Structural aspects of the B*3564 molecule, a novel HLA-B*35 allele identified by sequence-based typing.
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Biomedical subjects
Publications and source records attributed to Y S Lim.
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Gram-negative bacilli with acquired metallo-beta-lactamase (MBL) production have been increasingly reported in some countries, necessitating their detection. The aim of this study was to evaluate the performance of the Hodge test and those of the imipenem (IPM)-EDTA, ceftazidime (CAZ)-mercaptopropionic acid (MPA), and CAZ-sodium mercaptoacetic acid (SMA) double-disk synergy tests (DDSTs). The efficiencies of testing CAZ-resistant and IPM-nonsusceptible isolates were also compared. Strains used for the evaluation were known IMP-1 and VIM-2 MBL-producing isolates and consecutive and CAZ-nonsusceptible isolates of pseudomonads and acinetobacters. The performance of the Hodge test was improved by addition of zinc sulfate (140 microg/disk) to an IPM disk. In DDSTs, EDTA (ca. 1,900 microg) disks were better at detecting MBL-producing strains among pseudomonads, while MPA (3 microl) and SMA (3 mg) disks performed better for acinetobacters. EDTA (ca. 750 microg)-plus-SMA (ca. 2 mg) disks performed better than EDTA, MPA, or SMA disks with both organisms. CAZ-SMA DDSTs failed to detect 22 of 80 (28%) MBL-producing acinetobacters. In conclusion, use of an IPM disk and an EDTA (750 microg)-plus-SMA (2 mg) disk improves performance, and testing IPM-nonsusceptible isolates rather than CAZ-resistant isolates could reduce screening work. Further evaluation of the test is required for the detection of other types of MBL-producing gram-negative bacilli.
By two-color pulse shaping, we simultaneously create virtual and real amplitudes for excitons in GaAs quantum wells, and monitor population and amplitude by pump-probe and four-wave mixing spectroscopies. Excited-state probability amplitude can be induced by the off-resonant, virtual excitations as well as by the resonant, real excitations. Population modulation in time-domain results from the interference between the virtual and real amplitudes, and the modulation depth reveals the relative contributions of these two amplitudes. The fact that virtual and real amplitudes have a phase difference of 90 degrees is demonstrated directly in time-domain.
We report on generation of coherent optical phonon oscillations in 150 microm thick bulk GaN. With photon energy far below the band gap, the generation mechanisms of coherent phonon modes of A1(LO), high- and low-frequency E2 are revealed to be the impulsive stimulated Raman scattering. We find that one among the two degenerate E2 modes is selectively detected with a proper choice of probe polarization. Dephasing times range from 1.5 to 70 ps for different modes, and phonon-three-photon absorbed carrier interactions are compared between the A1(LO) and the E2 mode.
We show that coherent optical phonons in GaAs multiple quantum wells are generated in a completely different way as compared to bulk GaAs. Unlike in bulk GaAs where the ultrafast screening of electric fields by photogenerated charge carriers is known to be dominant, three distinctive generation mechanisms contribute simultaneously in multiple quantum wells. The interplay between impulsive Raman scattering, forbidden Raman scattering, and screening of surface electric fields, whose relative strengths are determined by laser intensity, detuning from the exciton resonance, and the barrier width, generates a rich variety of new phenomena.
In the present study, the mechanical basis of a traditional herbal prescription, Debo. on cytotoxic damage of the brain cells including C6 glial and PC12 cells has been studied. Traditionally, Debo has been employed for the purpose of preventing responses to trauma, ischemia, and other diseases in the nervous system. C6 glial cells were exposed to oxidative stress through the imployment of ZnCl2, and generates H2O2 and hydroxyl radicals by fenton reaction. ZnCl2-induced death of C6 glial cells, which was revealed as apoptosis by chromatin condensation as well as DNA fragmentation. Pretreatment of Debo significantly prevented apoptotic death of C6 glial cells via inhibition of H2O, generation as well as the recovering of an antioxidant, reduced glutathione (GSH). Also, deprivation of serum and glucose, found in ischemia, deceased the viability of PC12 cells up to 60% via generation of H2O2. However, Debo significantly protected cells from ischemic damage through decrease in H2O, generation. Furthermore, Debo markedly inhibited the transcriptional activation of NF-kappaB by ZnCI, in C6 glial cells. These results suggest that Debo may function as an antioxidant system against free radicals and be applicable to protect brain cells against oxidative or ischemic stresses.
