Coexistent minocycline-induced systemic lupus erythematosus and autoimmune hepatitis

BACKGROUND AND OBJECTIVES: The K-ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K-ras codon 12 mutations in this type of tumor. METHODS: Forty-seven patients who had undergone resection for DBDC were analyzed to reveal the incidence of K-ras codon 12 mutations, the locus most frequently involved. A rapid and simple two-step, semi-nested polymerase chain reaction (PCR) technique was used to detect mutations in paraffin-embedded tumor samples. RESULTS: The PCR mismatch amplification technique demonstrated that 35 (75%) of the 47 tumors harbored a point mutation in codon 12 of the K-ras oncogene. Patients with mutated tumors had no statistically different survival time compared to those patients without a mutation in the tumor. In contrast, negative microscopic margins proved to be a significant prognosticator. CONCLUSIONS: K-ras codon 12 mutations are common in DBDC and may be useful in the diagnosis and early detection of these tumors. However, no prognostic value of these mutations could be identified in this analysis. The results of this study also suggest that negative surgical margins remain the mainstay of prognostication in resectable DBDC. However, due to the small number of patients included in this study, the results obtained should be interpreted with care.     

皮肌炎合并甲状腺功能异常的临床及免疫学特征分析

目的:探讨合并甲状腺功能异常的皮肌炎(dermatomyositis,DM)患者临床及免疫学特征.方法:回顾性分析70例DM患者的临床表现、肌酶水平、自身抗体、红细胞沉降率(erythrocyte sedimentation rate,ESR)、C反应蛋白(C-reactive protein,CRP)、免疫球蛋白、血脂等指标,依据甲状腺功能情况进行分组比较.结果:70例DM患者中甲状腺功能异常者达48%,主要表现为甲状腺功能减低,但患者多无甲状腺功能减低的临床症状.与甲状腺功能正常组比较,甲状腺功能异常组的患者多见发热、V型征、Gottron征,也常出现CRP、IgG升高,两组患者系统器官受累情况及肿瘤发生率比较差异无统计学意义.结论:DM患者甲状腺功能异常的发生率高,常表现为亚临床型甲状腺功能减低,可能与两种疾病存在共同的免疫机制有关,临床上应予重视.     

Contribution of immuno-hematology in understanding autoimmune phenomena

Acquired hemolytic anemia (AHA) can be considered under four aspects: 1) The nature and specificity of involved autoantibodies correspond to weakly differentiated structures of high frequency but normal human blood group antigens. 2) The pathologic role of autoantibody can be experimentally demonstrated by parallel measures of the specific red cell survival. 3) In certain cases of AHA--secondary to infections (Mycoplasma pneumoniae, infectious mononucleosis) or drugs (methyl dopa), or related to tumours (dermoid ovarian cyste, ovary teratoma) or tissue damages (haemorragic rectocolitis)--the relation between a clinical precise circumstance and the production of autoantibody can actually be demonstrated. 4) In idiopathic AHA, in addition to various autoantibodies, an immunological disorder is observed, including the production of allo- and heteroantibodies and, in 50% of the cases, a global deficit in immunoglobulin. 5) On these bases, the nature of autoimmunity is discussed. If specific modifications can explain secondary AHA, they can hardly account for idiopathic AHA. Cellular non-specific anomalies should be considered.     

Clinical and experimental study on improving cellular immunological function of uterine myoma patients by xiaoliu tablet

Dehiscences of the bony horizontal segment of the facial canal are rather common in human adults. These facial canal dehiscences occur most often in the region of the oval window. This study presents the observations of the facial canal in the oval window region in 427 operations for otosclerosis. The incidence of dehiscences in the facial canal to the middle ear space in otosclerosis was studied. Dehiscences were observed in 14 of the 427 patients (3.27%) who had a stapedotomy. This incidence is very low compared to the anatomical studies of the facial nerve in human cadaver temporal bones. Dehiscences of the facial canal are a variation of the normal anatomy of the facial nerve and these dehiscences occur sporadically in otosclerosis.     

Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer

Anti-CD3 mAb and interleukin 2 (IL-2) were used in a Phase I study to treat 29 patients with cancer. The anti-CD3 was given as an i.v. bolus infusion over 10 min followed by two i.v. 96-h continuous infusions of IL-2 at 3 x 10(6) units/m2/day with a 3-day rest between the IL-2 infusions. Four patients were treated with 6, 18, 60, and 300 microgram/m2 anti-CD3. One patient received 3000 microgram/m2 anti-CD3. This patient developed profound hypotension and the IL-2 infusions were delayed for 2 weeks. Two patients were treated at an intermediate dose of 600 microgram/m2. These patients developed dose-limiting toxicities including hypotension, dyspnea and increased blood urea nitrogen, creatinine, and bilirubin. They were unable to complete their first course of therapy. In an effort to achieve a dose of anti-CD3 which would activate T cells in vivo, pentoxifylline was given to blunt the toxicities seen with anti-CD3 thought to be due predominantly to the cytokine syndrome and tumor necrosis factor release. Four patients received p.o. pentoxifylline to cover an anti-CD3 dose of 600 microgram/m2. The IL-2 infusion was initiated 1 week after the mAb. While there was an anti-CD3 dose-dependent increase in serum tumor necrosis factor level 1 h after mAb infusion, pentoxifylline did not reduce the serum tumor necrosis factor level. There was also an anti-CD3 dose-dependent increase in the serum soluble IL-2 receptor levels. Other immune parameters monitored, including in vitro cytotoxic and proliferative responses and lymphocyte count, were similar to treatment courses with IL-2 alone. Fourteen of 26 patients examined developed human anti-murine antibodies following a single dose of anti-CD3. There were no objective antitumor responses. We conclude that in vivo treatment with anti-CD3 did not enhance T cell activity or expansion with subsequent IL-2 infusion and that the combination of anti-CD3 followed by IL-2 did not improve upon the antitumor activity previously seen with IL-2 alone.     

Clinical and immunological analysis of Birch pollenosis

In recent years, the number of cases Birch pollenosis has increased, but there have been very few reports, and therefore we decided to carry on this clinical and immunological analysis as follows. (1) Statistical analysis of Birch pollenosis patients who visited the Department of Otorhinolaryngology of Hokkaido University School of Medicine, Sapporo. (2) Study of atmospheric birch pollen counts and investigation of the relationship between the incidence of pollenosis and pollen count. (3) Allergen analysis of Japanese Birch pollen using Western blotting method. (1) From 1990 to 1992, 392 cases of nasal allergy visited our hospital and 74 cases (18.9% of all cases) were birch pollenosis. There was a significant increase in the number of cases birch pollenosis, compared with previous reports. (2) Atmospheric pollen grains of birch pollen were collected by Durham's pollen trap at Hokkaido University School of Medicine, Sapporo from 1990 to 1992. In this study, birch pollen was collected from the beginning of April to the middle of June. The first day when birch pollen was collected in this study was about one month earlier than previously reported. We suspected that the mean temperature rise of Sapporo city in April is one of the factors that lead to the increase of incidence of birch pollenosis. (3) Allergens in birch pollens from Betula platyphylla Sukatchev var. japonica and Betula Ermanii Cham in Japan were identified by Western blotting, following separation by SDS-PAGE, transfer to PVDF membranes and incubation with sera from 35 birch pollenosis patients. In almost all cases, 17kd molecular from B. platyphylla and B. Ermanii pollen proteins were detected as the major IgE binding components.     

Clinical and immunological characteristics of transplant recipients with recurrent acute rejection episodes

Diet may play a key role in the pathogenesis of cancer and evidence for the role of a reduced intake of micronutrients with antioxidant properties have been increasingly reported. Until now, epidemiologic research in humans has focused on the negative effect of different diets containing excessive caloric intake and relatively little is known on the possible correlation between slimming diets and the incidence of acute leukemia. In this report we describe the temporal association of imbalanced slimming regimens and the subsequent diagnosis of acute leukemia in three cases. This association may be coincidental or perhaps suggests a possible relationship of the diet with the development or progression of acute leukemia.     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Clinical immunological classification of tuberculous uveitis

Clinical and immunological studies carried out in 251 patients with tuberculous uveitis (TU) revealed three types of inflammatory reactions in the uveal tract in this patient population: productive, exudative, and productive-exudative (mixed), differing by the type of immune disorders. The findings helped develop a clinical immunological classification of TU, taking account of the clinical form of uveitis, type of inflammatory reaction of the uveal tract, disease pattern, involvement of one or both eyes, complications, and the immunopathological variants of TU course.     

