Insulin resistance in Cushing's syndrome

Insulin resistance is well established in Cushing's syndrome, but its mechanisms are not completely understood. We performed the euglycemic insulin clamp technique on four patients with Cushing's syndrome, five obese patients and five normal volunteers, in order to determine the role of impairments in insulin responsiveness and insulin clearance in hypercorticism and obesity. Insulin was infused at 0.3, 1, 3 and 10 mU/kg/min, and steady-state glucose-infusion rates required to maintain euglycemia were determined. Glucose disposal at maximal insulin levels was 11.9 +/- 0.4 mg/kg/min in normals, with a 29% decrease in obese and a 42% decrease in Cushing's syndrome patients. Half maximally effective insulin concentrations were increased in both abnormal groups compared to normals. Maximal insulin clearance rates were 1460 +/- 200 ml/min/m2 in normals, not significantly changed in obese and 40% decreased in Cushing's syndrome patients. These results indicate that the insulin resistance in Cushing's syndrome is distinct from that occurring in obesity and is characterized by both decreased insulin responsiveness and decreased insulin clearance. These impairments could be caused by a common defect which may be at or distal to the glucose transport level.     

Priming immunization against cholera toxin and E. coli heat-labile toxin by a cholera toxin short peptide-beta-galactosidase hybrid synthesized in E. coli.

A synthetic oligodeoxynucleotide encoding for a small peptide was employed for the expression of this peptide in a form suitable for immunization. The encoded peptide, namely, the region 50-64 of the B subunit of cholera toxin (CTP3), had previously been identified as a relevant epitope of cholera toxin. Thus, multiple immunizations with its conjugate to a protein carrier led to an efficient neutralizing response against native cholera toxin. Immunization with the resulting fusion protein of CTP3 and beta-galactosidase, followed by a booster injection of a sub-immunizing amount (1 microgram) of cholera toxin, led to a substantial level of neutralizing antibodies against both cholera toxin and the heat-labile toxin of Escherichia coli.     

Stationary underwater prey missed by reef herons,Egretta gularis: head position and light refraction at the moment of strike

Summary This paper attempts to verify the importance of spatial positioning of the eyes of reef heronsEgretta gularis schistacea, when coping with light refraction at the air-water interface. The herons' striking of prey, while their approach angle was restricted, was observed. (a) The herons' capture success in the restricted situation was markedly lower than in the unrestricted situation. (b) The points of strike (STR) in unsuccessful strikes differed from those of successful strikes, and from those of the unrestricted situation. (c) The larger the difference between the observed and the predicted ratio of prey depth to apparent prey depth, the higher the probability of missing a prey. These results support predictions of a model presented elsewhere (Katzir and Intrator 1987) that a heron will attempt to reach spatial positions at which prey's real depth and apparent depth are linearly correlated.     

Effect of an acute bout of exercise on glucose disposal in human obesity

The effect of acute exercise on insulin action has been studied in six obese (150-250% ideal body weight) non-insulin-dependent diabetics (OD), seven obese normoglycemics (ON), and six lean healthy controls (LC). Using a three-stage euglycemic clamp, the metabolic clearance rate (MCR) of glucose under increasing insulin concentrations was measured. The insulin dose-response curve was assessed on two separate occasions: 1) a base-line test and 2) 1 h after aerobic treadmill exercise at a steady-state heart rate of 150-160 beats/min. In the base-line test, under all insulin levels, glucose MCR was significantly lower in obese compared with lean individuals (P less than 0.01). Exercise increased glucose MCR at the highest hormonal concentrations applied to 124 and 134% of base line in OD and in ON, respectively (P less than 0.05); the insulin concentration required for one-half of the maximal clearance rate of glucose achieved in this study decreased from 200 to 130 and from 160 to 95 microU/ml in OD and ON, respectively (P less than 0.05). The changes in these parameters were insignificant in LC. It is suggested that acute exercise affected the insulin dose-response curve in OD and in ON but not in LC; although enhanced by exercise, glucose MCR remained significantly lower in both obese groups compared with control subjects. We concluded that insulin resistance, which accompanies extreme obesity, could be markedly decreased but not completely reversed by one bout of exercise.     