We report the case of a female infant with failure to thrive, generalized seborrheic dermatitis, and intermittent diarrhea. Results of laboratory investigation revealed low serum immunoglobulin G IgG levels. She failed to gain additional weight and experienced recurrent infection. She died 3 months later.
Samultang has been traditionally used for treatment of ischemic heart and brain diseases in oriental medicine. However, little is known about the mechanism by which Samultang rescues the myocardial and neuronal cells from ischemic damage. This study was designed to evaluate whether the water extract of Samultang may modulate the production of nitric oxide (NO) in LPS and PMA treated-C6 glial cells to protect the cells from NO-induced cytotoxicity. C6 glial cells treated with both LPS and PMA significantly produced a large amount of NO compared to untreated, PMA, or LPS-treated cells. In parallel with NO production, cotreatment of LPS and PMA induced the severe apoptotic death of C6 glial cells. However, Samultang significantly reduced both cell death and NO production by LPS/PMA in a dose-dependent manner. In addition, the modulatory effects of Samultang on LPS/PMA-induced cytotoxicity and NO production could be mimicked by exogenous treatments of N(G)MMA, a nitric oxide synthase (NOS) inhibitor, and pyrrolidine dithiocarbamate (PDTC), a strong NF-kappaB inhibitor. Treatment of C6-glial cells with LPS/PMA induced the transcriptional activation of NF-kappaB, which was markedly inhibited by Samultang. Taken together, we suggest that the protective effects of Samultang against LPS/PMA-induced cytotoxicity may be mediated by the suppression of NO synthesis via down-regulation of NF-kappaB activation.
Cutaneous necrotizing eosinophilic vasculitis is a recently identified type of vasculitis that is characterized by an eosinophil-predominant necrotizing vasculitis affecting small dermal vessels. Clinically, it presents with pruritic erythematous and purpuric papules and plaques, peripheral eosinophilia and a good response to systemic steroid therapy. This vasculitis can be idiopathic or associated with connective tissue diseases. Although the pathogenic roles of eosinophil-derived granule proteins and interleukins have been documented in diseases associated with eosinophilia, a role of CD40 (a glycoprotein of the tumour necrosis factor receptor superfamily) has rarely been described. We describe two patients with idiopathic hypereosinophilic syndrome (HES) presenting with multiple erythematous patches and plaques on the lower extremities and Raynaud's phenomenon. They satisfied the criteria for the diagnosis of HES by clinical and laboratory investigations. Histopathology of the cutaneous lesions revealed prominent eosinophilic infiltration with local fibrinoid change in vessel walls in the dermis and subcutis. Immunohistochemical detection of CD3, CD4, CD8 and CD40 was performed. Infiltrating eosinophils were strongly stained by anti-CD40 monoclonal antibody. One patient improved with prednisolone, pentoxifylline and nifedipine, without recurrence. The other patient initially improved with steroids, but after self-withdrawal of steroid developed digital ischaemia that evolved to severe necrosis and required amputation. Cutaneous necrotizing eosinophilic vasculitis, Raynaud's phenomenon and digital gangrene may develop as cutaneous manifestations of HES. CD40 may play a part in the pathogenesis of eosinophilic vasculitis in HES.
