Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells

In many cell types, p53-mediated growth inhibition is dependent on induction of p21, which is an inhibitor of cyclin-dependent kinases that are required for cell cycle progression. Failure of mutant p53 proteins to transactivate p21 may lead to uncontrolled proliferation. Because many ovarian cancers have mutations in the p53 gene, we examined p21 levels in normal and malignant ovarian epithelial cells to determine whether p21 expression is dependent on wild-type p53. Normal ovarian epithelial cells and two ovarian cancer cell lines with wild-type p53 expressed readily detectable levels of p21, whereas in p53 null and mutant cell lines, expression of p21 was diminished strikingly. A correlation between the status of the p53 gene and p21 expression also was noted in 23 primary epithelial ovarian cancers. Normal levels of p21 RNA were seen in 4/7 (57%) cancers with wild-type p53, whereas 14/16 (88%) cancers with mutant p53 had reduced p21 expression (P < 0.05). In addition, we found that lambda-irradiation of normal and malignant ovarian epithelial cells with wild-type, but not mutant, p53 resulted in induction of p21. These data are suggestive that induction of p21 is a feature of p53-mediated growth inhibition in normal ovarian epithelial cells. Conversely, mutation of the p53 gene in ovarian cancers usually is associated with decreased p21 expression. The lack of an absolute correlation between p21 expression and the status of the p53 gene in ovarian cancers is consistent with other studies that have suggested that p21 may also be regulated by p53-independent pathways.     

Trauma patients 75 years and older: long-term follow-up results justify aggressive management

BACKGROUND: Long-term survival rate and functional status after trauma for one of the fastest growing segments of the population, patients 75 years and older, is poorly documented. METHODS: Trauma patients 75 years and older who were discharged from our Level I trauma center between June 1988 and July 1992 (n = 279) were contacted by mail or phone. Public death records were used to identify patients who had died. A stepwise logistic regression analysis was performed to determine predictors of poor outcome (death within 6 months). Main outcome measures included mortality and self-assessed functional status. RESULTS: A minimum 4-year follow-up was obtained for 81% of the 279 study patients. The mean follow-up period was 5.4 +/- 1.1 years. Mean age at time of injury was 81 +/- 5 years (range, 75-101 years); mean Injury Severity Score was 9.4 +/- 7.7. At follow-up, 132 patients (47%) had died, 93 patients (33%) were contacted, and 54 patients (19%) could not be located. Twelve percent of patients survived less than 6 months after discharge. Poor survival was predicted by preexisting diseases (dementia, p = 0.001; hypertension, p = 0.02; and chronic obstructive pulmonary disease, p = 0.05) and not by age or severity of injury. The mean age of patients still living was 85 +/- 3.9 years (range, 79-99 years), and 77 of 93 patients were living in an independent setting (33 alone, 44 with spouse or family); of these, 57% reported no difficulties in performing 12 of 14 activities of daily living. CONCLUSION: Despite higher than expected mortality after discharge, aggressive management of trauma patients 75 years and older is justified by the favorable long-term outcome.     

Spindle cell hemangioendothelioma: a case presentation and literature review of a rare lower extremity tumor

The authors present a rare soft tissue mass of the lower extremity that has been presented in the podiatric literature only once. Spindle cell hemangioendothelioma was first identified 9 years ago, and approximately 45 cases have been documented in the literature. This lesion presents as a slow growing and often painless lesion of the extremities, with low malignant potential and high local recurrence. This patient was treated with surgical excision after a mass, which had been present for more than 10 years, began enlarging and became painful. A review of the literature and the case presentation will be given.     

Monobloc distraction osteogenesis during infancy: report of a case and presentation of a new device

Adrenomedullin(AM) is a potent hypotensive peptide originally isolated from human pheochromocytoma. AM exerts various biological actions such as vasodilation, bronchodilation and natriuresis, by stimulating cAMP production and increasing free Ca2+ levels through the specific receptors. Although an orphan receptor cloned from rat lung, which contained seven transmembrane domains, was proved to be one of the AM receptors, it is now considered by many studies that other receptor subtypes should be present. The precise signal transduction mechanism for the AM receptor is not fully elucidated yet, but it is supposed that AM acts against proliferative changes of vascular and mesangial cells as seen in hypertensive states, at least partly by inhibiting the MAP kinase pathway. Further studies on the AM receptor subtypes and their intracellular signaling mechanisms are needed to clarify the role of AM in various pathophysiological conditions.     

