Biomedical subjects

W C Wang

Publications and source records attributed to W C Wang.

At least 19 recordsLinked to original sources

PubMed1998

Comparative studies on mammalian Hoxc8 early enhancer sequence reveal a baleen whale-specific deletion of a cis-acting element.

Variations in regulatory regions of developmental control genes have been implicated in the divergence of axial morphologies. To find potentially significant changes in cis-regulatory regions, we compared nucleotide sequences and activities of mammalian Hoxc8 early enhancers. The nucleotide sequence of the early enhancer region is extremely conserved among mammalian clades, with five previously described cis-acting elements, A-E, being invariant. However, a 4-bp deletion within element C of the Hoxc8 early enhancer sequence is observed in baleen whales. When assayed in transgenic mouse embryos, a baleen whale enhancer (unlike other mammalian enhancers) directs expression of the reporter gene to more posterior regions of the neural tube but fails to direct expression to posterior mesoderm. We suggest that regulation of Hoxc8 in baleen whales differs from other mammalian species and may be associated with variation in axial morphology.

Animals↗

PubMed1998

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline.

Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.

Base Sequence↗

PubMed1998

A conserved aspartate is essential for FAD binding and catalysis in the D-amino acid oxidase from Trigonopsis variabilis.

To evaluate the possible contribution of Asp206 of Trigonopsis variabilis D-amino acid oxidase (DAO) to its flavin adenine dinucleotide (FAD) binding and catalytic function, six mutant enzymes were constructed by site-directed mutagenesis. Western immunoblot analysis revealed that a protein with an apparent molecular mass of about 39.2 kDa was present in the cell-free extracts of wild-type and mutant strains. Replacement of Asp206 with Leu, Gly, and Asn resulted in the loss of DAO activity and characteristic absorption spectrum for flavoenzyme, while the other mutant DAOs, Asp206Glu, Asp206Ser, and Asp206Ala, exhibited a similar spectral profile to that of wild-type enzyme and retained about 6-90% of the enzyme activity. These results suggested that Asp206 of T. variahilis DAO might play an important role in the binding of FAD.

Amino Acid Sequence↗

PubMed1998

Characterization of the C-terminal domain of Helicobacter pylori vacuolating toxin and its relationship with extracellular toxin production.

Helicobacter pylori vacuolating cytotoxin (VacA) induces gastric epithelial necrosis. Its C-terminal domain is hypothesized to be responsible for extracellular translocation of the mature cytotoxin. In this study, genetic-structural properties of VacA C-terminal domain and the level of cytotoxin secretion were investigated. Sau3AI-HaeIII restriction fragment length polymorphism (RFLP) analysis of the 1.1-kb PCR-amplified vacA fragment revealed 14 distinct combined patterns among 87 clinical isolates. Of the 4 popular groups (A-a, A-b, A-f, and B-a), A-a strains produced a higher level of the VacA protein than A-b strains and than A-f strains (P < 0.05). Sequence analysis and secondary structure prediction supported a beta-barrel structure that might act as a selective export channel like Iga beta-core of IgA proteases. Sequence differences in the predicted beta-barrel were present among strains of different RFLPs.

Amino Acid Sequence↗

PubMed1998

Differential expression and function of L-selectin on CD56bright and CD56dim natural killer cell subsets.

NK cells are the first line of defense against foreign cells, virally infected cells, and tumors. The mechanisms whereby NK cells accumulate in extralymphoid sites in response to pathogenic stimuli are not well understood. The L-selectin adhesion molecule (CD62L) plays a primary role in mediating the initial interaction of leukocytes with vascular endothelium, a crucial step in the extravasation of immune effector cells into tissues. In this report, we show L-selectin to be uniquely expressed on a subset of resting human NK cells (CD56bright). Notably, CD56bright NK cells expressed L-selectin at a higher density than all other peripheral blood leukocytes. NK activation by PMA, IL-2, IL-15, or TGF-beta down-regulated L-selectin on the CD56bright subset, while increased L-selectin levels were observed in both the CD56bright and CD56dim NK subsets in response to IL-12, IL-10, or IFN-alpha. Moreover, CD56bright NK cells bound with high efficiency to physiologic L-selectin ligands on peripheral lymph node high endothelial venules (HEV). In sharp contrast, CD56dim NK cells adhered poorly to HEV and were predominantly L-selectin- or expressed L-selectin only at low density. In CD56bright cells and a subpopulation of CD56dim cells, L-selectin ligation by mAb cross-linking activated lymphocyte function-associated Ag 1 (LFA-1), a second adhesion molecule required for leukocyte extravasation. LFA-1 was expressed on both NK subsets, although its density was constitutively higher on CD56dim cells. Taken together, evidence of differential expression of L-selectin and LFA-1 on CD56bright and CD56dim NK subsets strongly suggests unique migratory properties and functions of these cells during the early immune response to foreign pathogens.

