Pathogenic anti-DNA antibodies in SLE: idiotypic families and genetic origins

We have adopted an idiotypic approach to study the double stranded DNA (dsDNA) binding antibodies of systemic lupus erythematosus (SLE). Three anti-idiotypic reagents, 8.12, 3I, and F4, identify cross reactive idiotypes that are each expressed on anti-dsDNA antibodies in the sera of many patients with SLE. These idiotypic antibodies are implicated in the pathogenesis of SLE as they are present in immune complex deposits in the kidneys of patients with SLE glomerulonephritis. The autoantibody associated idiotypes are also expressed on antibodies that do not bind DNA. We are investigating the origin of the pathogenic anti-dsDNA antibodies of SLE by comparing the autoantibodies, the antibodies to foreign antigens, and the myeloma proteins that express each SLE associated idiotype. In conjunction with serological analysis of these idiotypic systems, molecular genetic studies indicate that both the 8.12 and the 3I autoantibody associated idiotypes may be germline encoded, while the F4 idiotype is generated by somatic mutation. The data further suggest that the antigenic specificity of the pathogenic anti-DNA antibodies of SLE is acquired through somatic mutation of germline immunoglobulin genes. By studying the regulation of genes capable of encoding pathogenic autoantibodies, in both SLE patients and non-autoimmune individuals, we may be able to elucidate the pathogenesis of autoimmune disease and begin to design more effective therapeutic interventions.     

Ewingella americana: recurrent pseudobacteremia from a persistent environmental reservoir.

From September 1981 through April 1984, 20 patients at one hospital were identified with Ewingella americana pseudobacteremia. Case-control studies demonstrated an association between having a positive blood culture for E. americana and having blood for culture obtained simultaneously with blood obtained for coagulation studies (15 of 19 case patients versus 4 of 38 controls; P = 4.5 X 10(-7)). Review of blood-drawing procedures showed that blood for coagulation studies and culture was drawn with the same syringe, and coagulation tubes were filled before blood culture tubes. Some phlebotomists were not using new sterile needles to inoculate blood culture bottles. Collection tubes for coagulation studies were prepared in the hospital, and E. americana was isolated from all 52 unused coagulation tubes tested. Solutions prepared in the hospital may constitute a persistent inanimate environmental reservoir for this uncommon microorganism. Pseudobacteremia can result in unnecessary antimicrobial therapy for some patients, incurring the risks of adverse drug reactions, selection of drug-resistant bacteria, and increased health care costs.     

Risk factors for HIV infection in injection drug users and evidence for onward transmission of HIV to their sexual partners in Chennai, India

OBJECTIVES: Determining HIV prevalence in injection drug users (IDUs) and their regular sex partners in Chennai, India. METHODS: A total of 226 IDUs and their regular sex partners were enrolled during April-July 2003. After informed consent was obtained, a semistructured questionnaire was administered and serum was tested for HIV antibody. RESULTS: The HIV seroprevalence was 30% (68/226) in IDUs and 5% in their regular sex partners (11/226). While in 25% of couples only the male partner was HIV positive, 5% of the couples were concordant for HIV infection and 70% were HIV negative. Fifty-seven percent of the HIV-positive IDUs and 45% of the HIV-infected women thought that they had "no chance" or "very little chance" of getting HIV, reflecting low HIV risk perception. More than 20% IDUs reported borrowing or lending of injection equipment. In univariate analyses "sex" and "condom use" with sex workers had no bearing but "more than twice a day injecting frequency," "history of incarceration," "tattoos," "recruitment from northern part of the city," and ever-injecting drugs in drug-selling places had significant association with HIV infection in IDUs. In an adjusted model, the odds of HIV infection were 2 times higher among IDUs who had ever injected drugs in drug-selling places and 6 times higher in those who were recruited from the northern part of central Chennai. CONCLUSION: Reducing sharing of injection equipment and unsafe tattooing through targeted and environmental interventions, increasing HIV risk perception, and promoting safer sex practices among IDUs and their sex partners are urgent program needs.     

Nosocomial Pseudomonas pickettii colonization associated with a contaminated respiratory therapy solution in a special care nursery.

Pseudomonas pickettii caused respiratory tract colonization in five infants in the special care nursery of a Chicago hospital. All organisms had the same antimicrobial susceptibilities. Endotracheal suctioning with saline from 5-ml unit-dose vials was identified by epidemiologic investigation as a risk factor for colonization. The vials of saline were contaminated with a strain of P. pickettii having the same antimicrobial susceptibility pattern as the isolates from patients. As part of an investigation of the manufacturing plant where the saline solution was produced, P. pickettii was recovered from deionized water used to make the product and from several sites in the processing line. Bypassing of a 180 degrees F (ca. 82 degrees C) water-holding tank appeared to be temporally related to product contamination. The ability of P. pickettii to survive and grow in this solution has been demonstrated in the laboratory. This outbreak demonstrates that, despite pertinent Food and Drug Administration regulations and company programs for identifying such contamination, intrinsically contaminated solutions can occasionally reach the bedside of the patient.     

