Biomedical subjects

Michael N Koss

Publications and source records attributed to Michael N Koss.

10 recordsLinked to original sources

PubMed2005

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus.

OBJECTIVE: To determine whether overexpression of BAFF can accelerate the development of systemic lupus erythematosus-associated end-organ disease in hosts with an underlying autoimmune diathesis. METHODS: We introduced a BAFF transgene (Tg) into autoimmune-prone B6.Sle1 and B6.Nba2 mice and evaluated these mice for serologic autoimmunity and renal pathology. RESULTS: B6.Sle1.BAFF and B6.Nba2.BAFF mice, but not non-Tg littermates, frequently developed severe glomerular pathology by 3 months of age. Age-matched B6.BAFF mice, despite renal Ig deposits and increases in B cells and Ig production similar to those in B6.Sle1.BAFF and B6.Nba2.BAFF mice, did not develop glomerular pathology. In B6.Sle1.BAFF and B6.Nba2.BAFF mice, severity of glomerular disease did not obligately correlate with circulating levels of IgG anti-chromatin and/or anti-double-stranded DNA antibodies or with amounts of these autoantibodies deposited in the kidneys. Even in mice with severe glomerular disease, renal tubulointerstitial infiltrates were very limited, and increased proteinuria was not detected. CONCLUSION: BAFF-driven effects on glomerular pathology may be mediated, at least in part, by autoantibodies with specificities other than chromatin and/or by autoantibody-independent means. There is an uncoupling of BAFF-driven precocious glomerular pathology from concomitant development of clinically apparent renal disease, strongly suggesting that BAFF overexpression works in concert with other factors to promote overt renal disease.

Animals↗

PubMed2005

Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung.

DNA methylation markers provide a powerful tool to make diagnoses based on genetic material obtained directly from tumors or from "remote" locations such as sputum, pleural fluid, or serum. In particular when limited cell numbers are available, amplifyable DNA markers can provide a very sensitive tool for cancer detection and classification. Malignant mesothelioma (MM), an aggressive cancer strongly associated with asbestos exposure, can be difficult to distinguish from adenocarcinoma of the lung when limited material is available. In an attempt to identify molecular markers for MM and adenocarcinoma, we examined the DNA methylation status of 14 loci. Analysis of methylation levels in 10 MM and 8 adenocarcinoma cell lines showed that methylation of APC was significantly elevated in adenocarcinoma compared to MM cell lines (P=0.0003), while methylation of CDH1 was higher in MM (P<0.02). Subsequent examination of the methylation status of the 14 loci in 6 MM and 7 adenocarcinoma primary tumors, which yielded similar methylation profiles, supported these observations. Comparison of methylation in MM cell lines and tumors versus non-tumor lung tissue indicated that APC exhibits less methylation in MM (P=0.003) while RASSF1, PGR1, ESR1, and CDH1 show more methylation in MM, the latter two showing the most significant difference between the two tissue types (P< or = 0.0001). Comparison of methylation in adenocarcinoma cell lines and tumors versus non-tumor lung tissue showed methylation of ESR1, PGR1 and RASSF1 to be significantly elevated in adenocarcinoma, with RASSF1 being most significant (P=0.0002). Thus, with the examination of 14 loci, we have identified 5 candidates that show potential for distinguishing between MM, adenocarcinoma and/or non-cancer lung. Our observations support the strong potential of methylation markers as tools for accurate diagnosis of neoplasms in and around the lung.

Adenocarcinoma↗

PubMed2005

The organizing pneumonias: an update and review.

PURPOSE OF REVIEW: Basic information as well as more recent concepts regarding cryptogenic organizing pneumonia and secondary forms of the disease. RECENT FINDINGS: More recently described and less well recognized illnesses associated with organizing pneumonia, such as organizing pneumonia associated with radiation, are enumerated. In vitro studies from separate laboratories are integrated to create a proposed model of the pathogenesis and repair mechanisms that occur in organizing pneumonias. Using current criteria, we note other interstitial lung processes, in addition to organizing pneumonia, are present in some earlier reports. SUMMARY: Cryptogenic organizing pneumonia has been reported to respond to corticosteroids with clinico-radiographic resolution in 70-80% of cases. Treatment duration is lengthy, and despite this, recurrences and late recurrences are common. Rapidly progressive, steroid resistant and poor prognostic forms of organizing pneumonia have been described and have been reported more frequently with secondary organizing pneumonia. Since other histologic interstitial patterns often coexist with organizing pneumonia, tissue sampling error or an incorrect morphologic diagnosis can be the reason for aggressive clinical behavior. Steroid nonresponsive patients have been treated with secondary non-steroidal agents. Good clinical outcomes have been reported. Inhaled antigens stimulate GM-CSF-mediated airway inflammation in organizing pneumonia. Repair requires the following: granulation tissue, upon which re-epithelialization occurs; a favorable stromal ratio of matrix metalloproteinase to tissue inhibitors of metalloproteinase; concurrent resolution of inflammation; and stromal fibroblast ingestion of collagen produced earlier in repair, reversing the initial fibrosis.

Bronchi↗

PubMed2004

CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome.

