Preparation and biological activity of taxol acetates

Synthesis and biological activity of 2′-acetyltaxol and 7-acetyltaxol are reported. Activity is measured $\text{in}\text{vivo}$ by cytotoxicity toward the macrophage-like cell line J774.2, and $\text{in}\text{vitro}$ by promotion of microtubule assembly in the absence of exogenous GTP. Addition of an acetyl moiety at C-2′ results in loss of $\text{in}\text{vitro}$ activity but not cytotoxicity. The properties of 7-acetyltaxol are similar to those of taxol in its effects on cell replication and on $\text{in}\text{vitro}$ microtubule polymerization. Therefore a free hydroxyl group at C-7 is not required for $\text{in}\text{vitro}$ activity and this position is available for structural modifications.     

Personal reflections on the nature of intelligence in humans and machines

Computers, the human mind, and social systems have common problems of inadequate memory and insufficient data manipulation speed. In each of these domains, information compression techniques have evolved to reduce storage and processing needs. Among the techniques for information compression, coding of information in procedures stands out as exceptionally powerful. Procedural information coding also gives rise to behavior that may be defined as intelligent. It is found in the human mind, in machines and in social systems. Its use in human thought is aided by language development which promotes regular review of abstract procedures. A practical consequence of better understanding of procedural information coding is the possibility of training people to exhibit greater mental capacity, a controversial possibility. This paper explores the impact of data processing resource limitations, data compression and procedural thinking in men and machines.     

The effect of three species of mites upon fungal growth on wheat

Every week, for 20 weeks, the growth of naturally occurring grain storage fungi on wheat infested with the three commonest British grain storage mites,Acarus siro, Glycyphagus destructor andTyrophagus longior, was compared with that on uninfested wheat.The number of colonies of theAspergillus glaucus group per gram were always less on grain infested with mites than on uninfested grain.Penicillium spp. were also less numerous on grain which was infested withA. siro but did not appear to be affected by the other mites. In contrast, two fungi which are pathogenic to mites,Aspergillus restrictus andWallemia sebi, were more abundant in the presence of certain mites. The former was associated withG. destructor, the latter withG. destructor andA. siro.The three species of mites either feed on theA. glaucus group andPenicillium spp., or inhibit them by an unknown secretion. Pathogenic fungi are probably avoided. Mites are therefore an important variable in studies on fungal growth during grain drying and storage.     

Cryptococcus neoformans: Comparisons of in vitro antifungal susceptibilities of serotypes AD and BC

Thirty-nine isolates of Cryptococcus neoformans, nineteen serotype AD and twenty serotype BC, were assayed for susceptibility to eight antifungal agents using an in vitro agar dilution assay. Media employed were Kimmig agar and yeast nitrogen base supplemented with 10% glucose. The antifungal agents used were ketoconazole, amphotericin B, 5-fluorocytosine, nystatin, miconazole, BAY N 7133, ICI 153,066, and itraconazole. No clinically significant differences in in vitro minimum inhibitory concentrations were detected between serotypes AD and BC against any of the compounds tested. An adverse medium effect was observed in two of the assays, but the outcome of the AD/BC comparison was not affected. This is the first report in which the in vitro antifungal susceptibilities of Cryptococcus neoformans serotypes are analyzed.     

Care Needs of the Elderly Treated at a Dental School1

Increased longevity and recently intensified emphasis on gerodontology mandate that dental students'exposure to clinical care of the elderly be enhanced. The extent to which individual students can be exposed to geriatric dental care depends on the availability of elderly patients to dental school clinics and the treatment needs of these patients. The purposes of this study were (1) to determine the dental treatment needs of geriatric patients who seek care at a dental school, and (2) to ascertain if differences exist between the needs of older versus relatively young geriatric patients. Data collected on 128 elderly patients during a three month period indicate that 57% of the aged were either edentulous at examination or treatment planned to become edentulous and receive two full dentures. The remaining 43% were treatment planned to remain dentulous and receive therapies other than full upper and lower dentures. More older geriatric patients required full dentures than their younger cohorts. More young elderly required prophylaxes, scalings, root planing therapy, dental restorations, and partial dentures. Additional to their denture requirements, aged patients appear to have sufficient non-prosthetic needs to allow for meaningful gerodontic experience by students.     

Fast-Transported Glycoproteins and Nonglycosylated Proteins Contain Sulfate

35SO4-labeled fast-transported proteins of bullfrog dorsal root ganglion neurons were separated by two-dimensional gel electrophoresis, and their mobilities were compared to similar species labeled with [3H]mannose or [3H]fucose. Fluorography revealed regions of poorly resolved, high molecular weight material, likely to represent sulfated proteoglycans, as well as many well resolved spots that corresponded in mobility to individual [35S]methionine-labeled fast-transported proteins. The majority of these well resolved spots appeared as "families," previously identified as glycoproteins based on their labeling with sugars. Thus, sulfate can be a contributor to the carbohydrate side-chain charge that underlies microheterogeneity. The most heavily 35SO4-labeled species, however, corresponded to fast-transported proteins that were not labeled by either sugar. The relative acid labilities of 35SO4 associated with individual species cut from the gel confirmed the assignments of these spots as glycoproteins or nonglycoproteins. A group of spots intermediate in their acid lability was also detected, suggesting that some proteins may contain sulfate linked to carbohydrate as well as to amino acid residues.     

Specific binding sites for vasoactive intestinal polypeptide on nonadherent peripheral blood lymphocytes

Vasoactive intestinal polypeptide (VIP), an octacosapeptide isolated from porcine duodenum and thought to have neuromodulator function in several functional systems (gastrointestinal tract, brain, lung, genital tract, heart), was recently detected in human neutrophils by radioimmunoassay. Subsequent studies demonstrated a VIP-mediated increase in lymphocyte adenylate cyclase. In this paper, VIP binding studies are presented using viable nonadherent human lymphocytes. Binding of 125I-VIP to nylon wool column-purified lymphocytes is specific, time dependent, rapid, and reversible. Bound radioactivity varies linearly with the number of cells used and is displaceable by non-iodinated VIP in a dose-dependent manner with complete displacement between 1 pM and 50 nM. Scatchard analysis of competition experiments demonstrates one class of specific binding sites with a KD of 0.47 +/- 0.23 nM and a Bmax of 24.9 +/- 7.0 pM. This Bmax represents 1700 binding sites/cell. secretin, gastric inhibitory polypeptide, and glucagon did not effectively compete with 125I-VIP for binding sites. This is the first demonstration of VIP receptors in a purified population of human lymphocytes; the data suggest that VIP may modulate lymphocyte function.