Effect of histamine and methacholine on nasal airway resistance in atopic and nonatopic subjects: Comparison with bronchial challenge and skin test responses

Serial nasal, intracutaneous, or bronchial challenges were carried out with solutions containing 2- or 3-fold increments in histamine (H) or methacholine (Meth) concentration until nasal airway resistance (NAR) increased by more than 100%, a large intracutaneous reaction was elicited, or FEV₁ decreased by 20% or more. Thirty nonatopic and 48 asymptomatic atopic subjects were studied, the latter group divided into rhinitic patients with and without asthma. Several types of data analysis demonstrated there was no significant difference in the nasal or cutaneous effects of H or Meth between the atopic and nonatopic groups. Comparable results were obtained in a subgroup of 39 subjects (13 normal, 13 atopic, and 13 atopic with asthma) who underwent all six test sequences (i.e., nasal, cutaneous, and bronchial with both drugs). As expected, the asthmatics showed significantly increased bronchial reactivity to both agents. In comparison with Meth, H had a much greater effect on the nasal mucosa and skin than on the bronchi. It is concluded that, contrary to bronchial responses, but in accord with cutaneous reactivity, the nasal responses of nonatopic subjects, atopic persons with allergic rhinitis alone, and subjects with both allergic rhinitis and asthma show no intergroup differences on testing with H or Meth.     

Adherence of Streptococcus pneumoniae to Human Bronchial Epithelial Cells (BEAS-2B)

Pneumococcal adherence to alveolar epithelial cells and nasopharyngeal epithelial cells has been well characterized. However, the interaction of Streptococcus pneumoniae with bronchial epithelial cells has not been studied. We have now shown that pneumococci bind specifically to a human bronchial epithelial cell line (BEAS-2B cells). Pneumococci adhered to BEAS-2B cells in a time- and dose-dependent manner. These results suggest that the bronchial epithelium may serve as an additional site of attachment for pneumococci and demonstrate the utility of the BEAS-2B cell line for studying mechanisms of pneumococcal infection.     

Behavioral and hormonal responses to stress in the newborn mouse: Effects of maternal deprivation and chlordiazepoxide

These studies investigated behavioral and hormonal responses to stress in developing mice. Experiment 1 examined the effects of 24-hr maternal deprivation on corticosterone (CORT) secretion and ultrasonic vocalization (UVZ) rate in 4-, 8-, and 12-day-old mice. At these ages, exposure to a novel environment resulted in minimal changes in CORT secretion. Maternal deprivation increased pups′ CORT secretion in an age-dependent fashion but did not affect their UVZ rate. The aim of experiment 2 was to test the effects of cholordiazepoxide (CDP), an anxyolytic compound, on CORT secretion and UVZ in both normally reared and in maternally deprived 8-day-old mice. CDP administration elevated CORT increases in deprived (DEP) animals. CDP affected UVZ only in nondcprived (NDEP) animals: UVZ ratewas decreased by high CDP doses Overall, these findings demonstrate that the infant mouse shows a period of stress hyp9oresponsiveness similar to the rat and that maternal presence contributes to inhibit adrenocorticalactivity. CDP administration, butnot novelty exposure, increased CORT secretion in 8-day- old normally reared mice suggesting that during the stress hyporesponsive period, the HPA axis is capable of responding only to specific stimuli. Changes in HPA axis activity and UVZ rateresulting from maternal deprivation and/or CDP challenge do not seem to be directly related. ©1994 John Wiley & Sons, Inc.     

Effect of atropine and vagotomy on response of transplanted pancreas.

It is well established that atropine and vagotomy inhibit pancreatic enzyme secretion in response to intestinal stimulants such as fat or amino acids. These effects are usually attributed to interference with hypothetical vagal cholinergic mechanisms that facilitate release of cholecystokinin. To determine whether atropine or vagotomy interferes with release of humoral stimulants of pancreatic enzyme secretion, we studied their effect on protein secretion from an autotransplanted portion of pancreas in response to intestinal stimulants in dogs. The transplanted pancreas was as sensitive as the intact pancreas to stimulation by exogenous caerulein, a cholecystokinin-like peptide, and this response was not altered by atropine or vagotomy. Therefore, if vagotomy or atropine interferes with release of humoral pancreatic stimulants, they would be expected to reduce the response of the transplanted pancreas just as they do of the intact pancreas. Truncal vagotomy caused no significant change in protein secretion from the transplant in response to intestinal perfusion with sodium oleate or tryptophan. Atropine was tested only against sodium oleate and caused no change in response. We conclude that release of humoral pancreatic excitants of protein secretion in response to intestinal stimulants is not significantly changed by atropine or vagotomy.     

Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic

In a sample of 5483 adults who had been legally adopted early in life by persons not biologically related to them, 33 were identified, from mental hospital records, for whom a diagnosis of definite schizophrenia (chronic, latent, or acute) could be agreed upon by four raters. An equal number of matched controls were selected from the sample of adopted individuals who had never been admitted to a mental hospital. Ninety percent of the living parents, siblings, and half-siblings, biological and adoptive, cooperated in an extensive psychiatric interview permitting a consensus diagnosis by three blind raters. Schizophrenia and uncertain schizophrenia were found to be significantly concentrated in the population genetically related to the schiziphrenic adoptees. Their adoptive relatives did not differ from the control populations in the prevalence of schizophrenic illness.This was presented at the Annual Meeting of the American Society of Human Genetics, Portland. Oregon, October 18, 1974.     

Maternal pituitary-adrenal responsiveness as a function of differential treatment of rat pups

The effects of litter separation and pup treatment on the maternal pituitary-adrenal system were investigated in 3 experiments. Lactating females did not show a pituitary-adrenal response to separation from their pups. However, the lactating females showed an increase in plasma corticosterone when their pups had been briefly removed and then returned. If, in addition, the pups were subjected to a noxious stimulus (electric shock) during the 2-min separation, mothers showed a further increase in corticosterone. When pups were returned after 3 hr of separation, mothers again showed a differential pattern of corticoid responsiveness. The magnitude of the mother's pituitary adrenocortical response depended upon the intensity of treatment given to the pups. These data lend physiological support to behavioral studies which have shown that maternal behavior is differentially influenced by pup-produced stimuli.