A Taxonomy of Continuing Medical Education Endeavour

Five basic forms of continuing educational endeavour by physicians are listed in rank order. These components constitute an indivisible unit bound together by self-learning. The scholarly habit of planned daily reading and study in a home library-sanctuary as an integral part of a physician''s workday heads the list. Day-to-day informal and formal colleague-association in patient care in the community and teaching hospital, in group practice and by consultation is the present major form of continuing educational endeavour. Emphasized is the sabbatical return every three to five years for three months at least to the teaching hospital to reinforce scholarly motivation and attitudes and to acquire new skills and knowledge. Attendance at scientific sessions of learned professional societies and short courses should be accompanied by presession and post-session guided reading to be undertaken in the physician''s home library-sanctuary.     

The binding of hydrogen ions to an acidic glycoprotein from bovine cortical bone

The H⁺ ion dissociation of bone sialoprotein in 0·2m-sodium chloride at 25° was studied. The total content of carboxyl groups available for titration was calculated by comparing the titration curve with the titration curves of three model systems and by the use of analytical data. This comparison showed that 7·0 carboxyl groups/mol. do not participate in the titration, and it is proposed that these are aspartic acid or glutamic acid carboxyl groups present as amides; this is also indicated by titration of the sialoprotein after acid hydrolysis. The titration of carboxyl groups was found to agree well with the Linderstrøm-Lang equation for spherical macroions.     

Fly pupae as attractant carriers for toxic baits for red imported fire ants (Hymenoptera: Formicidae)

Eight laboratory-reared ant species were fed baits of house fly, Musca domestica L., pupae treated with hydramethylnon. Two fire ant species, Solenopsis invicta Buren and Solenopsis geminata (F.), and Pheidole morrissi (Forel) were killed; average percentage of mortality of the five other species was less than 20%. In contrast, all species that were fed the commercial fire ant bait containing hydramethylnon (Amdro) died or were adversely affected. In the field, applications of house fly pupae and eye gnat, Hippelates pusio Loew, pupae dipped in acetone solutions of fenoxycarb significantly reduced population indices of the red imported fire ant, S. invicta, compared with commercial formulations of fenoxycarb (Logic) and hydramethylnon (Amdro). Field observations showed that the pupae of either species can be carried or moved by one or two worker ants. The smooth, hard cuticle of the pupae make them easy to handle and apply with application equipment. The current cost of house fly pupae is considerably more than the cost of a granular carrier, pregel defatted corn grits. However, if mass-production methods reduce this price differential, fly pupae could become an effective and more species-specific fire ant bait carrier.     

Serine-palmitoyl transferase activity in cultured human keratinocytes

Sphingolipids comprise approximately 25% of the stratum corneum lipids and are considered critical constituents of the epidermal permeability barrier. Whether sphingoid base structures are synthesized in the epidermis or whether they are derived from circulating or dermal sources is not known. We report here the initial characterization of serine-palmitoyl transferase (EC 2.3.1.50; SPT), the rate-limiting enzyme in the synthesis of sphingolipids, from cultured human neonatal keratinocytes. Subcellular fractionation studies demonstrated that 79% of the total cellular SPT activity was associated with the microsomes. The specific activity of keratinocyte SPT was 270 +/- 20 pmol/min per mg of microsomal protein, a level significantly higher than activities reported in other tissues. Keratinocyte SPT showed an apparent Km for L-serine of 0.40 (+/- 0.04 mM, with an alkaline pH optimum (8.2 +/- 0.4). Keratinocyte SPT utilizes palmitoyl-CoA preferentially over other saturated or unsaturated acyl-CoA substrates; increasing acyl-CoA chain lengths above C16 by one or two carbons was less detrimental to activity than similar decrements in chain length. Finally, the mechanism-based inhibitors L-cycloserine and beta-chloro-L-alanine, demonstrated potent inhibition of keratinocyte SPT activity, with 50% inhibitory concentrations of approximately 3.0 and 25 microM, respectively. In summary, we have found that cultured human neonatal keratinocytes contain unusually high levels of serine-palmitoyl transferase activity, and that the substrate specificity of keratinocyte SPT may determine the base composition of epidermal sphingolipids.     

