Nutrient-induced spatial patterning of human duodenal motor function

The spatiotemporal patterning of duodenal motor function has been evaluated comprehensively for the first time in humans, with a novel 21-lumen manometric assembly. In nine young, healthy volunteers (6 male, 3 female), duodenal motility was recorded during fasting and three 45-min intraduodenal (ID) nutrient infusion periods (Intralipid at 0.25, 0.5, and 1.5 kcal/min). Pressures were recorded along the length of the duodenum with an array of 18 sideholes at 1.5-cm intervals. Pressure patterns were compared for the final 20 min of each of the four periods. Compared with fasting, ID lipid was associated with regional variation in pressure wave (PW) sequences, with fewer proximally and more distally; this was not observed during fasting (P < 0.001). During fasting and all rates of lipid infusion, most (87-90%) PW sequences were short (1.5-4.5 cm), with a small number (2-4%) of 10.5 cm or longer. At all times, antegrade PW sequences occurred more frequently than retrograde sequences over all distances examined (3, 4.5, and >6 cm), and the proportion of antegrade sequences increased with greater PW sequence length (P = 0.0001). Increasing ID lipid rates appeared to produce dose-related suppression of PW sequences (P < 0.001). The frequency and spatial patterning of human duodenal motor function show substantial variability in response to different nutrient delivery rates. These complex patterns are likely to be involved in duodenal modulation of flow and gastric emptying rate.     

The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors

Flap endonuclease-1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. Sensitization to DNA damaging agents is a potential method for the improvement of the therapeutic window of traditional chemotherapeutics. In this paper, we describe the identification and SAR of a series of low nanomolar FEN1 inhibitors. Over 1000-fold specificity was achieved against a related endonuclease, xeroderma pigmentosum G (XPG). Two compounds from this series significantly potentiate the action of methyl methanesulfonate (MMS) and temozolamide in a bladder cancer cell line (T24). To our knowledge, these are the most potent endonuclease inhibitors reported to date.     

Preregistration house officers in the Thames regions: changes in quality of training after four years.

OBJECTIVE--To measure changes in the training and workload of preregistration house officers over four years. DESIGN--Postal questionnaire. SETTING--The Thames health regions. PARTICIPANTS--1049 preregistration house officers. RESULTS--Response rate was 69% (725 replies). The proportion of house officers officially on duty > 83 hours a week fell from at least 42% to 21%, and the proportion officially on duty < or = 72 hours rose from no more than 9% to 40%. Adequate guidance in breaking bad news increased from 25% to 46% (p < 0.0001; 95% confidence interval for difference, 16.2% to 25.8%) and guidance in pain control increased from 36% to 46% (p < 0.01; 5.0% to 15.0%). The number of house officers attending an induction course increased from 61% to 94% (p < 0.001; 28.9% to 37.1%). There was no change in the proportion unable to attend formal educational sessions because of clinical commitments or in levels of satisfaction with consultants'' educational supervision. The median number of inpatients under house officers'' care fell from 20 to 17, but the numbers of patients clerked in an average week showed little change. House officers were less satisfied with the clinical experience their post provided (proportion dissatisfied rose from 30% to 39%; p < 0.01; 4.2% to 13.8%) and less enthusiastic about recommending their post to a friend (proportion neutral or not recommending rose from 30% to 42%, p < 0.0001; 7.9% to 16.9%). CONCLUSION--Despite progress in reducing hours of duty and providing induction courses, the training that hospitals and consultants provide for house officers is still unsatisfactory and inconsistent with the General Medical Council''s recommendations.     

Hyperpigmented patches in the skin of the newt Notophthalmus viridescens

In the integument of the red-spotted newt there occasionally appear patches of skin which are at the same time melanistic and iridescent. Such hyperpigmented patches have been found on the back, on the tail and on the dorsal surface of both fore and hind limbs. Cytological examination of several such areas revealed the presence of large numbers of chromatophores distributed throughout the dermis. The majority of the chromatophores consisted of atypically large and dendritic melanophores, which contained typical pigment granules. The iridescence resulted from a high incidence of iridophores. Xanthophores also were found in considerable abundance. This extensive and apparently random intermingling of melanophores, iridophores and xanthophores in limited areas constitutes a striking exception to the usual distributional patterns of pigment cells in this animal.     

On the identity of the thyrotropic cell in the red-spotted newt

Summary Although the pars distalis of the red-spotted newt has previously undergone extensive cytological examination, the identity of its thyrotropic cells has remained uncertain. From the present ultrastructural study, cells of type 3 (Masur, 1969) containing granules 150–180 nm in diameter are concluded to be the thyrotropes. Such cells were found to be present in the regions of the pars distalis where thyroidectomy cells arise after ablation of the thyroid gland. Cells of type 3 are probably identical with a population of cells containing granules which stain with silver methenamine indicating the presence of a glycoprotein such as thyroid stimulating hormone (TSH). Thyroidectomy cells containing a few residual granules 150–180 nm in diameter were occasionally found in partes distales from newts killed 3 or 7 days after ablation of the thyroid gland, and were abundant in pituitaries 21 days after thyroidectomy. Only cells of type 3 responded (by vacuolation of granules) when animals were immersed in water containing 10 g/l of thyroxine. No cells of the pars distalis showed cytological change after administration of synthetic thyrotropic releasing hormone (TRH) giving additional support to the view that this hormone has no stimulatory role in amphibians.Work supported in part by research grant 1 R01 AM 16731-01 from the Institute of Arthritis, Metabolism and Metabolic Diseases and in part by grant PCM 75-17637 from the National Science Foundation     

Physiological Properties of Yeast Cells Grown in the Proteolipid-Supplemented Media

Koji mold proteolipid (PL), a high concentration alcohol-producing factor, promoted yeast growth, and also affected the physiological properties of yeast cells: in the conditions of statical cultures, the cells grown anaerobically in PL-supplemented media showed the highest fermentative activity and the highest alcohol-durability by the dipping method in 20% alcohol for 48 hr, at 20°C, that was similar to moromi (main mash) yeasts in Japanese sake brewing; the cells grown in the stationary culture (with cotton plug) supplemented with PL showed the lowest fermentative activity and relatively low alcohol-durability, similar to moto (seed mash) yeasts; the cells grown anaerobically in PL-unsupplemented media showed high fermentative activity but the lowest alcohol-durability.