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Biomedical subjects

D E Larson

Publications and source records attributed to D E Larson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Do obese eat faster than lean subjects? Food intake studies in Pima Indian men.

Food intake rate has previously been derived from observation of eating behavior in laboratory settings or in public eating establishments. Although it has been suggested that obese individuals eat faster than lean individuals, observations of such an "obese eating style" have yielded mixed results. In the present study, the relationship between ad-libitum food intake rate and obesity was evaluated over 4 days on a metabolic ward in 28 healthy Pima Indian men (Mean +/- SD; 29 +/- 7 y, 100.4 +/- 27.1 kg, 33 +/- 10% body fat) using an automated food selection system containing a large variety of foods. Total energy intake averaged 18829 +/- 3299 kJ/d consisting of 47 +/- 4, 40 +/- 3, and 13 +/- 1 percent of carbohydrate, fat and protein, respectively. The average meal duration was 25 +/- 7 min. Food intake rate was 68 +/- 21 g/min while carbohydrate, fat and protein intake rates were 23 +/- 6, 9 +/- 3 and 6 +/- 2 g/min, respectively. Food intake rate correlated negatively with % body fat (r = -0.61, P < 0.01). Similar relationships were found between the intake rates of carbohydrate, fat and protein and body fatness. Only prospective studies will indicate whether a slow food intake rate may contribute to the etiology of obesity by possibly reducing satiety.

Adult↗
PubMed1994

Body fat distribution and energy metabolism in obese men and women.

OBJECTIVE: Upper body obesity seems to be associated with a better prognosis for weight loss than does lower body obesity. However, the impact of body fat distribution on energy metabolism is not clear. SUBJECTS: One hundred fifteen non-diabetic obese Caucasians (64 males and 51 females) and 108 Caucasian lean controls (82 males and 26 females) were studied. METHODS: Body composition was assessed by hydrodensitometry and body fat distribution was estimated by the waist-to-thigh circumference ratio (W/T). Values of 24-hour energy expenditure (24h-EE), basal metabolic rate (BMR), sleeping metabolic rate (SMR) and respiratory quotient (RQ) were measured in a respiration chamber. RESULTS: BMR, adjusted for differences in fat-free mass, fat mass, age and sex, correlated with W/T in obese males (r = 0.40; p < 0.01), but not in obese females. Obese male subjects with upper body obesity had BMR significantly higher than those with lower body obesity (2189 +/- 268 vs 1974 +/- 141 kcal/day; p < 0.01), independently of differences in fat-free mass, fat mass and age. No correlations were found between W/T and adjusted 24h-EE, SMR or RQ in all examined groups. CONCLUSION: These findings indicate that in obese males, upper body obesity is associated with increased metabolic rate, possibly related to higher levels of lipid turnover in visceral fat.

Adipose Tissue↗
PubMed1994

Relationship between sleep stages and metabolic rate in humans.

Differences in sleeping metabolic rate (SMR) among subjects may be related to different levels of energy expenditure associated with sleep stages. The relationship between energy expenditure and sleep stages was investigated overnight in 29 subjects (14 Caucasians and 15 Pima Indians, 18 males and 11 females; mean +/- SD, 31 +/- 7 yr, 83 +/- 26 kg, 27 +/- 11% fat). Sleep stages were determined by electroencephalogram recording, whereas energy expenditure was measured in a 1,000-liter Plexiglas sleep box constructed around a bed as a fast-response open-circuit indirect calorimeter. Eighty-five percent of the interindividual variability in SMR was explained by differences in fat-free mass, fat mass, age, sex, and race (r2 = 0.85). The intra-individual variance in SMR over time was related to sleep stages and to clock time. Within subjects, SMR in stage 3 was significantly lower than in stage 2 (-39 +/- 18 kcal/day; P < 0.05) and rapid eye movement sleep (-51 +/- 23 kcal/day; P < 0.05). Also, sleep stages were associated with different respiratory quotients. Because sleep stages are associated with only small differences in energy metabolism, our results suggest that sleep stages play a minor role in the variance of SMR among subjects. However, the duration of sleep may contribute to the variability of 24-h energy expenditure.

