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Biomedical subjects

C R Wang

Publications and source records attributed to C R Wang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Bridging bronchus in an infant demonstrated by direct coronal computed tomography and three-dimensional rendering display.

Bridging bronchus is a rare anomaly in which the right lower lobe bronchus arises from the left main bronchus and bridges the lower mediastinum. The first reported case was diagnosed at autopsy in 1976. The second reported case was diagnosed by bronchography confirmed at autopsy in 1980. We describe a 9-month-old infant with such an anomaly. Our patient presented with cough, shortness of breath, and rhinorrhea with no fever or sputum production. The physical examination revealed only coarse breath sound and chest retraction with no other abnormalities. Chest radiography showed decreased lung volume and shifting of the mediastinum to the left. Diagnosis of this anomaly was not possible with computed tomography (CT) axial imaging. Direct coronal CT and 3D rendering with the surface-shaded display technique showed a small right upper lobe bronchus and proximal stenotic left main bronchus, with the intermediate bronchus originating from the left main bronchus and crossing the midline to enter the contralateral lung.

Bronchi↗
PubMed2001

Deep neck infections in children.

From December 1989 through 1998, a total of 68 children with deep neck infection were enrolled into this study. The mean age was 5.9 years (range, 1 month-15.8 years). Infections in the retropharyngeal space (36.7%) were most common, followed by parapharyngeal space (30.8%), peritonsillar space (20.6%), and submandibular space (11.9%). Fever, neck pain, and swelling were the most frequent symptoms. The most common pathogens were viridans streptococci (41%, 16/39) and Staphylococcus aureus (26%, 10/39). Other isolates included Prevotella spp., Veillonella spp., Klebsiella pneumoniae, Escherichia coli, Morganella spp., and Enterobacter spp. Mixed infection was found in 46% (18/39) of patients. The mean duration of hospitalization was 12.4 days (range, 2-45 days). Complete resolution was achieved in 61 (89.7%) children. Complications occurred in 7 patients, including recurrence, mediastinal spread, bacteremia, and suppurative thyroiditis; the patient with mediastinal spread plus bacteremia died. Five patients had congenital cyst and 4 of them had complications or recurrence/relapse. In conclusion, infections in the retropharyngeal space and polymicrobial infections were most common in deep neck infection of Taiwan children.

Anti-Bacterial Agents↗
PubMed2000

MHC class Ib-restricted CTL provide protection against primary and secondary Listeria monocytogenes infection.

Infection of B6 mice with the intracellular pathogen Listeria monocytogenes (LM) results in the activation of CD8(+) T cells that respond to Ag presented by both MHC class Ia and class Ib molecules. Enzyme-linked immunospot analysis reveals that these CTL populations expand and contract at different times following a primary sublethal LM infection. Between days 4 and 6 postinfection, class Ib-restricted CTL exhibit a rapid proliferative response that is primarily H2-M3 restricted. The peak response of class Ia-restricted CD8(+) T cells occurs a few days later, after the majority of bacteria have been cleared. Although class Ia-restricted CTL exhibit a vigorous recall response to secondary LM infection, we observe limited expansion of class Ib-restricted memory CTL, even in MHC class Ia-deficient mice (B6.K(b-/-)D(b-/-)). Despite this lack of enhanced expansion in vivo, class Ib-restricted memory CTL retain the ability to proliferate and expand when provided with Ag in vitro. Furthermore, we demonstrate that in vivo depletion of CD8(+) T cells in LM-immune B6.K(b-/-)D(b-/-) mice severely impairs memory protection. Together, these data demonstrate that class Ib-restricted CTL play an important role in clearing a primary LM infection and generate a memory population capable of providing significant protection against subsequent infection.

Animals↗
PubMed2000

Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers.

A major group of natural killer (NK) T cells express an invariant Valpha14(+) T cell receptor (TCR) specific for the lipoglycan alpha-galactosylceramide (alpha-GalCer), which is presented by CD1d. These cells may have an important immune regulatory function, but an understanding of their biology has been hampered by the lack of suitable reagents for tracking them in vivo. Here we show that tetramers of mouse CD1d loaded with alpha-GalCer are a sensitive and highly specific reagent for identifying Valpha14(+) NK T cells. Using these tetramers, we find that alpha-GalCer-specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1(-) but tetramer-binding T cells present in the lymph nodes and the intestine. Injection of alpha-GalCer leads to the production of both interferon gamma and interleukin 4 by nearly all NK T cells in the liver and the majority of the spleen within 2 h. These cells mostly disappear by 5 h, and they do not reappear after 1 wk. Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. In summary, the data presented here demonstrate that alpha-GalCer-specific NK T cells undergo a unique and highly compartmentalized response to antigenic stimulation.

