Autoimmune liver diseases: the relation to other autoimmune pathology

Nebraska Hospital Market Areas (HMAs) with significantly and consistently high admission rates for Ambulatory Care Sensitive Conditions (ACSC) were identified using the Blue Cross and Blue Shield of Nebraska (BCBSN) small area analysis data. Two-thirds of those hospitalized were surveyed by Wiese Research of Omaha, Nebraska to determine if the cause for the high admission rates was related to outpatient care quality. BCBSN members living in HMAs without high admission rates were also surveyed for comparison purposes. The survey revealed that satisfaction with outpatient care was high, and that access (geographic or financial) was not a problem for either the test or control group. The test group did delay (for a short time) obtaining outpatient care when compared to the control group. Most of the control group stated that they obtained outpatient care the day symptoms started. Although the majority of the test group obtained outpatient care within a week, they were not as prompt in obtaining outpatient care as the control group. The types of conditions studied (ACSCS) are conditions that can rapidly become severe, therefore prompt treatment is imperative. The main reason given for chronic delays of both groups were that the condition "suddenly became serious." There may be implications for providers to use more "compliance-gaining" strategies in problem area, and for insurers to offer contract endorsements which would encourage members to obtain prompt treatment and preventive healthcare.     

Immunohistochemical study of inflammatory infiltrates in minor salivary glands in Sj?gren's syndrome and other autoimmune diseases

BACKGROUND: A study of the phenotype, activation and adhesive cells factors and cytokines in minor salivary glands in patients with primary Sj?gren's syndrome (pSS), secondary Sj?gren's syndrome (sSS) and autoimmune diseases (AD) without Sj?gren's syndrome. PATIENTS AND METHODS: We have studied the minor salivary glands in 30 patients with pSS, 30 patients with sSS, 19 patients with AD without SS and 18 controls, using immunohistochemical techniques to analyze the molecular expression of CD3, CD4, CD8, CD20, CD25, CD14, CD56, CD11a, CDw50 (ICAM-3), HLA-DR, IL-1, TNF-alpha and IFN-gamma in lymphocytic infiltration and epithelial cells. RESULTS: Phenotype features were similar in patients with pSS and sSS, except that CD20+ lymphocyte expression was significantly higher in the sSS group (p = 0.023). The patients affected by AD without SS had activated lymphocytes in minor salivary glands in a similar manner to patients affected by pSS and sSS. No significant differences were found in HLA-DR expression in epithelial cells. We found unusual CD25 expression in epithelial cells in patients with SS but not in patients with AD without SS. The differences between pSS and sSS are related to SS theoretical time development and to immunosuppressive treatments. CONCLUSIONS: The immunohistochemical pattern of minor salivary glands is similar in patients with pSS and sSS. Patients with AD are likely to develop immunological changes in minor salivary glands attributable to activated lymphocytes.     

Prolactin in autoimmune diseases

The immune system is still regarded by many as autonomous, and prolactin (Prl) has traditionally been considered as a lactogenic hormone. Over the last 10 years, the total number of publications considering Prl is decreasing, while the number of those investigating its role in immunity sustainly increased. In addition to the pituitary gland, Prl-like peptides can be produced by activated leukocytes and fibroblasts. Elevated serum levels of Prl in (rat) adjuvant arthritis, (murine) collagen type II-induced arthritis, (murine and human) systemic lupus erythematosus (SLE), and (murine and rat) autoimmune type I diabetes may influence the outcome of the disease. It is suggested that mild hyperprolactinemia is a risk factor for the development of autoimmunity. This can occur under certain circumstances, for example adrenocortical deficiency or postpartum. In human SLE, Prl appears to favor the production of anti-double stranded DNA. While glucocorticoids would damp the immune reactivity, Prl constitutes a stimulatory link between the neuroendocrine and immune systems. Future directions should include: 1) multicenter projects for evaluation of the therapy with Prl-inhibiting compounds in SLE, considering for example the HLA-DRB1 *0301 status; and 2) the regulation of extra-pituitary Prl-like cytokines ("proliferins") (e.g., in rheumatoid arthritis synovium) and their role in the production of catabolic enzymes.     

