Thymoma and hypogammaglobulinemia (Good's syndrome): a case report.

Good's syndrome is extremely rare and refers to an acquired B and T cell immunodeficiency in thymoma patients. We report a 51-year-old female thymoma patient who presented with recurrent herpes zoster, pneumonia, diarrhea and opportunistic infections. She was found to have acquired hypogammaglobulinemia with absent B cells. Despite repeat intravenous immunoglobulin replacement and antibiotic therapy, she died of bacterial pneumonia-induced acute respiratory distress syndrome. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with recurrent infections.     

Mutation screening analysis of the retinoblastoma related gene RB2/p130 in sporadic ovarian cancer and head and neck squamous cell cancer.

AIMS: To investigate the involvement of the RB2/p130 gene in the pathogenesis of sporadic ovarian cancer in addition to head and neck squamous cell carcinoma (HNSCC). METHODS: Paired tumour and patient matched normal DNA samples from 43 sporadic ovarian tumours and 39 normal/tumour HNSCC DNA samples were screened. The mutation screen used polymerase chain reaction (PCR) amplification followed by single strand conformation polymorphism analysis and direct sequencing of the PCR products. Exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus) were analysed for mutations. These exons were chosen because most of the point mutations in RB2/p130 are located in the C-terminal region and mutations in these exons have been identified previously in nasopharyngeal carcinomas and primary lung tumours. RESULTS: No abnormal band shifts were seen in the samples analysed, and no bands directly sequenced revealed the presence of mutations. CONCLUSIONS: Genetic alterations in the RB2/p130 gene (exons 19-22) are unlikely to be involved directly in the pathogenesis of sporadic ovarian cancer or HNSCC.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Chlamydia pneumoniae (TWAR).

Chlamydia pneumoniae (TWAR) is a recently recognized third species of the genus Chlamydia that causes acute respiratory disease. It is distinct from the other two chlamydial species that infect humans, C. trachomatis and C. psittaci, in elementary body morphology and shares less than 10% of the DNA homology with those species. The organism has a global distribution, with infection most common among children between the ages of 5 and 14 years. In children, TWAR infection is usually mild or asymptomatic, but it may be more severe in adults. Pneumonia and bronchitis are the most common clinical manifestations of infection, and TWAR is responsible for approximately 10% of cases of pneumonia and 5% of cases of bronchitis in the United States. The microimmunofluorescence serologic assay is specific for TWAR and can distinguish between recent and past infections. The organism can be isolated in cell culture; however, PCR techniques have recently facilitated its detection in tissues and clinical specimens.     

Screening for cognitive impairment in older adults attending an eye clinic

PURPOSE: We conducted a cross-sectional study examining potentially modifiable factors associated with cognitive impairments (mild or severe) in older whites, African Americans and Hispanics attending an outpatient eye clinic. METHODS: In-clinic interviews and physical examinations assessed social, demographic and health information from 100 consecutive Hispanic, African-American and white adults aged > or = 55. Our primary outcome was presence of any cognitive impairment (mild or severe) using the St. Louis University Mental Status Examination (SLUMS) scale. RESULTS: Of the 100 subjects, 65 screened positive for cognitive impairments on the SLUMS cognitive instrument: 46 with mild cognitive impairment and 19 with severe impairment (possible dementia). African-American and Hispanic adults (nonwhites) were significantly more likely to have cognitive impairment compared to white adults (OR 2.80: 95% CI = 1.05-7.44), independent of age, years of education and systolic blood pressure. Subjects with diabetes also had increased odds of cognitive impairments (OR 3.28, 95% CI = 1.21-8.90) even after adjusting for relevant confounders. There was a nonsignificant trend between visual acuity impairment and cognitive impairment (p = 0.059). CONCLUSIONS: Sixty-five percent of adults aged > or = 55 attending the eye clinic screened positive for cognitive impairments, with higher rates among nonwhites and adults living with diabetes.     

