Potential Function of Granulysin,Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy.Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9⁺Vδ2⁺ T cells, CD4⁺ T cells and CD8⁺ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection.Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry.Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8⁺ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed.Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection.     

Burkitt's lymphoma in Thai children: an analysis of 25 cases

Twenty five cases of Burkitt's lymphoma in Thai children were diagnosed at the Department of Pediatrics, Siriraj Hospital during the period of 13 years (January 1969 to April 1982). Males were more affected than females with the ratio of 1.7:1. The age ranged from 2 to 11 years with the median age of 4-5 years. The most common clinical manifestations were abdominal mass associated with nausea vomiting, abdominal pain, anorexia, weight loss and generalized lymphadenopathy which occurred in 50-60% of cases. Additional symptoms and signs included anemia, hepatosplenomegaly, edema and pleural effusion. Jaw tumor was found in only 37.5% of the patients. Definite diagnosis depended on the characteristic starry sky appearance of the lymph node biopsy or section of abdominal mass. In advance cases, the tumor cells could be discovered in bone marrow aspiration, ascitic fluid pleural fluid and cerebrospinal fluid. The typical blast cells were detected in the peripheral blood in 4 cases. Antibody to Epstein-Barr virus could be detected in almost all cases with high titers in some cases. Most patients responded very well to local irradiation and chemotherapy with prednisolone plus cyclophosphamide and vincristine or methotrexate. However, relapse occurred rapidly and 80% of the patients died within 3 months after diagnosis with the median survival of only 1 month. Five cases expired early before any specific treatment. The main causes of death were disease, sepsis, excessive bleeding and hyperkalemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute scrub typhus in Northern Thailand: EKG changes

The electrocardiographic (EKG) manifestations of scrub typhus were prospectively evaluated in 29 adult patients who acquired Orientia tsutsugamushi infection in Chiang Rai, Northern Thailand. EKGs were normal in 22 of the 29 patients (76%); minor non-specific changes were found in the other 7 patients; ie ST segment/T wave changes (10%), U waves (7%), and premature ventricular contractions (4%). These results suggest that EKG changes in scrub typhus acquired in areas of diminished antibiotic susceptibility are similar to those observed in O. tsutsugamushi infection acquired elsewhere.     

ENAMEL BONDING WITH SELF-ETCH RESINS

Resin adhesion has revolutionized restorative dentistry because it allows conservative preparations and bonding of various substrates to the tooth structure. Until recently all adhesive systems used an etching agent prior to the priming and bonding steps. Despite excellent clinical and laboratory test results for these three-step systems, simplified adhesive systems were desired and consequently developed to reduce the number of steps during the bonding procedure. Currently there are essentially two philosophies of simplification: the total-etch systems, with a separate etchant and a primer/adhesive; and the self-etching systems, which combine etching and priming in one bottle and have a separate adhesive agent or which combine all three steps in a single solution and application. Unfortunately, despite simplification of bonding products, technique sensitivity, substrate variability, and concerns about enamel bonds have increased. This Critical Appraisal addresses a primary concern about self-etching primers: enamel bonding.     

An Association between Thalassaemia and Autoimmune Haemolytic Anaemia (AIHA)

An association between thalassaemia and autoimmune haemolytic anaemia (AIHA) has not been previously recognized. 10 patients with thalassaemic diseases were found to give positive results to antiglobulin test with polyvalent antiserum. Tests with monovalent antisera revealed immunoglobulins on the red cells in all cases. From history of blood transfusion, auto-antibodies following alloimmunization were very unlikely. IgG, either alone or together with IgM or IgA, was the predominant antibody on the red cells. All cases had warm type AIHA and responded dramatically well with steroid treatment except 3 who eventually needed splenectomy which responded in 2 and failed in 1.     