Animals↗
PubMed2000

CD1d-specific NK1.1+ T cells with a transgenic variant TCR.

The majority of T lymphocytes carrying the NK cell marker NK1.1 (NKT cells) depend on the CD1d molecule for their development and are distinguished by their potent capacity to rapidly secrete cytokines upon activation. A substantial fraction of NKT cells express a restricted TCR repertiore using an invariant TCR Valpha14-Jalpha281 rearrangement and a limited set of TCR Vbeta segments, implying recognition of a limited set of CD1d-associated ligands. A second group of CD1d-reactive T cells use diverse TCR potentially recognizing a larger diversity of ligands presented on CD1d. In TCR-transgenic mice carrying rearranged TCR genes from a CD1d-reactive T cell with the diverse type receptor (using Valpha3. 2/Vbeta9 rearrangements), the majority of T cells expressing the transgenic TCR had the typical phenotype of NKT cells. They expressed NK1.1, CD122, intermediate TCR levels, and markers indicating previous activation and were CD4/CD8 double negative or CD4+. Upon activation in vitro, the cells secreted large amounts of IL-4 and IFN-gamma, a characteristic of NKT cells. In mice lacking CD1d, TCR-transgenic cells with the NKT phenotype were absent. This demonstrates that a CD1d-reactive TCR of the "non-Valpha 14" diverse type can, in a ligand-dependent way, direct development of NK1.1+ T cells expressing expected functional and cell-surface phenotype characteristics.

Animals↗
PubMed2000

Role of IL-16 in delayed-type hypersensitivity reaction.

Interleukin (IL)-16 is a chemoattractant cytokine for CD4(+) leukocytes. Because delayed-type hypersensitivity (DTH) reaction is mediated by T helper 1 (Th1) cells and CD4(+) T cells can be chemoattracted by IL-16, we have investigated the involvement of IL-16 in the DTH reaction. Immunohistochemical analysis revealed the IL-16 expression in infiltrating cells and epithelial cells in the DTH footpads. The IL-16 expression was also detected intracellularly in the infiltrating cells. In addition, markedly increased production of IL-16 was detected in the DTH footpad extracts, but not in the control footpad extracts, by an enzyme-linked immunosorbent assay and also by Western blot analysis. The DTH footpad extracts exhibited a strong chemoattractant activity toward splenic T cells, which was significantly inhibited by the inclusion of neutralizing monoclonal antibody (mAb) against IL-16 in the migration assay. Furthermore, treatment of sensitized mice in vivo with the anti-IL-16 neutralizing mAb significantly suppressed the footpad swelling induced by an antigen challenge, together with decreased infiltration of leukocytes including not only CD4(+) T cells but also CD8(+) T cells and macrophages into the DTH footpads. Decreased production of macrophage inflammatory protein 1alpha was also observed in the DTH footpad extracts by the mAb treatment. These results suggest that IL-16 plays an important role in the recruitment of leukocytes-presumably including antigen-specific Th1 cells, which secrete cytokines and chemokines mediating the following hypersensitivity reaction after activation by the interaction with Langerhans cells carrying the antigen-for the elicitation of DTH response. (Blood. 2000;95:2869-2874)

Animals↗
PubMed2000

Cutting edge: the Ets1 transcription factor is required for the development of NK T cells in mice.

Ets1-deficient mice develop B and T cells but display a severe defect in the development of the NK cell lineage. In this report, we demonstrate that Ets1 is also required for the development of NK1.1+ T (NK T) cells. We observed significantly decreased numbers of NK T cells in the thymus, spleen, and liver of Ets1-deficient mice. These organs also contained markedly decreased levels of the canonical Valpha14-Jalpha281 TCRalpha transcript seen in NK T cells. Unlike wild-type NK T cells, Ets1-deficient thymocytes failed to produce detectable levels of IL-4 following anti-CD3 stimulation. The absence of NK T cells in the Ets1-deficient mice was not associated with defective expression of CD1, an MHC class I molecule required for NK T cell development. We conclude that Ets1 defines a novel transcriptional regulatory pathway that is required for the development of both the NK and NK T cell lineages.

Animals↗
PubMed2000

Comparative contribution of CD1 on the development of CD4+ and CD8+ T cell compartments.