3T3 Cells↗

PubMed1998

Fever-range hyperthermia enhances L-selectin-dependent adhesion of lymphocytes to vascular endothelium.

The L-selectin leukocyte adhesion molecule plays an important role in controlling leukocyte extravasation in peripheral lymph nodes and at sites of tissue injury or infection. Although febrile responses during infection and inflammation are associated with enhanced immune activity, the contribution of fever-range temperatures to controlling lymphocyte recruitment to tissues has not been previously examined. In this report we provide evidence that direct exposure of lymphocytes to fever-range temperatures (38-41 degrees C) in vitro for 9 to 24 h resulted in a >100% increase in L-selectin-dependent adhesion of these cells to lymph node high endothelial venules (HEV). Moreover, culture of lymphocytes under hyperthermia conditions markedly enhanced the ability of these cells to traffic in an L-selectin-dependent manner to peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. In contrast, febrile temperatures did not increase LFA-1 function as assessed by measuring lymphocyte adhesion to ICAM-1-3T3 transfectants. Fever-range hyperthermia further did not increase L-selectin surface density on lymphocytes or L-selectin-dependent recognition of soluble carbohydrate substrates; however, a marked increase in ultrastructural immunogold-labeling of L-selectin was observed in response to thermal stimuli. These results suggest that elevated temperatures enhance L-selectin adhesion and/or avidity through the regulation of L-selectin conformation or organization in the plasma membrane. Finally, the observed thermal effects on L-selectin adhesion were attributed to soluble factors in the conditioned medium of heat-treated cells. Taken together, these data provide new insight into the potential physiologic role of the febrile response in enhancing lymphocyte recruitment to tissues through the regulation of L-selectin adhesion.

Cell Adhesion↗

PubMed1998

Malignant infantile osteopetrosis: otolaryngological complications and management.

OBJECTIVES: To inform otolaryngologists about upper airway obstruction requiring tracheotomy and other otolaryngological manifestations of malignant infantile osteopetrosis (MIOP) and to discuss pathophysiological features, management, and new treatment strategies in MIOP. DESIGN: Ongoing case series combined with a retrospective chart review. SETTING: International tertiary pediatric hospital. INTERVENTIONS: Patients with MIOP were initially referred for treatment and routine follow-up. Tracheotomy was performed to manage obstructive sleep apnea. Audiograms were also performed at regular intervals. RESULTS: The records of 9 patients were examined. The otolaryngological findings of hearing loss, obstructive sleep apnea (sometimes requiring tracheotomy), otitis media, and chronic osteomyelitis with facial fistulas were identified. CONCLUSIONS: Osteopetrosis is a rare condition caused by a failure of the osteoclast to resorb bone. This results in thickened dense, deformed, and easily fractured bone. As a result, growth failure, anemia, hypoplastic dentition, chronic infections, facial fistulas, blindness, hearing loss, nasal congestion, and upper airway obstruction may occur. The management of otolaryngological problems in a child with osteopetrosis is an important component in comprehensive care. To our knowledge, this study represents the largest case series of MIOP in the otolaryngology literature.

Face↗

PubMed1998

Abnormalities of the central nervous system in very young children with sickle cell anemia.

OBJECTIVE: To determine whether abnormalities of the CNS are present in very young children with sickle cell anemia. STUDY DESIGN: Thirty-nine children with hemoglobin SS between the ages of 7 and 48 months were examined with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). No child had a history of clinical stroke, although 3 had a history of seizures (2 neonatal). Twenty-one patients underwent developmental testing with the Bayley or McCarthy Scales. RESULTS: The overall prevalence of CNS abnormalities in asymptomatic children was 4 of 36 (11%, confidence interval 3, 26%). One patient had a silent infarct observed on MRI and a stenotic lesion on MRA; 3 other patients had stenotic lesions on MRA. The 3 patients who had a history of seizures all had lesions consistent with infarcts on MRI. Of the asymptomatic patients who had psychometric testing, 1 of 18 was developmentally delayed. One of 3 with a history of seizures had mild developmental delay. CONCLUSIONS: Very young children with sickle cell anemia (and no history of clinical stroke) have infarction in the brain and/or stenosis of major cerebral arteries, similar to those reported in older children. These findings indicate a need for larger studies to define the incidence of CNS lesions in this age group and to determine the need for early therapeutic intervention to prevent CNS sequelae of sickle cell disease.

