A region within murine chromosome 7F4, syntenic to the human 11q13 amplicon, is frequently amplified in 4NQO-induced oral cavity tumors

Our previous reports have shown that two thirds of 4-nitroquinoline-1-oxide (4NQO)-induced murine oral squamous cell carcinomas (SCC) have Hras1 mutations. Loss of heterozygosity (LOH) involving the distal portion of chromosome (Chr) 7 occurred in half of the tumors with Hras1 mutations. Here, we demonstrate that five of six tumors with LOH have 4-8-fold amplification involving the distal portion of Chr 7 (7F4). Ccnd1. Fgf4 and Fgf3, within the most telomeric region of Chr 7 (70.5 cM), are co-amplified. The region is syntenic to a previously identified human amplicon at 11q13. Only one out of eight tumors without LOH at Chr 7 had twofold amplification; the other seven had no detectable amplification. Significant amplification is restricted to the chromosome with the Hras1 mutation. Gene amplification occurred without overexpression since only one of five tumors with amplification and one of six tumors without Ccnd1 amplification expressed increased protein. Although amplification of 11q13 occurs rather frequently in human tumors, 4NQO-induced oral cavity tumors in inbred mice are the first example of a murine tumor with consistent amplification. Our observations are strikingly similar to human head and neck SCC where overexpression of genes within the 11q13 amplicon is inconsistently detected. The amplification of genes localized to human 11q13 and the syntenic region on murine Chr 7 during tumorigenesis suggests that similar structural elements are present which predispose these regions to amplification during malignant transformation.     

The nervous system function of patients with periodontitis

Analysis of the function of the nervous system, based on clinical, neurological, and psychological studies in 78 patients with generalized periodontitis, revealed central regulation disorders without signs of organic lesions of the brain in 76% patients. The authors claim that stress and a high level of personal anxiety may be responsible for the development of these disorders, which was confirmed by the results of psychological testing.     

Use of a subcutaneous glucose sensor to detect decreases in glucose concentration prior to observation in blood

The development of a hypoglycemic alarm system using a subcutaneous glucose sensor implies that a decrease in blood glucose is rapidly followed by a decrease in the signal generated by the sensor. In a first set of experiments the linearity and the kinetics of the response of sensors implanted in the subcutaneous tissue of normal rats were investigated during a progressive increase in plasma glucose concentration: the sensitivities determined between 5 and 10 mM and between 10 and 15 mM were not significantly different, and a 5-10 min delay in the sensor's response was observed. In a second set of experiments, performed in diabetic rats, the kinetics of the decrease in subcutaneous glucose concentration following insulin administration was monitored during a decrease in plasma glucose level, from 15 to 3 mmol/L. During the 20 first min following insulin administration, the sensor monitored glucose concentration in subcutaneous tissue with no lag time. Subsequently, the decrease in the estimation of subcutaneous glucose concentration preceded that of plasma glucose. This phenomenon was not observed when the same sensors were investigated in vitro during a similar decrease in glucose concentration and may be due to a mechanism occurring in vivo, such as the effect of insulin on glucose transfer from the interstitial space to the cells surrounding the sensor. It reinforces the interest of the use of implantable glucose sensors as a part of a hypoglycemic alarm.     

Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin

PURPOSE: Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed. PATIENTS AND METHODS: Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test. RESULTS: A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors. CONCLUSION: The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.