Search

Unlike other agents associated with drug-induced lupus, the isoprenoid alkane pristane induces autoantibodies pathognomonic of lupus, including anti-Sm, anti-dsDNA, and anti-ribosomal P in BALB/c and SJL/J mice. The susceptibility of other strains of mice to pristane-induced lupus is unknown and is the focus of the present study. Anti-nRNP/Sm, anti-Su, and anti-ribosomal P autoantibodies were produced by most strains of mice surveyed within several months of pristane treatment, although there was marked interstrain variability in their frequencies, levels, and times of onset. In sharp contrast, the production of autoantibodies against the double-stranded RNA binding proteins NF45/NF90/p110 was restricted to B6 and B10.S mice. We conclude that pristane selectively induces lupus-specific autoantibodies in virtually any strain of mouse regardless of its genetic background. However, H-2-linked as well as non-H2 genes influenced the expression of individual autoantibody markers. The widespread susceptibility of pristane-treated mice to lupus autoantibody production and the relatively small effect of MHC are unique features of this chemically induced lupus syndrome, with potential implications for understanding the pathogenesis of autoantibodies in idiopathic human systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

HLA phenotypes have been determined in 79 patients as part of a prospective study of factors governing the immune response to injected insulin. IgG insulin antibody levels 6 months after starting treatment with bovine insulin were significantly higher in patients bearing HLA-DR7 and this in conjunction with the lack of a similar pattern in the lgG response to Helix pomatia haemocyanin, suggests the presence of an immune response gene for insulin. The hyporesponsiveness of HLA-B8/DR3/C4AQ0 positive individuals is more likely to reflect a non-specific abnormality of immunity. [ABSTRACT FROM AUTHOR]

Antibodies reactive with the C-peptide portion of proinsulin can be detected in the sera of patients on conventional bovine insulin regimes which include the soluble form. Direct and competitive binding studies demonstrate that C-peptide antibodies show species specificity but do not recognize free homologous C-peptide. This is likely to be due to conformational change following cleavage of C-peptide from the proinsulin molecule. Examination of sera from a large group of patients established on a standard insulin regime shows that C-peptide and insulin antibody levels do not correlate with each other and are likely to show different patterns of genetic control. [ABSTRACT FROM AUTHOR]

Insulin antibodies are detectable in the sera of most patients within 3-4 months of starting treatment with conventional bovine insulins. Various factors determine the immunogenicity of insulin preparations including the genetic background of the recipient. This causes wide variation in response. Solid phase absorption studies as well as competitive binding in fluid phase indicate that the antibodies formed are almost always specific for determinants shared by the endogenous human molecule. This has important implications for the metabolic effect of insulin antibodies in vivo as well as for mechanisms of autoantibody production in man. [ABSTRACT FROM AUTHOR]

Neutrophil phagocytosis and killing of Candida albicans were examined using a radiometric assay in 25 patients with insulin-dependent diabetes and 17 controls under various in vitro metabolic conditions. Glucose was present at 5, 10 and 50 mM, βhydroxybutyrate at 1, 5 and 20 mM and glucose with β-hydroxybutyrate in combinations of 10 with 5 and 50 with 20 mM, respectively. Phagocytosis occurred at similar levels in diabetics and controls at all the glucose and β-hydroxybutyrate concentrations used. The ability of neutrophils from diabetics to kill candida was inhibited by increased concentrations of glucose and β-hydroxybutyrate, both independently and in combination. Candida killing (mean±s.e.) was 20±2-4, 19±2-3 and 13±2-7% at glucose concentrations of 5, 10 and 50 mM; and 20± 3.4, 20±3 and 13±3% at β-hydroxybutyrate concentrations of 1, 5 and 20 mM, respectively, and in glucose and β-hydroxybutyrate combinations of 10 with 5 and 50 with 20 mM was 20 ±2.8 and 10 ±2.8%, respectively. Inhibition was not observed with control neutrophils. These data indicate that although phagocytosis occurs at similar levels in diabetics and controls, killing of candida by the diabetic neutrophil is impaired under conditions of hyperglycaemia and ketosis. The biochemical basis for this effect is discussed. [ABSTRACT FROM AUTHOR]

The article comments on the second report of the British Society of Immunology working party on clinical immunology. The report of 1968 on Hospital Scientific and Technical Services recognized the immediate need for immunological services within the National 1-kaith Service. The Royal College of Pathologists recognized immunology as an independent speciality in 1969 and soon after created a separate examination in immunology. In 1972, the report of the Joint Committee on Clinical Immunology stressed the need for specialist immunological laboratories in hospitals as well as the need to have parts created for immunologists with wide laboratory training, both for clinicians and non-clinicians.

