Complement is an acute-reacting non-specific effector system. Activation and consumption of individual components of this multicomponent system occur secondarily to specific complement fixing events. The complement system is therefore an indirect and imprecise diagnostic tool and can be used clinically only as a general indicator of the severity of a particular disease or as a monitor of its progress. An exception is the case of the very rare inherited complement deficiencies where examination of the system does become directly diagnostic. The 11 proteins of the classical pathway, three additional ones of the alternative pathway
{"title":"Complement activation profiles in disease.","authors":"D L Brown","doi":"10.1136/jcp.s3-13.1.116","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.116","url":null,"abstract":"Complement is an acute-reacting non-specific effector system. Activation and consumption of individual components of this multicomponent system occur secondarily to specific complement fixing events. The complement system is therefore an indirect and imprecise diagnostic tool and can be used clinically only as a general indicator of the severity of a particular disease or as a monitor of its progress. An exception is the case of the very rare inherited complement deficiencies where examination of the system does become directly diagnostic. The 11 proteins of the classical pathway, three additional ones of the alternative pathway","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"116-9"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11379197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cold-reactive lymphocytotoxic antibodies are present in the serum of most patients with systemic lupus erythematosus (SLE) (Mittal et al., 1970; Terasaki et al., 1970). They appear to be equally cytotoxic for autologous and heterologous lymphocytes (Stastny and Ziff, 1971). Studies of the nature of these antibodies showed that their cytotoxic effect is temperature-dependent and maximal at 15°C, that their immunoglobulin class is IgM, and that they are equally reactive with T and B lymphocytes (Winfield et al., 1975a). Studies of the clinical significance of cold-reactive lymphocytotoxic antibodies in SLE have shown a consistent association with neuropsychiatric complications (Butler et al., 1972; Bluestein and Zvaifier, 1976; Bresnihan et al., 1977b). In other respects, however, clinical studies have been inconclusive, which may partly be related to the retrospective nature of most series. Previous studies have suggested an association between cold-reactive lymphocytotoxic antibodies and lymphopenia (Winfield et al., 1975b; Utsinger, 1976). A detailed prospective clinical analysis of SLE began at Hammersmith Hospital in 1973. In all, 50 patients have been investigated, and their clinical features have been described elsewhere (Grigor et al., 1978). This report relates the clinical features in these patients to the presence of lymphocytotoxic antibodies.
{"title":"Lymphocytotoxic antibodies in systemic lupus erythematosus: their clinical significance.","authors":"B Bresnihan, R R Grigor, G R Hughes","doi":"10.1136/jcp.s3-13.1.112","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.112","url":null,"abstract":"Cold-reactive lymphocytotoxic antibodies are present in the serum of most patients with systemic lupus erythematosus (SLE) (Mittal et al., 1970; Terasaki et al., 1970). They appear to be equally cytotoxic for autologous and heterologous lymphocytes (Stastny and Ziff, 1971). Studies of the nature of these antibodies showed that their cytotoxic effect is temperature-dependent and maximal at 15°C, that their immunoglobulin class is IgM, and that they are equally reactive with T and B lymphocytes (Winfield et al., 1975a). Studies of the clinical significance of cold-reactive lymphocytotoxic antibodies in SLE have shown a consistent association with neuropsychiatric complications (Butler et al., 1972; Bluestein and Zvaifier, 1976; Bresnihan et al., 1977b). In other respects, however, clinical studies have been inconclusive, which may partly be related to the retrospective nature of most series. Previous studies have suggested an association between cold-reactive lymphocytotoxic antibodies and lymphopenia (Winfield et al., 1975b; Utsinger, 1976). A detailed prospective clinical analysis of SLE began at Hammersmith Hospital in 1973. In all, 50 patients have been investigated, and their clinical features have been described elsewhere (Grigor et al., 1978). This report relates the clinical features in these patients to the presence of lymphocytotoxic antibodies.