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IgG4-related disease has been recently defined as a distinct clinic-pathologic entity, characterized by dense IgG-4 plasmacytic infiltration of diverse organs, fibrosis, and tumefactive lesions. Salivary and lacrimal glands are a target of this disease and, when affected, may clinically resemble Küttner tumor, Mikulicz disease, or orbital inflammatory pseudotumor. In some patients, the disease is systemic, with metachronous involvement of multiple organs, including the pancreas, aorta, kidneys, and biliary tract. We report a 66-year old man who presented with salivary gland enlargement and severe salivary hypofunction and was diagnosed with IgG4-related disease on the basis of a labial salivary gland biopsy. Additional features of his illness included a marked peripheral eosinophilia, obstructive pulmonary disease, and lymphoplasmacytic aortitis. He was evaluated in the context of a research registry for Sjögren syndrome and was the only one of 2594 registrants with minor salivary gland histopathologic findings supportive of this diagnosis.
PMCID: PMC3574629  PMID: 23146570
2.  Biobanking Past, Present and Future: Responsibilities and Benefits 
AIDS (London, England)  2013;27(3):303-312.
This review explores the field of biobanking as it has evolved from a simple collection of frozen specimens to the virtual biobank. Biorepository and biospecimen science has evolved in response to the changing landscape of external regulatory pressures, the advances made in the biological sciences, and the advent of the computer chip. Biospecimen banking is a growing enterprise crucial to health science research and other biological sciences. In this review we discuss the history of biobanking, highlight current and emerging issues, discuss demands and responses, and describe an example of a biobank, the UCSF AIDS Specimen Bank that has functioned for 30 years.
PMCID: PMC3894636  PMID: 23135167
Biological Specimen Bank; Biorepository; Human Biobank; AIDS Specimen Bank
3.  Primary Sjögren’s Syndrome as a systemic disease: a study of participants enrolled in an international Sjögren’s Syndrome registry 
Arthritis care & research  2012;64(6):911-918.
To study the prevalence of extra-glandular manifestations (EGM) in primary Sjögren’s Syndrome (pSS) among participants enrolled in the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry.
1927 participants in the SICCA registry were studied, including 886 participants who met the 2002 American-European consensus group (AECG) criteria for pSS, 830 “intermediate” cases who had some objective findings of pSS but did not meet AECG criteria, and 211 control individuals. We studied the prevalence of immunologic and hematologic laboratory abnormalities; specific rheumatologic examination findings; and physician confirmed thyroid, liver, kidney disease and lymphoma among SICCA participants.
Laboratory abnormalities, including hematologic abnormalities, hypergammaglobulinemia and hypocomplementemia, frequently occurred among pSS cases, and were more common among the intermediate cases than among control participants. Cutaneous vasculitis and lymphadenopathy were also more common among pSS cases. In contrast, the frequency of physician confirmed diagnoses of thyroid, liver and kidney disease, and lymphoma was low and only primary biliary cirrhosis was associated with pSS cases status. Rheumatologic and neurologic symptoms were common among all SICCA participants, regardless of case status.
Data from the international SICCA registry support the systemic nature of pSS, manifest primarily in terms of specific immunologic and hematologic abnormalities. The occurrence of other systemic disorders among this cohort is relatively uncommon. Previously reported associations may be more specific to select patient subgroups, such as those referred for evaluation of certain neurologic, rheumatologic or other systemic manifestations.
PMCID: PMC3595164  PMID: 22238244
5.  The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma 
AIDS Research and Treatment  2012;2012:634523.
Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP), Kaposi's sarcoma (KS), or non-Hodgkin lymphoma (NHL). Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84%) showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94%) in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.
PMCID: PMC3423820  PMID: 22924124
6.  Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjögren’s Syndrome (SS) among 1726 registry participants 
Arthritis and rheumatism  2011;63(7):2021-2030.
The Sjögren’s International Collaborative Clinical Alliance (SICCA) is an ongoing NIH-funded registry whose cohort ranges from those with symptoms of possible Sjögren’s syndrome (SS) to those with obvious disease. Using this database we examined associations between labial salivary gland (LSG) histopathology and other phenotypic features of SS.
LSG biopsy specimens from SICCA participants underwent protocol-directed histopathological assessments. Among 1726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular and serological assessments.
LSG specimens included 61% with focal lymphocytic sialadenitis, (FLS; 66% of which had focus scores [FS] ≥ 1 per 4 mm2) and 38% with non-specific or sclerosing chronic sialadenitis (NS/SCS). FS ≥ 1 was strongly associated with positive serum anti-SS-A/-B, rheumatoid factor and the ocular component of SS, but not with symptoms of dry mouth or eyes. Those with positive anti-SS-A/-B were 9 times more likely to have a FS ≥ 1 (95% CI: 7.4; 11.9) than FS<1 or another pattern, while those with unstimulated whole salivary flow < 0.1 ml/min were only 2 times more likely to have a FS ≥ 1 (95% CI:1.7; 2.8) than FS<1 or another pattern, while controlling for other phenotypic features of SS.
Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining FS. A diagnosis of FLS with FS ≥ 1 per 4 mm2, as compared to FLS with FS< 1 or with NS/SCS, was strongly associated with the ocular and serological components of SS and reflects SS autoimmunity.
PMCID: PMC3128201  PMID: 21480190
8.  Epstein-Barr Virus (EBV)-Infected Monocytes Facilitate Dissemination of EBV within the Oral Mucosal Epithelium▿  
Journal of Virology  2007;81(11):5484-5496.
Epstein-Barr virus (EBV) causes hairy leukoplakia (HL), a benign lesion of oral epithelium that occurs primarily in the setting of human immunodeficiency virus (HIV)-associated immunodeficiency. However, the mechanisms of EBV infection of oral epithelium are poorly understood. Analysis of HL tissues shows a small number of EBV-positive intraepithelial macrophages and dendritic/Langerhans cells. To investigate a role for these cells in spreading EBV to epithelial cells, we used tongue and buccal explants infected ex vivo with EBV. We showed that EBV first infects submucosal CD14+ monocytes, which then migrate into the epithelium and spread virus to oral epithelial cells, initiating productive viral infection within the terminally differentiated spinosum and granulosum layers. Incubation of EBV-infected monocytes and oral explants with antibodies to CCR2 receptor and monocyte chemotactic protein 1 prevented entry of monocytes into the epithelium and inhibited EBV infection of keratinocytes. B lymphocytes played little part in the spread of EBV to keratinocytes in our explant model. However, cocultivation of EBV-infected B lymphocytes with uninfected monocytes in vitro showed that EBV may spread from B lymphocytes to monocytes. Circulating EBV-positive monocytes were detected in most HIV-infected individuals, consistent with a model in which EBV may be spread from B lymphocytes to monocytes, which then enter the epithelium and initiate productive viral infection of keratinocytes.
PMCID: PMC1900306  PMID: 17376918
9.  In Vivo Analysis of Secreted Aspartyl Proteinase Expression in Human Oral Candidiasis 
Infection and Immunity  1999;67(5):2482-2490.
Secreted aspartyl proteinases are putative virulence factors in Candida infections. Candida albicans possesses at least nine members of a SAP gene family, all of which have been sequenced. Although the expression of the SAP genes has been extensively characterized under laboratory growth conditions, no studies have analyzed in detail the in vivo expression of these proteinases in human oral colonization and infection. We have developed a reliable and sensitive procedure to detect C. albicans mRNA from whole saliva of patients with oral C. albicans infection and those with asymptomatic Candida carriage. The reverse transcription-PCR protocol was used to determine which of the SAP1 to SAP7 genes are expressed by C. albicans during colonization and infection of the oral cavity. SAP2 and the SAP4 to SAP6 subfamily were the predominant proteinase genes expressed in the oral cavities of both Candida carriers and patients with oral candidiasis; SAP4, SAP5, or SAP6 mRNA was detected in all subjects. SAP1 and SAP3 transcripts were observed only in patients with oral candidiasis. SAP7 mRNA expression, which has never been demonstrated under laboratory conditions, was detected in several of the patient samples. All seven SAP genes were simultaneously expressed in some patients with oral candidiasis. This is the first detailed study showing that the SAP gene family is expressed by C. albicans during colonization and infection in humans and that C. albicans infection is associated with the differential expression of individual SAP genes which may be involved in the pathogenesis of oral candidiasis.
PMCID: PMC115994  PMID: 10225911
10.  T and B Lymphocytes in Peripheral Blood and Tissue Lesions in Sjögren's Syndrome 
Journal of Clinical Investigation  1974;53(1):180-189.
Lymphocyte heterogeneity was studied in peripheral blood and salivary gland lesions in 24 patients with Sjögren's syndrome. Peripheral blood B cells, measured by immunofluorescence with specific antiserum to immunoglobulins or by rosette assay with complementcoated erythrocytes, were increased in most patients. Peripheral blood T cells, measured by immunofluorescence with rabbit antiserum to human thymocytes or by rosette assay with sheep erythrocytes, were reduced in eight patients. Three had associated rheumatoid arthritis, two had a generalized lymphoproliferative disorder, and one each had scleroderma, systemic lupus erythematosus, and neuropathy.
The salivary gland lymphocytic infiltrates present in labial biopsy specimens were compared in 10 patients using an indirect immunofluorescent method with anti-human T cell serum and a quantitative focus-scoring method. In general, there was a correlation between the number of T cells and the extent of the infiltrate. Striking accumulations of T cells were present in some patients, but clusters of presumed B cells were also seen. These results indicate an increase in peripheral blood B cells in most patients, a decrease in T cells in some, and a mixed T and B cell infiltrate in the salivary gland lesions.
PMCID: PMC301452  PMID: 4586872

Results 1-10 (10)