CD1 molecules are MHC class I-like glycoproteins whose expression is essential for the development of a unique subset of T cells, the NK T cells. To evaluate to what extent CD1 contributes to the development of CD4+ and CD8+ T cells, we generated CD1oIIo and CD1oTAPo mice and compared the generation of T cells in these double-mutant mice and IIo or TAPo mice. FACS analysis showed that the number of CD4+ T cells in CD1oIIo mice was reduced significantly compared with the corresponding population in IIo mice. Both CD4+ NK1.1+ and the CD4+ NK1.1- population were reduced in CD1oIIo mice, suggesting that CD1 can select not only CD4+ NK1.1+ T cells but also some NK1.1- CD4+ T cells. Functional analysis showed that the residual CD4+ cells in CD1oIIo can secrete large amounts of IFN-gamma and a significant amount of IL-4 during primary stimulation with anti-CD3, suggesting that this population may be enriched for NK T cells restricted by other class I molecules. In contrast to the CD4+ population, no significant differences in the CD8+ T cell compartment can be detected between TAPo and CD1oTAPo mice in all lymphoid tissues tested, including intestinal intraepithelial lymphocytes. Our data suggest that, unlike other MHC class I molecules, CD1 does not contribute in a major way to the development of CD8+ T cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

A pivotal role of cell-bound but not soluble CD4 molecules in full development of lupus-like manifestations in MRL-Fas(lprcg)/Fas(lprcg) mice.

The role of CD4 molecules in the autoimmune and lymphoproliferative syndrome caused by murine Fas mutations was studied using the novel systemic lupus erythematosus (SLE) model, MRL-Fas(lpr(cg))/Fas(lprcg) (MRL-lpr(cg)) mice, in combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead of membrane-bound CD4 (mCD4). For this purpose, various autoimmune manifestations were compared among MRL-lpr(cg) mice homozygous (CD4slprcg), heterozygous (CD4s/mlpr(cg)), and wild-type (CD4mlpr(cg)) for the CD4 mutation. The mortality, glomerulonephritis, proteinuria, and lymphadenopathy were significantly ameliorated in CD4slprcg compared with CD4mlpr(cg) and CD4s/mlpr(cg) mice, both being comparable in these clinical characteristics. In parallel with the clinical improvement, the serum levels of immunoglobulin, anti-DNA antibodies, anti-nuclear antibodies and immune complexes, and the extent of glomerular immune deposition, were significantly lower in the former. The results indicate that mCD4 is important and can not be replaced by sCD4 in full development of SLE-like manifestations, and suggest that CD4+ T cells may aggravate the autoimmune disease by stimulating autoreactive B cells to produce autoantibodies through their helper activity in Fas mutant models. The sCD4 levels in the serum and spleen elevated with the increased accumulation of B220+CD4-CD8- (double-negative (DN)) T cells in CD4slpr(cg) mice. This, together with the significantly milder lymphadenopathy associated with lower DN T cell contents in CD4slpr(cg) than CD4mlpr(cg) mice, implies that some of abnormal DN T cells may be derived from cells of the CD4 lineage.

Animals↗
PubMed2000

Impaired delayed-type hypersensitivity response in mutant mice secreting soluble CD4 without expression of membrane-bound CD4.

Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell-mediated immunity. We examined the DTH response to methylated bovine serum albumin of a novel mutant strain of mice that have soluble CD4 (sCD4) in their circulation without expression of CD4 on the cell surface. The DTH response of the mutant mice was severely impaired, although the response of CD4 knockout (KO) mice, generated by homologous recombination, was comparable to that of wild-type mice. The response of the mutant mice was restored by the neutralization of sCD4 with anti-CD4, and that of CD4KO mice was markedly reduced by the implantation of a diffusion chamber containing sCD4 cDNA transfectant cells. The restored DTH response of the mutant mice treated with anti-CD4 was abolished by treatment with anti-interferon-gamma (IFN-gamma). IFN-gamma production by CD4 mutant and CD4KO mice was consistent with their DTH response and inversely related to the presence of sCD4 in their circulation, indicating that sCD4 impairs the DTH response by blocking the production of IFN-gamma in our mutant mice. These results raise the possibility that sCD4 could impair cell-mediated immunity. Our mutant mice would provide a useful tool with which to analyse the mechanisms of the DTH reaction.

Animals↗
PubMed2000

Natural killer 1.1(+) alpha beta T cells in the periimplantation uterus.

