The course of development of glucose intolerance in the monkey (Macaca mulatta).

Longitudinal studies of the rhesus monkey reveal a syndrome of diabetes mellitus in those that become middle-aged and obese. The sequence of events in the development of the disease progresses from normoinsulinemia with normoglycemia through stages of hyperinsulinemia followed by below normal insulin levels with hyperglycemia and glycosuria. We believe the rhesus to be an excellent nonhuman primate model for maturity-onset diabetes in humans.     

Some comparisons of cellulases from two different strains of aspergillus fumigatus

Michaelis-Menten kinetics for exoglucanase, endoglucanase and β-glucosidase activities from two different strains of Aspergillus fumigatus were compared in the absence and the presence of ammonium ions. Inhibitory effects, evident in only one strain, were quantified, suggesting non-competitive inhibition for endoglucanase and β-glucosidase, but competitive inhibition of exocellulase. Possible reasons are discussed.     

Preparation of scirpentriol and triacetoxyscirpenol in good yield from cultures of Fusarium sambucinum NRRL 13495

Crude extracts of filtrates of cultures of Fusarium sambucinum NRRL 13495 were acetylated or hydrolyzed. After chromatography on cartridge columns of silica gel and recrystallization three times from mixtures of ethyl acetate and hexane, 3,4,15-triacetoxyscirpenol (435 +/- 10 mg/liter of filtrate; mean +/- standard error [n = 3]) and the parent alcohol scirpentriol were isolated (261 +/- 29 mg/liter of filtrate; mean +/- standard error [n = 3]) in 68 and 53% yield for a 130- and 14-fold improvement, respectively, over prior reports.     

Influence of platelet-activating factor on leukotriene D4-induced contractions of the guinea pig parenchymal strip

Platelet-activating factor (PAF) and sulphidopeptide leukotrienes, such as leukotriene D4 (LTD4), are potent constrictors that are probably released simultaneously in a variety of inflammatory respiratory events. The purpose of the present study was to determine whether LTD4-induced contractions of guinea pig parenchymal lung strips (GPPS) are modified in the presence of PAF. The contractile responses of isolated GPPS to cumulative doses of LTD4, acetylcholine, histamine, and potassium chloride in the presence of PAF (0.1 nM, 0.1 microM) were compared with parallel controls. There was no significant alteration of the response to acetylcholine and potassium chloride and the PAF-induced inhibition of the response to histamine, although significant, was not concentration dependent. In contrast, PAF in a concentration range from 0.1 nM to 1.0 microM caused a marked, concentration-dependent reduction of LTD4-induced contractions. Pretreatment with the PAF receptor antagonist, BN52021, prevented the attenuation of LTD4-induced contraction by PAF. The attenuation of LTD4-induced contraction by PAF was also prevented by pretreatment with indomethacin or with the thromboxane synthase inhibitor U63,557A, but not by pretreatment with the lipoxygenase inhibitors BW755c or nordihydroguaiaretic acid. Thus inhibition of LTD4-induced GPPS contraction by PAF is receptor dependent and probably secondary to thromboxane generation. The respiratory smooth muscle response to leukotrienes may be modified significantly by concomitant PAF release.     

Characteristics of the upper airway pressure-flow relationship during sleep

In examining the mechanical properties of the respiratory system during sleep in healthy humans, we observed that the inspiratory pressure-flow relationship of the upper airway was often flow limited and too curvilinear to be predicted by the Rohrer equation. The purposes of this study were 1) to describe a mathematical model that would better define the inspiratory pressure-flow relationship of the upper airway during sleep and 2) to identify the segment of airway responsible for the sleep-related flow limitation. We measured nasal and total supralaryngeal pressure and flow during wakefulness and stage 2 sleep in five healthy male subjects lying supine. A right rectangular hyperbolic equation, V = (alpha P)/(beta + P), where V is flow, P is pressure, alpha is an asymptote for peak flow, and beta is pressure at a flow of alpha/2, was used in its linear form, P/V = (beta/alpha) + (P/alpha). The goodness of fit of the new equation was compared with that for the linearized Rohrer equation P/V = K1 + K2V. During wakefulness the fit of the hyperbolic equation to the actual pressure-flow data was equivalent to or significantly better than that for the Rohrer equation. During sleep the fit of the hyperbolic equation was superior to that for the Rohrer equation. For the whole supralaryngeal airway during sleep, the correlation coefficient for the hyperbolic equation was 0.90 +/- 0.50, and for the Rohrer equation it was 0.49 +/- 0.25. The flow-limiting segment was located within the pharyngeal airway, not in the nose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contractile and calcium regulating capacities of myocardia of different sized mammals scale with resting heart rate

The purpose of this study was to determine if selected biochemical parameters representing the contractile and calcium regulating systems of cardiac muscle scaled among mammals having inherently different resting heart rates (RHR). Eight mammalian species with RHR ranging from 51 to 475 beats per minute (bpm) were studied.The oxidative capacity of the myocardium is highly correlated with the RHR. The hypothesis of the present study was that the capacities of the energy utilizing processes of contraction and calcium regulation would also be correlated to the functional demand imposed on the muscle as represented by the RHR.Myosin (M) and myofibrillar (MF) ATPase activities, myosin isoenzyme distribution and sarcoplasmic reticulum (SR) ATPase activity were determined. Animals with RHR above 300 bpm express V₁ myosin while animals with lower RHR express primarily V₃. M and MF ATPase activities correlated with RHR, but the major difference in activities occurred at the threshold RHR of about 300 bpm at which the switch from V₃ to V₁ appears to occur. SR ATPase activity per mg of microsomal protein was for the most part constant among different mammals, but the SR ATPase activity per g of heart tissue was significantly correlated with RHR as slower beating hearts tended to yield less SR protein per unit mass.We conclude that both the contractile and calcium regulating systems are scaled to the functional parameter of RHR among different mammals. The contractile system uses a slow myosin ATPase isoform at low resting heart rates whereas above the postulated threshold RHR of about 300 bpm a switch in gene expression to a fast myosin ATPase isoform occurs. For the calcium regulating system, the heart does not seem to have the choice of altering the quality of the SR ATPase isoform and thus calcium regulating capacity is set by alterations in the quantity of SR per unit of heart mass.     

Interferon-gamma modulates protein kinase C activity in murine peritoneal macrophages

The content of Ca2+-, phospholipid-dependent protein kinase activity (protein kinase C) in murine peritoneal macrophages treated with recombinant interferon-gamma (IFN-gamma) has been investigated. Protein kinase C activity was solubilized by nonionic detergent extraction of sonicated cells and separated by high performance liquid chromatography on a TSK 4000 SW gel filtration column. The enzyme eluted from the column in a molecular weight range of 60-80 X 10(3) and was identified by virtue of Ca2+ and phospholipid requirements. Macrophages treated with recombinant IFN-gamma exhibited a substantial increase in total protein kinase activity which could be accounted for entirely by increased protein kinase C activity. This activity was enhanced as much as 5-fold over that seen in untreated macrophages and was specific for IFN-gamma in that other agents known to signal changes in macrophage function had no effect. The time required for the elevation of kinase activity was identical to that required for induction of other functions by IFN-gamma in macrophages. These observations suggest that protein kinase C may be a focus of regulatory action in IFN-gamma-mediated macrophage activation.