Gene therapy in autoimmune diseases

The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.     

A comparative nuclear localization study of galectin-1 with other splicing components

Thirty-two African American nurses (AAN) and 78 Caucasian nurses (CN) were compared on breast self-examination (BSE) practice and health beliefs. Relationships between these variables were also examined. The Health Belief Model provided the framework for the study. The sample is a subset of 269 women from a larger study. AANs were recruited from a professional nurses' group. CNs were recruited from a list of female employees of a university medical centre. The results of t-tests revealed no significant group differences on BSE frequency (P = 0.06) or BSE proficiency (P = 0.10). Noted was that 42% of AANs compared to 20% of CNs examined their breasts 12 or more times during the year. AANs were more likely to consider BSE beneficial (P = 0.002) and to feel confident (P = 0.006) about doing BSE; CNs perceived more barriers (P = 0.001) to BSE. For AANs, BSE frequency and proficiency were positively related to confidence and inversely related to barriers; BSE frequency was also related to health motivation. For CNs, BSE frequency and proficiency were inversely related to seriousness. Implications include additional research to validate findings and to increase the knowledge base of all nurses regarding BSE.     

Antilactoferrin antibodies in autoimmune liver diseases

OBJECTIVE: Lactoferrin, an immunoregulatory protein in mucosal secretions, is one of the target antigens to perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs). Circulating lactoferrin is cleared in the liver, but little is known about the implication of lactoferrin in hepatic inflammation. To evaluate the implication of immunological response to lactoferrin, we examined antilactoferrin antibodies in autoimmune liver diseases. METHODS: Fourteen patients with primary biliary cirrhosis (PBC), 14 with autoimmune hepatitis (AIH), five with autoimmune cholangitis (AIC), six with chronic hepatitis C, and five with chronic hepatitis B were studied. We evaluated autoantibodies to lactoferrin in the sera of the patients by the Western Immunoblotting method. RESULTS: Sera of five of the 14 patients (35.7%) with PBC, four of the 14 patients (28.6%) with AIH, and five of the five patients (100%) with AIC contained autoantibodies to human lactoferrin, but none with hepatitis B or C had them. The higher prevalence of serum antibodies to human lactoferrin was shown to be higher in patients with AIC than with hepatitis B (p < 0.01), hepatitis C (p < 0.01), PBC (p < 0.05), and AIH (p < 0.05). CONCLUSION: Lactoferrin located in bile ducts and liver cells is one of the candidates of target antigens in autoimmune liver diseases, especially in AIC.     

Successful therapy with danazol in refractory autoimmune thrombocytopenia associated with rheumatic diseases

The objective was to assess the efficacy of therapy with danazol in refractory immune thrombocytopenia associated with different rheumatic diseases. Patients with severe immune thrombocytopenia (platelet counts < 40 x 10(9)/l) with a bone marrow biopsy showing megakaryocytes in normal or increased number and normal morphology were included if they fulfilled at least one of the following criteria: (a) thrombocytopenia refractory to prednisone (> or = 1 mg/kg/day during > or = 4 weeks); (b) patients requiring an unacceptably high dose of prednisone for > 2 months (prednisone dose > or = 20 mg/day); (c) no response to at least another drug besides corticosteroids. Other causes of thrombocytopenia were excluded. They were treated with danazol (100-200 mg q.i.d.) and followed for at least 12 months. Four patients diagnosed with systemic lupus erythematosus, two with rheumatoid arthritis and one with primary antiphospholipid syndrome met the inclusion criteria. All of them achieved acceptable platelet counts within the first 4 weeks of danazol therapy that allowed the prednisone dosage to be tapered. No important side-effects related to danazol therapy were observed. Danazol therapy seems to be a useful and well-tolerated treatment for refractory immune thrombocytopenia associated with different rheumatic diseases.     

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.     

Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematosus and other autoimmune diseases

Expression of the highly conserved 90 kDa heat shock protein (Hsp90) is elevated in the peripheral blood mononuclear cells of approximately 25% of patients with SLE. Conflicting data have been published about the frequency of antibodies to Hsp90 with the previous methodology using a complex Western blot system. We now describe an ELISA to measure autoantibodies to Hsp90 and Hsp70 in SLE patients, healthy controls and patients with a variety of autoimmune rheumatic diseases. IgG and IgM antibodies were elevated in 26 and 35% of SLE patients, respectively. These results show autoantibodies to Hsp90 (but not Hsp70) are elevated in a significant proportion of patients with SLE (P < 0.025) compared to healthy controls; and that those with raised antibody levels were more likely to have renal disease and a low C3 level (P < 0.02).     

An imbalance between Th1 and Th2-like cytokines in patients with autoimmune diseases--differential diagnosis between Th1 dominant autoimmune diseases and Th2 dominant autoimmune diseases

An imbalance between T helper cell (Th)1 and Th2-like cytokines has been described in several autoimmune diseases. Organ specific autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBD) are caused by Th1 dominant immune responses. On the contrary, systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Sj?gren's syndrome(SS) are characterized by Th2 dominant imbalance of cytokine production. It might be useful for differential diagnosis among patients with various autoimmune diseases such as SLE, SS, IBD, and MS to measure the serum levels of cytokines such as IL-10, IFN gamma, and TNF alpha using ultrasensitive enzyme-linked immunosorbent assay system.     

Sensitivity of Aeromonas hydrophila carbapenemase to delta3-cephems: comparative study with other metallo-beta-lactamases

Ceftriaxone and ceftriaxone S-oxide behaved as inactivators against the metallo-beta-lactamase of Aeromonas hydrophila AE036 and as substrates for the zinc beta-lactamase produced by Bacillus cereus (569/H/9) and Stenotrophomonas maltophilia ULA 511. Moreover, RO 09-1428, a catechol-cephalosporin, was not recognized by the A. hydrophila enzyme. Panipenem, cephalosporin C, cephalosporin C-gamma-lactone, and loracarbef were substrates for the three studied beta-lactamases.     

Three-dimensional computed tomography in the head and neck diseases with bony abnormalities

The purpose of this study was to define the role of three-dimensional (3D) computed tomography (CT) in the head and neck diseases with bony abnormalities. Thirty-two patients were examined with a low dose radiation technique. Three-dimensional CT clearly delineated bony lesions in 27 of 32 patients. Three-dimensional CT could not demonstrate subtle bony erosions infiltrated by tumor, a temporal bone fracture, and a blow-out fracture, although two-dimensional (2D) images obtained before the 3D reconstructions clearly depicted those lesions. These two kinds of CT technique were thought to be complimentary.     

Lymphocyte nucleolar activation as a marker of autoimmune disorders. II. Observations in patients with systemic lupus erythematosus and other connective tissue diseases

An increased number of lymphocytes with active nucleoli was found in the peripheral blood of most patients suffering from connective tissue diseases associated with autoimmunity.     

Coping with illness in myasthenia gravis in comparison with other chronic neuromuscular diseases

Seventy-nine patients with chronic neuromuscular diseases were examined by psychodiagnostic tests. The most frequently used coping strategies were "compliance and confidence in the physician", "self encouragement", "to relative by comparison" and "problem-solving". Comparison of the test sample and our total sampling group and the groups divided by diagnosis showed more common features than differences in the coping process. This might be caused by similar general problems in chronic diseases. Less "compliance and confidence in the physician" was the only significant difference between the myasthenic patients and the remaining test group. We supposed less treatment possibilities and/or longer duration of illness (remaining test group) to be responsible for this result. Duration of illness in common seems to have an influence on coping. Patients suffering a longer illness showed reduced values in "self encouragement". Common and specific problems and circumstances of illness seem to be more significant for the coping process than the diagnosis. The patients' mood, which we took as a measure for partial aspects of adaptivity of coping, correlated significantly with the strength of the complaints felt. Classification into adaptive and maladaptive coping forms is not possible.