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J Med Virol. 2000 Nov;62(3):383-91.
Picornavirus proteins share antigenic determinants with heat shock proteins 60/65.

Harkonen T, Puolakkainen M, Sarvas M, Airaksinen U, Hovi T, Roivainen M.

Enterovirus Laboratory, National Public Health Institute, Helsinki, Finland. taina.harkonetl.fi

Immunological cross-reactions between enteroviruses and islet cell autoantigens have been suggested to play a role in the etiopathogenesis of insulin dependent diabetes mellitus (IDDM). In the nonobese diabetic mouse, an autoimmune model of IDDM, one of the reactive beta cell autoantigens is the heat shock protein 60 (HSP60). These studies were prompted by sequence homology discovered between the immunogenic region in HSP60 and two regions in enterovirus capsid proteins, one in the VP1 protein and the other in the VP0, the precursor of VP2 and VP4 proteins. Possible immunological cross-reactions between enterovirus proteins and heat shock proteins were studied by EIA and immunoblotting by using purified virus preparations, viral expression proteins VP1 and VP0, and recombinant HSP60/65 proteins, and corresponding polyclonal antisera. The HSP60/65 family of proteins is highly conserved and there is a striking degree of homology between bacterial and human heat shock proteins. Rabbit antibodies to HSP65 of Mycobacterium bovis that reacted with human HSP60 were also found to recognise capsid protein VP1 of coxsackievirus A9, VP1, and/or VP2 of coxsackievirus B4. Both viruses were also recognised by antisera raised against HSP60 of Chlamydia pneumoniae. In addition to the capsid proteins derived from native virions, antisera to both bacterial HSP proteins recognised expression protein VP1 of coxsackievirus A9. The cross-reactivity was also demonstrated the other way around; antisera to purified virus particles reacted with the HSP 60/65 proteins to some extent. These results suggest that apart from the well-documented sequence homology between the 2C protein of coxsackieviruses and the beta-cell autoantigen glutamic acid decarboxylase, there are other motifs in picornavirus proteins homologous to islet cell autoantigens, which might induce cross-reacting immune responses during picornavirus infections.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11055249&dopt=Abstract



Mol Med. 2000 Aug;6(8):648-59.
Expression of the proteinase specialized in bone resorption, cathepsin K, in granulomatous inflammation.

Diaz A, Willis AC, Sim RB.

Department of Biochemistry, University of Oxford, UK. adiailbo.edu.uy

BACKGROUND: The cysteine proteinase cathepsin K has aroused intense interest as the main effector in the digestion of extracellular matrix during bone resorption by osteoclasts. The enzyme is not a housekeeping lysosomal hydrolase, but is instead expressed with striking specificity in osteoclasts. In this work, we present evidence for the association of cathepsin K with the granulomatous reaction. Granulomas are inflammatory tissue reactions against persistent pathogens or foreign bodies. We came across cathepsin K while working on Echinococcus granulosus, a persistent tissue-dwelling, cyst-forming parasite that elicits a granulomatous response. MATERIALS AND METHODS: The walls of hydatid cysts from infected cattle were solubilized. Strong proteolytic activity was detected in the extracts. The proteinase responsible was purified by anion exchange and gel filtration. The purified protein was subjected to N-terminal sequencing, and its identity further confirmed by Western blotting, with a cathepsin K-specific antibody. The same antibody was used to localize the proteinase in paraffin-embedded sections of the parasite and the local host response. RESULTS: A proteinase was purified to near homogeneity from hydatid cyst extracts. The enzyme was unequivocally identified as host cathepsin K. Both the proenzyme and the mature enzyme forms were found. Cathepsin K was then immunolocalized both to the parasite cyst wall and to the epithelioid and giant multinucleated cells of the host granulomatous response. CONCLUSIONS: In the granulomatous response to the hydatid cyst, cathepsin K is expressed by epithelioid and giant multinucleated cells. We propose that, by analogy with bone resorption, cathepsin K is secreted by the host in an attempt to digest the persistent foreign body. Both processes, bone resorption and granulomatous reactions, therefore tackle persistent extracellular material (the bone matrix or the foreign body), and utilize specialized cells of the monocytic lineage (osteoclasts or epithelioid/giant cells) secreting cathepsin K as an effector.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11055584&dopt=Abstract



Pediatr Infect Dis J. 2000 Oct;19(10):954-8.
Yersinia enterocolitica infection in children.

Abdel-Haq NM, Asmar BI, Abuhammour WM, Brown WJ.

Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit 48201, USA.