When the developing embryo implants into the uterine wall, resident maternal immune cells may encounter antigens present on the fetal tissues. The nature and constituents of the ensuing maternal immune response, and its regulation, are of considerable interest in understanding normal and abnormal pregnancy. Here, we report the presence of natural killer (NK)1.1(+) alpha beta T cells in the murine periimplantation uterus. These cells account for a large portion of both the T-cell and natural killer cell populations in early pregnancy, while their numbers in the non-pregnant uterus and later in pregnancy are greatly reduced. Phenotypically, these NK1.1+ alpha beta T cells belong to a previously described subset of cells that bear a V alpha 14-J alpha 281-encoded T-cell receptor. Unlike other organs, where both CD4(+) and CD4(-)/CD8(-) NK1.1(+) alpha beta T cells are found, the placental/decidual population appears to be entirely CD4(-)/CD8(-). The V beta repertoire of the placental/decidual population is also altered from that of other organs, with a majority of cells expressing V beta 3. Together, these features suggest the possibility of local development. NK1.1(+) alpha beta T cells are known to recognize the class I-like CD1 molecule. Consistent with this association, we demonstrate CD1 expression by tissues within the pregnant uterus. Our findings define an additional organ-specific immune environment where NK1.1(+) alpha beta T cells may play a role, and continue to demonstrate the specialized nature of the maternal intrauterine immune system during pregnancy.

Animals↗
PubMed2000

Affinity of thymic self-peptides for the TCR determines the selection of CD8(+) T lymphocytes in the thymus.

Experiments with synthetic antigen peptides have suggested that a critical parameter that determines the developmental fate of an immature thymocyte is the affinity of interaction between TCR and self-peptide/MHC expressed on thymic stromal cells. To test the physiological relevance of this model for thymocyte development, we determined the affinity of the anti-HY TCR (B6.2.16) expressed on CD8(+) cells for thymic self-peptide/H-2D(b) tetramers, then examined the ability of these self-peptides to determine the outcome of B6.2.16 CD8 cell selection in the thymus. The B6.2.16 TCR bound the male HY self-antigen with high affinity. Thymic self-peptides, which are highly abundant on the surface of thymic epithelial cells, bound the B6.2.16 TCR with low affinity. The ability of self-peptides to trigger positive or negative selection of B6.2.16 CD8 cells in cultured fetal thymi was determined by the relative affinity of self-peptide/H-2D(b) for the B6.2.16 TCR. High-affinity binding of the HY self-peptide resulted in B6.2.16 TCR complex zeta chain phosphorylation and the negative selection of B6.2.16 CD8 cells. Low-affinity binding of thymic self-peptides to B6.2.16 TCR resulted in the positive selection of B6.2.16 CD8 cells. Differences between the binding affinities of self-peptides to B6.2.16 TCR accounted for the self-peptide specificity of B6.2.16 CD8 cell positive selection. We conclude that the relative affinity of TCR for thymic self-peptide/class I MHC is a critical parameter in determining fate of CD8(+) cells during thymic selection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Radiologic diagnosis and surgical treatment of urethral diverticulum in women. A reappraisal of voiding cystourethrography and positive pressure urethrography.

OBJECTIVE: To reappraise the optimum radiologic procedure for the diagnosis of urethral diverticula in women and to assess the results of surgery. STUDY DESIGN: From January 1994 to December 1997, 132 urine-continent women with pelvic prolapse and the most characteristic symptoms of urethral diverticulum underwent pelvic repair. In addition to routine urologic evaluations and pelvic examinations, the women underwent voiding cystourethrography (VCUG) and positive pressure urethrography (PPUG) with a double-balloon catheter. The x-ray examination was scheduled as follows. One hundred thirty-two women initially underwent VCUG followed by a PPUG. Another VCUG was subsequently performed on women with a negative PPUG finding. Twelve patients were excluded because they were unable to urinate for the first VCUG; thus, the study group was composed of the remaining 120 patients. Subsequently those patients underwent various pelvic operations, including total abdominal/vaginal hysterectomy, abdominal colposacropexy, Manchester's operation, sacrospinous ligament suspension, diverticulectomy and colporrhaphy. RESULTS: Both VCUG and PPUG were able to demonstrate the diverticula in 20 of the 120 women. Another 13 women showed positive findings on PPUG. Ten of the 87 cases with a negative PPUG had a positive finding in the subsequent VCUG. Forty-two diverticula were detected in 39 patients during pelvic repair. The only complication of urethral diverticulectomy was urethrovaginal fistula, which occurred in 3 of the 39 patients. CONCLUSION: Though VCUG is not as sensitive as PPUG, it still has merits and can be used as a screening test. If VCUG is inconclusive but clinical suspicion persists, particularly when PPUG is doubtful, magnetic resonance imaging should be considered.