The response of lung epithelium to well characterised fine particles

Diesel particles form a large component of the fine particle fraction (PM10) in urban air in the UK. During pollution episodes small increases in PM10 have been linked to detrimental health effects. The comparative toxicological effects of diesel exhaust and other well-characterised particles (carbon black, amorphous and crystalline silica) on rat respiratory epithelium were investigated in the present study. The effects of small masses of particles (1 mg) delivered by intratracheal instillation were monitored by changes in components of lavage fluid. Respirable, crystalline quartz, produced significant increases in lung permeability, persistent surface inflammation, progressive increases in pulmonary surfactant and activities of epithelial marker enzymes up to 12 weeks after primary exposure. Ultrafine amorphous silica did not induce progressive effects but it promoted initial epithelial damage with permeability changes and these regressed with time after exposure. By contrast, ultrafine/fine carbon black had little, if any, effect on lung permeability, epithelial markers or inflammation, despite being given at a dose which readily translocated the epithelium and which has been reported to induce inflammation. Similarly, diesel exhaust particles produced only minimal changes in lavage components, although they were smaller individual particles and differed in surface chemistry from carbon black. It is concluded that diesel exhaust particles are less damaging to respiratory epithelium than silicon dioxide and that the surface chemistry of a particle is more important than ultrafine size in explaining its biological reactivity.     

Eating barley too frequently or in excess decreases lambs'' preference for barley but sodium bicarbonate and lasalocid attenuate the response

Three susceptibility testing procedures were compared to determine fluconazole, itraconazole, and ketoconazole MICs against 47 Candida albicans strains isolated sequentially from the oral cavities of five AIDS patients undergoing azole therapy. They included the broth microdilution method (BM), performed according to the National Committee for Clinical Laboratory Standards' tentative standard, the agar dilution method (AD), and the Etest; the latter two tests were performed both in Casitone agar (AD-Cas and Etest-Cas) and in RPMI (AD-RPMI and Etest-RPMI). Twenty-four- and 48-h MICs obtained by AD and Etest were compared with 48-h MICs obtained by BM. The MICs of all the azoles determined by BM were usually lower than those obtained by the other methods, mainly due to different reading criteria. In order to assess the most appropriate way of evaluating the agreement of MICs obtained by different methods with those produced by the proposed reference method (BM), we used the mean differences calculated according to Bland and Altman's method. Comparison of fluconazole MICs obtained by BM and AD-Cas yielded a mean difference of 3, and the percentages of agreement within +/-2 dilutions were 98 and 100% at 24 and 48 h, respectively. For ketoconazole and itraconazole MICs, lower mean differences were noted, and agreement ranged from 96 to 100%. Agreement between the AD-RPMI and BM results was poor for all azoles, and an increase in MICs was always observed between the 1st- and 2nd-day readings. Similarly, Etest-Cas gave better agreement with BM than did Etest-RPMI for all the azoles. BM, AD-Cas, and Etest-Cas each demonstrated a progressive increase in fluconazole MICs against strains isolated sequentially from a given patient, in accordance with the decreased clinical response to fluconazole.     

Food flavor and nutritional characteristics alter dynamics of food preference in lambs

We addressed two questions involving food preference. First, we determined how a food's flavor and nutritional characteristics affected preference. In three trials, we offered lambs isonitrogenous foods differing in energy (trial 1, 90% TDN; trial 2, 100% TDN; trial 3, 110% TDN); each food was offered in apple and maple flavors. We hypothesized that preference for apple- or maple-flavored food would decrease with increasing duration of exposure (1, 2, or 4 d), and we speculated that the change in preference would intensify when food contained inadequate or excessive levels of energy. After eating food in one flavor, lambs preferred the alternative flavor, even after only a 1-d exposure, and preference for the alternative flavor was greater when the food had inadequate or excessive energy (P < .05). The second experiment determined whether eating a food with rapidly or slowly digestible sources of energy in the morning affected lambs' food preferences in the evening. We speculated that lambs fed rapidly digestible food in the morning may prefer a slowly digestible food in the afternoon because slowly digestible food better maintains nutrient status throughout the night or because preference for the rapidly digestible food decreases after exposure in the morning. We offered lambs isonitrogenous and isocaloric foods, that differed in rates of digestion, in apple and maple flavors. Lambs fed rapidly digestible food in the morning preferred slowly digestible food in the alternative flavor in the evening. However, lambs fed slowly digestible food in either flavor in the morning preferred slowly digestible food in both flavors in the evening (P < .05). These results show that lambs' preferences change as a result of food ingestion, and the degree of change in preference depends on the nutritional characteristics of the food. These findings further suggest food intake might be increased by providing a variety of foods to livestock on rangelands, pastures, or in confinement.     

Child development and marital relations

This article examines aspects of the marital relationship and its assessment relevant to scholars of child development. The case for attending to marriage in child research is outlined before reviewing what is known about the construct of marital quality, behavior, emotional responding, and cognition in marriage. Practical recommendations are made for assessing each of these areas before arguing that the child's perspective of the marriage is critical for understanding children's behavior. Several limitations and promises of marital research for understanding children are also discussed.