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"112-5"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11508069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypogammaglobulinaemia refers to the low levels of circulating antibodies associated with a decreased gammaglobulin zone on electrophoresis. Since IgG is the predominant immunoglobulin a deficiency of it will most readily affect the gammaglobulin zone. Deficiencies of IgA and IgM will not necessarily result in a visual decrease in the latter. For practical purposes the clinically important states are the low immunoglobulin levels associated with disease. For IgG, severe hypogammaglobulinaemia is defined as a serum level in an adult of less than 2.0 g/l (MRC Working Party, 1969). At this level 70% of patients suffer severe infection (Hobbs, 1968). During the first six months of life infants commonly have levels below 2-0 g/l, so that in this period 1-0 g/l is better taken as the critical level. If the onset occurs before the age of 3 years (during which time children are building up their memory bank of IgG responses) the residual IgG is poorer in quality than in an adult and infection is much more of a problem. In adults the quality can be so good that down to 1.0 g/l there is no obvious infection, but the usually preceding loss of IgA and IgM can predispose to gut disturbances and malabsorption and loss of weight are common. In some cases primary humoral responses may be affected and infection with organisms not previously encountered may occur long before low levels of immunoglobulins are seen. Hypogammaglobulinaemia may be a result of a longer term inhibition of the humoral immune system, which may be preceded in the early stages by failure to mount a primary response. A normal gammaglobulin level does not necessarily exclude specific humoral response deficiencies (Hobbs, 1966; Hobbs, 1969). The immunoglobulin deficiency can arise from a variety of immunological abnormalities, which may be genetically determined or may be secondary to some other condition. Secondary hypogammaglobulinaemia is 10-100 times more common than the primary forms. In this paper we shall consider clinical conditions which give rise to secondary hypogammaglobulinaemia, with particular reference to the mechanisms producing it. These may be considered under five broad headings (Table 1; Hobbs, 1971).
{"title":"Mechanisms in secondary hypogammaglobulinaemia.","authors":"P G Riches, J R Hobbs","doi":"10.1136/jcp.s3-13.1.15","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.15","url":null,"abstract":"Hypogammaglobulinaemia refers to the low levels of circulating antibodies associated with a decreased gammaglobulin zone on electrophoresis. Since IgG is the predominant immunoglobulin a deficiency of it will most readily affect the gammaglobulin zone. Deficiencies of IgA and IgM will not necessarily result in a visual decrease in the latter. For practical purposes the clinically important states are the low immunoglobulin levels associated with disease. For IgG, severe hypogammaglobulinaemia is defined as a serum level in an adult of less than 2.0 g/l (MRC Working Party, 1969). At this level 70% of patients suffer severe infection (Hobbs, 1968). During the first six months of life infants commonly have levels below 2-0 g/l, so that in this period 1-0 g/l is better taken as the critical level. If the onset occurs before the age of 3 years (during which time children are building up their memory bank of IgG responses) the residual IgG is poorer in quality than in an adult and infection is much more of a problem. In adults the quality can be so good that down to 1.0 g/l there is no obvious infection, but the usually preceding loss of IgA and IgM can predispose to gut disturbances and malabsorption and loss of weight are common. In some cases primary humoral responses may be affected and infection with organisms not previously encountered may occur long before low levels of immunoglobulins are seen. Hypogammaglobulinaemia may be a result of a longer term inhibition of the humoral immune system, which may be preceded in the early stages by failure to mount a primary response. A normal gammaglobulin level does not necessarily exclude specific humoral response deficiencies (Hobbs, 1966; Hobbs, 1969). The immunoglobulin deficiency can arise from a variety of immunological abnormalities, which may be genetically determined or may be secondary to some other condition. Secondary hypogammaglobulinaemia is 10-100 times more common than the primary forms. In this paper we shall consider clinical conditions which give rise to secondary hypogammaglobulinaemia, with particular reference to the mechanisms producing it. These may be considered under five broad headings (Table 1; Hobbs, 1971).","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"15-22"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11598742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The association between hypergammaglobulinaemia and raised serum viscosity has been recognised for more than 40 years. Waldenstrom (1944) described three patients in whom macroglobulinaemia was associated with increased serum viscosity, and even earlier than this there had been reports of raised plasma viscosity in myelomatosis (Albers, 1937). Since these early reports many of the clinical features of macroglobulinaemia have been recognised to be a direct consequence of the increased plasma viscosity, and in 1965 Fahey and his colleagues defined the condition now known as the hyperviscosity syndrome (Fahey et al., 1965). Initially it was believed that the hyperviscosity syndrome (HVS) was almost invariably associated with Waldenstrom's macroglobulinaemia and that it was a rare complication of myelomatosis. During the last few years, however, it has become increasingly recognised as a complication of certain types of myelomatosis (Preston et al., 1978; Tuddenham et al., 1974).