Adult↗
PubMed1994

Dietary effects on exercising muscle metabolism and performance by 31P-MRS.

To determine how diet modulates short-term exercise capacity, skeletal muscle pH and bioenergetic state were examined by 31P-magnetic resonance spectroscopy in nine healthy volunteers. Subjects performed incremental quadriceps exercise to exhaustion after 5 days of high-carbohydrate (HCHO) or high-fat (HFAT) diet randomly assigned in crossover fashion and separated by a 2.5-day period of ad libitum mixed diet. Simultaneous measurements were made of pulmonary gas exchange, minute ventilation, and quadriceps muscle pH and phosphorylation potential. At rest and peak exercise, respiratory exchange ratio and minute ventilation were higher after HCHO than after HFAT (P < 0.05), reflecting greater CHO utilization. Peak O2 consumption (VO2) was not increased after HCHO (P > 0.05), but exercise duration was (339 +/- 34 s for HCHO vs. 308 +/- 25 s for HFAT; P < 0.05). HCHO was associated with a blunted early fall of phosphocreatine (PCr)/Pi vs. VO2 (-4.1 +/- 0.7 x 10(-2) min/ml for HCHO vs. -5.6 +/- 1.2 x 10(-2) min/ml for HFAT; P < 0.05). On both study days, the slope of PCr/Pi vs. VO2, before and after the PCr threshold, was correlated with exercise time. The results suggest that a diet rich in CHO improves exercise efficiency through beneficial effects on intracellular phosphorylation potential.

Adult↗
PubMed1993

Repression of histone gene transcription in quiescent 3T6 fibroblasts.

Maintaining murine 3T6 fibroblasts in serum-depleted medium for a period of three days results in a resting cell population that does not synthesize DNA. Histone mRNA levels, closely tied to the cell-proliferation rate, are low due to a reduced rate of synthesis. A comparison of histone gene transcription in vitro by nuclear extracts of quiescent or proliferative 3T6 cells showed that a 200-bp segment of the promoter was responsible for repressing gene activity when cells were in a G0 state. In the absence of the distal promoter region (-200 to -400), gene transcription remained high in quiescent cells, indicating the proximal promoter region (+1 to -200) was responsible for basal gene activity. Alterations in protein binding to the distal promoter region correlated with histone H4 gene activity, suggesting that repression of histone gene transcription is linked to the attachment of a specific nuclear protein. During G1, the histone H4 gene was efficiently transcribed in vitro, but an inability to process the histone pre-mRNA limited the cellular content of mature histone mRNA. This distinction between transcriptional (in G0) and post-transcriptional (in G1) mechanisms for modulating histone mRNA levels suggests that gene-regulatory factors are specifically activated in quiescent cells to reduce expression of non-essential genes.

Animals↗
PubMed1993

Coordinated decreases in rRNA gene transcription factors and rRNA synthesis during muscle cell differentiation.

rRNA synthesis decreases significantly during the differentiation of rat L6 myoblasts to myotubes. Nuclear run-on assays demonstrated that the decrease was attributable to decreased rates of rRNA gene transcription. Immunoblot analysis indicated a marked reduction in amounts of the RNA polymerase I transcription factors UBF1 and UBF2 (upstream binding factors 1 and 2, respectively). The levels of these factors dropped in parallel with the down-shift in rRNA gene transcription. The amount of UBF does not fall due to a general decrease in cellular protein, as myosin heavy-chain protein accumulates markedly during this same time. RNA blots of total RNA isolated from myoblasts and differentiating myotubes showed a decrease in the mRNA for UBF, at the same time the mRNA for myogenin was accumulating. The down-shift in UBF mRNA levels preceded the decrease in the protein levels for UBF. There have been reports that the acute response of the rRNA gene transcription system to physiological signals in many systems involves an RNA polymerase I-associated factor. However, our results imply that the regulation of rRNA gene DNA transcription in response to physiological processes, such as differentiation, may involve multiple regulatory pathways.

