Smooth muscle antibody in bronchial asthma

Circulating IgG antibodies reactive with smooth muscle antigens have been found in 21% of patients with intrinsic asthma contrasting with an incidence of 2·9% in extrinsic asthma and 3·7% in chronic bronchitis. This antibody is neither organ nor species specific and does not cross-react with cardiac or skeletal muscle.

In some sera the pattern of fluorescence is distinct from that commonly seen in patients with liver disease and has a `streaky' appearance outlining the surface of individual muscle fibres, similar to the inter-myofibrillary pattern of some cardiac antibodies.

Other autoantibodies were found in seven of the eleven positive sera, suggesting a heightened immunological reactivity in these patients with intrinsic asthma.

There is no evidence from this study that the presence of smooth muscle antibodies is related to pathogenesis of asthma.

     

Autoantibodies in three populations of Burkitt''s lymphoma patients.

Autoantibodies against actin, intermediate filaments, single stranded DNA and histones were found in the sera of Burkitt's lymphoma (BL) patients and normal controls from tropical Africa, where there is a high incidence of BL. Both groups had significantly higher levels of these autoantibodies than Caucasian normal controls or patients with other malignant diseases, as well as Epstein-Barr (EB) virus positive and EB virus negative BL patients from regions of North Africa and France where the incidence is lower than in tropical Africa. No linear correlation could be seen between autoantibody levels and anti-EB virus/VCA or EBNA titres in patients and controls from tropical Africa. The results suggest that a factor independent of EB virus causes an immunological imbalance and autoantibody production in the population from tropical Africa. This factor may be one of several which results in a high incidence of BL in tropical Africa.     

Nuclear DNA content of non-endemic Burkitt''s lymphoma.

The nuclear DNA content of 26 non-endemic Burkitt's lymphomas was studied by flow cytometry. Eighteen of the tumours showed a pattern characteristic for diploid chromosome distribution, while eight of the tumours were aneuploid. Six of the aneuploid tumours showed an almost diploid, aneuploid DNA index, while two were tetraploid tumours. Patients with aneuploid tumours had a significantly worse prognosis (p less than 0.005) than those with diploid tumours. One of the aneuploid tumours was positive for Epstein-Barr virus DNA.     

Circumstances favoring jaw tumors in Burkitt''s lymphoma

In Burkitt's lymphoma, dental structures may provide the route for Epstein-Barr virus (EBV) in saliva to penetrate the jaws, thereby promoting tumor formation. In children, EBV could enter tooth sockets exposed following deciduous tooth loss and thereby contact jaw marrow lymphocytes stimulating neoplastic transformation. Marrow contact by EBV probably also occurs through carious teeth. Jaw tumors are rare in adults because their jaw marrow is no longer hematopoietic and so lacks the lymphoid substrate for the virus. In adults, jaw marrow lymphocytosis, as accompanies infectious mononucleosis and perhaps malaria, or which could develop around the roots of carious teeth having chronic periapical infection, could provide the substrate for EBV. EBV could then contact the jaw marrow lymphocytes when teeth are extracted and so favor jaw tumor development. Therefore, prevention of dental caries might reduce jaw tumor prevalence in Burkitt's lymphoma except among children ages 6-13 whose jaw marrow would unavoidably become infected by salivary EBV when the latter is present at the time of deciduous tooth loss.     

Reactivity of radioiodinated serum antibody from Burkitt's lymphoma and nasopharyngeal carcinoma patients against culture lines derived from Burkitt's lymphoma

The IgG serum immunoglobulin fraction of two Burkitt's lymphoma (Mutua and Kiliopa) and one African nasopharyngeal carcinoma patient (Kipkoech) was conjugated to iodine-131 (¹³¹I). It is known from previous studies with fluorescein labelled conjugates that all three sera contain antibody against the Epstein–Barr virus (EBV)-associated membrane antigen complex, present on the surface of lymphoblastoid cells in EBV-carrier cultures. All three radioiodinated conjugates attached to live cells of an EBV-carrying Burkitt line (Maku), but not to EBV-free Raji cells. A Swedish control serum (Berith) did not block the binding of any of the three conjugates, whereas unconjugated sera of Mutua, Kiliopa and Kipkoech showed various degrees of blocking and cross-blocking. The blocking patterns were in good agreement with previous tests, performed with the same sera against their fluorescein conjugated derivatives.

Antibody release tests, involving preincubation of live cells with one of the three conjugates, followed by incubation with unlabelled serum revealed a certain `hierarchy' between the three sera with regard to their ability to displace radioiodinated surface-coupled immunoglobulin. This ability could be related to the competitive behaviour of the same sera in the cross blocking tests. The results are believed to reflect differences in the affinity of the three antibodies, due either to differences in fit in relation to the surface antigen(s) carried by the Maku target cell, or to differences in the duration of immunization in the three patients.

