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Biomedical subjects

A H Rowley

Publications and source records attributed to A H Rowley.

At least 19 recordsLinked to original sources
PubMed2001

CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease.

The pathogenesis of coronary arterial inflammation in acute Kawasaki disease (KD) is unclear. To test the hypothesis that the KD vascular lesion is an activated T lymphocyte-dependent process, immunohistochemical studies were done on coronary artery aneurysms from 8 fatal acute KD cases by using antibodies to CD45RO (activated or memory T lymphocyte), CD8 (cytotoxic T lymphocyte), CD4 (helper T lymphocyte), HAM56 (macrophage), and CD20 (B lymphocyte). Acute KD coronary arteritis was characterized by transmural infiltration of CD45RO T lymphocytes with CD8 T lymphocytes predominating over CD4 T lymphocytes. Macrophages were present primarily in the adventitial layer; B lymphocytes were notably absent. These data lend support to the hypotheses that KD results from infection with an intracellular pathogen, such as a virus, whose antigens are presented by major histocompatibility complex class I molecules, and that CD8 T lymphocytes and macrophages are important in the pathogenesis of KD coronary aneurysms.

Antigens, CD20↗
PubMed2001

Oligoclonal IgA response in the vascular wall in acute Kawasaki disease.

Kawasaki Disease (KD) is a potentially fatal acute vasculitis of childhood. Although KD is the leading cause of acquired heart disease in children in developed nations, its pathogenesis remains unknown. We previously reported the novel observation that IgA plasma cells infiltrate the vascular wall in acute KD. We have now examined the clonality of this IgA response in vascular tissue from three fatal cases of KD to determine whether it is oligoclonal, suggesting an Ag-driven process, or polyclonal, suggesting nonspecific B cell activation or a response to a superantigen. We first sequenced VDJ junctions of 44 alpha genes isolated from a primary, unamplified KD vascular cDNA library. Five sets of clonally related alpha sequences were identified, comprising 34% (15 of 44) of the isolated alpha sequences. Furthermore, point mutations consistent with somatic mutation were detected in the related sequences. Next, using formalin-fixed coronary arteries from two additional fatal KD cases, we sequenced VDJ junctions of alpha genes isolated by RT-PCR, and a restricted pattern of CDR3 usage was observed in both. We conclude that the vascular IgA response in acute KD is oligoclonal. The identification of an oligoclonal IgA response in KD strongly suggests that the immune response to this important childhood illness is Ag-driven.

Acute Disease↗
PubMed2001

Surface and cytoplasmic immunoglobulin expression in circulating B-lymphocytes in acute Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis of young childhood predominantly affecting the coronary arteries. IgA plasma cells have been found to infiltrate vascular and nonvascular tissues in fatal acute KD. To determine whether IgA B-lymphocytes were increased in the peripheral blood of patients with KD, we performed three-color flow cytometry to detect surface and cytoplasmic immunoglobulin expression (IgA, IgM, IgD, and IgG) of peripheral B-lymphocytes in KD patients during the acute, subacute, and convalescent stages of illness and in age-matched febrile and afebrile pediatric controls. Surprisingly, absolute numbers of B-lymphocytes expressing IgA were found to be significantly lower in peripheral blood of acute KD patients compared with febrile and afebrile pediatric controls. These findings indicate that IgA plasma cells are not present in KD tissue as a result of excess numbers of these IgA B-lymphocytes in peripheral blood. We speculate that IgA B-lymphocytes are selectively withdrawn from the peripheral circulation into KD target tissues as part of a specific IgA immune response.

Acute Disease↗
PubMed2000

IgA plasma cell infiltration of proximal respiratory tract, pancreas, kidney, and coronary artery in acute Kawasaki disease.

The etiology and pathogenesis of Kawasaki disease (KD) remain unknown. As previously reported, in US patients with acute KD, IgA plasma cells (PCs) infiltrate the vascular wall. To determine whether IgA PCs are increased at mucosal sites in KD and to determine whether other nonvascular KD tissues are infiltrated by IgA PCs, the cells were immunolocalized and quantitated in tissue sections taken from 18 US and Japanese patients who died of acute KD and from 10 age-matched controls. IgA PCs were significantly increased in the trachea of patients who died of acute KD, compared with controls (P<.01), a finding that was similar to findings in children with fatal respiratory viral infection. IgA PCs also infiltrated coronary artery, pancreas, and kidney in all KD patients. These findings strongly support entry of the KD etiologic agent through the upper respiratory tract, resulting in an IgA immune response, with systemic spread to vascular tissue, pancreas, and kidney.

Acute Disease↗
PubMed1999

Kawasaki syndrome.

Kawasaki syndrome is a fascinating worldwide illness of young children. This acute self-limited vasculitis has become the most common cause of acquired heart disease in children in the United States and Japan. KS causes significant coronary artery disease that may lead to myocardial infarction and sudden death. Clinical and epidemiologic features of KS support an infectious cause, but the etiology remains unknown. Clearly, additional research on the cause of KS and its pathogenesis is needed urgently to allow for improved diagnosis; more specific therapy; and, ultimately, prevention of the disorder.

Acute Disease↗
PubMed1998

Kawasaki syndrome.