{"title":"Antibody-mediated tissue damage. Hyperviscosity and other complications of paraproteinaemia.","authors":"F E Preston","doi":"10.1136/jcp.s3-13.1.85","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.85","url":null,"abstract":"The association between hypergammaglobulinaemia and raised serum viscosity has been recognised for more than 40 years. Waldenstrom (1944) described three patients in whom macroglobulinaemia was associated with increased serum viscosity, and even earlier than this there had been reports of raised plasma viscosity in myelomatosis (Albers, 1937). Since these early reports many of the clinical features of macroglobulinaemia have been recognised to be a direct consequence of the increased plasma viscosity, and in 1965 Fahey and his colleagues defined the condition now known as the hyperviscosity syndrome (Fahey et al., 1965). Initially it was believed that the hyperviscosity syndrome (HVS) was almost invariably associated with Waldenstrom's macroglobulinaemia and that it was a rare complication of myelomatosis. During the last few years, however, it has become increasingly recognised as a complication of certain types of myelomatosis (Preston et al., 1978; Tuddenham et al., 1974).","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"85-9"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.85","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11598748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lymphocytes in the blood and central lymphoid tissues participate in a variety of host defence mechanisms against virus infections. These include cell-mediated reactions against infected cells and particularly those involving cytotoxic T lymphocytes, co-operation in the induction of antibody responses, and the production of immune interferon. During the early stages of many virus infections the invading virus replicates in lymphoreticular cells, and this is of advantage to the host because of the increased efficiency with which the resulting immune responses are induced. Indeed, in many virus infections of man viral antigens can readily be detected in circulating blood lymphocytes. Nevertheless, this association with lymphocytes does not always benefit the host and may increase the virulence of the virus and enhance its persistence. There are many examples of experimental virus infections in which this train of events has been observed. For example, in inbred mouse strains infected with lymphocytic choriomeningitis (LCM) virus, either by intracerebral injection at birth or congenital in-utero infection, virus can be detected in all the major subpopulations of mononuclear cells-namely, T lymphocytes, B lymphocytes, and cells of the monocyte-macrophage series (Doyle and Oldstone, 1978). This infection of mononuclear cells of the peripheral and central lymphoid system persists throughout the life of the animal. It has also been suggested that by infecting lymphocytes the virus may on occasion prevent the induction of an appropriate immune response to the infecting agent. This suppression may be more likely if the host is infected at a time of immunological immaturity determined by the age at which the animal is infected or by other factors that have a general immunosuppressive effect. In other words, the virus may delete precisely that clone of reactive cells which is programmed to respond to the invading agent. Another undesirable consequence of lymphocyte infection is the dissemination of virus in association with cells. It has been proposed, for example, that canine distemper virus enters the central nervous system in this manner (Summers et al., 1978). To demonstrate that similar considerations apply to 39 human infections by pathogenic viruses is obviously more difficult. However, the damage to the immune system that may accompany congenital rubella infection is a clear indication that the same principles apply. Moreover, transient immunosuppression accompanies many virus infections of man. There are now precise means of examining the interactions between different viruses and human lymphocytes, and the findings of such experiments are reviewed in this paper. The results are considered in two waysfirstly, the effects of virus infection on lymphocyte function and, secondly, the effects of residence in lymphocytes on the biological properties of viruses.