The beneficial effect of cervical cytology in reducing the incidence of invasive cervical cancer is well accepted, but many issues regarding specific patterns of screening remain to be resolved, and preventive programmes need to be adapted to regional characteristics. In a case-control study conducted in Latin America, we investigated cytological screening histories of 759 cases of invasive cervical cancer and 1430 controls, with participation rates of 99% and 96%, respectively. Fifty per cent of the cases and 29% of the controls reported never having been screened. Screening was less common among older, less educated and less parous women; non-users of oral contraceptives and women without histories of venereal diseases. There was also evidence that older women and those with multiple partners had longer intervals between examinations. The relative risk (RR) associated with no prior screening was approximately 3 and was not modified by other risk factors. Women reporting a Pap smear within 24–47 months before interview had the same RR as those examined within 12–23 months. Women tested longer ago had higher risks, but still much lower than women never examined. There was evidence that one examination is associated with less reduction in risk than two, regardless of the interval since last Pap smear. Screening appeared to reduce risk of both squamous cell carcinomas and adenocarcinornas. As expected, cases presenting at advanced stages were less likely to have been screened and reported longer intervals since their last examination. These results support the need to concentrate limited resources in the groups that need screening most, mainly older and less educated women who have never been screened. [ABSTRACT FROM PUBLISHER]

Vaccination of humans against rotavirus (RV) diarrhea may be accomplished by oral immunization with attenuated animal strains known to be antigenically very similar to human strains. To define better the degree of infectivity in nature of these animal strains for humans, we conducted surveillance for RV infection/diarrhea in 180 farm workers, their 161 family contacts, and the 566 animals (512 cattle, 35 pigs, and 19 sheep) on 14 farms in rural Panama. No correlation between the high infection rates in farm workers (72%) and their family contacts (78%) and in cattle (56%) could be demonstrated. Heads of families with four or more children with RV infection experienced a twofold greater rate of RV infection compared with heads of families of similar size without RV infection. Despite the close similarity between human and bovine RV,in Panama intrafamilial (particularly child-to-child or child-to-parent) rather than interspecies transmission appeared to be the most important route for the spread of this highly infectious virus. [ABSTRACT FROM PUBLISHER]

For better understanding of the role of humoral immunity in ameliorating infections with rotavirus (RV) and Norwalk virus (NW), 305 Cuna Indians living on two isolated islands located off Panama's Carribean coast were surveyed daily for diarrhea over a seven-month period. Nine (8%) of 108 persons with a baseline RV antibody titer of greater than 1:4 developed RV infection compared with 70 (46%) of 151 persons with a baseline RV antibody titer of less than 1:4 (P less than .001). Thirty-eight (25%) of 151 persons of all ages with baseline RV antibody titer of less than 1:4 had at least one episode of RV diarrhea compared with 6 (6%) of 108 persons who had baseline RV antibody titers of greater than 1:4 (P less than .001). Thirty-two (47%) of 68 persons of all ages who had a baseline NW antibody titer of less than 1:100 developed NW infection compared with 30 (13%) of 237 persons with a baseline NW titer of greater than 1:100 (P less than .001). The high NW and RV infection rates and the excellent levels of protection provided by specific preexisting humoral antibody to these agents should promote activities aimed at developing vaccines for preventing these infections. [ABSTRACT FROM AUTHOR]

Thirty five female Cebus albifrons monkeys (16 adolescents and 19 adults) were infected vaginally with herpes simplex virus (HSV) type 2. Fifteen developed spontaneous recurrent genital HSV infections. All 35 were killed for study eight to 12 months after primary infection, and tissue from the vagina, cervix, uterus, ovary, paracervical autonomic plexus, and lumbosacral dorsal root ganglia was examined for latent HSV. HSV type 2 was recovered from the lumbosacral dorsal root ganglia of eight animals. Host age was the most important variable influencing viral latency; 69% of adolescents and 42% of adults had latent HSV type 2 infections. Animals that developed latent infections were significantly easier to infect, shed virus during the primary infection significantly longer, and had more severe primary disease than those who did not become latently infected. [ABSTRACT FROM PUBLISHER]

