Degradation of dipalmitoyl phosphatidylcholine by isolated rat granular pneumocytes and reutilization for surfactant synthesis.

We investigated metabolic utilization of exogenous (modelled after lung surfactant) phospholipids by granular pneumocytes in primary culture. Cells were incubated for 21, 65, and 140 min with [3H-methyl]dipalmitoylphosphatidylcholine (DPPC) containing liposomes prepared from synthetic lipids. Radioactivity in cellular phosphatidylcholine (PC) declined steadily to 50% of the total trypsin-resistant cell-associated radioactivity. The proportion of radioactivity increased with time in cytidine-5'-diphosphate-choline and phosphorylcholine, which suggested reutilization of choline for PC synthesis. Cells incubated with liposomes for 2 h revealed that of the total cell-associated radioactivity, 7% was in lamellar bodies and 10% in the microsomal fraction. The lipid-associated radioactivity was 24% in "soluble," 96% in lamellar bodies, and 92% in the microsomal fraction. Percent of total PC label recovered in disaturated PC of microsomal fractions decreased (slope = -5.27%/h) with time of incubation (r = 0.67). Incubation of cells with liposomes containing ([3H-methyl]choline-[14C]palmitoyl) DPPC led to altered isotope ratios in both lamellar bodies and microsomes. These observations indicate that granular pneumocytes degrade exogenous PC and resynthesize PC from degradation products.     

Factors associated with breast cancer clinical trials participation and enrollment at a large academic medical center.

PURPOSE: The practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials. PATIENTS AND METHODS: From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment. RESULTS: The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P =.0005) and black women (21% of blacks offered v 42% of whites; P =.0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%). CONCLUSION: It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women.     

Emergence of GABAergic-dependent regulation of input-specific plasticity in the adult rat prefrontal cortex during adolescence

Objective

The prefrontal cortex (PFC) receives multiple cortical and subcortical afferents that regulate higher order cognitive functions, many of which emerge late in adolescence. However, it remains unclear how these afferents influence PFC processing, especially in light of the protracted, late adolescent maturation of prefrontal GABAergic function. Here we investigated the role of PFC GABAergic transmission in regulating plasticity elicited from the ventral hippocampus and basolateral amygdala, and how such modulation undergoes functional changes during adolescence in rats.

Methods

In vivo local field potential recordings, combined with prefrontal microinfusion of the GABA-A receptor antagonist picrotoxin, were employed to study the impact of ventral hippocampal and basolateral amygdala high-frequency stimulation on PFC plasticity.

Results

Ventral hippocampal-induced PFC plasticity begins to appear only by postnatal days (P) 45–55 with a transient suppression of the evoked response. A switch from transient to long-lasting depression (LTD) of the PFC response emerges after P55 and throughout adulthood (P65–120). Recordings conducted in the presence of picrotoxin revealed that PFC GABAergic transmission is critical for the expression of LTD. In contrast, basolateral amygdala stimulation resulted in PFC long-term potentiation, a form of plasticity that is already enabled by P30 and is insensitive to picrotoxin.

Conclusions

The development of ventral hippocampal-dependent PFC LTD is contingent upon the recruitment of local prefrontal GABAergic transmission during adolescence whereas plasticity elicited from the basolateral amygdala is not. Thus, different mechanisms contribute to the refinement of prefrontal plasticity during adolescence as inputs from these two regions are critical for shaping PFC functions.     

An analysis of the cost of clinical surveillance after primary therapy for women with early stage invasive breast cancer

Summary Routine surveillance for distant metastases in women with early stage breast cancer has limited clinical utility and can result in large medical care costs. In order to estimate breast cancer surveillance costs, we used the results of a survey administered to a random sample of physician members of the American Society of Clinical Oncology. The survey measured the frequency in which radiographic and laboratory tests are ordered for postmenopausal women with stage I or II breast cancer after the completion of surgery and radiation or adjuvant chemotherapy if indicated. There were 209 completed surveys representing a response rate of 48%. The volume of tests ordered was expressed in terms of Medicare's relative value units (RVUs) and 1993 cost equivalents. The mean total RVUs over 5 years post-diagnosis was 43.8 (interquartile range 30.1–54.2) which represents a cost of $1369 using the 1993 Medicare conversion factor of $31.249. A cumulative logistic regression model categorized RVUs according to intensity of care (minimal, average, and intensive). While medical oncologists compared to surgeons and radiation oncologists, and physicians practicing in the Northeast and Midwest, compared to those practicing in the South and West, were more likely to adopt an intensive practice style, these differences were not statistically significant (p = 0.1). None of the other provider characteristics evaluated, including gender, prior experience, and practice type, had a significant effect on physician practice in a multivariate model. The data showed a wide variation among providers in surveillance practice patterns that was largely unexplained by physician demographics. These results are consistent with the physician practice style hypothesis which suggests that wide variations in treatment patterns result from uncertainty regarding effectiveness of care.     

Contrasting patterns of Y chromosome and mtDNA variation in Africa: evidence for sex-biased demographic processes

To investigate associations between genetic, linguistic, and geographic variation in Africa, we type 50 Y chromosome SNPs in 1122 individuals from 40 populations representing African geographic and linguistic diversity. We compare these patterns of variation with those that emerge from a similar analysis of published mtDNA HVS1 sequences from 1918 individuals from 39 African populations. For the Y chromosome, Mantel tests reveal a strong partial correlation between genetic and linguistic distances (r=0.33, P=0.001) and no correlation between genetic and geographic distances (r=-0.08, P>0.10). In contrast, mtDNA variation is weakly correlated with both language (r=0.16, P=0.046) and geography (r=0.17, P=0.035). AMOVA indicates that the amount of paternal among-group variation is much higher when populations are grouped by linguistics (Phi(CT)=0.21) than by geography (Phi(CT)=0.06). Levels of maternal genetic among-group variation are low for both linguistics and geography (Phi(CT)=0.03 and 0.04, respectively). When Bantu speakers are removed from these analyses, the correlation with linguistic variation disappears for the Y chromosome and strengthens for mtDNA. These data suggest that patterns of differentiation and gene flow in Africa have differed for men and women in the recent evolutionary past. We infer that sex-biased rates of admixture and/or language borrowing between expanding Bantu farmers and local hunter-gatherers played an important role in influencing patterns of genetic variation during the spread of African agriculture in the last 4000 years.