In the Caenorhabditis elegans embryo, some ventral midline motoneurons extend a process circumferentially to the dorsal midline and a process longitudinally along ventral nerve cord interneurons. Circumferential migrations are guided by netrin UNC-6, which repels motoneuron axons dorsally. Although the motoneuron cell bodies and the longitudinal axons are positioned along UNC-6-expressing interneurons in the ventral nerve cord, the circumferential processes extend only from the motoneuron cell bodies and from defined locations along some longitudinal axons. This implies a mechanism regulates motoneuron branching of UNC-6-responsive processes. We show that expression of unc-6DeltaC, which encodes UNC-6 without domain C, partially rescues circumferential migration defects in unc-6 null animals. This activity depends on the netrin receptors UNC-5 and UNC-40. These results indicate that UNC-6DeltaC can provide the circumferential guidance functions of UNC-6. Furthermore, we show that expression of unc-6DeltaC causes motoneuron branching and the extension of processes from abnormal positions along the ventral nerve cord. This activity is also UNC-5- and UNC-40-dependent. We propose that local interactions mediated by domain C regulate motoneuron branching and responsiveness to the UNC-6 cue.
In order to maintain in vivo anti-tumor efficacy of antigen (Ag)-specific T cells in adoptive immunotherapy for a prolonged period, we constructed a fusion protein (OVA/IL-2) containing ovalbumin (OVA) as a model tumor Ag, co-valently linked to murine interleukin-2 (IL-2). The OVA/IL-2 protein produced in a baculovirus expression system displayed potent IL-2 bio-activity. Immunization with the OVA/IL-2 protein after adoptive transfer of OVA-specific T cells maintained the OVA-specific cytotoxicity and cell number of adoptively transferred T cells long term in vivo, while a simple mixture of recombinant OVA (rOVA) and rIL-2 did not. The response was dependent on the injection doses and times of the OVA/IL-2 protein. Furthermore, weekly re-stimulation of adoptively transferred OVA-specific T cells with the OVA/IL-2 protein cured 70% of tumor-bearing mice. In contrast, re-stimulation with a mixture of rOVA and rIL-2 could not significantly prolong the survival period of tumor-bearing mice. These studies suggest that the co-valent linkage between IL-2 and antigen confines the effect of IL-2 to antigen-specific T cells, leading to efficient maintenance of the anti-tumor activity of adoptively transferred T cells.
PURPOSE: We assessed the utility of the resistance index ratio (RIR) in distinguishing between obstructive and nonobstructive upper urinary tract dilatation in children. METHODS: Twenty-three children (7 days-14 years old) with unilateral dilated collecting systems and a contralateral normal kidney were prospectively evaluated by duplex Doppler sonography. We measured the resistance index (RI) of the intrarenal arteries and calculated the RIR. Ninety-six normal kidneys in 48 controls were also evaluated. RESULTS: Twelve kidneys were proved to be obstructed at the ureteropelvic junction, and 11 were found by renal scintigraphy with furosemide and/or by surgery to have nonobstructive dilatation. The mean RIR differed significantly between the obstructed and dilated nonobstructed kidneys (1.16+/-0.04 versus 1.04+/-0.04, respectively; p < 0.01). After surgical correction of ureteropelvic junction obstruction, the obstructed kidneys showed significant drops in the RIR (1.18+/-0.03 to 1.07+/-0.03, p < 0.01). The RIR showed no statistically significant relationship with age (r = -0.268, p > 0.01); however, the RI declined with increasing age (r= -0.414, p < 0.01). An RIR cut-off value of > or = 1.10 provided a good discriminatory level, resulting in a sensitivity of 92%, a specificity of 97%, a positive predictive value of 85%, and a negative predictive value of 97%. CONCLUSIONS: An RIR cut-off value of > or = 1.10 appears to be an effective parameter for evaluation and follow-up of unilateral obstructive hydronephrosis in children.