Anemia, Sickle Cell↗

PubMed1998

The serum selenium concentrations in children and young adults: a long-term study during the Finnish selenium fertilization programme.

OBJECTIVE: To investigate the effects of the Finnish nationwide selenium (Se) fertilization programme on the Se status of the population. DESIGN AND SUBJECTS: Serum Se concentrations from 1985-1992 from 1568 healthy children and young adults in southwestern Finland were determined using direct electrothermal atomic absorption spectrometry. RESULTS: The mean concentration in young adults increased from 1.04 micromol/L in 1985 to 1.59 micromol/L in 1990. Children younger than 15 y had lower concentrations than adults, with an increase from 0.87 micromol/L in 1985 to 1.31 micromol/L in 1990. The younger the children, the lower the Se concentrations tended to be. At the age of about seven months no significant difference was noted between breast-fed and formula-fed infants. From 1991, when the amount of Se added to fertilizers was reduced and less foreign high-Se cereal was imported, the Se concentrations decreased in all age groups. CONCLUSIONS: The nationwide Se supplementation programme has succeeded in elevating the Se intake and the serum Se concentrations in the Finnish population.

Adolescent↗

PubMed1998

Vacuolating toxin production in clinical isolates of Helicobacter pylori with different vacA genotypes.

A vacuolating cytotoxin encoded by vacA in Helicobacter pylori is known as a potential virulent determinant. The relationship between different vacA alleles, vacuolating ability, and H. pylori-related diseases was investigated. Genetic analysis of 119 isolates from Taiwanese patients revealed that 104 strains were s1a/m2, 13 strains were characterized as the s1a/m1T type, which was more homologous to the s1a/m1 strains, and 2 were characterized as the s1a/m1Tm2 chimeric type. Production of high-grade cytotoxin among 11 strains with s1a/m1T was higher (72.7%) than among 66 strains with s1a/m2 (21.2%) (P < .01). Peptic ulcer occurred in 76.9% of 13 patients with s1a/m1T strains compared with 46.2% of 104 patients with s1a/m2 strains (P < .05). These results suggest that s1a/m1T strains are associated with increased cytotoxic activity and higher ulcer prevalence than are s1a/m2 strains.

Amino Acid Sequence↗

PubMed1998

Rasch analysis of distractors in multiple-choice items.

In order to apply the Rasch model to multiple-choice items, incorrect responses to distractors are usually aggregated to a single category. In doing so, information of individual distractors disappears. In this paper, a Rasch-type analysis is proposed where one parameter is assigned to each distractor. The information is thus preserved. The proposed distractor model can be applied to investigate the performance of distractors, which is useful for item revision. This model is a necessary condition of the Rasch model, that is, fitting the distractor model will fit the Rasch model, but not vice versa. The results of a small simulation study show that parameter recovery of the distractor model is very satisfactory. A real data set of twenty multiple-choice items was analyzed. Some items were found to fit the Rasch model rather than the distractor model. It is this diagnostic value that makes the distractor model suitable for multiple-choice items.

College Admission Test↗

PubMed1998

Measuring individual differences in change with multidimensional Rasch models.

Item response models have been developed to explore change measurement, including those proposed by Fischer and his colleagues (e.g., Fischer & Pazer, 1991; Fischer & Ponocny, 1994), Andersen (1985) and Embretson (1991). In this article, we propose another multidimensional Rasch model, the multidimensional random coefficient multinomial logit (MRCML) model (Adams, Wilson, & Wang, 1997). All these models are briefly reviewed and compared. The MRCML can be applied to not only polytomous items but also investigation of variations in item difficulties. Based on variations in difficulties across occasions and items, five kinds of models are proposed. Some simulation studies were conducted to examine parameter recovery of the MRCML model under various testing situations. All the parameters were recovered very well. A real data set was analyzed to show applications of the MRCML to measuring individual differences in change.

