The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland

Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism occurring in most cell types. However, this housekeeping gene is expressed at very high levels in a number of mammalian tissues including the lactating mammary epithelium, suggesting additional roles for XOR in these tissues. Mice with targeted disruption of XOR were generated to assess these potential additional roles. XOR-/- mice are runted and do not live beyond 6 wk of age. Strikingly, however, XOR+/- females, although of healthy appearance and normal fertility, are unable to maintain lactation and their pups die of starvation 2 wk postpartum. Histological and whole-mount analyses showed that in XOR+/- females the mammary epithelium collapses, resulting in premature involution of the mammary gland. Electron microscopy showed that XOR is specifically required for enveloping milk fat droplets with the apical plasma membrane prior to secretion from the lactating mammary gland. We present evidence that XOR may have primarily a structural role, as a membrane-associated protein, in milk fat droplet secretion and thus XOR provides another example of "gene sharing". About 5% of women experience primary lactation insufficiency. The above observations suggest that human females suffering from xanthinuria, a deficiency in XOR, are potential candidates for lactation problems.     

Reactivation of Epstein-Barr virus in Sj?gren''s syndrome

Summary Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by severe dryness of the eyes and mouth, resulting from lymphocytic infiltration of the lacrimal and salivary glands. SS may exist as a primary condition (primary SS, 1° SS) or as a secondary condition (2° SS) in association with rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis. In some 1° SS patients, there may be involvement of the extraglandular organs, including skin, kidney, liver, lung and nervous system. Furthermore, these patients may develop a lymphoproliferative syndrome that includes lymphadenopathy and increased risk of lymphoma. In the pathogenesis of SS, a role for Epstein-Barr virus (EBV) has been suggested because: (a) EBV is present in salivary gland epithelial cells of normal individuals and exaggerated immune responses against EBV could play a role in the destruction of salivary glands in SS; (b) SS salivary gland biopsies contain increased levels of EBV DNA in comparison to normal salivary glands, indicating viral reactivation and inability of lymphoid infiltrates to control EBV replication in SS patients; and (c) salivary gland epithelial cells in SS patients express high levels of HLA-DR antigens and may present EBV-associated antigens to immune T cells in SS patients. Therefore, SS may represent a situation in which genetically predisposed individuals (i. e., HLA-DR3-DQA4-DQB2) have a persistent but ineffectual T cell immune response against EBV at its site of latency. Among 14 non-Hodgkin's lymphomas that developed in SS patients, EBV DNA was detected in increased amounts in the tumor tissue of one patient. Characterization of this tumor DNA revealed: (a) polyclonal immunoglobulin gene rearrangements; (b) EBV DNA with an unusual restriction fragment length polymorphism pattern involving the Bam M fragment; and (c) EBV terminal repeat sequences suggestive of viral replication, similar to those reported in EBV lymphomas occurring in other immunocompromised individuals. Early recognition of this clinical problem may allow beneficial use of antiviral agents.     

Anaphylaxis: a 7-year follow-up survey of 46 children.

BACKGROUND: Little is known about the frequency of and the features associated with recurrent anaphylaxis in pediatric populations. During 1994 to 1996, we enrolled 76 children affected by anaphylaxis in a prospective study to analyze their clinical and allergic features. OBJECTIVE: To undertake a follow-up study of these children to ascertain how many experienced a recurrence of anaphylaxis. METHODS: After a mean interval of 7 years, a pediatric allergist conducted a telephone interview of patients who had been enrolled in our 1994-1996 study. RESULTS: A telephone interview was successfully completed in 46 (61%) of the 76 patients who had been enrolled in our 1994-1996 study. Of these 46 patients, 14 (30%) had experienced a recurrence of anaphylaxis. Children with atopic dermatitis either during 1994 to 1996 (64% vs 34%; P = .04) or at the time of the current study (43% vs 16%; P = .03) and those with urticaria-angioedema at the time of the current study (93% vs 31%; P = .0002) were found to be at a significantly higher risk for recurrent anaphylaxis. Furthermore, those children who were sensitive to at least 1 food allergen during 1994 to 1996 were more likely to have experienced a recurrence of anaphylaxis (93% vs 56%; P < .04). CONCLUSIONS: This study suggests that patients may have a greater risk of recurrence of anaphylaxis if they have atopic dermatitis, urticaria-angioedema, or at least 1 positive result of skin prick tests to food allergens.     