Divergent pathways of photosynthetic electron transfer: The autonomous oxygenic and anoxygenic photosystems

The aim of this article is to assemble and integrate, from a personal perspective of a research participant, seldom examined evidence that is incompatible with some basic tenets of photosynthetic electron transport, the cornerstone of which is the Z scheme. The nonconforming evidence pertaining to the mode of ferredoxin reduction and the role of the copper redox protein, plastocyanin, indicates that contrary to the Z scheme ferredoxin is reduced in two experimentally distinguishable ways: oxygenically by PS II (renamed the oxygenic photosystem), without the participation of PS I, and anoxygenically by PS I (renamed the anoxygenic photosystem). It also indicates that plastocyanin is not only, as the Z scheme asserts, the electron donor to the reaction center chlorophyll of PS I (P700) but also to the reaction center chlorophyll of PS II (P680). Other unconventional findings include evidence that the fully functional oxygenic photosystem, when operating separately from the anoxygenic photosystem, reduces plastoquinone to plastoquinol and subsequently oxidizes plastoquinol by two pathways acting in concert: one being the universally recognized DBMIB-sensitive pathway via the Rieske iron-sulfur center of the cytochrome bf complex and the other, a hitherto unrecognized, DBMIB-insensitive electron transport pathway around P680 that centers on cytochrome b-559. These nonconforming findings form the basis of an alternate hypothesis of photosynthetic electron transport that modifies and complements the Z scheme.Abbreviations PS photosystem - PQ oxidized plastoquinone - PQH₂ reduced plastoquinone (plastoquinol) - Q_A and Q_B specialized membrane-bound forms of PQ - PC plastocyanin - Fd ferredoxin - BISC F_AF_B, membrane-bound iron-sulfur centers of PS I - DBM1B 2,5-dibromo-3-methyl-6-isopropyl-n-benzoquinone (dibromothymoquinone) - DNP-INT dinitrophenol ether of iodonitrothymol - NADP⁺ NADPH, oxidized and reduced forms of nicotinamide adenine dinucleotide phosphate - FCCP carbonylcyanide-p-trifluoromethoxyphenyl-hydrazone - CCCP carbonyl cyanide-3-chlorophenylhydrazone - SF 6847 2,6,-di-(t-butyl)-4-(2,2-dicyanovinyl) phenol - diuron (DCMU) 3-(3,4-dichlorophenyl)-1,1-dimethylurea - EPR electron paramagnetic resonance - DCIP 2,6-dichloro-phenolindophenol - UHDBT 5-(n-undecyl)-6-hydroxy-4-7-dioxobenzothiazole; cytochrome b-559_HP-cytochrome b-559_LP, high- and low potential states of cytochrome b-559 - oxygenic reductions reductions in which water is the electron donor - BBY PS II preparation made according to Berthold et al. (1981) Dedicated to Professor Achim Trebst on his 65th birthday.Based in part on lecture in Advanced Course on Trends in Photosynthesis Research, Palma de Mallorca, Spain, September 18, 1990.     

Immunochemical and biochemical investigation of hexosaminidase S.

Hexosaminidase S (HEX S), the residual isozyme found in tissues and body fluids of children with the O variant of GM2 gangliosidosis, was purified from tissues of variant individuals and biochemically and immunochemically characterized. This enzyme has an apparent molecular weight of 103,000 with an isoelectric point of 4.2, is heat labile to the same extent as HEX A, and loses most of its activity following heating for 30 min at 50 degrees C. HEX S reacts immunologically with the antisera against either HEX A or B, but the reaction is considerably stronger with the anti-A serum or with antibody preparations which react exclusively with the A isozyme. Results obtained by a radioimmunoassay using the various antisera indicated that there is no antigenically cross reacting material which lacks enzymatic activity in the variant tissues. These findings are in accord with a suggested molecular structure of two subunits, each composed of two alpha chains (alpha2 alpha2) for HEX S; it also implies that alpha and beta chains have some structural similarity which is manifested in antigenic cross-reactivity.