Rates of hepatitis B virus infection varied significantly among Panamanian Indian tribes. Chocó and Mainl~_nd Cuna Indians had a greater prevalence of antibody to hepatitis B surface antigen than Guaymi and Island Cuna Indians. The village water supply appeared to be the major environmental difference that distinguished the tribes from one another. Since contaminated water plays a role in the transmission of enterovirus, an attempt was made to assess relative exposure to contaminated water by determination of the prevalence of antibodies to reovirus and coxsackievirus B in children 10 years old or younger. Infection with coxsackievirus B occurred more frequently in Chocó and Mainland Cuna Indians than in Guaymi or Island Cuna Indians. Although essentially all children tested were exposed to reoviruses, Mainland euna Indians had the highest geometric mean titers of antibody, followed by Chocó, Guaymi, and Island Cuna Indians in descending order. This parallel in rates of hepatitis B and enterovirus infection supports the hypothesis that fecal-oral transmission of hepatitis B virus is important in certain populations. [ABSTRACT FROM PUBLISHER]

Several authors have suggested that the host genome determines the occurrence of chronic HBs Ag (hepatitis B surface antigen). In attempts to evaluate this possibility, total infection rate and the combined frequencies of HBs Ag and antibody to HBs Ag in the population have not been analyzed. Using counterelectrophoresis to assay HBs Ag and radioimmunoprecipitation to measure antibody to HBs Ag, we tested sera from 255 Panamanian Guaymi Indians. They represented 48 families and 32 living units. Clusters of chronically antigenemic individuals were found in families. Clusters of infection were not found in families or living units. Differences in family composition (age and sex) did not explain the increased occurrence of HBs Ag. These findings support the hypothesis that some humans have an inherited susceptibility to chronic infection with hepatitis B virus after exposure. [ABSTRACT FROM PUBLISHER]

An exploratory case-control study was conducted to assess whether the many reported differences in the immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of CFS. Although many studies have reported differences between cases and controls in various measures of immune function, none of these differences were found in all studies. In this study, no differences were found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels; delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface markers in the total CFS population. However, when the patients were subgrouped by type of disease onset (gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences were seen. [ABSTRACT FROM AUTHOR]

The production of autoantibodies characteristic of different autoimmune disease subsets is thought to be controlled primarily by genetic factors, whereas non-genetic factors are generally believed to be of secondary importance. A patient with systemic lupus erythematosus (SLE) and polymyositis (PM) who experienced frequent relapses associated with changing clinical manifestations and autoantibody specificities is reported. Her initial presentation as SLE with anti-Sm antibodies shifted to the onset of PM with temporal production of a different set of autoantibodies. The latter antibodies disappeared when myositis resolved, followed by the reappearance of autoantibodies and clinical manifestations characteristic of SLE. The shifts of autoantibody profiles in association with variable clinical manifestations in this patient argue that environmental factors may play a more important role in autoimmunity than previously supposed, and that interplay between environmental triggers and genetic predisposing factors may lead to the constellation of autoimmune disease manifestations exhibited at a particular time. [ABSTRACT FROM PUBLISHER]

DNA-dependent protein kinase (DNA-PK) consists of a DNA binding subunit (Ku autoantigen), and catalytic subunit (DNA-PKes). In the present study, human autoantibodies that recognize novel antigenic determinants of DNA-PK were identified. One type of autoantibody stabilized the interaction of DNA-PKes with Ku and recognized the DNA-PKes-Ku complex, but not biochemically purified DNA-PKes. Another type recognized purified DNA-PKes comprise a linked autoanitbody set, since antibodies recognizing purified DNA-PKes were strongly associated with stabilizing antibodies, whereas stabilizing antibodies were strongly associated with anti-Ku. This hierarchial pattern of autoanitbodies specific for components of DNA-PK (anti-Ku > stabilizing antibodies > anti-DNA-PKes) may have implications for the pathogenesis of atuoimmunity to DNA-PK and other chromatin particles. The data raise the possibility that altered antigen processing and/or stabilization of the DNA-PKes-Ku complex due to autoantibody binding could play a role in spreading autoimmunity from Ku to the weakly associated antigen DNA-PKes. [ABSTRACT FROM AUTHOR]

