Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice

Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumablyApoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus.     

Regional ventilation in statically and dynamically hyperinflated dogs

Hubmayr, Rolf D., and Susan S. Margulies. Regionalventilation in statically and dynamically hyperinflated dogs.J. Appl. Physiol. 81(4):1815-1821, 1996.Using the parenchymal marker technique innormal anesthetized dogs, we compared the dynamics of regional lungexpansion between two ventilation strategies designed to increase meanthoracic volume. Dynamic hyperinflation (DH) was produced byventilating the lungs at a rate of 50 breaths/min and with a duty cycleof 0.5. Static hyperinflation (SH) was produced throughthe application of extrinsic positive end-expiratory pressure while thelungs were ventilated at a rate of 15 breaths/min and with a duty cycleof 0.15. Regional tidal volume(VT,r), regional functionalresidual volume, and the time delay between regional expansion and the flow signal at the common airway were computed for upto 100 regions/lobe in 5 animals. Ventilation strategy had no effect onthe overall variance of VT,rwithin lobes. Although the VT,rmeasured during SH correlated withVT,r measured during DH, theaverage correlation coefficient was only 0.69. Ventilation rate-relateddifferences in VT,r and regionalfunctional residual capacity varied with the regional time delay inways qualitatively consistent with parallel inhomogeneity of unit timeconstants. However, a large component of frequency-dependent behaviorremains unexplained by established mechanisms. We conclude that DH and SH should not be considered equivalent lung unit recruitmentstrategies.

     

Insulin-like growth factor I levels decrease in the development of diabetes inMacaca nigra

Members of the monkey speciesMacaca nigra spontaneously develop impairments in insulin secretion and glucose clearance, and eventually become overtly diabetic. Changes in certain metabolic signals such as clearance of glucose and insulin increment secreted in an intravenous glucose tolerance test have allowed the identification of four stages in the progression from non-diabetes to diabetes in monkeys — non-diabetic, hormonally impaired, borderline diabetic, and diabetic. Recently, another metabolic stage, hyperinsulinemic, was also identified in these animals. In recent years, other factors besides those listed above have been implicated to be correlated with the metabolic progression from a nondiabetic to a diabetic state. One of these factors, is insulin like growth factor I (IGF-I). In diabetic humans who are in poor metabolic control, and in rats with streptozotocin induced ketotic diabetes, serum levels of IGF-I are lowered by as much as 40–50% of control non-diabetics. If indeed decreased IGF-I levels are correlated with the onset of diabetes then changes in IGF-I concentrations prior to the clinically diagnosed disease state would be expected. Using serum samples collected from different animals in a colony ofMacaca nigra in a variety of metabolic states, we have found that IGF-I and insulin levels decrease in each defined metabolic state as the animals progress from nondiabetic to diabetic. Since IGF-I and insulin levels decrease in a similar fashion in the progression of this disease then this maybe indicative of the coordinate expression of these two factors.     

Construct Validity of the Impact of Weight on Quality of Life Questionnaire

KOLOTKIN, RONETTE L, SUSAN HEAD, ALAN BROOKHART. Construct validity of the Impact of Weight on Quality of Life questionnaire. The Impact of Weight on Quality of Life questionnaire (IWQOL) is a 74-item self-report, condition-specific instrument that (1) assesses the effect of weight on quality of life in eight key areas, and (2) may be used as a treatment outcome measure and/or an evaluation tool for healthcare policy makers and third-party payers. This study explores IWQOL construct validity and provides new information on internal consistency, treatment effects, and differences between men and women. IWQOL total scores correlated highly with other measures of overall quality of life, and subscale scores correlated well with counterparts in the assessment battery. Internal consistency estimates for the IWQOL scales generally were high. For the women, 4-week participants, and the total sample, pretreatment-posttreatment differences were significant for all IWQOL scales and total score. For men, treatment differences were significant for the total score and all subscales except for Work and Mobility. Treatment differences for 2-week participants were significant for all scales except for Work. Consistent with previous IWQOL study results, the Comfort With Food scale scores reflected more discomfort at posttreatment as compared with pretreatment. The IWQOL, already translated into French and Italian, currently is demonstrating clinical and research utility as a quality-of-life outcome measure for clinical trials of antiobesity drugs and surgical treatments for patients with obesity.     