Effect of Group A Streptococcal Cysteine Protease on Invasion of Epithelial Cells

Cysteine protease of group A streptococci (GAS) is considered an important virulence factor. However, its role in invasiveness of GAS has not been investigated. We demonstrated in this study that two strains of protease-producing GAS had the ability to invade A-549 human respiratory epithelial cells. Isogenic protease mutants were constructed by using integrational plasmids to disrupt the speB gene and confirmed by Southern hybridization and Western immunoblot analyses. No extracellular protease activity was produced by the mutants. The mutants had growth rates similar to those of the wild-type strains and produced normal levels of other extracellular proteins. When invading A-549 cells, the mutants had a two- to threefold decrease in activity compared to that of the wild-type strains. The invasion activity increased when the A-549 cells were incubated with purified cysteine protease and the mutant. However, blockage of the cysteine protease with a specific cysteine protease inhibitor, E-64, decreased the invasion activity of GAS. Intracellular growth of GAS was not found in A-549 cells. The presence or absence of protease activity did not affect the adhesive ability of GAS. These results suggested that streptococcal cysteine protease can enhance the invasion ability of GAS in human respiratory epithelial cells.     

An extensive study of human IgE cross-reactivity of Blo t 5 and Der p 5

BACKGROUND: Dual sensitization by Blomia tropicalis and Dermatophagoides pteronyssinus mites is common in tropical and subtropical countries. The human IgE cross-reactivity between clinical important group 5 allergens, Blo t 5 and Der p 5, remains controversial. OBJECTIVE: This study was undertaken to assess the levels of the IgE cross-reactivity between Blo t 5 and Der p 5 by using sera from a large cohort of asthmatic children in subtropical and tropical countries. METHODS: Purified recombinant Blo t 5 and Der p 5 were produced in Pichia pastoris and tested against sera from 195 asthmatic children. The IgE cross-reactivity was examined by direct, inhibitory and competitive human IgE enzyme-linked immunosorbent assay as well as skin prick tests. RESULTS: The Blo t 5 IgE responses were 91.8% (134 of 146) and 73.5% (36 of 49) for Taiwanese and Malaysian sera, respectively. The Blo t 5 specific IgE titers were significantly higher than those of Der p 5 (P <.02). The correlation of IgE reactivity between Blo t 5 and Der p 5 was low, and only limited cross-reactivity was observed. This was further confirmed by the dose-response inhibition studies. Skin prick tests performed on asthmatic children in Thailand also showed differential IgE response to Blo t 5 and Der p 5. CONCLUSION: By using a large panel of asthmatic sera and a combination of in vitro and in vivo assays, the major allergen of B tropicalis in tropical and subtropical regions, Blo t 5, exhibits low levels of IgE cross-reactivity with homologous Der p 5. These findings suggest that highly specific clinical reagents are necessary for precise diagnosis and immunotherapeutic treatment of sensitization to group 5 mite allergens.     

Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1. Structure, gelation rate and mechanical properties

Alginate gels have been used in both drug delivery and cell encapsulation applications in the bead form usually produced by dripping alginate solution into a CaCl2 bath. The major disadvantages to these systems are that the gelation rate is hard to control; the resulting structure is not uniform; and mechanically strong and complex-shaped 3-D structures are difficult to achieve. In this work controlled gelation rate was achieved with CaCO3-GDL and CaSO4-CaCO3-GDL systems, and homogeneous alginate gels were formulated as scaffolds with defined dimensions for tissue engineering applications. Gelation rate increased with increasing total calcium content, increasing proportion of CaSO4, increasing temperature and decreasing alginate concentration. Mechanical properties of the alginate gels were controlled by the compositional variables. Slower gelation systems generate more uniform and mechanically stronger gels than faster gelation systems. The compressive modulus and strength increased with alginate concentration, total calcium content, molecular weight and guluronic acid (G) content of the alginate. MC3T3-E1 osteoblastic cells were uniformly incorporated in the alginate gels and cultured in vitro. These results demonstrated how alginate gel and gel/cell systems could be formulated with controlled structure, gelation rate, and mechanical properties for tissue engineering and other biomedical applications.