Reduced levels of IgG subclasses and IgA in young children with asthma

Serum immunoglobulins including IgG subclasses were measured in 73 unselected children with asthma. The results showed that 22 (30%) had partial IgA and/or IgG₄ subclass deficiency. Clinical assessment showed that 21 children were infection-prone, and 52 were not. Further analysis showed that infection-prone children were significantly different from non-infection-prone children with regard to familial history of allergy (29% vs 60%, p = 0.015), elevated IgE (62% vs 33%, p = 0.021), IgA deficiency (38% vs 15%, p = 0.38) and IgG subclass deficiency (24% vs 4%, p = 0.018). These results suggest that there may be subgroups of children with asthma who are also immunodeficient.     

Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet-activating factor

The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED₅₀ values in the range 20–30 mg/kg/3 days. Both were also equiptent in suppression of PMN infiltration induced by PAF with ED₅₀ values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen-induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis.     

Migration patterns of pathogenic and nonpathogenic Naegleria spp.

Four species of Naegleria were tested for their ability to migrate under agarose. Pathogenic N. fowleri strains exhibited rapid locomotion at 37 degrees C. Environmental isolates of N. fowleri moved faster than clinical isolates which had been kept in axenic culture for longer periods, and this result was confirmed by using the 84-2205-7 strain kept in axenic culture for 1 or 5 months. Nonpathogenic N. gruberi strains migrated actively at 28 degrees C but not at 37 degrees C; moreover, even at 28 degrees C, active amoebae constituted only a small proportion of the whole. The temperature-tolerant, nonpathogenic species N. lovaniensis moved more slowly than N. fowleri at 37 degrees C. In contrast, N. australiensis, which is temperature tolerant as well as pathogenic for mice, migrated at a rate comparable to that of N. fowleri. There appears to be a direct correlation between the locomotive ability of free-living amoebae and their pathogenic potential.     

Effect of twenty-three chemotherapeutic agents on the adherence and growth of Giardia lamblia in vitro

The sensitivity of Giardia lamblia to 23 chemotherapeutic agents was evaluated in vitro with a Growth Inhibition Assay and a recently developed Adherence Inhibition Assay. Of the four established anti-giardia drugs, tinidazole, metronidazole, and furazolidone were found to have strong inhibitory effects on both growth and adherence, while mepacrine had a strong effect on growth only. Three drugs (mefloquine, doxycycline and rifampin) not previously used in giardiasis were found to have significant activity in vitro and may deserve consideration for clinical evaluation of efficacy. Also, the concurrent use of these two in vitro methods provided significant insights into the modes of action of some of these drugs on G. lamblia.     

Training in clinical genetics and genetic counseling in Asia

The status of training in clinical genetics and genetic counseling in Asia is at diverse stages of development and maturity. Most of the training programs are in academic training centers where exposure to patients in the clinics or in the hospital is a major component. This setting provides trainees with knowledge and skills to be competent geneticists and genetic counselors in a variety of patient care interactions. Majority of the training programs combine clinical and research training which provide trainees a broad and integrated approach in the diagnosis and management of patients while providing opportunities for research discoveries that can be translated to better patient care. The background on how the training programs in clinical genetics and genetic counseling in Asia evolved to their current status are described. Each of these countries can learn from each other through sharing of best practices and resources.     