Australia↗

PubMed1997

Expression, purification, and characterization of a murine CD4 fragment containing the first two N-terminal domains.

CD4 is a membrane glycoprotein on T lymphocytes that binds to the same peptide:major histocompatibility complex (MHC) class II molecules recognized by the antigen-specific T cell receptor (TcR). Recent evidence supports the importance of coaggregation of CD4 and TcR for effective T cell activation. Here, we report that a transfected Chinese hamster ovary (CHO) cell line expressing a murine CD4 fragment containing the first two N-terminal domains secretes both monomeric molecules and disulfide-linked multimers. Elimination of the predicted N-linked glycosylation site at residue 161 that is next to the fourth cysteine does not affect the formation of interchain disulfide bonds. N-Terminal amino acid sequencing of the purified CD4 fragment demonstrates that the leader signal sequence is properly cleaved off the expressed protein. Circular dichroism studies suggest that both monomeric and disulfide-linked proteins are folded as primarily beta-sheet.

Animals↗

PubMed1997

Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease.

Streptococcus pneumoniae sepsis is the most common invasive infection among patients with sickle cell disease. The risk of a recurrent episode of sepsis and subsequent death in those patients who have had a previous septic event is much higher. Patients with sickle disease who have had pneumococcal sepsis should continue penicillin prophylaxis indefinitely and should not be candidates for out-patient management of febrile episodes.

Anemia, Sickle Cell↗

PubMed1997

Orbital compression syndrome in sickle cell disease.

BACKGROUND: Orbital complications are an uncommonly reported finding in sickle cell disease. METHODS: The authors review the reported orbital manifestations of sickle cell disease and discuss a patient with hemoglobin sickle beta(0) thalassemia in whom rapidly progressive bilateral orbital compression developed. RESULTS: Computed tomography of the orbits in a patient with fever, headache, orbital swelling, and optic nerve dysfunction displayed bilateral superior subperiosteal cystic masses. Surgical exploration showed bilateral liquefied hematomas, which were evacuated. Recovery was complete 13 days after surgery. A mild recurrence 14 months later resolved with conservative treatment. The literature contains 11 reports of 16 young patients with sickle cell disease (15 sickle cell disease [Hb SS] and 1 hemoglobin sickle cell disease [Hb SC]) with rapidly developing findings ranging from frontal headache, fever, and eyelid edema to bilateral complete orbital compression syndrome. Including our patient, 60% had orbital hemorrhage on computed tomography. Ten of 12 patients tested were found to have orbital bone marrow infarctions. Sixteen of 17 patients had complete recovery; 13 were treated conservatively and 4 surgically. Only 2 of 17 had recurrence. CONCLUSIONS: Orbital complications in sickle cell disease are unusual manifestations in which a vaso-occlusive process in the marrow space around the orbit results in frontal headache, fever, eyelid edema, and often orbital compression syndrome. Subperiosteal hematomas are common and appear to result from bone marrow infarctions. Appropriate management requires a thorough evaluation to exclude other hemorrhagic, infectious or neoplastic processes, as well as vigilant ophthalmic monitoring. Supportive care is effective, unless optic nerve dysfunction or large hematomas are present, which would indicate that surgical evacuation is warranted to prevent loss of vision and to speed recovery.

Anemia, Sickle Cell↗

PubMed1997

Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia with a low blast count.

