Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000

OBJECTIVE: To describe the clinical and biologic evolution of HIV-1 infection in Africa. METHODS: One hundred four HIV-1-infected individuals were identified prospectively from regular blood donors in Abidjan, C?te d'Ivoire. The date of seroconversion was estimated from results of sequential serologic tests. Biologic and clinical follow-up was performed every 6 months, starting as early as possible after seroconversion. Case management followed national guidelines. RESULTS: The median interval between estimated seroconversion and study inclusion was 9.7 months, and the median window of seroconversion was 2.8 months. At baseline, all but two patients were asymptomatic; the median CD4 + cell count was 527/mm 3 (interquartile range [IR], 395-684), and the median plasma HIV RNA level was 4.6 log 10 copies/ml (IR, 3.8-4.9). The median follow-up was 23.9 months, and 95% of the patients received primary prophylaxis with co-trimoxazole for opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3 developed tuberculosis, and 17 had a Centers for Disease Control and Prevention category B-defining event. The 3-year AIDS-free and symptom-free probabilities were 96.7% (95% confidence interval [CI], 87.0-99.2] and 79.3% (95% CI, 67.5-87.2), respectively. During the first 3 years of follow-up, we observed that the median plasma viral load stabilized at >4 log 10 copies/ml and that the median CD4 + cell count declined by 20 to 25/mm 3 per year. CONCLUSION: These African seroconverters were moderately immunosuppressed. The median HIV RNA level was high and varied very little during the first 3 years, and there were few clinical events.     

Role of the htrA gene in Klebsiella pneumoniae virulence

We recently described the use of mini-Tn5 to generate complement-sensitive mutants derived from a complement-resistant Klebsiella pneumoniae clinical isolate deficient in the lipopolysaccharide O side chain. One mutant with a reduced capacity to survive in nonimmune human sera carried the transposon inserted in the htrA gene. We cloned and sequenced the gene and predicted from the deduced amino acid sequence that the putative HtrA homolog contains structural features similar to those of previously described HtrA proteins. To investigate the biological functions and the role of the htrA gene in the virulence of K. pneumoniae, we constructed an isogenic mutant by insertion-duplication mutagenesis. Characterization of the mutant showed that it had greater sensitivity to temperature (50 degrees C) and oxidative stress (H(2)O(2)) than the parent strain. Furthermore, the htrA mutant produced less capsule, bound more molecules of complement component C3, and was more sensitive to complement and whole-blood killing than was the parent strain. Finally, disruption of the htrA gene in a virulent K. pneumoniae strain caused a reduction of its virulence in a mice model. Our results indicate that the htrA gene plays an important role in the virulence of K. pneumoniae.     

C3 promotes clearance of Klebsiella pneumoniae by A549 epithelial cells

The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense.     

Characterization of Aeromonas caviae antigens which cross-react with Shigella boydii 5.

Live and boiled cells of 16 strains of Aeromonas caviae, isolated from patients with diarrhea, agglutinated with Shigella boydii 5 antiserum in a slide test. Further studies with seven selected strains showed agglutination with boiled cells in a tube test. Lipopolysaccharide antigen extracted from one of these strains cross-reacted with S. boydii 5 in enzyme-linked immunosorbent assay and immunoblot studies. Either all or the majority of the seven strains possessed properties deemed to be diarrheagenic.     

Metachronous and multiple aneurysmal bone cysts: a rare variant of primary aneurysmal bone cysts

In 1942, Jaffe and Lichtenstein introduced the term aneurysmal bone cyst (ABC). Primary ABC is characterized by the presence of spongy or multi-cameral cystic tissue filled with blood. The process is benign, but it is locally destructive and has a high propensity for recurrence. In this paper, we present the third case of multiple metachronous primary ABCs as a rare variant of ABC. We describe the 10-year history of a 12-year-old boy with metachronous multiple primary ABCs at five different sites (right proximal humerus, right ulna, bilateral distal radius and right lateral clavicle). Furthermore, our patient suffered from vascular malformations, such as aortic isthmus stenosis, hypoplastic thoraco-abdominal aorta and bilateral renal artery stenosis. To date, in contrast to solitary ABC, the multiple lesions have been found more frequently in male individuals. Using interphase cytogenetics, we analyzed three of five of the patients ABCs and one of these was also analyzed by GTG-banding. No chromosomal abnormalities were found. Significantly, we excluded the missense mutation of codon 201 in guanine nucleotide-binding protein 1 gene consistently found in McCune-Albright syndrome (MAS) and in non-MAS cases of polyostotic fibrous dysplasia of bone with or without secondary ABC.     

Results of a high-resolution genome screen of 437 Alzheimer's disease families

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.     

Monoclonal antibodies to the enterotoxin of Bacteroides fragilis: production, characterization, and immunodiagnostic application.

A monoclonal antibody, ICT11, specific for the toxin of enterotoxigenic Bacteroides fragilis (ETBF) neutralized the cytotoxic effect of the toxin on human colonic cell line HT-29/C1. In an evaluation using 115 diarrheal stool specimens and culture as the "gold standard," the assay showed a sensitivity of 85% and a specificity of 100%. An ICT11-based sandwich enzyme-linked immunosorbent assay showed a sensitivity of 100% and a specificity of 98% for direct detection of toxin from stool samples compared with those of culture. Thus, ICT11-based assays will be useful for screening for ETBF.     

Schistosomiasis: an unusual cause of tubal infertility

A case report of a Nigerian woman having an unusual cause oftubal infertility is presented. On histological examinationof the Fallopian tube, ova of Schistosoma haematobium enclosingliving miracidia were found in the smooth muscle layer of theFallopian tube and its mesosalpinx. Mechanisms of tubal involvementare analysed. The case indicates the need to consider schisto-somiasisas a possible aetiological factor in patients with tubal infertilitycoming from areas where the disease is endemic.     

Adapting industry-style business model to academia in a system of Performance-based Incentive Compensation.

Performance-Based Incentive Compensation (PBIC) plans currently prevail throughout industry and have repeatedly demonstrated effectiveness as powerful motivational tools for attracting and retaining top talent, enhancing key indicators, increasing employee productivity, and, ultimately, enhancing mission-based parameters. The University of Arkansas for Medical Sciences (UAMS) College of Medicine introduced its PBIC plan to further the transition of the college to a high-performing academic and clinical enterprise. A forward-thinking compensation plan was progressively implemented during a three-year period.After the introduction of an aggressive five-year vision plan in 2002, the college introduced a PBIC plan designed to ensure the retention and recruitment of high-quality faculty through the use of uncapped salaries that reflect each faculty member's clinical, research, and education duties. The PBIC plan was introduced with broad, schoolwide principles adaptable to each department and purposely flexible to allow for tailor-made algorithms to fit the specific approaches required by individual departments.As of July 2006, the college had begun to reap a variety of short-term benefits from Phase I of its PBIC program, including increases in revenue and faculty salaries, and increased faculty morale and satisfaction.Successful implementation of a PBIC plan depends on a host of factors, including the development of a process for evaluating performance that is considered fair and reliable to the entire faculty. The college has become more efficient and effective by adopting such a program, which has helped it to increase overall productivity. The PBIC program continues to challenge our faculty members to attain their highest potential while rewarding them accordingly.