Clinical, haematological and molecular studies in patients with chromosome translocation t(7;11): a study of four Chinese patients in Taiwan

We examined the association between the polymorphism of the apolipoprotein E (apoE) and the ACE genes and the intima-media thickness (IMT) of the carotid and femoral arteries measured using ultrasonography. The values of IMT of each artery were significantly higher in NIDDM patients (n = 356) than in control subjects (n = 235). The E4 allele or the D allele did not affect clinical characteristics, including age, fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, or blood pressure, in NIDDM or control subjects. No difference in the carotid IMT value was noted among the apoE genotypes in control or diabetic subjects. The carotid IMT was significantly higher in diabetic patients with the DD genotype (1.200 +/- 0.586 mm) than in those with the II genotypes (0.990 +/- 0.364 mm). Neither the E4 allele nor the D allele affected the femoral IMT in control or diabetic subjects. Multiple regression analysis demonstrated that the carotid IMT of NIDDM patients was associated with age, the D allele, and LDL cholesterol but not with the E4 allele, whereas that of control subjects was associated with age, sex, systolic blood pressure, LDL cholesterol, and HDL cholesterol, inversely. These results suggested that the E4 allele was not associated with the carotid or femoral IMTs, but that the D allele was statistically associated with carotid IMT in NIDDM patients but not control subjects. However, since the association was weak (2.3% explanatory power), its biological significance remains to be determined.     

Clinical picture of autoimmune hemolytic anemia

We describe a boy who has gelastic epilepsy, precocious puberty, hypothalamic hamartoma, and agenesis of the corpus callosum. We believe that this is the first documented case in which agenesis of the corpus callosum has been associated with hypothalamic hamartoma and gelastic epileptic syndrome in a child.     

Antiplatelet glycoprotein autoantibodies in patients with autoimmune diseases with and without thrombocytopenia

The presence and specificity of antiplatelet autoantibodies in 32 patients with primary and 18 patients with secondary autoimmune thrombocytopenic purpura (AITP), as well as 11 non-thrombocytopenic patients with systemic autoimmune diseases, were studied. By means of the direct and indirect monoclonal antibody immobilization of platelet antigen (MAIPA) assay, antiplatelet autoantibodies were detected using monoclonal antibodies specific for platelet glycoproteins (GPs) Ib, IIb/IIIa, Ia/IIa, and IV. Serum antiplatelet autoantibodies were found in 18 of 32 primary AITP patients (56%), 6 of 18 secondary AITP patients (33%), and 5 of 11 nonthrombocytopenic patients (45%). Platelet-associated autoantibodies were detected in five of eight patients with primary (62%) and in four of eight patients with secondary AITP (50%) and in two of four patients without thrombocytopenia (50%). Multiple antibody reactivity, mainly against GPs IIb/IIIa and Ib and, in a few patients, against Ia/IIa, was found. Using MAIPA, platelet xylene eluates from 20 patients were also studied. Antiplatelet elutable autoantibodies were related to thrombocytopenia; autoantibodies against membrane GPs Ib and IIb/IIIa were demonstrable in 84 and 63% of eluates from patients with primary and secondary AITP, respectively, but not in eluates from nonthrombocytopenic patients. The presence of antiplatelet antibodies thus appears to be a common feature of many autoimmune diseases apart from the thrombocytopenia, but the (primary or secondary) etiology of the immune thrombocytopenia cannot be differentiated on the grounds of their specificity.     

Autoimmune hepatitis and autoimmune manifestations in patients with chronic viral hepatitis

Mucosal adherence and germ tube formation have been considered as important virulence factors of Candida albicans. We investigated 11 clinical isolates (among them six isolates from oesophageal thrush) for quantification of adherence to buccal epithelial cells and germ tube formation in the continuous flow culture in vitro, and correlated the results with the clinical data of the patients. Adherence varied considerably between the different C. albicans strains. Strains recovered from clinically, culturally and serologically confirmed oesophageal thrush adhered stronger to buccal epithelial cells. Isolates from cases with heavy colonisation but clinically without candidosis were less adherent. Only after 30 min germ tube formation was observed in the continuous flow culture. Strains with stronger adherence also showed significantly faster and increased germ tube formation. The patients with oesophageal thrush did not suffer any particular immunosuppression such as HIV infection, although in most cases chronic alcoholism was apparent. We conclude, that in cases with minor immunosuppression the expression of the virulence factors adherence and germ tube formation plays an important role in the pathogenesis of candidosis, whereas it may be of less importance in cases with severe immunosuppression. In the latter they may, however, influence outcome.     

Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies

Lupus anticoagulant (LA) antibodies are acquired inhibitors of coagulation belonging-together with anticardiolipid (aCL) antibodies-to the family of antiphospholipid antibodies. Since LA antibodies affect coagulation reactions via recognition of the complex of lipid-bound prothrombin, they may be better named anti-prothrombin antibodies. We studied their immunological properties in the plasma of 59 patients with antiphospholipid antibodies by means of specific ELISA systems that allowed the characterization of the interaction of these antibodies with human prothrombin and anionic phospholipids. The mode of presentation of prothrombin was found to greatly influence the reactivity of anti-prothrombin antibodies. In fact, when plain polystyrene plates were used to immobilize prothrombin, virtually no binding was observed. Conversely, when prothrombin was coated on high-activated PVC ELISA plates, 34 samples (58%) contained antibodies that recognize human prothrombin in solid phase. In particular, IgG antibodies were found in 21 plasmas and IgM in 22; both IgG and IgM isotypes were present in 9 of these cases. A higher prevalence was observed in the ELISA for the detection of the antibodies directed at the calcium-mediated complex of phosphatidylserine (PS)-bound prothrombin: 53 samples (90%), preadsorbed with cardiolipin liposomes to remove aCL antibodies, showed the presence of IgG and/or IgM anti-prothrombin antibodies. When the results were analyzed according to the immunoglobulin isotypes, 44 (75%) and 39 (66%) samples were found to contain IgG and IgM anti-prothrombin antibodies, respectively. Both IgG and IgM were present in the plasma of 30 patients. Only half of these samples reacted also with PVC-bound prothrombin. Apparently, the higher rate of positivity of the ELISA for the detection of antibodies to the complex of PS-bound prothrombin was not due to differences in the amount of antigen available in the 2 systems, as judged by binding experiments performed with a rabbit polyclonal anti-human prothrombin antiserum. Finally, the anticoagulant properties of 14 total IgG preparations (12 of them contained anti-prothrombin antibodies positive in both ELISA systems, whereas the other 2 cases reacted either with PVC-bound prothrombin only or with PS-bound prothrombin only) were evaluated by diluted Russell's Viper Venom Time and by diluted activated Partial Thromboplastin Time. To rule out the beta 2-glycoprotein I (beta 2-GPI)-dependent anticoagulant effect of the aCL antibodies contained in the preparations, the coagulation tests were performed in beta 2-GPI deficient plasma. Six preparations failed to show anticoagulant activity in both assay systems, suggesting that 2 types of IgG anti-prothrombin antibodies exist, that differ with respect to their anticoagulant properties. These findings suggest that anti-prothrombin antibodies resemble aCL antibodies with respect to the behaviour in "in vitro" coagulation reactions and underline the wide heterogeneity of antiphospholipid antibodies.     

Clinical and immunological profile of SLE: some unusual features

OBJECTIVE: To study the clinical and immunological profile of children with systemic lupus erythematosus (SLE). DESIGN: Retrospective hospital based study. SETTING: Tertiary level center of North India. SUBJECTS: Sixteen children in the age group 4-12 years. METHODS: Medical records of children with SLE were analyzed. Clinico pathological features were compared with 2 other series from India. RESULTS: Mean age of children at the time of diagnosis was 10 yr and 8 (50%) children were less than 10 yr of age. The female to male ratio was 7:1. Fever (56.2%), rash (87%) and arthritis (87%) were the common clinical manifestations, Renal involvement was noted in 56.2% of cases. Other clinical features included hemolytic anemia (31.2%), thrombocytopenia (18.6%) and Raynaud's phenomenon (12.5%). Cardiac involvement in the form of severe myocarditis and endocarditis occurred in one patient each. Pulmonary hypertension was the presenting feature in one child with right heart failure. One child had multiple sclerosis along with SLE--a rare combination. ANA positivity was seen in all children. Five children died; two had severe cardiac involvement. Three children had renal involvement and one died of pulmonary hypertension. Two-thirds of subjects with renal involvement improved after therapy according to NIH, Bethesda protocol. CONCLUSIONS: SLE must be considered in any child with multisystem disease, as the disease may have certain unusual presentations.