Clinical manifestation and humoral immuno-function of myasthenia gravis patients with abnormal and normal thymus gland

BACKGROUND： Myasthenia gravis （MG） is an autoimmune disease which mainly affects neuromuscular junctions. The ages, modified Osserman classification and clinical manifestation and humoral immunol function of MG with and without thymic abnormality are different. OBJECTIVE： To explore the clinical manifestation and humoral immuno-function of MG with abnormal and normal thymus gland. DESIGN ： Contrast observation SETTTNG ： Department of Neurology, the Third Affiliated Hospital of Sun Yat-sen University PARTZCZPANTS ： A total of 49 inpatients with MG were selected from the Third Affiliated Hospital of Sun Yat-sen University from March 2000 to August 2005. All the patients had typical clinical manifestation of MG and positive neostigmine test. All the patients knew and agreed the laboratory examinations. There were 22 males and 27 females of 2-69 years old. Chest MRI or CT scan were performed to reveal thymus gland abnormality. According to whether there was tumor in superior mediastinum, all patients were divided into 2 groups, abnormal and normal groups. Normal thymus gland group （n=30） contained 16 males and 14 females of 6-43 years old. Abnormal thymus gland group （n=19） contained 6 male and 13 female of 2-69 years old, METHODS： ① All patients were questioned about initial symptoms. Meanwhile, main clinical manifestations were recorded at hospital admission. ② 7180A automatic biochemical analyzer and automatic microplate reader were used in detecting seroimmunity index. The levels of C3, C4, IgG, IgA, IgM and CH50 in blood serum were analyzed by nephelometry. ③ Clinical classification is based on modified Osserman classification. The patients with MG were divided into six types： I （Ocular myasthenia）, Ⅱ a （Mild generalized myasthenia）, Ⅱb （Moderately severe generalized myasthenia）, Ⅲ （Acute fulminating myasthenia）, Ⅳ（Late se- vere myasthenia）. MAZN OUTCOME MEASURES： ① Differences of initial symptoms and clinical manifestation of two group patients. ② Differences of age of onset and modified Osserman classification of two groups. ③The humoral immuno-functions of two groups were compared. RESULTS： All the 49 patients were involved in the final analysis of results. ① Differences of initial symptoms： Ptosis was the most common initial symptoms in both groups. Patients with ptosis of normal thymus gland were 25 （83%, 25/30）. Patients with ptosis of abnormal thymus gland were 13 （68%, 13/19）. Patients with normal thymus gland： dysphagia 2 （7%, 2/30）, diplopia 4 （13%, 4/30）, fatigue 4 （13%, 4/30）, dysarthria 3, （10 %, 13/30）. Patients with abnormal thymus gland： dysphagia 3 （16%, 3/19）, diplopia 6 （32%, 6/19）, fatigue 3 （16%, 3/19）, dysarthria 2 （10%, 2/19）. ② Differences of clinical manifestation of two groups： Ptosis was the most common clinical manifestation in both groups. Patients with ptosis of normal thymus gland were 29 （97%, 29/30）. Patients with ptosis of abnormal thymus gland were 15 （79%, 15/19）. The rates of fatigue and breathing disorder in patients with abnormal thymus gland were higher than patients with normal thymus gland. Myasthenia crisis occurred in 3 patients （16 %, 3/19） in abnormal thymus gland group, with 1 （3%, 1/30） in abnormal thymus gland group. ③ Differences of age of onset and modified Osserman classification： The rate of type ｜ （63%, 19/30） in patients with normal thymus gland was higher than patients （42%, 8/19） with abnormal thymus gland. The rates of type Ⅱ a, Ⅱ b and Ⅲ （58 %） in patients with abnormal thymus gland were higher than patients （37%, 8/19） with normal thymus gland. But no differences were found between two groups （P 〉 0.05）. Patient number of onset from 20 to 29 year old in abnormal group （47%） was higher than that in normal group （20%）. Comparison of two groups was X2=4.10 and P 〈 0.05.④ Comparison of the humoral immunol indexes of two groups： The levels of IgG, IgA, C3 and CH50 in abnormal group were higher than those in normal group. But no differences were found between two groups （P 〉 0.05）. CONCLUSZON： ① Ptosis was the most common initial symptom and clinical feature in both groups. ② Clinical manifestation in abnormal group were more severe, and ages of onset in abnormal group were more young.③ The humoral immuno indexes of two groups were not significantly different.

