Isolated human hepatocytes in culture display markedly different gene expression patterns depending on attachment status

In vitro human hepatocyte cultures are a key tool in the investigation of xenobiotic toxicity and metabolism. In most in vitro hepatocyte studies, the cells are allowed to adhere to an extracellular matrix, such as collagen. Unfortunately, the ability of freshly isolated hepatocytes to adhere to collagen varies from donor to donor. We used microarray analysis to determine what gene expression differences exist between hepatocytes in suspension and hepatocytes attached to collagen. Results from different donors showed a considerable difference in gene expression patterns between the two hepatocyte populations. In addition, we also compared the gene expression profiles of hepatocytes in culture with liver tissue. The results showed that both hepatocytes in suspension and hepatocytes attached to collagen display significant gene expression differences compared with liver tissue. Finally, we show that both populations of hepatocytes are responsive to dexamethasone and regulate some of the same genes. Overall, our results suggest that either significant gene expression changes occur in isolated hepatocytes or that suspended and attached cells represent different populations of hepatocytes found in intact livers.     

Public–Private Collaboration in Health and Human Service Delivery: Evidence from Community Partnerships

The collaboration among public–private partnerships that applied to the Community Care Network (CCN) demonstration program of the Hospital Research and Educational Trust is examined. These partnerships link broad-based community coalitions with health and human service providers in efforts to improve community health and local service delivery. Although they willingly collaborated in identifying community health needs, coordinating services, and reporting to the community, partnership participants showed less alacrity in joining forces to reduce redundancy and increase efficiency. Such patterns suggest that organizations might best profit from working together on activities that maintain existing power relations and that have the potential to add prestige and attract new clients. Collaboration in these areas may be essential to building a foundation of trust that leads to future cooperation in more sensitive areas.     

On the Importance of Age-Adjustment Methods in Ecological Studies of Social Determinants of Mortality

Objective. To illustrate the potential sensitivity of ecological associations between mortality and certain socioeconomic factors to different methods of age-adjustment.
Data Sources. Secondary analysis employing state-level data from several publicly available sources. Crude and age-adjusted mortality rates for 1990 are obtained from the U.S. Centers for Disease Control. The Gini coefficient for family income and percent of persons below the federal poverty line are from the U.S. Bureau of Labor Statistics. Putnam's (2000) Social Capital Index was downloaded from http://www.bowlingalone.com ; the Social Mistrust Index was calculated from responses to the General Social Survey, following the method described in Kawachi et al. (1997) . All other covariates are obtained from the U.S. Census Bureau.
Study Design. We use least squares regression to estimate the effect of several state-level socioeconomic factors on mortality rates. We examine whether these statistical associations are sensitive to the use of alternative methods of accounting for the different age composition of state populations. Following several previous studies, we present results for the case when only mortality rates are age-adjusted. We contrast these results with those obtained from regressions of crude mortality on age variables.
Principal Findings. Different age-adjustment methods can cause a change in the sign or statistical significance of the association between mortality and various socioeconomic factors. When age variables are included as regressors, we find no significant association between mortality and either income inequality, minority racial concentration, or social capital.
Conclusions. Ecological associations between certain socioeconomic factors and mortality may be extremely sensitive to different age-adjustment methods.     

Death of a classified worker probably caused by overexposure to gamma radiation.

This paper describes the case of an industrial radiographer who was seriously overexposed to gamma radiation. The exact circumstances of this exposure were not established but it was concluded that he was repeatedly irradiated probably to a total average whole body dose of at least 10 Gy over several years. Also, a much larger dose to a hand required its partial amputation. He developed myelodysplasia, which progressed to acute myeloid leukaemia from which he died. Karyotypic examination of the leukaemic blasts showed changes very similar to those associated with secondary leukaemia that may develop after radio or chemotherapy. The paper describes his medical case history, the investigation of his workplace, and the attempts to estimate his radiation dose by chromosomal analysis of blood lymphocytes and electron spin resonance of dental enamel and bone.     

Comorbidities in head and neck cancer: agreement between self-report and chart review.

OBJECTIVES: To determine the accuracy of self-reported comorbidities compared with medical record review and the clinical and sociodemographic characteristics associated with accuracy of self-reported comorbidities. STUDY DESIGN: We conducted a prospective study of 458 newly diagnosed head and neck cancer patients using self-administered questionnaire and medical chart review data. Overall and itemwise consistency between self-report and chart review was evaluated. Social, clinical, and demographic characteristics of consistent versus inconsistent responders were analyzed. RESULTS: Seventy-four percent of patients had at least one comorbidity. There was good overall consistency between self-report and chart review (kappa = 0.50). Compared with consistent responders, inconsistent responders were found to be older (P < 0.05), have lower sleep (P < 0.05) and physical activity scores (P < 0.05), be more depressed (P < 0.05), and have more severe comorbidities (P < 0.05). CONCLUSIONS AND SIGNIFICANCE: Self-report may be considered as an alternative to chart review for comorbidity assessment in head and neck cancer patients. Younger patients, those with good general health, fewer depressive symptoms, and mild comorbidities, are more likely to give responses consistent with chart review.     

