Henry Ford Hospital medical journal最新文献

We studied the expression of the ret proto-oncogene (proto-ret) in human medullary thyroid carcinomas (MTCs) and pheochromocytomas of multiple endocrine neoplasia type 2A (MEN 2A) by Northern blot analysis. Expression of the normal-sized transcripts was detected in all 12 MTCs and in 6 of 8 pheochromocytomas. In situ localization of proto-ret mRNA revealed that the signal was confined to the cytoplasm of MTC cells. By Southern blot analysis neither amplification nor gross genetic changes of proto-ret were found in the tumors. Although no transcripts were detected in the normal portion of the thyroid from one MEN 2A patient, faint signals were detected in normal adrenal glands by Northern blot analysis, probably due to minor populations of C-cells and chromaffin cells in specimens from which MTC and pheochromocytoma might later develop. Proto-ret may play an important role in differentiation of a specific cell lineage from neuroectoderm, and it may be involved in development of MEN 2A tumors.

We have analyzed DNA marker typing data contributed by six independent groups to estimate the pairwise genetic distances between these markers and the locus for multiple endocrine neoplasia type 2A (MEN 2A). We used LIPED to calculate these distances for female, male, and sex-average linkage maps and to determine the corresponding LOD scores. The preliminary analyses of this large data set (89 MEN 2A families and five non-MEN 2A references families, with 1,934 total individuals) are reported here. These refined estimates of the genetic map in this region will aid in the assignment of presymptomatic diagnoses. This study clearly points out the limitation of pairwise linkage analysis in further refining the position of MEN2A in this small region of chromosome 10. Further refinement of the genetic map position of MEN2A will be best accomplished by finding, verifying, and accurately mapping crossovers in specific families.

Hyperparathyroidism is a central component of multiple endocrine neoplasia type 1 (MEN 1), and both sporadic and familial forms of parathyroid disease may share certain pathogenetic features. We recently identified a gene that is clonally rearranged with the PTH locus in a subset of sporadic parathyroid adenomas. This candidate oncogene, PRAD1 (previously D11S287), appears to contribute to parathyroid tumorigenesis in a fashion analogous to activation of C-MYC or BCL-2 by rearrangement with tissue-specific enhancers of the immunoglobulin genes in B-lymphoid neoplasia. The PRAD1 gene maps to 11q13 and has been linked to the BCL-1 breakpoint locus, although not to the most tightly linked MEN 1 markers, by pulsed field gel electrophoresis. PRAD1 may, in fact, be the long-sought BCL-1 lymphoma oncogene. PRAD1 encodes a novel type of cyclin protein and thus may normally function in controlling the cell cycle, perhaps through direct interaction with cdc2 or a related kinase. PRAD1's possible primary, or more likely secondary, involvement in the pathogenesis of MEN 1-related tumors is unknown and under investigation.

We describe how the federal government, the City of Chicago, and the State of Illinois worked together to increase the availability and accessibility of health care services on Chicago's underserved west side by reopening a bankrupt, federally-funded community health center. The federal government made the building available to the City which then contracted with a state university medical center to be the provider of services. This partnering has allowed the Chicago Department of Health to offer services in a previously underserved area. The University has gained an opportunity for community-based primary care teaching, as well as community relations. Patients have increased access to a wide variety of specialty and inpatient care. If public health providers are to be successful in this financial climate, they must look to new partners and new ways of delivering services to increase availability of services at a time when they are greatly needed.

One of the characteristic features of prostate carcinoma is its marked variation in biologic behavior. DNA quantitation has been studied in prostate carcinoma using a variety of techniques. Evaluation of tumor ploidy suggests that this may be the best predictor of the biologic behavior of prostate cancer in individual patients. This comprehensive review addresses the current studies, stage by stage, to clarify the clinical significance of these findings.

The pattern in the ratio of disease rates over strata is a summary statistic used to describe the changing risk of disease in one group relative to another. While patterns of the ratios of disease rates over strata appear to correspond to specific changes in disease rates, plots of the disease rates over strata seem to contradict the information yielded by the ratios. For example, if disease rates from populations A and B have identical rates of decline (parallel lines), the difference in the rates (A-B) at each strata remains constant, while the ratio of the rates (A/B) increases over strata. Through simple algebraic manipulation, one can show that the pattern of the rate ratio is a function of the rate difference relative to the endemic disease rate. Thus, rather than describing the behavior of the disease rates, ratio patterns reflect the importance of exposure relative to the disease rate in the unexposed population.

In response to poor coordination among health and social service providers, health care consortia have emerged in many areas of the United States. Consortia link multiple providers in a common structure to create comprehensive systems of care. They can be formally structured or informal combinations of providers that engage in coordination but otherwise do not comprise an independent organization. The functions most common among all types of consortia are shared services and service coordination; however, a number of consortia also operate outreach/education programs. Consortia represent an innovative response to the need both for vertical integration--case management of all levels of care--and horizontal integration to prevent duplication among primary care providers. We outline the history of consortia in which federally-funded community health centers have participated. We also suggest an analytical framework for the various types of consortia; discuss lessons learned about building and maintaining consortia; and provide preliminary outcome data.

Neuroendocrine features and cytogenetic abnormalities of one continuous cell line (MTC-SK) and two long-term cultures (GER, STAH) derived from three sporadic cases of human medullary thyroid carcinomas (MTCs) were studied. Specific neuroendocrine markers (NSE, chromogranins, calcitonin, calcitonin gene-related peptide) were identified by electron microscopy and immunocytochemistry. In situ hybridochemistry and Northern blot analysis confirmed endocrine activity. Cytogenetic studies of the cell line MTC-SK revealed three consistent marker chromosomes, t(3;10), 11p+, and 22p+. Cells of long-term cultures GER and STAH exhibited a consistent translocation t(2;18), a trisomy 7, and two consistent marker chromosomes der3 and 5p+, respectively. Recently, we have isolated 12 stable clones of this MTC-SK cell line, which showed two different growth patterns. Quantitative measurement of mitotic activity flow cytometry and semiquantitative analysis of AgNOR-, Ki67-, and Cyclin/PCNA-(immuno)reactivity showed different DNA composition and duplication rates, indicating at least two subpopulations. Some of our clones developed a new consistent marker (i.e., an unbalanced translocation between mar11p+ and 1q). However, no correlations between chromosome findings, growth rate, and neuroendocrine markers were observed.

Results of follow-up studies in four large multiple endocrine neoplasia type 2A families (total of 95 patients affected) have shown a positive effect on the course of the disease since early screening and intervention were initiated in 1974.