Kawasaki syndrome (KS) is an acute, sometimes fatal vasculitis of young children. KS has replaced acute rheumatic fever as the most common cause of acquired heart disease in children in the United States. The illness is manifested by prolonged fever, conjunctival injection, enanthem, exanthem, erythema and swelling of the hands and feet, and cervical adenopathy. These acute features of illness are self-limiting, but coronary artery abnormalities occur in 20% of untreated patients. The etiology of the illness is unknown, but its clinical and epidemiologic features are most consistent with an infectious cause. Common cardiovascular manifestations of the illness include myocarditis, pericardial effusion, and coronary artery aneurysm formation. Treatment with intravenous gamma globulin (IVGG) and aspirin within the first 10 days of illness reduces the prevalence of coronary artery abnormalities from 20% in those treated with aspirin alone to 4%. Patients who develop coronary artery aneurysms, particularly those who develop giant coronary artery aneurysms, may suffer myocardial infarction secondary to thrombosis or stenosis in the abnormal vessel. Additional research to determine the cause of KS is urgently needed to allow for improved diagnosis, more specific therapy, and prevention of the disorder.

Aspirin↗
PubMed1997

IgA plasma cells in vascular tissue of patients with Kawasaki syndrome.

The etiology and pathogenesis of Kawasaki syndrome (KS) remain unknown. Clinical and epidemiologic features of KS are consistent with an infectious cause. To search for an etiologic agent of KS, a phage cDNA expression library was constructed from the aorto-iliac junction of a patient with fatal acute KS and screened with convalescent KS serum followed by anti-human Ig. Unexpectedly, 0.1% of the clones in the library react with anti-human Ig, indicating the presence of many Ig-producing B lymphocytes in the vasculitic tissue. To confirm this finding and to determine the isotypes produced, frozen vascular tissue sections from the patient and paraffin sections from coronary arteries from six additional patients with fatal acute or subacute KS were incubated with Abs to Ig isotypes. Histopathology of the tissues revealed the presence of many plasma cells in the inflammatory infiltrate. IgA was the predominant isotype produced in vascular tissue in all seven KS patients. IgM- and IgG-producing cells were less often detected. We conclude that there is a marked plasma cell response within the vasculitic tissue in KS, with unusual IgA production locally in this nonlymphoid, nonmucosal tissue. We suggest that the prominence of IgA plasma cells in the vascular infiltrate in the early, acute, and subacute stages of KS indicates an Ag-driven immune response to an etiologic agent with a respiratory or gastrointestinal portal of entry and speculate that this unusual immune response is integral to the pathogenesis of the illness.

Adolescent↗
PubMed1997

Characteristics of typhoid fever in children and adolescents in a major metropolitan area in the United States.

To examine the epidemiology of typhoid fever in children in an area that was not endemic, we analyzed 55 cases of typhoid fever in children and adolescents who were < or = 18 years and whose cases were reported to the Chicago and suburban Cook County Health Departments over 7 years. Cases had positive blood and/or stool cultures for Salmonella typhi. The ethnic distribution of the patients was as follows: 25% Asian, 22% Hispanic, 15% African American, 9% Caucasian, 18% other, and 11% unknown. Of the 55 cases, 35% were aged 0-5 years, 25% were aged 6-10 years, 31% were aged 11-15 years, and 9% were aged 16-18 years. Twelve patients did not have a history of travel. All patients recovered; none became carriers. Symptoms in 41 patients whose charts were available for review included fever (100%), diarrhea (77%), vomiting (50%), and dehydration (30%). Bacteremia was documented in 27 (66%) of 41 cases. In 17 of 41 cases, the household contacts were food handlers or health care workers. Eight (31%) of 26 isolates were resistant to both ampicillin and trimethoprim-sulfamethoxazole. The findings in our study were as follows: typhoid fever occurred frequently in children aged 0-5 years (in contrast with reports from areas of endemicity), approximately 20% of patients did not have a history of travel, and multidrug-resistant strains were prevalent.

Adolescent↗
PubMed1995

Lack of detection of enteroviral RNA or bacterial DNA in magnetic resonance imaging-directed muscle biopsies from twenty children with active untreated juvenile dermatomyositis.

OBJECTIVE: To investigate for the presence of increased titers of circulating antibody to putative infectious agents and for detectable viral RNA or bacterial DNA in children with active recent-onset juvenile dermatomyositis (DM). METHODS: Magnetic resonance imaging-directed muscle biopsies were performed in 20 children with active, untreated, recent-onset juvenile DM and in age-matched children with neurologic disease. Sera were tested for complement-fixing antibody to Coxsackievirus B (CVB), influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae, mumps, respiratory syncytial virus, and Reovirus; and by immunofluorescence for IgG antibody to Toxoplasma gondii cytomegalovirus and IgM antibody to Epstein-Barr virus. Muscle from juvenile DM patients and control children, CD-1 Swiss mice with and without CVB1 infection, and viral stock positive for CVB1-6 were tested using reverse-transcriptase polymerase chain reaction with 5 primer sets, 4 probes (1 Coxsackievirus, 3 Enterovirus), and universal primers for DNA. RESULTS: No increased antibody, viral RNA, or bacterial DNA was present in the juvenile DM patients or the control children. CONCLUSION: Juvenile DM may be triggered by unidentified agent(s) in the genetically susceptible host.

Adolescent↗
PubMed1995

Pediatric tuberculosis: an update.

The incidence of tuberculous infection and disease in children has risen significantly over the last decade. The management of TB has become more complicated by the changing epidemiology of this disease and the emergence of resistant MTB. Many new recommendations have recently been made to address these issues. It is crucial that pediatricians become familiar with this disease again and have a good working knowledge of pediatric TB.

Antitubercular Agents↗