     

Centromere spreading and out-of-phase chromatid separation in Burkitt's lymphoma and nasopharyngeal carcinoma

Chromosomes with various degrees of centromere spreading and completely separated chromatids, as well as metaphasic chromosomes, were observed simultaneously in the same Burkitt's lymphoma cell. In another study, a pair of prematurely and completely separated chromatids was found in a metaphase of nasopharyngeal carcinoma cell. Based on these and other observations, the possible significance of centromere spreading and out-of-phase sister chromatid separation in the origin of chromosome nondisjunction in tumor cells is suggested and discussed.     

Smooth muscle autoantibodies and autoantigens.

Smooth muscle autoantibody (SMA) was first found in the sera of patients with chronic active hepatitis and subsequently in the sera of patients with other autoimmune liver diseases, viral infections, certain cancers, heroin addicts and female infertility. SMA from patients with chronic active hepatitis reacts with many muscle and 'non-muscle' tissues while SMA from patients with other diseases usually reacts only with smooth muscle. These differences in immunofluorescent staining reactions suggest that SMA is a heterogeneous group of autoantibodies reactive with different smooth muscle autoantigens. As further evidence for this are findings that broad-reacting SMA can be absorbed out by actin, whereas autoantibodies reactive only with smooth muscle cannot, and that different SMAs give different immunofluorescent staining patterns using fibroblasts in tissue culture. Such staining patterns correspond to reactivity with either microfilaments, microtubules or intermediate filaments, ubiquitous cytoplasmic structures which make up the 'cytoskeleton'. Autoantibodies to actin-like microfilaments appear specific for chronic active hepatitis, autoantibodies to microtubules occur in infectious mononucleosis whereas autoantibodies to intermediate filaments occur in infectious hepatitis, chickenpox, measles and mumps. Predictably, future studies will show that presence of SMA with specificities for other proteins in the three types of cytoplasmic filaments, and given more information on antigenicity of the proteins and pathogenicity of the corresponding autoantibodies.     

Nasopharyngeal carcinoma in situ in nasopharyngeal carcinoma.

AIMS: To assess the presence of carcinoma in situ (CIS) in patients with nasopharyngeal carcinoma (NPC) and to see if the number of biopsy sites facilitates detection of CIS. METHODS: Formalin fixed, paraffin wax embedded biopsy specimens (n = 285) from 187 patients with NPC in 1987 were studied for the presence of CIS as well as for the histological assessment of the subtype of CIS. RESULTS: Fifteen (8.0%) patients had CIS, representing 8.3% of all new patients with NPC and 11.6% of patients with persistent disease or relapse. CIS was undifferentiated or poorly differentiated, no cases of well differentiated squamous cell CIS were identified. There was no significant difference in the incidence of CIS when multiple endoscopic biopsy specimens were taken rather than single forceps biopsy specimens. CONCLUSIONS: CIS can only be identified in a few patients with NPC largely because of late presentation with advanced disease at the time of diagnosis and the focal nature of the dysplastic process. The presence of dysplasia in relapses of NPC suggests that these tumours may be second growths rather than regrowths of a primary tumour.     

Smooth muscle in lymph node capsule and trabeculae.

This study focuses on the confusion in existing literature concerning the presence of smooth muscle in the capsule and trabeculae of lymph nodes. Human and bovine nodes from several anatomical areas and several individuals of each species were examined by conventional light, electron and fluorescence microscopy. Smooth muscle cells, independent of blood vessels, were demonstrated in the trabeculae and capsules of lymph nodes of both species examined by all three techniques. The need for further study on the function of these cells is indicated.     

Smooth muscle antibodies in Mycoplasma pneumoniae infection.

Paired sera from forty-five cases of Mycoplasma pneumoniae (MP) infection associated with acute lower respiratory tract illness were examined by immunofluorescence for antibodies to smooth muscle. Twenty-five (56%) of these cases had smooth muscle antibodies (SMA) of IgM class. A significant (greater than or equal to 4-fold) increase in titre of these antibodies was demonstrated in fifteen of thirty-five patients with a significant rise in titre of MP antibodies. SMA of IgG class occurred in eleven of forty-five cases (24%), but a 4-fold rise in antibody titre was found only in two cases. Three of forty-five sera (7%) from healthy donors contained SMA of IgM class and eight sera (18%) SMA of IgG class. MP antigen did not absorb SMA. Liver tests were performed in twenty-nine patients. In eighteen patients SGPT values were moderately or slightly elevated. There was no correlation between the occurrence of increased levels of transaminases and the presence of SMA in serum. In a patient with active chronic hepatitis, who had had a high titre of SMA exclusively of IgG class for 2 years, SMA of IgM class appeared transiently in association with an acute respiratory illness due to MP.     

