Psychomotor and intellectual development after deep hypothermia and circulatory arrest in early infancy

Somatic, psychomotor, and intellectual development were studied in 11 patients who had total correction of congenital cardiac malformation in early infancy by the method of surface-induced deep hypothermia and circulatory arrest up to 43 minutes. Time between operation and re-evaluation ranged from 3 to 11 years (average 7 years). Somatic development was normal in all children. Psychomotor and intellectual behavior, measured by a battery of specially adapted test methods, failed to show a statistically significant difference when compared between the study group, a matched control group, and the normal population. Normal scores in psychomotor tests and normal intelligence quotients (I.Q.) were present in 8 patients; mental retardation was found in 2 patients: and unstable behavior, evident from different tests, was present in one. Except for the last case, in none of the patients was the method was found to be the primary cause of the abnormal behavior. Deep hypothermia and circulatory arrest in early infancy does not appear to have a negative influence on somatic, psychomotor, or intellectual development.     

O6-alkylguanine-DNA alkyltransferase inactivation by ester prodrugs of O6-benzylguanine derivatives and their rate of hydrolysis by cellular esterases

To modulate the bioavailability and perhaps improve the tumor cell selectivity of O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT inactivators and as substrates for cellular esterases. The potential prodrugs examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7- and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9-esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8-bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at least 75 times less potent than the corresponding benzylated purine against the pure human AGT. In contrast, the activities of esters and their respective benzylated purine were similar in crude cell extracts and in intact cells. The increase in potency of esters in cellular extracts could be explained by a conversion of the respective prodrug to the more potent benzylated purine in the presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor cell hydrolysis of the esters varied considerably as a function of cell type and prodrug structure. These data suggest that these or related prodrugs may be advantageous for selective AGT inactivation in certain tumor types.     

Reaction and total cross sections for low energy pi + and pi - on isospin zero nuclei

We calculated the electrostatic force between a planar interface, such as a planar-supported lipid bilayer membrane, and the tip of a stylus on which another lipid bilayer or some other biomacromolecular system might be deposited. We considered styli with rounded tips as well as conical tips. To take into account the effect of dynamical hydrogen-bonded structures in the aqueous phase, we used a theory of nonlocal electrostatics. We used the Derjaguin approximation and identified the systems for which its use is valid. We pointed out where our approach differs from previous calculations and to what extent the latter are inadequate. We found that 1) the nonlocal interactions have significant effects over distances of 10-15 A from the polar zone and that, at the surface of this zone, the effect on the calculated force can be some orders of magnitude; 2) the lipid dipoles and charges are located a distance L from the hydrophobic layer in the aqueous medium and this can have consequences that may not be appreciated if it is ignored; 3) dipoles, located in the aqueous region, can give rise to forces even though the polar layer is unchanged, and if this is ignored the interpretation of force data can be erroneous if an attempt is made to rationalize an observed force with a knowledge of an uncharged surface; 4) the shape of the stylus tip can be very important, and a failure to take this into account can result in incorrect conclusions, a point made by other workers; and 5) when L is nonzero, the presence of charges and dipoles can yield a force that can be nonmonotonic as a function of ionic concentration.     

In vivo electrochemical studies of dopamine clearance in subregions of rat nucleus accumbens: differential properties of the core and shell

The effects of the rodent hepatocarcinogens clofibric acid and diprofibrate on the activity of the peroxisomal fatty acyl-CoA oxidase, DNA synthesis, and apoptosis were compared in cultured rat and human hepatocytes. Rat hepatocytes expressed a 10-fold greater level of the peroxisomal fatty acyl-CoA oxidase compared to human hepatocytes. At the highest concentration (1.0 mM), both drugs induced a two- to threefold increase in this enzyme activity in both rat and human hepatocytes. Ciprofibrate (0.1 and 0.2 mM) caused a twofold increase in DNA synthesis in rat hepatocytes, whereas clofibric acid had no effect on DNA synthesis in these cells. In contrast, increasing concentrations of both clofibric acid and ciprofibrate produced inhibition of DNA synthesis in human hepatocytes. By using the terminal transferase dUTP-biotin nick end labeling technique, it was observed that 0.1 and 0.2 mM clofibric acid and ciprofibrate suppressed transforming growth factor-beta (TGF beta)-induced apoptosis by 50% in rat hepatocytes, but they had no effect on TGF beta-induced apoptosis in human hepatocytes. Although clofibric acid and ciprofibrate diminished TGF beta-induced apoptosis, they had no effect on the basal apoptotic levels in the rat hepatocyte cultures. However, both drugs significantly increased the percent of apoptotic cells in the human hepatocyte cultures. It is concluded that primary rat and human hepatocyte cultures respond differently to peroxisome proliferators. The differences in effects on DNA synthesis and apoptosis support the hypothesis that human liver cells are refractory to peroxisome proliferator-induced hepatocarcinogenesis.     