Comparative identification of protein profiles and major allergens of saliva, salivary gland and whole body extracts of mosquito species in Thailand

Allergic reactions to mosquito bites, such as generalized urticaria or severe local reactions are common problems worldwide. The diverse sources of allergen prepared from different mosquito body parts usage are a major obstacle to obtaining safe and effective tests and immunotherapy for mosquito bite allergy. Thus, the reactions are often not recognized and allergen immunotherapy is seldom used for severe reaction to mosquito bites. In a search for appropriate allergen sources, the protein profiles of saliva, salivary glands and whole body extracts were comparatively analyzed from 4 common mosquito species of Thailand and/or South East Asia; viz. Culex quinquefasciatus, Aedes aegypti, Aedes albopictus and a zoophilic strain, Anopheles minimus. The major allergens in the extracts which elicited specific IgE responses in the pooled sera of subjects allergic to mosquito bites were identified. It was concluded that mosquito saliva was the best source of allergens. Additionally, both species-specific and species-shared allergens of the 4 mosquito species were identified. The major saliva allergens having MWs of 36, 32 and 22 kDa were identified. The identificstion of major allergens should facilitate the production of specific recombinant allergens and contribute to improvement in the diagnosis and specific immunotherapy of Thai mosquito bite allergy patients.     

Screening scheme development for active TB prediction among HIV-infected patients

The objective of this study was to develop and evaluate a simple scoring scheme to screen for active tuberculosis (TB) among HIV-infected patients. Two hundred fifty-seven HIV-infected patients were enrolled in the study between April 2009 and May 2010 from Mae Sai District Hospital and Lampang Regional Hospital. Participants underwent routine evaluations to diagnose TB. Data collection included demographics, medical history, signs and symptoms and laboratory results. Of the 257 HIV-infected patients enrolled, 66 (25.7%) were diagnosed with active TB. Six variables were statistically significant predictors of active TB (p < 0.05): BMI < or = 19 kg/m2, cough > 2 weeks, shaking chills > or = 1 week not taking antiretroviral drugs, a CD4+ cell count level < 200 cells/microl, and had a history of TB. A risk score (ranging from 0 to 16) gave a 92.1% sensitivity of being associated with active TB. A low risk score (< or = 2.0), a moderate risk score (3.0-7.0), and a high risk score (>7.0) gave positive likelihood ratios (LHR+) of 0.04 (95% CI 0.01-0.24), 2.56 (95% CI 1.71-3.85), and 11.72 (95% CI 4.91-27.96), respectively. This screening tool may be useful to identify patients who should have further diagnostic testing for TB, but requires further validation before adoption due to the variability of predicting factors and the prevalence of TB in the target population.     

Association between circulating full-length osteopontin and IFN-gamma with disease status of tuberculosis and response to successful treatment

The T helper type 1 (Th1) immune response plays an important role in protective immunity, pathophysiology and development of tuberculosis (TB). To investigate whether osteopontin (OPN) and other Th1 response-related molecules are associated withTB disease status, including co-infection with HIV, and response to anti-TB treatment, circulating levels of full-length OPN (F-OPN), thrombin-cleaved N-terminal fragment of OPN (N-half OPN), IFN-gamma, IP-10, IL-18, IL-12/ IL-23 (p40), IL-10, IL-15 and C-reactive protein (CRP) were measured before and after anti-TB treatment. Patients with newly active pulmonary TB had significantly higher plasma levels of F-OPN, IFN-gamma and CRP than healthy controls (HC). F-OPN, N-half OPN, IFN-gamma, IP-10, IL-18 and IL-10 levels were higher in patients with extensive TB/HIV co-infection than in patients with a single disease of TB or HIV. Plasma levels of F-OPN correlated well with those of IP-10, IL-18 and N-half OPN among patients with active TB. The F-OPN, IFN-gamma, IP-10 and CRP levels decreased significantly after effective anti-TB treatment. These data suggest that circulating OPN and Th1 response-related molecules, including IFN-gamma, may be regulated in response to expansion of active TB and could serve as markers of disease activity before and during treatment.