Responses to the sensory properties of fat of neurons in the primate orbitofrontal cortex

The primate orbitofrontal cortex is a site of convergence of information from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the orbitofrontal cortex that responds to fat in the mouth. The neurons respond, when fatty foods are being eaten, to pure fat such as glyceryl trioleate and also to substances with a similar texture but different chemical composition such as paraffin oil (hydrocarbon) and silicone oil [Si(CH3)2O)n]. This is evidence that the neurons respond to the oral texture of fat, sensed by the somatosensory system. Some of the population of neurons respond unimodally to the texture of fat. Other single neurons show convergence of taste inputs, and others of olfactory inputs, onto single neurons that respond to fat. For example, neurons were found that responded to the mouth feel of fat and the taste of monosodium glutamate (both found in milk), or to the mouth feel of fat and to odor. Feeding to satiety reduces the responses of these neurons to the fatty food eaten, but the neurons still respond to some other foods that have not been fed to satiety. Thus sensory-specific satiety for fat is represented in the responses of single neurons in the primate orbitofrontal cortex. Fat is an important constituent of food that affects its palatability and nutritional effects. The findings described provide evidence that the reward value (or pleasantness) of the mouth feel of fat is represented in the primate orbitofrontal cortex and that the representation is relevant to appetite.     

The coenzyme A-synthesizing protein complex and its proposed role in CoA biosynthesis in bakers'' yeast

An improved procedure is described for the recovery and purification of the coenzyme A-synthesizing protein complex (CoA-SPC) of Saccharomyces cerevisiae (bakers' yeast). The molecular mass of the CoA-SPC, determined prior to and following its purification, is estimated by Sephacryl S-300 size exclusion chromatography to be between 375,000-400,000. Two previously unreported catalytic activities attributed to CoA-SPC have been identified. One of these is CoA-hydrolase activity which catalyzes the hydrolysis of CoA to form 3',5'-ADP and 4'-phosphopantetheine, and the other is dephospho-CoA-pyrophosphorylase activity which catalyzes a reaction between 4'-phosphopantetheine and ATP to form dephospho-CoA. The dephospho-CoA then reacts with ATP, catalyzed by the dephospho-CoA-kinase, to reform CoA. This sequence of reactions, referred to as the CoA/4'-phosphopantetheine cycle, provides a mechanism by which the 4'-phosphopantetheine can be recycled to form CoA. Each turn of the cycle utilizes two mol of ATP and produces one mol of ADP, one mol of PPi, and one mol of 3',5'-ADP. Other than the hydrolysis of CoA by CoA-SPC, the 4'-phosphopantetheine for the cycle apparently could be supplied by alternate sources. One alternate source may be the conventional pathway of CoA biosynthesis. Intact CoA-SPC has been separated into two segments. One segment is designated apo-CoA-SPC and the other segment segment is referred to as the 10,000-15,000 M(r) subunit. The 5'-ADP-4'-pantothenic acid-synthetase, 5'-ADP-4'-pantothenylcysteine-synthetase, 5'-ADP-4'-pantothenylcysteine-decarboxylase, and CoA-hydrolase activities reside in the apo-CoA-SPC segment of CoA-SPC. Whereas the dephospho-CoA-kinase and the dephospho-CoA-pyrophosphorylase activities reside in the 10,000-15,000 M(r) subunit. Thus, the 10,000-15,000 M(r) subunit mimics the bifunctional enzyme complex that catalyzes the final two steps in the conventional pathway of CoA biosynthesis.     

Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle

The three dimensional organization of microtubules in mitotic spindles of the yeast Saccharomyces cerevisiae has been determined by computer-aided reconstruction from electron micrographs of serially cross-sectioned spindles. Fifteen spindles ranging in length from 0.6-9.4 microns have been analyzed. Ordered microtubule packing is absent in spindles up to 0.8 micron, but the total number of microtubules is sufficient to allow one microtubule per kinetochore with a few additional microtubules that may form an interpolar spindle. An obvious bundle of about eight interpolar microtubules was found in spindles 1.3-1.6 microns long, and we suggest that the approximately 32 remaining microtubules act as kinetochore fibers. The relative lengths of the microtubules in these spindles suggest that they may be in an early stage of anaphase, even though these spindles are all situated in the mother cell, not in the isthmus between mother and bud. None of the reconstructed spindles exhibited the uniform populations of kinetochore microtubules characteristic of metaphase. Long spindles (2.7-9.4 microns), presumably in anaphase B, contained short remnants of a few presumed kinetochore microtubules clustered near the poles and a few long microtubules extending from each pole toward the spindle midplane, where they interdigitated with their counterparts from the other pole. Interpretation of these reconstructed spindles offers some insights into the mechanisms of mitosis in this yeast.     