Identifying recent HIV infections using the avidity index and an automated enzyme immunoassay

We evaluated a procedure for identifying recent HIV infections, using sequential serum samples from 47 HIV-positive persons for whom the seroconversion date could be accurately estimated. Each serum sample was divided into two aliquots: one diluted with phosphate-buffered saline and the other diluted with 1 M guanidine. We assayed the aliquots with the automated AxSYM HIV1/2gO test (Abbott Diagnostics Division), without modifying the manufacturer's protocol. We then calculated the avidity index (AI): the ratio of the sample/cutoff value for the guanidine aliquot to that of the phosphate-buffered saline aliquot. We analyzed 216 serum samples: 34 samples were collected within 6 months of seroconversion (recent seroconversions), and 182 were collected after 6 months. The mean AIs, by time from seroconversion, were 0.68 +/- 0.16 (within 6 months) and 0.98 +/- 0.10 (after 6 months) (P < 0.0001). AI of <0.90 correctly identified 88.2% of recent infections but misclassified as recent infections 13.2% of serum samples collected afterward. The probability of an infection being classified as recent and having AI of > or = 0.90 would be 0.7% in a population with 5% recent infections. AI can identify with a certain degree of accuracy recent HIV infections, and being a quantitative index, it provides different levels of sensitivity and specificity, depending on the selected cutoff value. The standard assay procedure is not modified. This test is simple and inexpensive and could be used for surveillance, decision-making in treatment, and prevention.     

Automated spoken dialogue system for hypertensive patient home management

Recent advances in automatic speech recognition and related technologies allow computers to carry on conversations by telephone. We developed an intelligent dialogue system that interacts with hypertensive patients to collect data about their health status. Patients thus avoid the inconvenience of traveling for frequent face to face visits to monitor the clinical variables they can easily measure at home; the physician is facilitated in acquiring patient information and cardiovascular risk, which is evaluated from the data according to noted guidelines. Controlled trials to assess the clinical efficacy are under way.     

Age-dependent changes in CXC chemokine ligand 10 serum levels in euthyroid subjects.

Circulating levels of cytokines are deeply influenced by aging, and few data about serum chemokines are available. The aim of this study was to evaluate the influence of aging on circulating CXCL10. One hundred forty healthy subjects (70 males and 70 females), 10-79 years of age, underwent fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and CXCL8 serum assay. Thyroid hormone testing for thyroid-stimulating hormone (TSH), antithyroglobulin (AbTg), and antithyroperoxidase (AbTPO) autoantibodies and thyroid ultrasonography were performed in all subjects to exclude the presence of clinical or subclinical thyroid disease. Serum CXCL10 levels were assayed in all subjects and found to be increased in 14 of 70 females (20%) and in 4 of 70 males (5.7%) (p = 0.01). In a multiple linear regression model including age, body mass index (BMI), systolic and diastolic blood pressure, glycemia, total cholesterol, HDL, LDL, triglycerides, TSH, AbTPO, AbTg, and CXCL8, only age was significantly related to CXCL10 [C.R. 1.30 (0.28-2.33), p = 0.001]. No relationship was present between CXCL8 serum levels and age, suggesting a specificity of CXCL10 elevation as a function of age. Results of this study, performed in healthy subjects on an age gradient, demonstrate an increase in serum CXCL10 with advancing age overall in females, supporting the hypothesis of enhanced Th1 immune responses in aging.