Arthritis Susceptibility in Mice Expressing Human Type II Collagen in Cartilage

Collagen type II (CII) induced arthritis (CIA) in mice is an experimental model for rheumatoid arthritis. Induction with non-self (e.g. human) CII induces severe arthritis whereas the mice are less susceptible to induction with self CII (i.e. mouse). To analyse whether an autoimmune response to human CII can develop and is pathogenic the authors have established transgenic mice expressing human CII in cartilage and backcrossed them into two different gene backgrounds susceptible to CIA (DBA/1 and C3H.Q). The transgenic human CII expression was restricted to cartilage and did not disturb cartilage morphology or lead to chondrodystrophy. In addition, development of stress-induced arthritis was not affected by the transgene. The cartilage specific expression of human CII reduced, but did not eliminate, the susceptibility to CIA irrespective of the species source (human, bovine, chick, rat) of CII used for immunization. A common denominator between these heterologous CII in comparison with mouse CII is the previously defined CII 256–270 epitope. An expression level dependent T-cell tolerance was seen in this epitope as well as to the entire CII. However, all human transgenic mouse lines could still mount significant autoreactive T- and B-cell responses. Approximately 10% of the transgenic mice developed arthritis after immunization with human CII. These findings show, therefore, that cartilage-located human CII induce tolerance but can nevertheless be a target for development of arthritis.     

Delphi survey of research priorities

Aim  To identify nurses' priorities for topics and issues to be addressed by a developing nursing research program at a county hospital.
Background  Delphi surveys have been effective at other hospitals to identify research priorities of nurses.
Methods  A Delphi survey was performed in two rounds. Questionnaires were distributed to all 415 nurses who worked at the hospital.
Results  A total of 274 nurses returned the Round I questionnaire (response rate, 66%), and 249 returned the Round II questionnaire (response rate, 60%).
Conclusions  The Delphi survey was successfully used to identify nurses' research priorities at a county hospital. A total of 39 topics were identified from content analysis of research areas described by nurses. Factor analysis revealed three factors: work environment, newborn issues and effects of leadership.
Implications for nursing management  The Delphi survey is a useful way to begin a program of research. Nurses who have a successful experience with research are more likely to become further involved in research, which will allow them to more effectively participate in decision making and improving the work environment. In addition, items were identified that needed to be addressed by nursing managers.     

The changing pattern of severe neonatal staphylococcal infection: A 10-year study

Abstract Forty-two cases of severe staphylococcal infection occurring over a 10-year period in the neonatal unit at Queen Mary Hospital are described. There was a 4.5-fold increase in incidence in the latter half of the study period, when methicillin-resistant Staphylococcus aureus (MRSA) emerged. The isolated MRSA were also resistant to gentamicin, but sensitive to vancomycin, fusidic acid, co-trimoxazole and amikacin. Comparison between MRSA and methicillin-sensitive cases showed that the former was associated with a longer hospital stay after diagnosis. Overall mortality was 9.5%. Two cases with meningitis died. MRSA is at least as virulent as its methicillin-sensitive counterparts. The treatment implications of severe neonatal staphylococcal infection are discussed.     

Synthesis and immunological characterization of a 134-mer synthetic peptide corresponding to the N-terminal half of the HIV-1 nucleoprotein,p24

A 134-mer peptide corresponding to the N-terminal sequence of p24 (residues 146–279 of the gag gene product of the LAV strain) was chemically synthesized using highly optimised protocols on an ABI 430A synthesizer. The crude peptide was obtained by treating the peptide-resin with HF, then purified by a combination of size exclusion and RP-HPLC. One hundred milligram of 90% pure 134-mer can be obtained within a month. Both mice and rabbit polyclonal antisera raised against a commercial preparation of recombinant p24, and a pooled sera from HIV-1 infected individuals reacted strongly with the 134-mer peptide in ELISA. Both mice and rabbits immunized with the free peptide emulsified in Freund's complete adjuvant generated strong anti-peptide and anti-p24 antibody responses as judged by immunoblots and ELISAs. Immunodominant epitopes were mapped to residues 201–227 (LKETINEEAAEWDRVHPVHAGPIAPG). These B-cell epitopes had previously been identified by mouse monoclonal antibodies raised against HIV-1 virus or gag gene products. Furthermore, murine T-cell lines generated against the 134-mer peptide were found to respond to two short peptides, P24B (residues 195–215) and P24D1 (residues 268–279). These two T-cell epitopes were previously reported as human helper T-cell and CTL epitopes, respectively. These results clearly indicate that the synthetic 134-mer peptide could elicit both T- and B-cell responses to HIV-1 similar to those obtained with the natural viral gag protein, and could be useful for the development of a synthetic HIV vaccine     