BACKGROUND: Yersinia enterocolitica can cause illness ranging from self-limited enteritis to life-threatening systemic infection. The present study was undertaken to review the epidemiology, clinical manifestations, complications and outcome of Y. enterocolitica enteritis in children seen at a large children's hospital. METHODS: The project consisted of a retrospective chart review of medical and microbiologic records of all children with stool cultures positive for Y. enterocolitica during a 7-year period. RESULTS: The review included 142 patients with Y. enterocolitica enteritis. Patients' ages ranged from 18 days to 12 years, and the majority (85%) were younger than 1 year. Most patients presented during November, December and January. History of exposure to chitterlings (raw pork intestines) at home was elicited in 25 of 30 cases. Y. enterocolitica accounted for 12.6% (142 of 1,120) of all bacterial intestinal pathogens isolated during the study period. Blood cultures were positive in 7(9%) of 78 patients; 6 were younger than 1 year and one 12-year-old had sickle cell disease. Of 132 isolates tested all were susceptible to trimethoprim-sulfamethoxazole, tobramycin and gentamicin; the majority were susceptible to cefotaxime (99%), ceftazidime (89%) and cefuroxime (88%). All bacteremic patients responded to cefotaxime treatment. Follow-up evaluation of 40 ambulatory patients revealed no difference in clinical improvement between those treated with oral trimethoprim-sulfamethoxazole (17 of 23) and those who were not treated (8 of 17) (P = 0.1). CONCLUSION: Y. enterocolitica is an important cause of enteritis in our young patient population during the winter holidays. Exposure of infants to chitterlings appears to be a risk factor. Infants younger than 3 months are at increased risk for bacteremia. Cefotaxime is effective in the treatment of Y. enterocolitica bacteremia; however, the role of oral antibiotics in the management of enteritis needs further evaluation.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11055595&dopt=Abstract



Pediatr Infect Dis J. 2000 Oct;19(10):972-9.
Effect of human immunodeficiency virus infection on episodes of diarrhea among children in South Africa.

Johnson S, Hendson W, Crewe-Brown H, Dini L, Frean J, Perovic O, Vardas E.

Perinatal HIV Research Unit, University of the Witwatersrand, South Africa.

BACKGROUND: Infection with HIV is increasing among children in South Africa. Diarrhea is a common cause of morbidity and mortality in Africa, and some studies have shown that HIV-infected children have episodes of severe diarrhea with higher mortality than HIV-uninfected children. OBJECTIVES: To compare the severity, pathogens and outcome of diarrhea in HIV-infected and uninfected children. METHODS: We studied 181 children ages 3 months to 4 years admitted for gastroenteritis to the Chris Hani Baragwanath Hospital in Soweto, South Africa. Demographic details of the children were recorded, as were the details of the episode of diarrhea. Stools specimens were collected and sent for microbiologic evaluation. The clinical course of the child's admission was recorded. Children were diagnosed as being infected with HIV if they tested positive by HIV enzyme-linked immunosorbent assay (ELISA) and were >15 months of age, or if they were ELISA-positive, were < 15 months of age and had clinical signs of HIV infection. RESULTS: Of the 176 children with an HIV ELISA result, 31 (17.6%) were classified as HIV-infected. More HIV-infected children were malnourished (80.6% vs. 39.5%, P < 0.001) and more likely to have had prolonged diarrhea (16.1% vs. 5.9%, P = 0.07) compared with HIV-uninfected children. HIV-infected children had a higher rate of a codiagnosis of pneumonia (43.3% vs. 9.2%, P < 0.0001) and were more likely to require a hospital stay of >4 days (prevalence odds ratio, 5.11; 95% confidence interval, CI 1.49 to 17.52). There were no significant differences in stool pathogens or in the level of dehydration on admission between the HIV-infected and uninfected children. CONCLUSION: HIV-infected children have the same spectrum of enteric pathogens as uninfected children but require more attention because of malnutrition and comorbidity.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11055599&dopt=Abstract



Pediatr Infect Dis J. 2000 Oct;19(10):1000-4.
Risk factors for sternal wound and other infections in pediatric cardiac surgery patients.

Mehta PA, Cunningham CK, Colella CB, Alferis G, Weiner LB.

Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, USA.

BACKGROUND: This study was undertaken to determine the incidence, pathogens and risk factors associated with development of sternal wound and other infections in children undergoing cardiac surgery. METHODS: Retrospective chart review was performed for all cardiac surgeries performed on children <18 years of age at Upstate Medical University at Syracuse between January, 1996, and June, 1998. For evaluation of risk factors for sternal wound infection, only patients undergoing sternotomy are included in the analysis: those with infection are compared with those without for preoperative, intraoperative and postoperative risk factors. RESULTS: Sternal wound infection developed in 10 of 202 (5%) children after median sternotomy. Superficial sternal wound infection developed in 6 (3%) children, and 4 (2%) had deep infection. Children with sternal wound infection had lower age, higher American Society of Anesthesiologist score, longer preoperative stay, longer period of ventilation and inotropic support, longer intensive care unit and total postoperative hospital stays and increased leukocyte band cell counts preoperatively and on Postoperative Day 1 than those without sternal infection. Causative agents for sternal wound infection were Staphylococcus aureus (6), Pseudomonas aeruginosa (1) and Haemophilus influenzae non-type b (1). In addition 32 bacterial infections occurred at nonsurgical sites after 28 procedures. Infections included pneumonia, urinary tract infection and bacteremia. Longer bypass time and longer operation time were two additional risk factors for nonwound infection. CONCLUSION: Infections continue to be a significant cause of morbidity in cardiac surgery patients. Knowledge of risk factors for infection could be useful in preventive and treatment strategies for these high-risk groups.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11055604&dopt=Abstract







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