Effects of vigorous exercise training and beta -agonist administration on bone response to hindlimb suspension

Bloomfield, Susan A., Beverly E. Girten, and Steven E. Weisbrode. Effects of vigorous exercise training and -agonist administration on bone response to hindlimb suspension.J. Appl. Physiol. 83(1):172-178, 1997.The effectiveness of dobutamine (Dob) inpreventing bone loss during 14 days of hindlimb suspension (Sus) wastested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats(age 155 days). One-half of each group was given Dob (2 mg · kg¹ · day¹)or saline (Sal). Histomorphometric measurements at midfemur revealed a17% smaller cortical bone area (CBA) and a 32% lower periostealmineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Salrats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similarbut nonsignificant effects on cross-sectional moment of inertia wereobserved. Nonsuspended Ex rats had no change in bone CBA when CBA isindexed to body weight. Sus appeared to uncouple the relationshipbetween soleus weight and CBA. Dob attenuated the 43% decline insoleus weight after Sus in Ex but not in Sed rats. In summary, vigorousEx before Sus does not affect loss of bone mass due to unloading; Dobeffectively maintains CBA in Sed rats subjected to suspension.

     

Mycoplasma pneumoniae Pneumonia—Experience at a Referral Center

Mycoplasma pneumoniae pneumonia is usually a benign illness, and respiratory complications and extrapulmonary manifestations occur rarely. In this series, patients admitted to a referral hospital with this disorder had unusual symptoms, signs and findings on chest roentgenograms and laboratory studies. Pneumonia was often severe and extrapulmonary manifestations were frequent, resulting in prolonged hospital stays and illnesses. Although this extreme end of the spectrum of disease caused by M pneumoniae is not representative of this type of pneumonia as seen in outpatients, it is important to realize that patients admitted to hospital with severe, complicated pneumonia frequently have unusual manifestations of a common disease.     

Discrimination by male ring-tailed Lemurs (Lemur catta) between the scent marks of male and those of female conspecifics

Olfaction plays an important role in the social communication of all prosimians. (The experiment reported in this paper forms part of an intensive chemobehavioral study of olfaction in Lemur catta (ring-tailed lemur) being carried out in this laboratory.) Five male Lemur cattawere tested on their behavioral responses to paired scent stimuli. Responses measured were (1) total investigation time, (2) arm-marking, (3) ABO/BO rubbing, and (4) flehmen. Males showed a strong discrimination between the scent stimuli,giving higher levels of response to female scent on measures 1, 3, and 4. This response suggests an olfactory-related preference by males for female scent under controlled conditions. This preference may be a consequence of the females’ dominance over males and the brevity of estrus in L. catta,both of which would favor such choice behavior.     

The effect of renal vasodilation and hypotonic volume expansion on water excretion in dogs after anesthesia and surgery

The possible effects of renal vasoconstriction from anesthesia and surgery on water excretion after hypotonic volume expansion (HVE) were studied in 18 well conditioned anesthetized dogs, with and without the infusion of phenoxybenzamine and acetylcholine into the renal artery of the cannulated kidney. In 6 dogs (Group 1 - Control) whose renal artery was infused with isosmotic saline, HVE resulted in a bilateral increase in GFR and UV (p < .05). ERPF, Cosm, C_H2O, U_NaV, U_KV, RBF, RVR and MAP did not change significantly. In 6 other dogs (Group 2), whose cannulated kidney was infused with phenoxybenzamine 50 μg/min before and during HVE, GFR increased on the infused side while CH₂O and UV increased bilaterally (p < .05). ERPF, Cosm, U_NaV, U_KV, RBF, RVR and MAP were not affected significantly. The addition of ADH, 2 mu/min into the phenoxybenzamine infusate, decreased ERPF, RBF and RVR bilaterally and CH₂O on the infused side (p < .05). It had no effect upon GFR, Cosm, U_NaV, U_KV and MAP. In another 6 dogs, (Group 3), whose cannulated renal artery was infused with acetylcholine (20 μg/min) before and during HVE, C_H2O, UV and RVR increased bilaterally (p < .05). ERPF and RBF decreased bilaterally (p < .05), whereas GFR, Cosm, U_NaV and MAP were unaffected. U_KV decreased on the infused side (p < .05). The addition of ADH (2 mu/min)_into the acetylcholine infusate, decreased C_H2O bilaterally and increased Cosm and U_KV on the control side (p < .05). It had no effect on ERPF, GFR, UV, U_NaV, RBF, RVR and MAP. These observations suggest that anesthesia and surgery produce renal vasoconstriction and this together with increased ADH release, interfere with water excretion by the kidney. Previous renal vasodilation prevents these influences of anesthesia and surgery.