{"title":"Lymphocyte function and virus infections.","authors":"A M Denman","doi":"10.1136/jcp.s3-13.1.39","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.39","url":null,"abstract":"Lymphocytes in the blood and central lymphoid tissues participate in a variety of host defence mechanisms against virus infections. These include cell-mediated reactions against infected cells and particularly those involving cytotoxic T lymphocytes, co-operation in the induction of antibody responses, and the production of immune interferon. During the early stages of many virus infections the invading virus replicates in lymphoreticular cells, and this is of advantage to the host because of the increased efficiency with which the resulting immune responses are induced. Indeed, in many virus infections of man viral antigens can readily be detected in circulating blood lymphocytes. Nevertheless, this association with lymphocytes does not always benefit the host and may increase the virulence of the virus and enhance its persistence. There are many examples of experimental virus infections in which this train of events has been observed. For example, in inbred mouse strains infected with lymphocytic choriomeningitis (LCM) virus, either by intracerebral injection at birth or congenital in-utero infection, virus can be detected in all the major subpopulations of mononuclear cells-namely, T lymphocytes, B lymphocytes, and cells of the monocyte-macrophage series (Doyle and Oldstone, 1978). This infection of mononuclear cells of the peripheral and central lymphoid system persists throughout the life of the animal. It has also been suggested that by infecting lymphocytes the virus may on occasion prevent the induction of an appropriate immune response to the infecting agent. This suppression may be more likely if the host is infected at a time of immunological immaturity determined by the age at which the animal is infected or by other factors that have a general immunosuppressive effect. In other words, the virus may delete precisely that clone of reactive cells which is programmed to respond to the invading agent. Another undesirable consequence of lymphocyte infection is the dissemination of virus in association with cells. It has been proposed, for example, that canine distemper virus enters the central nervous system in this manner (Summers et al., 1978). To demonstrate that similar considerations apply to 39 human infections by pathogenic viruses is obviously more difficult. However, the damage to the immune system that may accompany congenital rubella infection is a clear indication that the same principles apply. Moreover, transient immunosuppression accompanies many virus infections of man. There are now precise means of examining the interactions between different viruses and human lymphocytes, and the findings of such experiments are reviewed in this paper. The results are considered in two waysfirstly, the effects of virus infection on lymphocyte function and, secondly, the effects of residence in lymphocytes on the biological properties of viruses.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"39-47"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11444286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Severe combined immunodeficiency (SCID), although a relatively rare congenital disorder, is an important disease because it has taught us much about the function and interactions of T and B lymphocytes. It is also the only disease where consistently encouraging results have been obtained with bone marrow transplantation. Furthermore, it was the first immunodeficiency disorder to be identified with an enzyme deficiency and is the first disease to be successfully treated by enzyme replacement therapy. Isolated T cell defects may appropriately be discussed together with SCID, particularly since it is now apparent that some SCID patients have a predominantly T cell defect. Now that in-vitro tests are available to analyse both T and B cell functions separately in these patients the classification is likely to change and become more precise in the next few years. A major advance in understanding the differences between T and B cells at a biochemical level has come from the finding of a purine enzyme deficiency which causes a predominantly T cell defect. This should ultimately lead to the production of drugs which will selectively affect T or B lymphocytes.
{"title":"Combined immunodeficiency and thymic abnormalities.","authors":"A D Webster","doi":"10.1136/jcp.s3-13.1.10","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.10","url":null,"abstract":"Severe combined immunodeficiency (SCID), although a relatively rare congenital disorder, is an important disease because it has taught us much about the function and interactions of T and B lymphocytes. It is also the only disease where consistently encouraging results have been obtained with bone marrow transplantation. Furthermore, it was the first immunodeficiency disorder to be identified with an enzyme deficiency and is the first disease to be successfully treated by enzyme replacement therapy. Isolated T cell defects may appropriately be discussed together with SCID, particularly since it is now apparent that some SCID patients have a predominantly T cell defect. Now that in-vitro tests are available to analyse both T and B cell functions separately in these patients the classification is likely to change and become more precise in the next few years. A major advance in understanding the differences between T and B cells at a biochemical level has come from the finding of a purine enzyme deficiency which causes a predominantly T cell defect. This should ultimately lead to the production of drugs which will selectively affect T or B lymphocytes.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"10-4"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11264453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this review I shall survey various properties of lymphocytes which allow clear distinctions to be drawn between different lymphocyte subsets. I shall discuss only thymus-derived (T) lymphocytes since these cells appear to play a key role in regulating the activities of other lymphoid cells (B cells and macrophages) as well as carrying out effector functions themselves. In the first section I shall discuss murine T lymphocytes since most of the most decisive experimental studies have been carried out in this species, while the concluding section of the review will deal with human T lymphocyte heterogeneity. Thymus