Regulatory T cells generated ex vivo from conventional mouse T cells have been used to prevent and alter the course of a stimulatory graft-vs-host disease with a lupus-like syndrome. DBA/2 mouse T cells induce this syndrome when injected into (DBA/2 x C57BL/6) F(1) mice. Stimulating DBA/2 T cells with irradiated C57BL/6 in the presence of IL-2 and TGF-beta induced both CD4(+) and CD8(+) cells to develop potent suppressive activity and enhanced their survival. The IL-2 and TGF-beta-treated T cells lost their ability to induce graft-vs-host disease and, instead, prevented other parental T cells from inducing lymphoid hyperplasia, B cell activation, and an immune complex glomerulonephritis. Moreover, a single transfer of TGF-beta-conditioned T cells to animals that had already developed anti-dsDNA Abs decreased the titer, suppressed proteinuria, and doubled survival. This study raises the possibility that autologous regulatory T cells generated ex vivo have the potential to be used as an adoptive immunotherapy to induce allograft tolerance and to control autoimmunity.

Adoptive Transfer↗

PubMed2004

Malignant and benign lymphoid lesions of the lung.

Lymphoid lesions of the lung produce a complex of problems for the practicing pathologist. Although these lesions are eventually referred to hematopathologists, it is still the general surgical pathologist who first encounters them and confronts the problem of formulating an initial diagnosis. Over the last 20 years there has been a revolution in our knowledge of the classification and natural history of the pulmonary lesions, a plethora of information which warrants a thorough review. The purpose of this discussion is to report the clinical features and courses, pathologic features and, when known, etiologies or pathogenesis of the major "primary" pulmonary lymphoid lesions and present a brief approach to differential diagnosis. I will divide the lesions into malignant and benign, discussing each in turn.

Diagnosis, Differential↗

PubMed2004

Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma.

It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.

Adult↗

PubMed2004

Nonspecific interstitial pneumonia: a provisional category of idiopathic interstitial pneumonia.

PURPOSE OF REVIEW: Idiopathic interstitial pneumonias (IIP) represent a complex group of relatively rare entities with similar clinical, vaguely similar radiographic and differing histologic features. The recent international multidisciplinary consensus statement produced by the American Thoracic Society/European Respiratory Society aiming to standardize the classification of IIP recognizes nonspecific interstitial pneumonia (NSIP) as a provisional category. While not representing a single disease, but rather a collection of pathologic processes with similar histomorphology, NSIP has been a great source of confusion for pulmonologists, radiologists, and pathologists. RECENT FINDINGS: Lacking diagnostic clinical or radiographic features, NSIP is an IIP with recognizable and reproducible morphologic patterns different from usual interstitial pneumonia (UIP)-pattern as well as other disease patterns. And while overlap with UIP-pattern can be seen in individuals with multiple biopsy samples, those with either cellular or fibrosing variants of NSIP have a better prognosis than UIP-pattern patients. SUMMARY: A morphologic diagnosis of NSIP-pattern alerts the clinician to a wide spectrum of potential clinical possibilities and enables researchers to study both this fibrosing interstitial pneumonia pattern and the more common and deadly UIP-pattern separately. Thus, this provisional category is useful to both clinicians and researchers.

Humans↗

PubMed2002

Extensive squamous metaplasia with cytologic atypia in diffuse alveolar damage mimicking squamous cell carcinoma: a report of 2 cases.

Squamous metaplasia in the setting of diffuse alveolar damage, a form of acute lung injury, in rare cases can be very extensive with cytologic atypia, mimicking squamous cell carcinoma. We describe 2 such cases that posed diagnostic difficulty in the evaluation of biopsy specimens. These cases demonstrate that histologic findings must be correlated with clinical and radiologic information to avoid a misdiagnosis of malignancy.

Adolescent↗

PubMed2002

Bronchiolitis: update 2001.

In this review, reports from last year on the following topics are summarized: (1) reviews of bronchiolitis in infants; respiratory syncytial virus (RSV)-associated illness, including possible viral mechanisms of alteration of airway function and results of an epidemiologic study of bronchiolitis-associated mortality. Studies evaluating (2) the use of serum eosinophilic cationic protein as a marker for development of subsequent persistent wheezing infants; (3) parental bronchial responsiveness as an indicator of genetic susceptibility to acute bronchiolitis; (4) prophylactic use of monoclonal antibody (Palivizumab) to control an outbreak of RSV in a hospital nursery; (5) a controlled clinical trial of ribaviron in acutely ill children; (6) reports of new associations with bronchiolitis obliterans organizing pneumonia (BOOP); (7) case reports of use of methotrexate as an alternate to corticosteroids in treatment of BOOP; (8) a newly described entity, eosinophilic bronchiolitis.

Acute Disease↗

PubMed2002

The pathology of sarcoidosis.

Sarcoidosis is a multisystemic disease characterized by a nonnecrotizing granulomatous inflammatory process that can progress through various stages of activity. The distinctive histology of sarcoidosis is often associated with various morphologic findings in the lung and other organs. The rare variants, necrotizing sarcoidal granulomas and nodular sarcoidosis, share some of the histologic features of typical sarcoidosis, but may have different clinical and pathologic manifestations. The clinician and pathologist should be aware of the diverse pathologic appearances of sarcoidosis.

Cytoplasm↗