Temporal arteritis in Hong Kong

Objective: To evaluate Chinese patients with biopsy‐proven temporal arteritis in Hong Kong, focusing on clinical presentation, frequency of occurrence, treatment regimen and complications, management and outcome of these patients. Design: A retrospective study. Method: A retrospective study was undertaken in which patients with biopsy‐proven temporal arteritis were identified from: (i) Statistical records of Hospital Authority (1996–1999); (ii) pathology records of regional hospitals in Hong Kong (1996–2000); and (iii) case records from rheumatologists in two university hospitals. Indexed hospital and out‐patient records were reviewed and analysed. Results: Nineteen patients with biopsy‐proven temporal arteritis were identified from 1996 to 2000 and the calculated annual incidence was 0.34 patients in 100,000 people aged 50 and above per year. There were six male and 13 female patients (male : female ratio 1:2.2). Sixteen (84%) patients were older than 70 years. The common presentations were similar to overseas studies and included headache (79%), muscular symptoms (42%), constitutional symptoms (37%), scalp tenderness (37%), visual loss (32%), jaw claudication (32%), abnormal temporal artery (32%), and fever (26%). The mean erythrocyte sedimentation rate before treatment was 104 mm/h (SD = 30 mm/h). Anemia (Hb < 12 g/dL) was present in 79% of patients. The mean duration of symptoms before diagnosis was 8.4 weeks. Seventeen (89%) patients received high‐dose steroid therapy but none received steroid‐sparing agents. Only 33% of patients reached a physiological dose of steroid (prednisolone 5 mg/day) after 1 year. Conclusion: Temporal arteritis is rare among Hong Kong Chinese. A rough estimate of annual incidence yielded less than one per 100,000 people aged ≥ 50. Overall clinical presentation was similar to overseas studies but there were: (i) longer duration of steroid therapy given; and (ii) more complications from steroid use. Steroid‐sparing agents should be considered early in difficult‐to‐control cases.     

Acute hemorrhagic edema of infancy with abdominal pain and elevated transaminases

Abstract: Acute hemorrhagic edema of infancy is a rare type of leukocytoclastic vasculitis characterized by a triad of fever, edema, and rosette‐shaped purpura, mainly over the face, auricles, and extremities in a nontoxic infant. Visceral involvement is infrequent in acute hemorrhagic edema of infancy. We report a case of acute hemorrhagic edema of infancy with abnormal liver function tests and abdominal pain.     

A novel strategy for the synthesis of the cysteine-rich protective antigen of the malaria merozoite surface protein (MSP-1)

The most promising antigen for a protective malaria vaccine is a cysteine-rich domain at the carboxyl terminus of the merozoite surface protein (MSP-1). Passive transfer of anti-MSP-1 antibody or immunization of MSP-1 against infection challenge confers protection in primate and rodent models. The antigen belongs to the three-disulfide epidermal growth factor (EGF) family based on the alignment of the six cysteines. In the K1 strain there are, however, only four cysteines corresponding to the four carboxyl cysteines of EGF. Furthermore, disulfide pairing would produce a non-EGF pattern. Because this cysteine-rich antigen is conformation-dependent, and reduction of the disulfide bonds abolishes antigenicity, we used a synthetic analog to investigate the probable disulfide pairing of this antigen. This paper describes the synthesis, folding and disulfide pairings of two 50-residue cysteine-rich peptides. One contains two disulfides (VK-50) derived from the native sequence of MSP-1 of the Thailand K1 strain (aa 1629–1679). The other contains an EGF-like, three-disulfide [Cys-9,14]VK-50 peptide. Both peptides were synthesized by a solid-phase method using Fmoc-chemistry. The crude peptide of VK-50 was folded, and the disulfide was oxidized by the DMSO method to obtain a structure with an expected disulfide pairing of 3–4, and 5–6. The specific pairing pattern of 1–3, 2–4 and 5–6 in [Cys 9,14]VK-50 corresponding to EGF in [Cys 9,14]VK-50 was obtained using a ‘knowledge-based’ (KB) strategy for their formation. Purified VK-50 and [Cys-9,14]VK-50 had the correct molecular weight, as shown by Cf-252 fission ionization mass-spectrometry. The disulfide pairings were confirmed by enzymatic digestion. These two peptides can be conjugated to the multiple peptide antigen core for immunization. The immunological results will allow us to conclude the correct disulfide pairing and the conformational importance of this antigen.     

PREVALENCE AND CORRELATES OF DSM-IV AND ICD-10 ALCOHOL DEPENDENCE: 1990 US NATIONAL ALCOHOL SURVEY

This paper describes DSM-IV and ICD-10 alcohol dependence prevalencerates and sociodemographic and drinking correlates. The sampleunder analysis (n = 2058) constitutes a multicluster probabilitysample of the US adult household population. The study responserate is 71%. The prevalence rate for current (past 12 month)DSM-IV alcohol dependence is 3.9%, and for current ICD-10 itis 5.5%. Agreement between DSM-IV and ICD-10 on whether respondentsare dependent or not is less than optimal (Kappa = 0.67). Thepredictors of ICD-10 alcohol dependence are the frequency ofdrinking five or more drinks on occasion and age (inverse relationship).For DSM-IV alcohol dependence the correlates are drinking fiveor more drinks on occasion, being unemployed and age (also aninverse relationship). Differences in results underline theimportance of understanding the variations among DSM-IV andICD-10 criteria for alcohol dependence and the implicationsof these differences for epidemiological research. The highprevalence of dependence among young men may be the result ofrecognizing consequences of episodic heavy drinking as signsof alcohol dependence.