The Family in Medical Decisionmaking

Should the authority to make treatment decisions be extended to the competent patient's family? Neither arguments from fairness nor communitarian concerns justify such an infringement on patient autonomy.     

Developmental Expression of Neuron-Specific Enolase Immunoreactivity and Cytochrome Oxidase Activity in Neocortical Transplants

The present study has examined certain metabolic markers in fetal neocortical tissue transplanted to the cortex, hippocampus, striatum, or ventricle. Particularly, the immunocytochemical expression of neuron-specific enolase (NSE) was studied in a series of host rats ranging between 10 days and 15 months postoperative. NSE is a major glycolytic pathway enzyme found in all neurons. The antibody to NSE is a very reliable marker for neuronal functional metabolic activity and developmental status and its onset has been shown to coincide with synaptic connections. In some grafts oxidative metabolic status was investigated using cytochrome oxidase (CO) histochemistry. In addition, the normal development of NSE expression in rat neocortex was also examined. In normal development, NSE was weakly expressed in fetal brain, but by 1-2 weeks postnatal the enzyme was strongly expressed in all neurons. Typical cortical laminar patterns were evident at 30 days with neurons in layer V and scattered interneurons the most strongly stained. In cortex-cortex transplants NSE expression was very weak; at 1-3 weeks postoperative, it was practically nonexistent; and at all later times only a minority of neurons had normal expression when compared to that in normal development even though by Nissl staining standards in adjacent sections they appeared "normal." Labeling indices ranged between 30 and 49%. Intraventricular grafts had consistently low NSE expression with labeling indices ranging between 18 and 46%. However, when the neocortical tissue was placed in other regions, neuronal NSE appeared only slightly below normal. CO histochemistry corroborated the NSE activity with regards to graft placement. Several possibilities that may account for reduced NSE profile in transplanted neurons include incomplete migration patterns, reduced synaptic connectivity, and potential ischemia causing lowered protein synthesis during reestablishment of vascular connections. If neuronal glycolysis is weakened, it is possible that neurotransmitter production or axonal transport are reduced. Since most energy capacity in brain is dependent on the glycolytic sequence for oxidative metabolism, reduced glycolytic capacity, as depicted by NSE expression, may suggest the presence of transplanted neurons that have adapted to their new environment with a relatively immature profile.     

Acetylcholinesterase Staining in Human Auditory and Language Cortices: Regional Variation of Structural Features

Cholinergic innervation of the cerebral neocortex arises fromthe basal forebrain and projects to all cortical regions. Acetylcholinesterase(AChE), the enzyme responsible for deactivating acetylcholine,is found within both cholinergic axons arising from the basalforebrain and a subgroup of pyramidal cells in layers III andV of the cerebral cortex. This pattern of staining varies withcortical location and may contribute uniquely to cortical microcircuitrywithin functionally distinct regions. To explore this issuefurther, we examined the pattern of AChE staining within auditory,auditory association, and putative language regions of whole,postmortem human brains. The density and distribution of acetylcholine-containing axonsand pyramidal cells vary systematically as a function of auditoryprocessing level. Within primary auditory regions AChE-containingaxons are dense and pyramidal cells are largely absent. Adjacentcortical regions show a decrease in the density of AChE-containingaxons and an increase in AChE-containing pyramidal cells. Theposterior auditory and language regions contain a relativelyhigh density of AChE-containing pyramidal cells and AChE-containingaxons. Although right and left posterior temporal regions arefunctionally asymmetrical, there is no apparent asymmetry inthe general pattern of AChE staining between homologous regionsof the two hemispheres. Thus, the pattern of AChE staining covarieswith processing level in the hierarchy of auditory corticalregions, but does not vary between the functionally distinctright and left posterior regions. An asymmetry in the size of layer III AChE-rich pyramidal cellswas present within a number of cortical regions. Large AChE-richpyramidal cells of layer III were consistently greater in sizein the left hemisphere as compared to the right. Asymmetry inlayer III pyramidal cell size was not restricted to language-associatedregions, and could potentially have a variety of etiologiesincluding structural, connectional, and activational differencesbetween the left and right hemisphere.