Smooth muscle differentiation in scleroderma fibroblastic cells.

Using antibodies to alpha-smooth muscle actin and desmin on paraffin-embedded formalin-fixed tissue sections, the authors demonstrate that fibroblastic cells of localized and systemic scleroderma lesions express features of smooth muscle differentiation. Eleven of eleven skin specimens of systemic sclerosis patients and two of four skin specimens of localized scleroderma displayed the presence of fibroblasts expressing alpha-smooth muscle actin, a cell population that predominated in areas of prominent collagen deposition. A similar fibroblastic phenotype was found in the esophagus, the liver, and the lung specimens obtained from four patients who died of progressive systemic sclerosis. Immunostaining for desmin, performed on adjacent tissue sections, demonstrated that a minority of these fibroblastic cells present in skin and visceral lesions contained this protein. The authors' observations indicate that scleroderma fibroblasts are phenotypically related to the stromal cells previously identified in hypertrophic scars, fibromatoses, and desmoplasia; they might provide novel criteria for the characterization of scleroderma lesions and help to identify the factors responsible for phenotypic modulations in fibroblastic cells.     

以Rtac2/3为抗原用于鼻咽癌病人检测的初步研究

目的 在大肠杆菌中表达EBV的早期基因BRLF1，并纯化这个重组蛋白。用纯化的蛋白作为抗原与鼻咽癌（NPC）病人血清中的特异性抗体发生反应，以寻找新的NPC筛检或诊断标志物。方法 用表达和纯化的BRLF1基因C端2／3部分蛋白（Rtae2／3）建立间接ELISA方法，检测了59份NPC患者血清中的抗Paa IgG抗体，同时59份健康者血清作对照。结果 59份NPC患者血清中50份阳性，而59份健康者对照血清中只有7份阳性。NPC组的阳性率与健康对照组之间差异有统计学意义（P〈0．01）。此方法的灵敏度为84．7％，特异性为88．1％。结论 （1）检测人血清中的抗Rta-IgG可以作为NPC诊断的重要标志物之一。（2）如果检测抗Rta-IgG与检测Zebra IgG抗体试验联合使用，用于NPC的筛检和诊断能够进一步提高灵敏度或特异性。     

Immunoglobin synthesis by fresh biopsy cells and established cell lines from Burkitt''s lymphoma

(1) Freshly dispersed cells from four Burkitt's lymphoma biopsies, and three `lymphoblast' cell lines (OB2, OB3 and OB6) derived from the tumour were tested for capacity to synthesize immunoglobulins in vitro.

Using labelled amino acid incorporation, electrophoretic, radio-immunoelectrophoretic and ultracentrifugation techniques, it was possible to demonstrate the release of labelled proteins with antigenic characteristics of immunoglobulins by all four biopsy samples, and the two cell lines tested by these techniques. Newly synthesized labelled proteins were demonstrable in the culture medium within 1 hour of incubation.

In a separate series of experiments, absorption and immunodiffusion techniques were used in the characterization of proteins synthesized by two cell lines (OB2 and OB3) growing as healthy continuous cultures.

(2) Freshly isolated cells from Burkitt's lymphoma are capable of immunoglobulin synthesis in vitro. Cells from all four fresh biopsy materials produced IgG. One cell line (OB2) produced IgG and type-κ light chains, while OB6 cell line produced IgA. Immunoglobulin synthesis was not detected in OB3 cell line by immunodiffusion technique.

(3) Cells from each biopsy specimen or cell line produced not more than one type of immunoglobulin, although there was a wide variation in the sedimentation coefficient of the protein molecules synthesized by one (OB6) and presumably all other cell lines.

     

Humoral immune response in Epstein-Barr virus infections. II. IgG subclass distribution in African patients with Burkitt's lymphoma and nasopharyngeal carcinoma

Native Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC) patients from Kenya were examined with regard to the serum concentrations and distribution of the four IgG subclasses, total IgG, and antibody activities to Epstein-Barr (EB) virus associated antigens. The results were compared with corresponding data of an African control group. As revealed by indirect immunofluorescence techniques, the patients displayed a pattern of IgG and IgA antibodies to EB virus associated antigens which is characteristic for these diseases. No significant differences could be detected between the total IgG levels of the diagnostic groups. The mean total IgG concentrations of our Kenyan patients were two to three times as high as those found in four different groups of Europeans, which is consistent with results of previous studies on Gambian, Nigerian, and Congolese Bantu populations. Quantitative determination of the four IgG subclasses by radial immunodiffusion revealed a unique pattern in the BL group which was characterized by a decreased proportion of IgG2 and significantly lower absolute IgG2 values as compared with the controls. The IgG subclass distribution pattern in the African NPC sera was essentially identical with that of European NPC and African control sera. The pathogenetic implications of these findings are discussed.