 0.4 micrograms/ml). In contrast, human platelets contain ninefold more Factor V antigen (2.01 +/- 1.09 micrograms/10(8) platelets) than do guinea pig were 2.85 +/- 0.30 U/ml plasma, 0.022 +/- 0.012 U/10(8) platelets, and 0.032 +/- 0.03 U/10(5) megakaryocytes, compared with human values of 0.98 +/- 0.02 U/ml plasma and 0.124 +/- 0.064 U/10(8) platelets. Isolated megakaryocytes were found to contain Factor V by cytoimmunofluorescence. The megakaryocytes were incubated with [35S]methionine, and radiolabeled intracellular proteins purified were on a human anti-Factor V immunoaffinity column. The purified protein exhibited Factor V coagulant activity and neutralized the inhibitory activity of a rabbit antihuman Factor V antibody, which suggests that megakaryocyte Factor V is functionally and antigenically intact. These results indicate that Factor V is synthesized by guinea pig megakaryocytes. Nonetheless, megakaryocyte Factor V was more slowly activated by thrombin and in the absence of calcium was more stable after activation than was plasma Factor Va. Electrophoresis in sodium dodecyl sulfate and autoradiography of the purified molecule showed a major band of Mr 380,000 and a minor band of Mr 350,000, as compared with guinea pig and human plasma Factor V, where the protein had an Mr of 350,000. Both forms of Factor V were substrates for thrombin. Possible explanations for the higher molecular weight and different thrombin sensitivity and stability observed are that a precursor of Factor V was isolated or that the megakaryocyte Factor V had not been fully processed before isolation.
Animals↗
Effect of myasthenia serum and anti-acetylcholine receptor monoclonal antibody on the distributions of T-cell subsets in myasthenia patients and normal subjects.
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Adolescent↗
Immune complexes containing factor V in a patient with an acquired neutralizing antibody.
An 82-year-old woman presented with extensive hematomas and melena associated with markedly decreased plasma factor V coagulant activity (FV:C). Using a competitive enzyme-linked immunosorbent assay developed in our laboratory, we made serial measurements of factor V antigen (FV:Ag) in plasma and found it to be normal or elevated. The patient's plasma was demonstrated to contain an IgG antibody that could neutralize FV:C in normal plasma. The antibody was of restricted heterogeneity (IgG1, IgG2,kappa). Circulating immune complexes containing antibody to factor V and FV:Ag were demonstrated directly in the plasma by immunoelectrophoresis with polyclonal monospecific antibody and with a monoclonal antibody using an enzyme-linked immunosorbent assay. Presence of neutralizing antibody could be demonstrated in vitro even at times when FV:C was within normal limits by heat inactivation of FV:C. Treatment with plasma and platelet transfusions as well as plasmapheresis induced definite but transient elevation of FV:C. Steroid therapy lowered the neutralizing antibody concentration and produced a rapid and persistent elevation of FV:C during two separate hospitalizations. This report describes a patient in whom levels of FV:Ag have been serially measured, and the presence of circulating immune complexes consisting of factor V and a neutralizing antibody have been directly demonstrated.
Aged↗
Heterogeneity of human factor V deficiency. Evidence for the existence of antigen-positive variants.