Adult↗
PubMed2000

Soluble CD4 suppresses delayed-type hypersensitivity reaction of CD4 loosing mice by inhibiting INFgamma production.

The CD4 loosing (CD4L) mice have a novel defect in CD4 expression where CD4 mRNA is alternatively spliced to delete a transmembrane portion to give rise to the secretion of soluble CD4 (sCD4) without the expression of membrane-bound CD4. To analyze the role of sCD4 in immune responses in CD4L mice, experiments have been done by comparing CD4L mice with CD4 knockout (CD4KO) mice on the same C57BL/6 background. Significantly reduced delayed-type hypersensitivity (DTH) response against methylated BSA (mBSA) was found in CD4L mice; however, CD4KO mice showed a comparable response to wild type mice. Anti-CD4 treatment in CD4L mice could restore DTH response. Moreover, implantation of CD4KO mice with a diffusion chamber containing sCD4 secreting cells suppressed DTH response. DTH response recovered by anti-CD4 treatment in CD4L mice was inhibited by anti-interferon gamma (IFNgamma). IFNgamma production of mBSA-stimulated lymph node cells was significantly reduced in CD4L mice as compared with that in CD4KO or wild type mice, and the reduction could be recovered by the anti-CD4 treatment. IFNgamma production of mBSA-stimulated lymph node cells was suppressed in CD4KO mice carrying a diffusion chamber containing sCD4 secreting cells as compared with those containing control cells. Taken together, results in this study strongly indicate that sCD4 suppresses DTH responses of CD4L mice by inhibiting IFNgamma production. The mutant mice could provide a good model to analyze the mechanism of IFNgamma involvement in the DTH response.

Animals↗
PubMed2000

[Cloning of E. coli mtl-D gene and its expression in transgenic Balizhuangyang (Populus)].

E. coli 1-phosphate mannitol dehydrogenase gene (mtl-D) was cloned using PCR method. Sequence analysis showed that the gene was the same as the published one except that codon CAT at position 416 was replaced by AAA and resulted in a Lys residue instead of His. This gene (mtl-D) was inserted in a binary vector and transformed into populas via agrobacteria. Several transgenic plants grow very well in 0.6% NaCl while controls can not survive even in 0.4% NaCl. PCR analysis and Northern blotting indicated that foreign gene was integrated into the genome of transgenic plant and transcribed successfully.

Base Sequence↗
PubMed2000

Bronchial atresia with mucocele in an adolescent girl: an uncommon cause of lobar emphysema.

Congenital bronchial atresia (CBA) is a congenital anomaly but is seldom diagnosed in children. They are usually asymptomatic and are found during screening chest radiographs in young adults. The characteristic chest radiographs of CBA consist of a hyperlucent lung, central branching but contrast non-enhancing mass and air-fluid lesion. Most of the cases reported in the past were managed surgically. The present study reported an 11-yr-old presenting with chest pains, exercise intolerance, and refractory wheezing. It is of utmost importance to consider the possibility of CBA in children with lobar emphysema in order to achieve early diagnosis and avoid unnecessary exploratory surgery.

Bronchi↗
PubMed1999

The selection of M3-restricted T cells is dependent on M3 expression and presentation of N-formylated peptides in the thymus.

The major histocompatibility complex (MHC) class Ib molecule H2-M3 binds N-formylated peptides from mitochondria and bacteria. To explore the role of M3 expression and peptide supply in positive and negative selection, we generated transgenic mice expressing an M3-restricted TCR-alpha/beta from a CD8(+) T cell hybridoma (D7) specific for a listerial peptide (LemA). Development of M3-restricted transgenic T cells is impaired in both beta2-microglobulin-deficient and transporter associated with antigen processing (TAP)-deficient mice, but is not diminished by changes in the H-2 haplotype. Maturation of M3/LemA-specific CD8(+) single positive cells in fetal thymic organ culture was sensitive to M3 expression levels as determined by antibody blocking and use of the castaneus mutant allele of M3. Positive selection was rescued in TAP(-/-) lobes by nonagonist mitochondrial and bacterial peptides, whereas LemA and a partial agonist variant caused negative selection. Thus, M3-restricted CD8(+) T cells are positively and negatively selected by M3, with no contribution from the more abundant class Ia molecules. These results demonstrate that class Ib molecules can function in thymic education like class Ia molecules, despite limited ligand diversity and low levels of expression.

Animals↗