PubMed Health⌕ Search

Biomedical subjects

P Biddinger

Publications and source records attributed to P Biddinger.

13 recordsLinked to original sources
PubMed1999

Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression.

We have previously reported that loss of p53 tumor suppressor protein results in centrosome hyperamplification, which leads to aberrant mitosis and chromosome instability. Since p53 is either deleted or mutated in human cancers at a high frequency, we investigated whether human cancers showed centrosome hyperamplification. Screening of advanced stage breast ductal carcinomas and squamous cell carcinomas of the head and neck (SCCHN) revealed that centrosome hyperamplification is frequent in both tumor types. Moreover, through the analyses of p53 in SCCHN samples by direct sequencing and by loss-of-heterozygosity test, we found that p53 mutations correlated with occurrence of centrosome hyperamplification. However, in some cases, we observed centrosome hyperamplification in tumors that retained wild-type p53. These tumors contained high levels of Mdm2. Since Mdm2 can inactivate p53 through physical association, we investigated whether Mdm2 overexpression induced centrosome hyperamplification. We found that Mdm2 overexpression, like loss of p53, induced centrosome hyperamplification and chromosome instability in cultured cells.

3T3 Cells↗
PubMed1999

Frequent loss of heterozygosity at chromosome 3p14.2-3p21 in human pancreatic islet cell tumours.

OBJECTIVE: Pancreatic islet betacell tumours occur either sporadically or as part of inherited neoplastic syndromes, most commonly multiple endocrine neoplasia (MEN) type 1. Recently, a transgenic mouse model has been established in which the expression of the SV40 large T antigen was targeted to betacells by the rat insulin promoter, leading to the development of multiple pancreatic betacell tumours. In the advanced stages of tumour evolution, these tumours exhibited a high prevalence of loss of heterozygosity (LOH) on mouse chromosomes 9 and 16, at regions syntenic with regions 3q, 3p21, 6q12, 15q24 and 22q of the human genome. DESIGN: Loss of heterozygosity in human islet cell tumours was analysed in a PCR based approach at regions of the human genome syntenic with the mouse loci linked to pancreatic betacell tumours as well as the MEN1 gene on chromosome 11q13. These included 35 microsatellite markers in the human chromosomal regions 3q, 3p21, 6q12, 11q13, 15q24 and 22q. PATIENTS: 21 patients diagnosed with insulinoma were analysed. Histologically, 16 tumours were benign, while 5 were malignant insulinomas. RESULTS: Thirteen of 21 (62%) tumours were found to have loss of genetic material on chromosome 3. The shortest region of overlap implicated a deletion at 3p14.2-3p21 region, corresponding to the marker D3S1295. We did not detect a substantial frequency of LOH in the other syntenic regions, except for the region of MEN 1 gene on 11q13 found to be deleted in 6 (29%) cases, including 3 of 4 tumours from MEN 1 families. Deletions of 3p14. 2-3p21 were observed in 8 of 15 (53%) benign tumours, and in 5 of 6 (83%) malignant neoplasms. CONCLUSIONS: These results indicate the high frequency of 3p14.2-3p21 deletions in human pancreatic betacell neoplasms. These finding suggest the presence of a tumour suppressor gene in this region, that may be important in the microevolution of these tumours towards malignancy.

Adult↗
PubMed1998

Hypersensitivity pneumonitis in a machinist.

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a patchy, interstitial lung disease that involves an immunologic reaction of the lung to repeated inhalation of foreign antigens. In this report, we describe a machinist with exposure to metalworking fluids (MWFs) and biopsy-confirmed HP. Return to work, which could be equated with a retrospective workplace-specific bronchoprovocation test, proved that working within an environment in which MWFs were used was associated with clinical deterioration in the patient's pulmonary status and with clinical improvement after removal from exposure.

Aerosols↗
PubMed1998

Tracheal chondrosarcoma: a case report.

BACKGROUND: Tracheal neoplasms are extremely rare, representing only 0.2% of malignancies of the respiratory tract. A case of tracheal chondrosarcoma, with airway obstruction, seen in the Department of Otolaryngology Head and Neck Surgery at the University of Cincinnati is presented. Review of the literature was undertaken, revealing 10 previously described cases. Clinical presentation and treatment options are described. METHODS: A literature review of all reports of tracheal chondrosarcoma was undertaken. RESULTS: From this review, we identified only 10 single case reports. The majority of patients were elderly men, with lesions in the mid to distal trachea. Treatment predominantly consisted of tracheal resection. Recurrence was associated with failure to achieve complete resection. CONCLUSIONS: We conclude that tracheal chondrosarcoma is an exceedingly rare upper airway neoplasm. Treatment should be aimed at complete surgical removal.

Aged↗
PubMed1997

Access to emergency care under TennCare: do patients understand the system?