Molecular mechanism of damage and repair of mouse thymus lymphocytes induced by radiation

OBJECTIVE: To investigate the role of apoptosis in radiation-induced mouse thymus lymphocyte damage and repair and provide the basis for understanding the molecular mechanism of radiation-induced lymphocyte damage and repair as well as the prevention and treatment of acute radiation sickness. METHODS: We studied the dynamic changes of apoptosis of mouse thymus lymphocytes and the expression of bax and bcl-2 gene products after 2, 4, 6 and 8 Gy of whole body gamma-irradiation using in situ terminal labeling, DNA electrophoresis and immunohistochemical techniques. RESULTS: At the early stage after irradiation, the percentage of apoptotic lymphocytes increased rapidly in accordance with the increasing of radiation doses, while the counts of the thymus and peripheral lymphocytes decreased sharply, showing an opposite change to lymphocyte apoptosis. After 6 Gy gamma-irradiation, typical morphological characteristics of thymus apoptotic lymphocytes in early, middle and late stages were found by transmission electron microscopy. The thymus lymphocytes displayed characteristic DNA ladders 4 hr and 8 hr after 2-6 Gy gamma-irradiation,using DNA gel electrophoresis techniques. Abnormal expression of bcl-2 and bax gene products were shown in irradiated lymphocytes. CONCLUSIONS: Apoptosis plays an important role in the process of radiation-induced mouse thymus lymphocyte damage and repair. Bcl-2 and Bax proteins may regulate the process of lymphocyte apoptosis.

Mathematical analysis of a model for thymus infection with discrete and distributed delays

In this paper, the dynamics of mathematical model for infection of thymus gland by HIV-1 is analyzed by applying some perturbation through two different types of delays such as in terms of Hopf bifurcation analysis. Further, the conditions for the existence of Hopf bifurcation are derived by evaluating the characteristic equation. The direction of Hopf bifurcation and stability of bifurcating periodic solutions are determined by employing the center manifold theorem and normal form method. Finally, some of the numerical simulations are carried out to validate the derived theoretical results and main conclusions are included.

Long-term prognostic analysis of thymectomized patients with myasthenia gravis

OBJECTIVE: To study the factors affecting the long-term prognosis of patients with myasthenia gravis (MG) after thymectomy. METHODS: 170 MG patients who had undergone thymectomies were studied retrospectively. Among them, 124 patients received long-term follow-up for more than 40 months postoperatively. The COX regression analysis model was used to analyze the factors that may influence the long-term prognosis. These factors included thymus pathology, patient gender, age, duration of disease at the time of surgery, preoperative Osserman classification and medication. RESULTS: The research showed that thymus pathology was the single independent factor that affected the postoperative long-term prognosis. The long-term survival rates differed significantly with thymus pathological types: hyperplasia > benign thymoma > atrophy > malignant thymoma (P

Five novel monoclonal antibodies to thymic epithelial cell surface antigens in rats

OBJECTIVE: To establish monoclonal antibodies (mAbs) against thymic epithelial cells and study the function of epithelial cells during T-cell differentiation in the thymus. METHODS: Hybridomas secreting mAbs against thymic epithelial cells were derived by immunization of Balb/c mice with two thymic epithelial cell lines, TaD3 and FTE. The distribution of antigens recognized by these mAbs was detected by immunochemical staining and cytofluorographic analysis, and the molecular weight of the antigens by immunoblotting. RESULTS: Five specific monoclonal antibodies (mAb) were obtained. On the basis of their distribution in the thymus determined by immunochemical staining, mAb RE-4D8 was regarded as clusters of thymic epithelium staining (CTES) type IIA: mAb RE-12B2, which showed a unique distribution pattern only in the medulla, was CTES type V: mAb RE-5C6 was CTES type IV: mAb RE-6D6 might be CTES type IIB: and mAb RE-1D4 was classified as type V. The molecular weight (MW) of antigen RE-4D8, RE-6D6 and RE-12B2 were 120 kDa, 220 kDa and 35 kDa, respectively. Antigen RE-1D4 is a novel marker of cortical epithelium, several established thymic epithelial cell lines were classified and their original intrathymic locations were determined by these mAbs. Thymic cell lines, TuD3 and FTE were cortical phenotypes whereas TaD3 had a medullar phenotype. CONCLUSIONS: These mAbs clearly demonstrate the heterogeneity of the thymic epithelium; they could detect antigens not only in the cytoplasm but also on the surface of thymic epithelial cells. Our data suggest that these newly established mAbs may help elucidate the interaction between thymocytes and epithelial cells during T cell maturation.