Biomedical subjects

John P T Higgins

Publications and source records attributed to John P T Higgins.

7 recordsLinked to original sources

PubMed2006

Gene array studies in renal neoplasia.

Renal cell carcinoma (RCC) is comprised of several distinct histologic subtypes many of which have characteristic cytogenetic abnormalities. The molecular pathogenesis of some of these neoplasms is beginning to be elucidated. Yet renal cell carcinoma is often discovered at an advanced clinical stage and effective pharmacologic therapies for this disease remain to be discovered. For these reasons, renal cell carcinoma is ideally suited to the genome scale investigation made possible by DNA microarrays. A number of DNA array studies of renal cell carcinoma have been published. Renal cell carcinomas have also been studied by array based comparative genomic hybridization. The purpose of this review will be to summarize these studies, to compare the results of the different studies, and to suggest future areas of investigation with a particular emphasis on clinically relevant advances.

Biomarkers, Tumor↗

PubMed2006

Intravenous Tamm-Horsfall protein polyps: report of a case in association with a hematoma that mimicked a renal neoplasm.

Tamm-Horsfall protein (THP) is a glycoprotein produced only in the thick ascending limb of the loop of Henle. Its primary physiological function is unknown, but it may have a role in host defense against infectious organisms. THP is the primary scaffolding protein in all varieties of tubular casts. Under certain conditions, THP may be extruded from tubular lumens into the interstitium and lymphatic channels. It even may be found within lymph nodes sampled for staging of neoplastic conditions. THP deposits were described in lumens of large veins. The pathogenetic basis of this finding is not known, but obstruction of renal outflow was suggested, and several cases were associated with macroscopic hematuria. We report a case of intravenous THP polyposis in which, in addition to abundant hemorrhage, there was formation of a hematoma. This measured 12 cm in diameter and caused clinical concern for the possibility of renal cell carcinoma. Although the cause of the hematoma was not apparent, the association with striking intravenous polyps of THP is noteworthy because this represents the first association of intravenous THP polyps with a large intraparenchymal hematoma.

Carcinoma, Renal Cell↗

PubMed2005

TMA-Combiner, a simple software tool to permit analysis of replicate cores on tissue microarrays.

We have previously published a suite of software tools that facilitates the reformulation of tissue microarray (TMA) data so that it may be analyzed using techniques originally devised for analysis of cDNA microarray data. However, current microarray data often feature multiple scores for a given tissue sample and antibody combination. Furthermore, an efficient and systematic method for combining scores that takes into account the differing staining properties of tissue epitopes has not been described. We thus present the TMA-Combiner, a new Microsoft Excel-based macro that permits analysis of data for which tissues may have two or more scores per antibody, and permits combination of data from multiple different tissue microarrays. It accomplishes this by rendering one score per tissue per antibody from two or more scores, using one of multiple user-selectable combination rules developed to account for the differing staining properties of tissue epitopes. This greatly facilitates analysis of tissue microarrays, particularly for users with large repositories of data, and may facilitate discovery of biological trends and help refine diagnostic accuracy of tissue markers in clinical samples.

Cluster Analysis↗

PubMed2004

Biochemical remission after resection of prostate cancer lung metastasis.

Once metastatic, prostate cancer was regarded as a systemic disease that is not amenable to surgical therapy. We present a case of a solitary pulmonary recurrence of prostate cancer after radical prostatectomy that was resected, resulting in 12 years of biochemical remission without additional therapy.

Adenocarcinoma↗

PubMed2003

Gene expression in the normal adult human kidney assessed by complementary DNA microarray.

The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied gene expression in dissected renal lobes of five adult human kidneys using cDNA microarrays representing approximately 30,000 different human genes. Total RNA was isolated from sections of the inner and outer cortex, inner and outer medulla, papillary tips, and renal pelvis and from glomeruli isolated by sieving. The results revealed unique and highly distinctive patterns of gene expression for glomeruli, cortex, medulla, papillary tips, and pelvic samples. Immunohistochemical staining using selected antisera confirmed differential expression of several cognate proteins and provided histological localization of expression within the nephron. The distinctive patterns of gene expression in discrete portions of the kidney may serve as a resource for further understanding of renal physiology and the molecular and cellular organization of the nephron.

Adult↗

PubMed2003

Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray.

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.

Adenocarcinoma, Clear Cell↗

PubMed2003

Expression of FKBP12 in benign and malignant vascular endothelium: an immunohistochemical study on conventional sections and tissue microarrays.

FKBP12 is a cytosolic FK506 binding protein that interacts with calcineurin and thereby mediates the immunosuppressive effects of FK506. Because initial immunohistochemical staining showed abundant expression of FKBP12 in vascular endothelial cells, we evaluated whether it could serve as a marker for vascular neoplasms. We performed immunohistochemical staining of conventional sections from formalin-fixed, paraffin-embedded tissue from 59 benign and malignant vascular neoplasms using a polyclonal rabbit antiserum against FKBP12. Western blot analysis of tissue from 6 angiosarcomas showed a single band at 12 kD, consistent with the published molecular weight for the FKBP12 protein. Together, CD31, CD34, and FKBP12 identified all 59 vascular neoplasms in this study. Specificity of immunohistochemical staining was assessed on 1,321 tissues represented on 7 tissue microarrays. All proteins were occasionally expressed in non-vascular tissue. Six of 8 vascular neoplasms represented on the arrays stained for FKBP12, as did normal vessels in numerous cores. The polyclonal antiserum shows comparable sensitivity (94.9%) and specificity (96.5%) to CD34 and CD31 and may be a useful additional marker for vascular differentiation. Because we have evaluated a large number of tissues by tissue microarray, we anticipate that our estimate of the specificity of immunostaining for FKBP12 as a marker for vascular endothelium will be accurate. In addition, our findings may explain the toxic effects of FK506 on vascular endothelium of the kidney.

Animals↗