Elastic constants of composites formed from PMMA bone cement and anisotropic bovine tibial cancellous bone

An ultrasonic pulse-transit time technique is used to determine the nine orthotropic engineering constants of 32 cement-cancellous bone composites as a function of volume fractions of bone ranging from 0.0 to 0.4. The composites are manufactured using well-aligned bovine cancellous bone from the proximal end of the tibia and low viscosity bone cement. Selected composites are also subjected to mechanical compression tests to compare with the ultrasonic results. There is excellent correlation between the dynamic or ultrasonically determined moduli and the static or mechanically determined moduli; the dynamic moduli are approximately twice the static moduli and this difference is thought to be due to the effect of strain rate. An orthotropic model is assumed requiring nine independent elastic constants to be determined. The dynamic Young's modulus in the direction of major trabecular alignment, E1, increases linearly from 4.9 to 10.4 GPa as bone volume fraction increases from 0 to 0.4; dynamic E2 and E3 values increase from 4.9 to 7 GPa as bone volume fractions increase from 0 to 0.4, with E2 being slightly higher than E3. The dynamic shear modulus, G12, increases from 1.8 to 3.0 GPa, and G31 and G23 increase slightly from 1.8 to 2.2 GPa as bone volume fractions increase from 0 to 0.4. The Poisson's ratios are more sensitive than the Young's moduli and shear moduli to experimental error in the velocity measurements. The mechanically tested modulus (static modulus) in the direction of major trabecular alignment, E1, increases with volume fraction of bone from 2.4 to 4.4 GPa as the bone volume fraction increases from 0 to 0.25; static E2 and E3 values are either equal to or lower than that of pure PMMA.     

Pentose phosphate pathway in rat colonic epithelium

The colonic cells of the large intestine are one of the most proliferative tissues of the animal body. The pentose pathway has an essential role in cell division and growth being the only pathway forming ribose 5-P necessary for all nucleotide and nucleic acid sunthesis. The pentose pathway may also provide reducing potential as NADPH for biosynthesis and C-3- C-8 glycolyl compounds. The maximum catalytic capacities of the reactions of the non-oxidative pentose pathway for the conversion of ribose 5-P to hexose and triose phosphates by the proximal and distal colon under feeding and starvation regimes are among the highest in the animal body. The qualitative presence of the oxidative pentose pathway was assessed by measurement of the C-1/C-6 ratio value of 1.67-1.82. Enzymes of the F-type and L-type pentose pathways are present in colonocytes and their maximum catalytic activities in colonocyte cytosol are reported. The contribution of the F-type pentose cycle to the total glucose metabolism of colonocytes, measured by the specific yield method, is negligibly low (approximately 1.5%). Colonic epithelial cells use glucose at a high rate (7.1 +/- 0.33 mumol min-1g-1 dry wt) and 79% of the glucose is converted to lactate. Arabinose 5-P has an intermediary role in the formation of keto pentose, sedoheptulose and hexose phosphates from ribose 5-P by colonocyte cytosol. The intermediary and reaction products of [1-13C] ribose 5-P dissimilation by colonocytes is investigated by 13C NMR spectroscopy. The 13C positional isotope distributions show labelling of C-1 and C-3 of hexose 6-phosphates consistent with either the theoretical predictions of the F-type pentose pathway or of the activities of exchange reactions catalysed by transketolase and/or transaldolase. Measurements of exchange reactions showed that the C-1/C-3 labelling of these compounds is mostly, if not wholly, attributable to exchange catalysis by these group transferring enzymes. The results suggest that the F-type PC has little role in the glucose metabolism of colonocytes and pentose phosphate formation may thus occur by a contribution (approx 20% of the total glucose metabolism) by the alternate L-type pathway.     

Significant extension in northern Australia of the known geographic range of the Shield Shrimp Triops australiensis (Crustacea: Notostraca)

The program BIOCLIM predicts the total geographic distribution of species, based upon the biogeoclimatic characteristics common to the localities at which they are known to occur. Field studies in the Northern Territory have located the Shield Shrimp Triops australiensis at localities substantially north of its known and predicted geographic distribution.     

Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002.

The immunosuppressant, rapamycin, inhibits cell growth by interfering with the function of a novel kinase, termed mammalian target of rapamycin (mTOR). The putative catalytic domain of mTOR is similar to those of mammalian and yeast phosphatidylinositol (PI) 3-kinases. This study demonstrates that mTOR is a component of a cytokine-triggered protein kinase cascade leading to the phosphorylation of the eukaryotic initiation factor-4E (eIF-4E) binding protein, PHAS-1, in activated T lymphocytes. This event promotes G1 phase progression by stimulating eIF-4E-dependent translation initiation. A mutant YAC-1 T lymphoma cell line, which was selected for resistance to the growth-inhibitory action of rapamycin, was correspondingly resistant to the suppressive effect of this drug on PHAS-1 phosphorylation. In contrast, the PI 3-kinase inhibitor, wortmannin, reduced the phosphorylation of PHAS-1 in both rapamycin-sensitive and -resistant T cells. At similar drug concentrations (0.1-1 microM), wortmannin irreversibly inhibited the serine-specific autokinase activity of mTOR. The autokinase activity of mTOR was also sensitive to the structurally distinct PI 3-kinase inhibitor, LY294002, at concentrations (1-30 microM) nearly identical to those required for inhibition of the lipid kinase activity of the mammalian p85-p110 heterodimer. These studies indicate that the signaling functions of mTOR, and potentially those of other high molecular weight PI 3-kinase homologs, are directly affected by cellular treatment with wortmannin or LY294002.