Factors affecting primary care physician participation in Medicare

OBJECTIVES: This study investigates the levels of participation and the relative association of economic and noneconomic factors on primary care physician participation in the Medicare program. METHODS: Demographic information, participation in Medicare, and attitudes toward both the Medicare program and Medicare patients were collected in a written survey mailed to half the primary care physicians in Iowa. Ordinary least squares and logistic regression analyses were conducted to determine factors associated with the percentage of Medicare patients in a practice and the acceptance of all new Medicare patients, respectively. RESULTS: Two thirds of physicians were accepting all new Medicare patients, whereas 16% were accepting no new Medicare patients. Factors associated with having a higher percentage of Medicare patients in a practice were as follows: (1) a larger proportion of Medicare recipients in the county, (2) practice as a general internal medicine physician, (3) more years in practice at the current location, (4) greater enjoyment treating elderly patients, (5) less concern about having too many Medicare patients, and (6) a stronger belief that the Medicare program respects their professional judgment. Physicians less concerned about having too many Medicare patients in their practice and physicians in counties with a higher percentage of Medicare patients were significantly more likely to accept all new Medicare patients. CONCLUSIONS: These results suggest that as Medicare reforms are discussed, careful consideration of the impact of these reforms on noneconomic issues is important to ensure adequate physician participation and access for elderly patients through the Medicare program.     

Evolution of the mitochondrial ATPase 6 gene in Drosophila: unusually high level of polymorphism in D. melanogaster

We have determined 1990 bp mitochondrial DNA sequence which extends from 3' end of the cytochrome oxidase subunit I (COI) gene to 5' end of the COIII gene from two sibling species of Drosophila, D. simulans and D. mauritiana. Analyses of the sequences and part of the NADH dehydrogenase subunit 2 gene and the COI gene together with those from D. melanogaster and D. yakuba revealed that amino-acid substitution rate of the ATPase 6 gene seems to be higher in some strains of D. melanogaster than in the other species. High level of amino-acid polymorphism in this gene was observed in D. melanogaster. Synonymous substitution rate is relatively constant in all the genes examined, suggesting that mutation rate is not higher in the ATPase 6 gene of D. melanogaster. The amino-acid substitutions found specifically in D. melanogaster are at the sites which are not conserved among mammals, yeast and E. coli. These sites of the ATPase 6 gene might lose the selective constraint in D. melanogaster, and the amino-acid substitutions can be explained by neutral mutations and random genetic drift.     

Approach and avoidance strength during goal attainment: regulatory focus and the "goal looms larger" effect

Three studies tested the hypothesis that regulatory focus, both as a chronic person variable and as a manipulated situational variable, differentially affects the strength of participants' approach and avoidance strategic motivations as they get closer to the goal. In 2 studies, flexion and extension arm pressure were used as on-line measures of approach and avoidance intensity, respectively. As predicted, the approach gradient was steeper for participants with a promotion focus on aspirations and gains than for participants with a prevention focus on responsibilities and nonlosses, whereas the reverse was true for the avoidance gradient. In a third study, the same pattern of results was found on a persistence measure of motivational strength. Participants with a promotion focus worked longer on anagrams closer to the goal when they were approach means for goal attainment than when they were avoidance means, whereas the reverse was true for participants with a prevention focus.     

Maintenance of remission of ulcerative colitis: a comparison between balsalazide 3 g daily and mesalazine 1.2 g daily over 12 months. ABACUS Investigator group

BACKGROUND: Despite widespread use of aminosalicylates as maintenance treatment for ulcerative colitis (UC), patients still report troublesome symptoms, often nocturnally. AIM: To compare the efficacy and safety of balsalazide (Colazide) with mesalazine (Asacol) in maintaining UC remission. METHODS: A randomized, double-blind comparison of balsalazide 3 g daily (1.04 g 5-ASA) and mesalazine 1.2 g daily for 12 months, in 99 (95 evaluable) patients in UC remission. RESULTS: Balsalazide patients experienced more asymptomatic nights (90% vs. 77%, P=0.0011) and days (58% vs. 50%, N.S.) during the first 3 months. Balsalazide patients experienced more symptom-free nights per week (6.4+/-1.7 vs. 4.7+/-2.8; P=0.0006) and fewer nights per week with blood on their stools or on the toilet paper, mucus with their stools or with sleep disturbance resulting from symptoms or lavatory visits (each P < 0.05). Fewer balsalazide patients relapsed within 3 months (10% vs. 28%; P=0.0354). Remission at 12 months was 58%, in both groups. Similar proportions of patients reported adverse events (61% balsalazide vs. 65% mesalazine). There were five serious adverse events (two balsalazide, three mesalazine) and four withdrawals due to unacceptable adverse events (three balsalazide, one mesalazine), of which one in each group was also a serious adverse event. CONCLUSIONS: Balsalazide 3 g/day and mesalazine 1.2 g/ day effectively maintain UC remission and are equally well tolerated over 12 months. At this dose balsalazide prevents more relapses during the first 3 months of treatment and controls nocturnal symptoms more effectively.