Robert I. Garver

Midkine and Pleiotrophin Expression in Normal and Malignant Breast Tissue

Background. Some growth factors may promote tumor growth by affecting tumor angiogenesis. The angiogenic growth factor, pleiotrophin, was demonstrated previously in human breast carcinoma tissues; however, the pattern of pleiotrophin expression in normal breast tissues has not been established.

Transforming growth factor β within fibrotic scleroderma lungs

Abstract purpose, patients, and methods: Since transforming growth factor β (TGFβ) has been implicated as an important mediator of pulmonary fibrosis, we measured TGFβ protein and gene expression in alveolar epithelial lining fluid (ELF) of fibrotic scleroderma lungs sampled by bronchoalveolar lavage (BAL). TGFβ protein was qualitatively examined by Western blot analysis, and quantitatively by radioreceptor assays. Gene expression was evaluated in BAL mononuclear cells by Northern blot analysis with quantification of relative gene expression by densitometric analysis of the autoradiograms. results: Normal and scleroderma subjects had a 24-kd protein that comigrated with defined human TGFβ and immunoreacted with anti-TGFβ antibody. The normal population had a significantly higher average TGFβ concentration (705 pM) compared with the scleroderma subjects (177 pM). The TGFβ gene was expressed in amounts that did not significantly differ between the scleroderma and normal groups. On an individual subject basis, the TGFβ concentration variability did not correlate with variations in BAL cellularity or TGFβ gene expression within the recovered mononuclear cells. conclusions: It is concluded that both normal and fibrotic lungs have TGFβ present at the alveolar epithelial surface. However, in the fibrotic scleroderma lungs, TGFβ protein content and gene expression were not increased at the alveolar epithelial surface. The simultaneous analysis of TGFβ protein content, gene expression, and cellular constituents within individual ELF specimens showed that the cellular components of the ELF do not appear to be major determinants of TGFβ protein concentration at the alveolar epithelial surface.

Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes

Adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the lung are morphologically distinguished in part by cyto-architectural features. However, little is known about the relative expression and distribution of cyto-architectural proteins among AC, SCC and ASC. Initial microarray analysis revealed significant differences in expression of two cyto-architectural genes in AC, SCC and ASC. Desmoplakin (DP) 1 and 2, which link desmosomes to intermediate filaments, was strongly expressed in SCC relative to AC and ASC. Cytokeratin 18 (CK18), an intermediate filament that is commonly linked to desmoplakin, was strongly expressed in AC and ASC relative to SCC. Western blot analysis demonstrated that AC and ASC had abundant CK18 protein, whereas CK18 was weakly detected in SCC. DP 1 and 2 are strongly expressed in SCC and minimally expressed in AC and ASC. However, the ratio of one to the other is the same in SCC and AC, but DP2 is lost in ASC. Microscopic analysis with fluorescence-labeled antibodies for CK18 and DP 1 and 2 revealed abundant membrane localization of DP and minimal perinuclear localization of CK18 in SCC. In contrast, in both AC and ASC, the CK18 protein was diffusely distributed within the cytoplasm, and DP showed both membranous and cytoplasmic localization. In conclusion, the data here shows that AC, SCC and ASC each have specific patterns of DP 1 and 2 and CK18 gene expression, protein content and biodistribution.

Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients

BACKGROUND The role of surveillance bronchoscopy in the care of lung transplant recipients remains controversial. Although there are no controlled studies to suggest a survival advantage, many transplant physicians support the practice. The procedure is generally safe but is associated with some complications. A review of practices at our institution revealed significant variation in patient preparation, management of risk related to the procedure, and in the technical aspects of the bronchoscopy itself. In an effort to minimize these differences and potentially improve outcomes, a standard set of procedural guidelines for all bronchoscopies was adopted in January 2000. METHODS Reports from 1028 surveillance bronchoscopies performed in our outpatient facility from January 1999 to December 2001 were reviewed. Baseline patient data and procedure-related complications were identified. Specific complications recorded included oversedation, the need for prolonged supplemental oxygen, major and minor bleeding, pneumothorax, bronchospasm, vomiting, arrhythmia, hypotension and death. Differences between groups were analyzed using chi-square or Students t-tests as appropriate. RESULTS The incidence of complications after the introduction of the guidelines (2000 and 2001) was significantly lower than in the year prior (1999) (1.95% vs 6.45%, p < 0.001). The lower rate of adverse events was mainly a result of a reduction in the incidence of minor bleeding (0.28% vs 2.26% p = 0.006) and of sedation-related complications (0.97% vs 2.90%, p = 0.04). CONCLUSIONS The use of a standardized set of guidelines for surveillance fiber-optic bronchoscopy reduces complication rates. Similar guidelines should be considered by transplant centers performing the procedure.