Functional human Factor V has been purified using a rapid immunoaffinity method. Following barium citrate adsorption of plasma, Factor V was precipitated with polyethylene glycol at a concentration between 5 and 14%. The resulting preparation was applied to a column containing an immobilized immunoadsorbent consisting of an IgG fraction containing a naturally occurring human monoclonal (IgG(4)lambda) antibody with inhibitory activity against human Factor V. The solid phase immunoglobulin quantitatively bound Factor V from human plasma. The bound Factor V was effectively eluted with a Tris buffer pH 7.2 containing 1.2 M NaCl and 1 M alpha-methyl-D-mannoside. The isolated native Factor V with high specific activity (92 U/mg) showed a single band (M(r), 350,000) on both reduced and nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Factor V was purified 5,100-fold over plasma with an overall yield of 77%. The purified Factor V when subjected to thrombin activation exhibited an 18-fold increase in coagulant activity. The isolated Factor V neutralized the inhibitory activities of the monoclonal antibody that was used to purify it, as well as the rabbit antibodies produced by immunizing the animals with the purified Factor V. Immunoelectrophoresis of purified Factor V against the polyclonal rabbit antiserum resulted in a single precipitin arc of identical mobility to the Factor V in normal human plasma. Analysis by double immunodiffusion showed a line of identity between plasma and purified Factor V and crossed immunoelectrophoresis showed a single species in normal plasma.A competitive enzyme-linked immunosorbent assay using the rabbit antibody against Factor V was applied to quantify Factor V antigen level in human plasma. Reconstitution of congenitally deficient or immunodepleted plasma with normal plasma or purified Factor V gave parallel dose-response curves. In 14 normal plasma the coagulant activity was 0.98+/-0.02 U/ml (mean+/-SEM) and antigen concentration was 11.1+/-0.4 mug/ml. A pool of 14 patients with congenital Factor V deficiency were studied. 10 patients had Factor V antigen ranging from 1.0 to 2.4 mug/ml with corresponding coagulant activities (0-0.17 U/ml) indicating a low concentration of normal Factor V, presumably due to decreased synthesis or increased degradation. When these patient plasmas and the normal plasmas were analyzed together an excellent correlation (r = 0.97, P < 0.01) was obtained. However, four patients with coagulant activity (0-0.08 U/ml) had Factor V antigen concentrations ranging from 4.4 to 6.1 mug/ml, indicating the presence of a reduced concentration of abnormal Factor V protein. The presence of patients with antigen similar in concentration to coagulant activity and antigen in excess of Factor V activity indicates the heterogeneity of congenital Factor V deficiency.
Animals↗
[Humoral and cell-mediated immunities in epileptic patients (author's transl)].
Humoral and cell-mediated immunities were studied in 50 epileptic patients receiving phenytoin treatment and in 20 normals. The mean serum concentrations of IgG, IgA and IgM showed no significant difference between these two groups; however, abnormally low serum IgA (less than 125 mg/dl) was found in 10 patients (10/50, 20%) and in one of them serum IgA was less than 50 mg/dl (1/50, 2%). The serum IgA was related neither to the duration of phenytoin therapy nor to the serum concentration of the drug. The mean serum C3 value was lower in the patient group than in the normals. The mean percentages of T cells, Tmu cells, T gamma cells and monocytes were also lower in the patients, especially in those with serum level of phenytoin over 20 micrograms/ml. These data indicate that phenytoin can suppress the cell-mediated immunity, whereas certain genetic factors, in addition to the effect of phenytoin, may contribute to the change of serum immunoglobulin levels in the epileptics. The incidence of positive antinuclear antibody among the epileptics was 18%, which was much higher than that in the general population. The occurrence of autoantibody did not correlate with the serum concentration of phenytoin.
Adolescent↗
Imbalances in T-cell subpopulations in myasthenia gravis.
Distributions of peripheral blood lymphocyte subpopulations and T-cell subsets were studied in 38 patients with myasthenia gravis (MG) and 23 healthy controls. T cells were detected by rosette formation with sheep red blood cells and B cells with erythrocyte-antibody-complement (EAC) complexes. T mu cells were identified by rosette formation of T cells with Ox RBC-IgM complexes, and T gamma cells with Ox RBC-IgG complexes. The means of total lymphocyte count and active T cell percentage were marginally significantly lower in MG patients than in normal controls (0.05 less than P less than 0.1). The mean percentage of T mu cells was higher in MG patients than in controls (50.2 +/- 11.8% vs. 38.5 +/- 15.3%, P less than 0.01), whereas that of T gamma cells in the former was lower than that in the latter (20.4 +/- 7.1% vs. 27.6 +/- 6.2%, P less than 0.001). Thus, the loss of regulatory suppressor T cells and the increase of helper T cells in the patients are in favour of regarding MG as an autoimmune disease. The fact that the percentage of T gamma cells was significantly decreased in MG patients after autologus serum incubation, and that no such a phenomenon was seen in normal controls, may suggest a possible role of serum factors in the pathogenesis of MG.
Adolescent↗
[The correlation between autoantibodies and leukocyte migration index in myasthenia gravis (author's transl)].