OBJECTIVE: To better understand genetic contributions to autoimmunity, immunogenetic markers were studied in two racially discrete and geographically isolated populations of patients with idiopathic inflammatory myopathy (IIM). METHODS: Clinical characteristics, as well as clinical and autoantibody subsets, were defined in 151 American white patients and 50 Korean patients with IIM. HLA-DRB1 and DQA1 genotyping was performed on patients and racially matched controls by standard molecular techniques. Gm allotypes and phenotypes were determined by the hemagglutination-inhibition method. RESULTS: HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif 9EYSTS13 were major genetic risk factors for the development of myositis in whites (corrected P [Pcorr] < 0.0004, odds ratio [OR] 11.2, 4.5, and 3.1, respectively, for each factor versus controls). Although both the white and Korean patients had a similar distribution of clinical characteristics, autoantibody profiles, and clinical groups, no HLA-DRB1 nor DQA1 allele or motif was found to be a risk factor for IIM in the Korean patients. However, DRB1*14 was a protective factor in Korean patients without myositis-specific autoantibodies (Pcorr = 0.004, OR 0.046). In addition, although no Gm phenotype or allotype was identified as a risk factor in whites, Gm 21 was a protective factor for the development of IIM in Koreans (Pcorr = 0.024, OR 0.3). CONCLUSION: Although myositis patients in the US and Korea share similar clinical and serologic features, the immune response genes predisposing to and protecting from myositis in each of these ethnic groups differ at two chromosomal loci. These data suggest that multiple genetic loci should be studied to identify risk and protective factors for some autoimmune diseases in various ethnic populations.
Churg Strauss granuloma (cutaneous extravascular necrotizing granuloma) is a distinct entity which is associated with systemic immunoreactive or autoimmune diseases in a majority of cases. Typically, Churg Strauss granuloma presents as symmetrical papules or nodules on the extremities. There are two histological patterns: the classic pattern reveals palisading granuloma with central degenerated collagen, interspersed polymorphonuclear leukocytes, and leukocytoclastic debris; the focal basophilic necrosis pattern does not show palisading granuloma. We report two cases of Churg Strauss granuloma with different histopathological patterns.
To determine whether the paracrine secretion of interleukin-12 (IL-12) can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transfected to secrete IL-12 (480 U/106 cells/48 hr) and their effect on MAC infection was investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IL-12 (rIL-12). Injection with IL-12-secreting fibroblasts (3T3-IL-12) during intranasal infection with MAC resulted in a significant decrease in the bacterial load of the lung during the entire 10-week observation period, while rIL-12 reduced the bacterial load initially, at 2 weeks, but not by 10 weeks postinfection. Lung CD4+ T cells in mice injected with the 3T3-IL-12 cells showed a persistent T helper type 1 (Th1) response throughout the 10-week period. Furthermore, immunization with the 3T3-IL-12 cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than did rIL-12 immunization. This work suggests that IL-12-secreting fibroblasts may serve as a vehicle for paracrine secretion of IL-12 for immunotherapy of MAC infection.
Clinically obvious panniculitis in association with dermatomyositis is rare. We reported a patient with panniculitis showing membranocystic changes in the dermatomyositis.
The cDNAs for interferon-gamma (IFN-gamma) and allogeneic H-2Kd molecules were transfected into highly metastatic B16F10 melanoma cells (H-2b), and the synergistic effects of the antitumor immune responses by the doubly transfected cells (B16/Kd/IFN-gamma cells) were investigated in C57BL/6 mice (H-2b). The singly transfected B16F10 cells with either IFN-gamma or H-2Kd cDNA (B16/IFN-gamma or B16/Kd cells) were used as controls. The B16/Kd/IFN-gamma cells secreted biologically active IFN-gamma, and strongly expressed both syngeneic and allogeneic MHC class I antigens (H-2Kb and H-2Kd) on the same cell construct. Immunization with the doubly transfected B16/Kd/IFN-gamma cells induced higher anti B16F10 cellular cytotoxic responses than the single transfected B16/IFN-gamma or B16/Kd cells. Lyt-2.2 (CD8)+ T-cells were a major effector cell-type involved in the anti B16F10 responses and their cytotoxic activities were augmented in the immunized mice with the B16/Kd/IFN-gamma cells, as demonstrated by in vitro depletion experiments. The survival period of melanoma-bearing mice treated with the B16/Kd/IFN-gamma cells was significantly longer than that treated with the B16/IFN-gamma or B16/Kd cells. Furthermore, the treatment with the B16/Kd/IFN-gamma cells was capable of greatly inhibiting lung metastasis from small, established B16F10 footpad tumors. These results suggest that the augmented immunotherapeutic potentials can be achieved by the vaccination with IFN-gamma and allogeneic MHC class I genes transfected B16F10 melanoma cells.