{"title":"Functional subsets of lymphocytes.","authors":"P C Beverley","doi":"10.1136/jcp.s3-13.1.59","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.59","url":null,"abstract":"In this review I shall survey various properties of lymphocytes which allow clear distinctions to be drawn between different lymphocyte subsets. I shall discuss only thymus-derived (T) lymphocytes since these cells appear to play a key role in regulating the activities of other lymphoid cells (B cells and macrophages) as well as carrying out effector functions themselves. In the first section I shall discuss murine T lymphocytes since most of the most decisive experimental studies have been carried out in this species, while the concluding section of the review will deal with human T lymphocyte heterogeneity. Thymus","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"59-62"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.59","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11379036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myasthenia gravis (MG) is a disorder of the neuromuscular junction characterised by weakness which increases on effort and is improved by rest and anticholinesterase treatment. Thymic abnormality with increased numbers of germinal centres is common, thymoma occurs in about 15% of cases, and thymectomy is often beneficial in thosewithoutatumour. The condition is commoner in women and typically becomes evident in early adult life. It can, however, present at any age, and there is a rare congenital form in which weakness dates from the neonatal period (see below). For a recent review see Drachman (1978). The main features of the normal and myasthenic neuromuscular junction are shown in Fig. 1. In MG the presynaptic nerve terminals are essentially normal although there is often elongation of the endplate with changes in the number of terminal expansions. There are, however, marked postsynaptic changes which include simplification of the postsynaptic membrane and loss of the secondary folds (Santa et al., 1972). These are associated with a decrease in the total number of acetylcholine receptors, as detected by oa-bungarotoxin binding (Fambrough et al., 1973), which are probably also reduced in number per unit area of postsynaptic membrane (Ito et al., 1978a). These changes are responsible for the underlying physiological defect in MG-namely, a pronounced reduction in the sensitivity to acetylcholine (ACh). As a result the effect of each packet or quantum of ACh (the miniature endplate potential) is reduced (Elmqvist et al., 1964) and the effect of nerve impulse-evoked release of 50 or so packets (the endplate potential) is insufficient to activate the muscle (for a fuller description, see Ito et al., 1978b).
{"title":"Tissue-specific antibodies in myasthenia gravis.","authors":"A Vincent","doi":"10.1136/jcp.s3-13.1.97","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.97","url":null,"abstract":"Myasthenia gravis (MG) is a disorder of the neuromuscular junction characterised by weakness which increases on effort and is improved by rest and anticholinesterase treatment. Thymic abnormality with increased numbers of germinal centres is common, thymoma occurs in about 15% of cases, and thymectomy is often beneficial in thosewithoutatumour. The condition is commoner in women and typically becomes evident in early adult life. It can, however, present at any age, and there is a rare congenital form in which weakness dates from the neonatal period (see below). For a recent review see Drachman (1978). The main features of the normal and myasthenic neuromuscular junction are shown in Fig. 1. In MG the presynaptic nerve terminals are essentially normal although there is often elongation of the endplate with changes in the number of terminal expansions. There are, however, marked postsynaptic changes which include simplification of the postsynaptic membrane and loss of the secondary folds (Santa et al., 1972). These are associated with a decrease in the total number of acetylcholine receptors, as detected by oa-bungarotoxin binding (Fambrough et al., 1973), which are probably also reduced in number per unit area of postsynaptic membrane (Ito et al., 1978a). These changes are responsible for the underlying physiological defect in MG-namely, a pronounced reduction in the sensitivity to acetylcholine (ACh). As a result the effect of each packet or quantum of ACh (the miniature endplate potential) is reduced (Elmqvist et al., 1964) and the effect of nerve impulse-evoked release of 50 or so packets (the endplate potential) is insufficient to activate the muscle (for a fuller description, see Ito et al., 1978b).","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"97-106"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.97","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11598751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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