Sera from 38 myasthenic patients and 15 non-myasthenic controls were surveyed by indirect immunofluorescence technique for reactivity against skeletal muscle, nuclei and mitochondria. Cell-mediated response to purified muscle antigen was detected by leukocyte migration inhibition assay. The positive rates for antiskeletal antibody (ASMA), antinuclear antibody (ANA), and antimitochondrial antibody (AMA) were 50%, 10.5% and 0%, respectively, in the myasthenic patients, and were 13.3%, 6.6% and 0%, respectively, in the controls. The mean titer of antiskeletal muscle antibody was 1:9.8 in the myasthenic patients and 1:1.8 in the controls. Both the positive rate and the mean titer of ASMA were higher and the migration index was lower in the patients with thymoma or thymic hyperplasia. To the contrary, among the group treated with corticosteroids, the correlation of the positive rate and mean titer of ASMA to migration index revealed a marginally significantly negative linear correlation (y = -0.72 chi + 84.69, r = -0.80, 0.1 greater than p greater than 0.05). This meant that the higher positive rate of ASMA was usually associated with the lower migration index. The facts of higher positive rate of ASMA in myasthenic patients and its negative correlation to migration index gave supportive evidence for a possible role of ASMA in the pathogenesis of myasthenia gravis.
Adolescent↗
Human leukocyte histamine release assays with whole ragweed and Alternaria antigens using Technicon autoanalyzer II.
A simple and commercially available automated technique for fluorometric analysis of histamine is described. It is applicable to histamine release experiments utilizing washed leukocytes, and analyzes 15 samples/h at histamine concentrations between 1 and 1000 ng/ml with a mean variance between 0.5% and 18%. This technique is applied to a cross sectional study of leukocytes from 14 ragweed sensitive patients (7 on and 7 off immunotherapy) as well as five normals. It was also applied to 17 Alternaria-sensitive patients (4 on and 12 off immunotherapy) in addition to six normals. While antigen induced in histamine release clearly separated the sensitive group from the normals, it did not correlate with immunotherapy, and a considerable variation was seen in the sensitive patients of both the treated and untreated groups.
Alternaria↗
Human cerebral asymmetries evaluated by computed tomography.
The handedness of seventy-five persons without evidence of neurological disease, was assessed with a standardised test. An analysis of the CT scans of the same persons was performed to determine (1) presence and lateralisation of frontal and occipital "petalia," (2) width of frontal and occipital lobes of each hemisphere, (3) direction of straight sinus deviation. Results suggest that handedness and cerebral asymmetries are independent variables. There were no significant differences between right-handers and non-right-handers. Also there were no significant differences between strongly left-handed and ambidextrous individuals, nor were there differences between right-handers with or without family history of left-handedness. Irrespective of handedness, left occipital "petalia" was more common than right (p < 0.01), right frontal petalia was more common than left (p < 0.01), and straight sinus deviation was more commonly toward the right. The study does not support the concept that cerebral "symmetry" or "reverse asymmetry" are associated with left-handedness or ambidexterity. The noted asymmetries are more likely to be direct correlates of cerebral language dominance, than of handedness. Furthermore, the possibility that outside forces acting on the bone contributes to the asymmetries cannot be excluded. CT scan may be of value as a direct predictor of cerebral dominance.
Cerebral Cortex↗
Leukocyte migration response to purified muscle antigen in myasthenia gravis patients.
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Adolescent↗
Effect of fatty acid modifications of cultured hepatoma cells on susceptibility to complement-mediated cytolysis.
The fatty acid composition of Morris Hepatoma 7777 cells was modified by exposure to culture media that were supplemented with 0.1 to 0.36 mM oleic or linoleic acid for 5 days. Changes occurred in the fatty acid composition of both the cellular phospholipid and the neutral lipid fractions. Exposure to linoleic acid caused a large increase in the polyunsaturated fatty acid content of the cell lipids, whereas enrichment in monoenoic fatty acids occurred when the cells were exposed to high levels of oleic acid. Cellular phospholipid content decreased, cholesterol content did not change, and triglyceride content increased as a result of fatty acid supplementation. The fatty acid-modified cells showed increased susceptibility to complement-mediated cytolysis as compared with control cells grown in unsupplemented culture media. The extent of the increase in susceptibility to cytolysis depended on the degree of lipid modification and also on the cell number and antibody titer used in the assay. Cells enriched with linoleic acid were the most susceptible, but oleic acid enrichment also produced increased susceptibility to immune cytolysis. The kinetic study showed that the initial rate of cytolysis was higher in fatty acid-modified cells than in the control cells. There was no difference in the osmotic fragility of the control and fatty acid-modified cells. These results indicate that changes in the lipid composition of a target cell can influence its susceptibility to complement-dependent cytolysis.
Animals↗