Epidemiologic analysis of sporadic Salmonella typhi isolates and those from outbreaks by pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) was used to compare and analyze 158 isolates of Salmonella typhi from five well-defined outbreaks of typhoid fever in Malaysia and also isolates involved in sporadic cases of typhoid fever occurring during the same period. Digestion of chromosomal DNAs from these S. typhi isolates with the restriction endonucleases XbaI (5'-TCTAGA-3'), SpeI (5'-ACTAGT-3'), and AvrII (5'-CCTAGG-3') and then PFGE produced restriction endonuclease analysis (REA) patterns consisting of 11 to 24 DNA fragments ranging in size from 20 to 630 kbp. Analysis of the REA patterns generated by PFGE after digestion with XbaI and SpeI indicated that the S. typhi isolates obtained from sporadic cases of infection were much more heterogeneous (at least 13 different REA patterns were detected; Dice coefficient, between 0.73 and 1.0) than those obtained during outbreaks of typhoid fever. The clonal nature and the close genetic identities of isolates from outbreaks in Alor Setar, Penang, Kota Kinabalu, Johor Bahru, and Kota Bahru were suggested by the fact that only a limited number of REA patterns, which mostly differed by only a single band, were detected (one to four patterns; Dice coefficient, between 0.82 and 1.0), although a different pattern was associated with each of these outbreaks. Comparison of REA patterns with ribotyping for 18 S. typhi isolates involved in sporadic cases of infection showed a good correlation, in that 72% of the isolates were in the same group. There was no clear correlation of phage types with a specific REA pattern. We conclude that PFGE of s. typhi chromosomal DNA digested with infrequently cutting restriction endonucleases is a useful method for comparing and differentiating S. typhi isolates for epidemiological purposes.     

Early decay of human neutrophil chemotactic responsiveness following isolation from peripheral blood.

The data presented show an early decay of chemotaxis and random mobility, compared to phagocytic and metabolic activity in neutrophils kept at 4 degrees C and 37 degrees C. Evidence is presented which suggests that hydrogen peroxide is one of the contributing factors in the loss of neutrophil chemotactic properties. The early decay of neutrophil chemotactic responsiveness is discussed in terms of the auto-oxidative damage caused to the cell membrane by hydrogen peroxide.     

Recombinant VP9-based enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Banna virus (genus Seadornavirus)

Banna virus (BAV, genus Seadornavirus, family Reoviridae) is an arbovirus suspected to be responsible for encephalitis in humans. Two genotypes of this virus are distinguishable: A (Chinese isolate, BAV-Ch) and B (Indonesian isolate, BAV-In6969) which exhibit only 41% amino-acid identity in the sequence of their VP9.The VP7 to VP12 of BAV-Ch and VP9 of BAV-In6969 were expressed in bacteria using pGEX-4T-2 vector. VP9 was chosen to establish an ELISA for BAV, based mainly on two observations: (i). VP9 is a major protein in virus-infected cells and is a capsid protein (ii). among all the proteins expressed, VP9 was obtained in high amount and showed the highest immuno-reactivity to anti-BAV ascitic fluid.The VP9s ELISA was evaluated in three populations: French blood donors and two populations (blood donors and patients with a neurological syndrome) from Malaysia, representing the region where the virus was isolated in the past.The specificity of this ELISA was >98%. In mice injected with live BAV, the assay detected IgG-antibody to BAV infection 21 days post-injection, which was confirmed by Western blot using BAV-infected cells.The VP9 ELISA permits to determine the sero-status of a population without special safety precautions and without any requirements to propagate the BAV. This test should be a useful tool for epidemiological survey of BAV.     

Lymphocyte-neutrophil interactions: opposite effects of interleukin-2 and tumour necrosis factor-beta (lymphotoxin) on human neutrophil adherence

Human neutrophil adherence was enhanced by recombinant human tumour necrosis factor-beta (TNF beta) but suppressed by recombinant human interleukin-2 (IL-2). The opposite effects of these two lymphokines were observed over a range of concentrations consistent with their other biological activities, occurred within 15 min of incubation, and were still evident after 60 min. Pretreatment of neutrophils with both IL-2 and TNF beta resulted in adherence values intermediate between the values obtained with the individual lymphokines. IL-2 suppressed the stimulatory effects of both the chemotactic peptide formyl-methionyl-leucyl-phenyl-alanine (FMLP) and the phorbol ester phorbol myristate acetate (PMA). The combination of TNF beta with either FMLP or PMA produced enhancement of neutrophil adherence which exceeded that of either agent alone. These effects of the lymphokines were not due to endotoxin contamination since their effects were sensitive to heating and insensitive to polymyxin B treatment. These experiments provide further evidence for the critical role of these lymphokines in the regulation of acute and chronic inflammatory processes.