STUDY OBJECTIVE: To determine patient understanding of how to properly gain access to urgent and emergency medical care under TennCare, a government-mandated managed health care initiative designed to replace Medicaid in Tennessee. METHODS: We prospectively surveyed a convenience sample of ED patients at university hospital ED with an annual census of 50,000 during two periods (summer 1994 and summer 1995). In 1994, 250 TennCare patients were enrolled (part 1). In 1995, 199 were enrolled (part 2). RESULTS: Patients from seven different TennCare managed care organizations (MCOs) were interviewed. Thirty-eight percent of part 1 patients and 37% of part 2 patients did not have or did not know the names of their primary care physicians (PCPs). Fifty-eight percent of the part 1 patients who knew their PCPs' names had never visited them. This figure had decreased to 25% by the time part 2 patients were surveyed. Seventy-three percent of part 1 patients interviewed did not call their PCPs before coming to the ED. This figure had decreased to 48% by the time part 2 patients were interviewed. Thirty-two percent of part 1 patients were aware that they were supposed to contact the PCP before visiting the ED, whereas 94% of part 2 patients were aware of this requirement. Thirty-one percent of part 1 patients and 40% of part 2 patients who tried to contact their PCPs were unsuccessful, most often because of a delay on the part of PCPs in returning calls. Fifty-six percent of part 1 patients and 69% of part 2 patients did not know that they might be held responsible for the bill if an ED visit was not considered a true emergency and was not approved by the MCO. CONCLUSION: Improvements in communication of pertinent information must be implemented in managed care systems such as TennCare to better inform participants of the proper use of the system. MCOs will not reduce inappropriate use of the ED if patients are not aware of their responsibilities and do not know their PCPs or how to gain access to them. PCP responsiveness to patients must also be improved.

Adult↗
PubMed1997

Prognostic indicators for squamous cell carcinoma of the oral cavity: a clinicopathologic correlation.

Fifty-three patients with T1 squamous cell cancer of the floor of mouth and ventral surface of the tongue with a known clinical outcome were retrospectively analyzed and arbitrarily divided into "aggressive" and "nonaggressive" groups based on their clinical behavior. Various host and tumor factors were then evaluated in an attempt to determine whether the tumor behavior could have been predicted. The paraffin-embedded tumor specimens were evaluated for tumor differentiation, tumor thickness and tumor invasion, microvessel density, and p53 expression. In addition, a composite morphologic grading score was obtained by combining cell differentiation, nuclear polymorphism, mitosis activity, depth of infiltration, type of infiltration, and lymphatic infiltration. No single technique appeared capable of identifying "aggressive" behavior, although possibly an evaluation of composite factors might show promise in the future.

Carcinoma, Squamous Cell↗
PubMed1993

Relationship between immunohistochemically detectable p53 protein and prognostic factors in head and neck tumors.

This study examined the relationship between immunohistochemically detectable p53 protein and prognostic factors in squamous cell carcinoma of the head and neck (SCCHN). Twenty-seven tumor specimens were evaluated utilizing a panel of three monoclonal antibodies (MAbs) directed against different epitopes of the p53 protein (PAb 421, PAb 1801, and PAb 240). The overall incidence of p53 protein detection with a panel of MAbs was 78%, which was significantly higher than with any one of the tested antibodies. Comparison of the tumors that were negative for p53 with tumors that stained positive with one or multiple antibodies, however, revealed no statistically significant differences with respect to the stage of disease, metastatic node involvement, size of the primary tumor, or degree of tumor differentiation. The results of our study suggest that levels of p53 protein, although commonly immunohistochemically detected in head and neck tumors, do not correlate with known prognostic factors for SCCHN.

Adult↗
PubMed1983

The amniotic band syndrome.

The amniotic band syndrome is characterized by severe cranial malformations and constriction defects of the limbs, due to fibrous bands that encircle the developing fetus. The obstetric course is usually unremarkable. One out of every 5,000 newborns has this condition. It is not genetically based and therefore must be differentiated from other forms of birth defects.

Amniotic Band Syndrome↗
PubMedDate not supplied

Improved immunohistochemical detection of p53 protein in paraffin--embedded tissues reveals elevated levels in most head and neck and lung carcinomas: correlation with clinicopathological parameters.

We have analyzed the expression of the p53 tumor suppressor gene in paraffin-embedded sections of normal and malignant head and neck and lung tumors by immunohistochemistry using the PAb 1801 monoclonal antibody (MAb). The PAb 1801 does not consistently detect its p53 epitope in tissue fixed in 10% buffered formaldehyde. However, the antibody is effective in AMeX-fixed specimens, thereby permitting the improved morphologic localization of p53 phosphoprotein in paraffin embedded tissue. Of 33 primary head and neck carcinomas analyzed from AMeX-fixed, paraffin-embedded sections, 21 (64%) showed heterogeneous staining with PAb 1801. All 33 normal samples of head and neck tissues were negative. Similarly, 13 out of 20 lung carcinomas (65%) showed heterogeneous staining while none of normal lung tissues were positive. The data indicate a strong positive correlation between p53 detection by PAb 1801 and carcinomas of the head and neck and of lung. However, there was no obvious correlation between p53 staining and the number of involved nodes, the stage of disease or the degree of differentiation in these carcinomas.

Biomarkers, Tumor↗