Supply and demand in cerebral energy metabolism: the role of nutrient transporters.

Glucose is the obligate energetic fuel for the mammalian brain, and most studies of cerebral energy metabolism assume that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter (GLUT) proteins deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood-brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters (MCT): MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte-neuron lactate shuttle hypothesis suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, that is capacity and affinity for substrate, which must be considered in any model of cerebral glucose uptake and utilization. Using concentrations and kinetic parameters of GLUT1 and -3 in BBB endothelial cells, astrocytes, and neurons, along with the corresponding kinetic properties of the MCTs, we have successfully modeled brain glucose and lactate levels as well as lactate transients in response to neuronal stimulation. Simulations based on these parameters suggest that glucose readily diffuses through the basal lamina and interstitium to neurons, which are primarily responsible for glucose uptake, metabolism, and the generation of the lactate transients observed on neuronal activation.     

Signs of ocular disease: A prevalence study in optometric practice

Data on the prevalence of all ocular conditions seen in 1500 consecutive optometric patients were obtained during an investigation into the effectiveness of routine visual field screening. In many instances, these are the first prevalence figures for optometric patient populations. Some of the estimates of prevalence are compared with other optometric and general population surveys. Many disorders were observed, the most frequent being slight to moderate increases in retinal arterial reflex and attenuation, optic cup/disc ratio of 0.4, shallow anterior chambers and family history of glaucoma. The occurrence of some conditions was sporadic, resulting from the relatively small sample. However, this survey may serve as an audit of ocular disease detection for other practitioners.     

The glaucoma suspect: Differentiation of the future glaucoma eye from the non-glaucomatous suspect eye

Visual-field areas to a I_2e stimulus were measured planimetrically using an X-Y digitizer and a computer program. Sampling of normal subjects and patients suspected of having glaucoma was done at two points in time. Calculations of eye-wall stress were done using ultrasonic data and intra-ocular pressure (IOP) measurements from patient records. For those suspected of having glaucoma who developed chronic open-angle glaucoma (COAG), the time of transition was the second point in time. The visual field area was regressed against patient age at the two points in time. No difference in the regression slopes was found for the normal subjects and unchanged patients. The patients who did develop glaucoma were significantly different. The mean annual rate of visual-field change (rate of decay) was calculated and found to be 28.5 mm²/year for the normals, 153.5 mm²/year for the suspects, and 376.4 mm²/year for those patients who developed glaucoma. The rate of visual-field decay only correlated with patient age (P = 0.03) and eye-wall stress (P < 0.01) in the patients who developed glaucoma.     

Childhood Malignant Thymoma: Clinical, Therapeutic, and Immunohistochemical Considerations

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.     

The relationship of proliferating cell density at the invasive tumour front with prognostic and risk factors in human oral squamous cell carcinoma

BACKGROUND: We hypothesise that the density of proliferating cells at the invasive tumour front (ITF) has a positive relationship with prognostic and risk factors in human oral squamous cell carcinoma (SCC). METHODS: Tissues from 47 human oral SCC specimens were collected and stained with a monoclonal antibody directed against the Ki-67 antigen using a horseradish peroxidase based two-step immunostaining method. Counting was performed on two parallel sections at the ITF using an image analyser. The Ki-67 labelling index (LI) was determined by measuring the number of nuclei/mm(2) of epithelium. RESULTS: Our results show that the density of proliferating cells is related to clinical staging, with advanced stage of disease having a significantly higher Ki-67 LI compared with early stage of disease (2111 +/- 905 vs. 1908 +/- 913; P = 0.03). Importantly, this study shows that tumours that have metastasised have a significantly higher Ki-67 LI than tumours where distant metastasis was not detected (3257 +/- 650 vs. 1966 +/- 881; P < 0.0001). CONCLUSIONS: Cell proliferation, as measured by the Ki-67 LI at the ITF, has a positive relationship with clinical staging, tumour thickness, smoking status of the patient and alcohol consumption. Further, we suggest that a multicenter study with a large cohort of patients is indicated to fully elucidate whether cell proliferation at the ITF is directly related to patient survival.