Neutrophil locomotion, phagocytosis and killing of Candida a/Means, and plasma opsonization of brewer's yeast were studied in 44 out-patients with chronic liver disease. There were four diagnostic groups: alcoholic liver disease (ALD), chronic active hepatitis (CAH), primary biliary cirrhosis (PBC) and cryptogenic cirrhosis (CC). Results were compared with a control group of patients with non-malignant disorders of the upper alimentary tract, Neutrophil locomotion induced by zymosan-activated autologous plasma was significantly depressed in patients with ALD and, to a lesser extent, in cryptogenic cirrhosis. With plasma from healthy donors, the patients' neutrophils showed normal locomotion. Plasma from patients with CAl-I gave slightly but significantly reduced phagocytosis of both Candida a/Means and brewer's yeast, but the patients' cells had normal phagocytic and killing activity in the presence of normal plasma. Thus, no intrinsic abnormality in neutrophil function was found in these patients, but plasma defects, which differed in cirrhoses of different underlying aetiology, led to impaired neutrophil locomotion or phagocytosis. No correlations were found between these plasma defects and circulating levels of C3, C4, immune complexes or IgA. [ABSTRACT FROM AUTHOR]

Sixty-eight per cent of a consecutive series of 65 renal biopsies showed immune deposits in extraglomerular blood vessels. Although they occurred with a variety of clinical disorders and histological diagnoses. they were associated in particular with an acute nephritic syndrome. focal proliferative glomerulonephritis and non-specific mesangial changes. IgM was the commonest immunoglobulin class to be deposited and higher levels of IgM-containing complexes were detected in the serum of those patients with vascular deposits. Hitherto, immunofluorescent studies of renal biopsies have concentrated mostly on glomeruli but this study suggests that the extraglomerular vasculature deserves closer attention. The mechanisms for this pattern of localization are discussed. [ABSTRACT FROM AUTHOR]

Counterelectrophoresis was used for testing of 1,623 sera from individuals from Panama's three major Indian tribes for hepatitis B antigen (HB Ag). A random subsample from each group was tested for antibody to HB Ag (HB Ab) by the radioimmunoprecipitation technique. HB Ag was significantly more prevalent among the Guaymi than among either Choco or Cuna Indians, but prevalence of both HB Ag and HB Ab among the Guaymi varied by village. The Chocó had a greater frequency of HB Ab in every age group than the Guaymi, indicating that although Chocó were more intensively exposed to HB Ag than Guaymi, fewer became chronically antigenemic. Using the prevalences of HB Ag and HB Ab, we calculated the percentage of infected individuals who remained chronically antigenemic and found it to be significantly higher among younger people. [ABSTRACT FROM PUBLISHER]

This article discusses a case of a male, aged 51 years, who was admitted as a medical emergency severely ill. Over 9 weeks he had become increasingly tired and weak and developed a rash on his trunk and limbs. For 3 weeks he had been feverish with a produ

This article discusses a case of dermatitis herpetiformis. In this case a lady suddenly developed widespread annular areas of erythema and blistering on her trunk and limbs. The blisters were up to 2 cm in diameter and the irritation was severe. There was

This article discusses a case of acquired CI esterase deficiency with cold agglutinin disease associated with monoclonal IgM antibodies. In the given case, 76 years-old male's was of Raynaud's phenomenon affecting his hands, feet and face for approximately 2 years. He also described darkening of his urine 2 hours after cold exposure sufficient to produce Raynaud's phenomenon. No abnormality discovered: in particular no evidence of hepatosplenomegaly or lymphadenopathy. His toes and feet became cold and blue during the examination.

This article discusses a case of pemphigus foliaceus associated with SLE. In the given case, a 41 year-old male was first seen in February 1973, with 3 month history of crusted lesions developing on his trunk. A clinical diagnosis of pemphigus foliaceus was supported by the histology. In April 1976 he developed tinea corporis which was treated with miconazole. One year later it returned but responded to griseofulvin therapy. There are no cutaneous signs of SLE but he usually has a few lesions characteristic of pemphigus foliaceus.

This article presents immunofluorescent and serological findings in 110 patients with suspected bullous skin disorders. One hundred and ten patients with suspected bullous skin disease were investigated immunologically. Clinically they consisted of 63 with overt bullae and 47 without. The latter were mostly characterized by the presence of "itchy papules" and are designated as such. The 47 patients in the itchy popular category were usually biopsied to seek diagnositic information in the presence of clinical uncertainty. Most biopsies were taken from nonlesional skin and examined by immunofluorescence for the presence of IgG, IgA, IgM, C3, CIq and fibrinogen.