Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification

Cyclin D1 proto-oncogene is a key regulator of the mammalian cell-cycle acting at the restriction point in late G1. Amplification of the cyclin D1 locus, located on chromosome 11q13, as well as cyclin D1 protein overexpression have been reported in several human malignancies. The purpose of this study was to evaluate cyclin D1 gene copy status and protein expression during the multistep process of head and neck tumorigenesis, using a combination of fluorescence in situ hybridization and immunohistochemistry techniques. From 29 selected patients presenting with head and neck squamous carcinoma and whose tumor cytospins had been previously screened for presence (16 cases) or absence (13 cases) of amplification at the 11q13 band, we analysed 46 paraffin-embedded tissue specimens that demonstrated, besides the primary tumor, the presence of contiguous adjacent normal tissue and/or premalignant lesions. Of the 16 amplified cases, nine demonstrated a continuous progression from premalignant to invasive carcinoma and seven (77.7%) of these cases showed cyclin D1 gene amplification in premalignant lesions prior to development of invasive carcinoma. Increased cyclin D1 protein expression was observed in all 16 amplified tumors and five of the 13 (38.4%) non-amplified tumors. Interestingly, dysregulated cyclin D1 expression was also found in the premalignant lesions adjacent to all 16 amplified tumors, and it appeared to precede cyclin D1 gene amplification. In contrast no dysregulated expression was detected in the premalignant lesions of the non-amplified tumors. In conclusion, these findings provide strong evidence for early dysregulation of cyclin D1 expression during the tumorigenesis process and suggest that dysregulated increased expression precedes and possibly enables gene amplification.     

Relationship of provider characteristics to outcomes, process, and costs of care for community-acquired pneumonia

OBJECTIVES: The authors describe the relation of provider characteristics to processes, costs, and outcomes of medical care for elderly patients hospitalized for community-acquired pneumonia. METHODS: Using Medicare claims data, Medicare beneficiaries discharged from Pennsylvania hospitals during 1990 with community-acquired pneumonia were identified. Claims data were used to ascertain mortality, readmissions, use of procedures and physician consultations, and the costs of care. The relationship of these measures to provider characteristics was analyzed using regression techniques to adjust for patient characteristics, including comorbidity and microbial etiology. RESULTS: Among 22,294 pneumonia episodes studied, 30-day mortality was 17.0%. After adjusting for patient characteristics, 30-day mortality and readmission rates were unrelated to hospital teaching status or urban location or to physician specialty. Use of procedures and physician consultations was more common and costs were 11% higher among patients discharged from teaching hospitals compared with nonteaching hospitals. Similarly, costs were 15% higher at urban hospitals compared with rural hospitals. General internists and medical subspecialists used more procedures and had higher costs than family practitioners. CONCLUSIONS: Processes and costs of care for community-acquired pneumonia varied by provider characteristics, but neither mortality nor readmission rates did. These differences cannot be explained by clinical variables in the database. Further studies should determine whether less costly patterns of care for pneumonia, and perhaps other conditions, could replace more costly ones without compromising patient outcomes.     

Locomotor activity rhythms in dogs vary with age and cognitive status.

Beagle dogs exhibited diurnal patterns of locomotor activity that varied as a function of age, cognitive status, and housing environment. Aged dogs housed in an indoor facility showed a delayed onset of activity following lights on and displayed shorter bouts of activity, with more rest periods during the day, compared with young dogs. Cognitively impaired aged dogs were more active and showed a delayed peak of activity compared with unimpaired aged dogs. Housing in continuous light did not disrupt activity rhythms. The effect of age was less prominent in dogs housed in an indoor/outdoor facility. This suggests that bright sunlight and natural light-dark transitions are better able to consolidate and synchronize the activity rhythms of the dogs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vitro pore-forming activity of the lantibiotic nisin. Role of protonmotive force and lipid composition

Human prostate cancer displays a high degree of variability in its rate of spread, which could be due largely to differences in the invasive potential of the tumor cells. The degradation of the basal lamina and stromal extracellular matrix is mediated in part by the secretion of matrix metalloproteinases (MMPs). Matrilysin (PUMP-1, MMP-7) and gelatinase A (M(r) 72,000 type IV collagenase, MMP-2) have been shown to be overexpressed in prostate carcinoma. We have expressed the single MMP matrilysin in the tumorigenic but nonmetastatic human prostate tumor cell line DU-145 to determine if matrilysin has a functional role in prostate tumor cell invasion. DU-145 cells expressing matrilysin were significantly more invasive than vector-only transfected cell lines as assayed by a severe combined immunodeficient mouse model of tumor cell invasion. Vector-only transfected DU-145 cells injected i.p. into severe combined immunodeficient mice invaded the diaphragm in only 1 of 9 mice (11%), whereas matrilysin-transfected DU-145 cells invaded the diaphragm in 12 of 18 mice (66%). The difference between the controls and matrilysin-transfected cells was statistically significant (P < 0.006). These results suggest a functional role for matrilysin in the initial invasion of prostate cancer through the epithelial basal lamina and into the surrounding stroma.     

Precoupling of Gi/G(o)-linked receptors and its allosteric regulation by monovalent cations

The ability of receptors (R) to activate G-proteins (G) is promoted by the binding of agonists, reflecting their induction of a receptor conformation which facilitates both the formation of a RG complex and guanine nucleotide exchange. Recent evidence from isolated membrane studies has indicated, however, that some receptors have the inherent ability to form RG complexes and promote GDP/GTP exchange in their unoccupied state. These receptors preferentially activate pertussis toxin-sensitive G-proteins (i.e. Gi/G(o)) and the interactions of R and G are modulated by monovalent cations (most notably Na+) both in the unoccupied and agonist-occupied states. Basal G-protein activation by such receptors is reduced both by increasing levels of cation and by antagonists which may act by inducing receptor conformations which are less favorable for RG complexation. This behaviour conforms to the predictions of a ternary complex model of receptor function and can be considered in structural terms for those receptors such as the alpha-2 adrenergic receptor where ligand binding and G-protein activation regions have been proposed.     

Notch in contrast sensitivity function of optical origin: diffraction effects of acrylic filters

It was for the first time that of the fifth year of monitoring of Plantago lanceolata L., reproduced within the thirty-kilometer zone of Chernobyl NPP disaster, the authors discovered high incidence of seedlings with various morphological abnormalities. It is suggested that the damages observed are related to the cumulative effect of radiation.     

Noninvasive hemodynamic assessment of the internal mammary artery in myocardial revascularization

Using transthoracic B-mode imaging and Doppler spectrum analysis it was found that the luminal diameter of the internal mammary artery and its hemodynamics were not significantly different among 15 preoperative patients (64 +/- 10 years) who underwent myocardial revascularization using the left internal mammary artery and young and older control groups (25 +/- 3 years and 61 +/- 9 years, respectively). These data indicate that older age does not significantly adversely influence the degree of intimal thickening and compliance in the internal mammary artery. Doppler spectrum analysis of the internal mammary artery in the patients who were operated on revealed conversion from a triphasic systolic waveform preoperatively to a unidirectional combined systolic/diastolic waveform at 1 week and 2 and 6 months postoperatively, characterized by a significant increase in the diastolic blood flow velocity and a significant decrease in the systolic blood flow velocity and the pulsatility and resistance indices. This study indicates that transthoracic B-mode imaging and Doppler spectrum analysis are promising noninvasive techniques in the preoperative assessment of internal mammary artery morphology and physiology. In addition, Doppler spectrum analysis can also be used in the long-term serial assessment of the internal mammary artery conduit after myocardial revascularization.