To evaluate diagnostic criteria, disease characteristics, and the clinical course of pediatric myelodysplastic syndrome (MDS), we reviewed 327 consecutive cases diagnosed with de novo acute myeloid leukemia (AML) or MDS at St Jude Children's Research Hospital between February 1980 and January 1993. Among 49 cases with <30% marrow blasts (consistent with FAB criteria and common diagnostic practice for MDS), eight had karyotypes associated with de novo AML (four with t(8;21)(q22;q22) and one each with inv(16)(p13q22), t(11;17)(q23;q21), t(9;11)(p22;q13), and i(1)(ql0)). We termed these cases AML with a low blast count (AML-LBC) and compared their clinical and morphologic features with those of the remaining 41 cases. AML-LBC cases had little or no hematopoietic dysplasia. MDS cases consisted of refractory anemia (RA, n=6), RA with ring sideroblasts (n=2), RA with excess blasts (RAEB, n=4), RAEB in transformation (n=14), and chronic myelomonocytic leukemia (n=15). Most had moderate/severe or multilineage hematopoietic dysplasia, with significantly higher dysplasia scores than AML-LBC cases (P=0.007). Only 30% of patients with MDS achieved complete remission (CR) after two cycles of AML-directed therapy, compared with 88% of patients with AML-LBC (P=0.0001); MDS patients tended to experience prolonged severe cytopenias with chemotherapy. The 4-year survival for MDS patients was 23% +/- 7% (s.e.), vs 50% +/- 18% (s.e.) for AML-LBC (P=0.048). AML-LBC patients frequently had chloromas; none were seen in MDS patients. We conclude that the 30% blast threshold is ineffective for separation of AML and MDS in pediatric patients, and that genetic data should be included in this decision process. AML-LBC, defined by <30% blasts in bone marrow and cyto- (or molecular) genetic abnormalities associated with de novo AML, and characterized by absent or mild marrow dysplasia, is biologically and clinically distinct from MDS and should be treated as de novo AML. Outcome in pediatric MDS remains poor, and new treatment strategies are needed for these patients.

Acute Disease↗

PubMed1997

Nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae in children with sickle cell disease.

OBJECTIVE: We studied the prevalence of nasopharyngeal (NP) carriage, antimicrobial susceptibilities, and serotypes of Streptococcus pneumoniae (SP) in children with sickle cell disease (SCD) in the Mid-South. In addition, we examined risk factors for NP carriage of penicillin-resistant SP (PRSP). STUDY DESIGN: Between July 1994 and December 1995, we obtained NP cultures from 312 children with SCD followed at the Mid-South Sickle Cell Center, 208 (67%) of whom were receiving penicillin prophylaxis. RESULTS: Among the 312 patients, colonization with SP occurred in 42 (13%), 30 (71%) of whom were receiving penicillin prophylaxis. Twenty-three of the 42 SP isolates (55%) were resistant to penicillin; 5 of the 23 (22%) were highly resistant. PRSP organisms were also resistant to cefotaxime (43%), trimethoprim-sulfamethoxazole (57%), and erythromycin (22%). Serotypes 6A, 6B, 14, 19A, and 23F accounted for 19 (90%) of 21 resistant strains. Children who were treated with antibiotics during the preceding month were more likely to carry PRSP than children who were not treated. CONCLUSIONS: There is a high prevalence of NP carriage of PRSP in children with SCD in the Mid-South, which raises concerns regarding the continued effectiveness of penicillin prophylaxis in these children. Further studies on the antimicrobial susceptibilities of resistant organisms and the relationship between NP carriage of SP and invasive disease are needed before developing new recommendations for prophylaxis and treatment.

Adolescent↗

PubMed1997

Genetic analysis of the cytotoxin-associated gene and the vacuolating toxin gene in Helicobacter pylori strains isolated from Taiwanese patients.

OBJECTIVE: Two virulence factors encoded by the cytotoxin-associated (cagA) gene and the vacuolating toxin (vacA) gene of Helicobacter pylori are known to be associated with gastroduodenal pathologic conditions. In this report, nucleotide sequence of cagA and vacA and the serum antibody response to the CagA antigen in H. pylori isolates from Taiwanese patients were studied. METHOD: cagA and vacA were characterized in 173 H. pylori strains by polymerase chain reaction and DNA hybridization analyses. The presence of serum IgG antibodies against CagA was assessed by Helico-blot Western blot system. Sequence analysis of polymerase chain reaction-amplified vacA and cagA was performed for two strains. RESULTS: cagA was detected in all the isolates with peptic ulcers and gastric cancer. Of 54 strains with non-ulcer dyspepsia, 51 were found to be cagA+. Serum antibodies to CagA were detected for 99.2% of cagA+ strains compared with 0% of strains lacking cagA. vacA was detected in all isolates. Sequence analysis of vacA and cagA indicated that sequences of two Taiwanese strains were closely related to each other (95.9% and 97% nucleotide identity, respectively) but less homologous to the published strains (90.9% and 91.4% mean nucleotide sequence identity, respectively). CONCLUSIONS: The strong association (98%) of cagA+ strains with Taiwanese patients suggests that the cagA+ phenotype could not be used as a single marker of high-risk patients in Taiwan. Moreover, sequence analysis indicates that Taiwanese strains contain different genetic sequences from those in other geographic regions.

Adolescent↗