6 Top Tools for Taming Big Data

The industry now has a buzzword, "big data," for how we’re going to do something with the huge amount of information piling up. "Big data" is replacing "business     

Pyropheophytin a and 1,2-Diacyl-glycerols Over Time Under Different Storage Conditions in Natural Olive Oils

The effect of storage conditions (light, temperature, container types) and time on the quality of natural olive oils from different cultivars and Australian regions were studied. The oils’ changing quality was monitored through several physico-chemical methods (free fatty acids, peroxide value, UV-spectrometry (K₂₃₂, K ₂₇₀ and ΔK), induction time, total polyphenol content, bitterness, pyropheophytin a and 1,2-diacyl-glycerol content) and sensory analysis over 24 months. Pyropheophytins a and 1,2-diacyl-glycerols criteria showed very good performance as indicators of overall olive oil quality and freshness as well as highlighting any problems during the storage of the product. Pyropheophytin a increment averaged 7 % per year and the 1,2-diacyl-glycerols decreased at an average of 23 % per year at normal storage conditions over time.     

Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR) do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.     

The application of dynamic insulation in buildings

Dynamic insulation, a form of ‘Breathing Wall’ construction which allows the movement of air and moisture through the external walls of a building, was seen as one possible method for reducing building envelope heat losses and achieving high indoor air quality. A research investigation was conducted to provide a firm scientific understanding of dynamic insulation. An important outcome of the work will be the development of building envelope designs which effectively and economically employ dynamic insulation in cold climates. This paper presents some general conclusions, confirming that the energy saving produced by dynamic insulation alone is small relative to that obtained in conjunction with conventional air heat recovery methods.     

Abnormalities in proliferation and protein synthesis in skin fibroblast cultures from patients with diabetes mellitus

Several aspects of in-vitro cell growth and protein synthesis were assessed in cultures of skin fibroblasts from subjects with juvenile-onset diabetes mellitus (JODM) or adult-onset diabetes mellitus (AODM) and from age-matched nondiabetic controls (C). There was an inverse correlation between increasing age and both the log-phase doubling rate and saturation density at confluence in C fibroblasts. JODM and AODM cells had a reduction in both indices of cell population growth in comparison with age-matched C fibroblasts. Fibroblasts grown in the presence of 0.3 micronM hydrocortisone were stimulated to grow more rapidly and to a greater saturation density. Stimulation of cell division by hydrocortisone accentuated the abnormalities in growth of JODM and AODM fibroblasts. Total protein and collagen synthesis was measured whtn the fibroblasts had grown to confluency in medium with or without hydrocorticone. Hydrocorticone did not produce a significant change in total protein and collagen synthesis per cell by C fibroblasts. Fibroblasts from AODM had a 180 per cent increase in total protein and collagen synthesis in the presence of hydrocortisone. In contrast, total protein and collagen synthesis decreased 40 per cent in fibroblasts from JODM when grown in the hydrocortisone medium. These studies indicate that skin fibroblast cultures from patients with diabetes exhibit abnormalities in cell proliferation. Furthermore, hydrocortisone appears to unmask diffeerences in protein synthesis that distinguish JODM and AODM fibroblasts in culture.     

Using the psychiatrist

The change in the practice of psychiatry has been sufficiently marked and sufficiently recent to generate uncertainty as to the psychiatrist's function, and particularly how he might best be used by other doctors. This article examines some issues relevant to the psychiatrist's function as a clinical consultant, as a contributor to preventive psychiatry, and as a mental health consultant in relationship to community medicine in general, and the family doctor in particular.