Adenosine Triphosphate↗
PubMed1993

Dexamethasone stimulates rRNA gene transcription in rat myoblasts.

The glucocorticoid analogue, dexamethasone, stimulated RNA synthesis more than two-fold in rat L6 myoblasts, without affecting the rate of cell proliferation. Treatment of myoblasts for 24 h with 10(-7) M dexamethasone resulted in a 30% increase in the cellular RNA level. More than a two-fold stimulation of pre-rRNA gene transcription by dexamethasone, as measured in isolated nuclei and by cell-free transcription, was accompanied by a corresponding increase in pre-rRNA levels. Co-incubation of myoblasts with cycloheximide and dexamethasone did not affect the enhanced pre-rRNA gene transcription demonstrating that de novo protein synthesis was unnecessary to manifest the dexamethasone effect on rDNA transcription. Support for this conclusion is provided by the finding that the levels of UBF1 and UBF2, rDNA upstream binding transcription factors, remain unchanged. The glucocorticoid antagonist RU38486 [11 beta-(4-dimethylaminophenyl)17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra- 4,9-dien-3-one] inhibited the dexamethasone-stimulated rRNA gene transcription suggesting that the glucocorticoid receptor is involved in the response mechanism.

Animals↗
PubMed1993

High-volume postobstructive choleresis after transhepatic external biliary drainage resolves with conversion to internal drainage.

We report high-volume postobstructive choleresis in two patients who underwent transhepatic external drainage for malignant biliary obstruction. Excessive loss of bicarbonate-rich biliary fluid (up to 6.5 L/day) caused orthostatic hypotension, prerenal insufficiency, hyponatremia, and a decrease in serum bicarbonate. Therapy with isotonic fluids containing sodium, chloride, lactate, bicarbonate, and potassium was based on measurement of biliary fluid volume and electrolyte concentrations. Biliary fluid loss was terminated by conversion to internal biliary drainage. The reason for this rare complication of external drainage of biliary obstruction is unknown, but such patients must be closely monitored for volume loss. When high-volume choleresis occurs, biliary fluid and electrolyte losses should be precisely measured and replaced, and external biliary drainage converted to internal drainage.

Adenocarcinoma↗
PubMed1993

Relationship between skeletal muscle lipoprotein lipase activity and 24-hour macronutrient oxidation.

A low ratio of whole-body 24-h fat/carbohydrate (CHO) oxidation has been shown to be a predictor of subsequent body weight gain. We tested the hypothesis that the variability of this ratio may be related to differences in skeletal muscle metabolism. Since lipoprotein lipase (LPL) plays a pivotal role in partitioning lipoprotein-borne triglycerides to adipose (storage) and skeletal muscle (mostly oxidation), we postulated that a low ratio of fat/CHO oxidation was associated with a low skeletal muscle LPL (SMLPL) activity. As an index of substrate oxidation, 24-h RQ was measured under sedentary and eucaloric conditions in 16 healthy nondiabetic Pima males. During a 6-h euglycemic, hyperinsulinemic clamp, muscle biopsies were obtained at baseline, 3, and 6 h. Heparin-elutable SMLPL activity was 2.92 +/- 0.56 nmol free fatty acids/g.min (mean +/- SD) at baseline, was unchanged (2.91 +/- 0.51) at the third hour, and increased significantly (P < 0.05) to 3.13 +/- 0.57 at the sixth hour of the clamp. The mean (of baseline and 3-h) SMLPL activity correlated inversely with 24-h RQ (r = 0.57, P < 0.03) but not with body size, body composition, or insulin-mediated glucose uptake. Since SMLPL activity is related to the ratio of whole body fat/CHO oxidation rate, a decreased muscle LPL activity may, therefore, predispose to obesity.

Carbohydrate Metabolism↗
PubMed1993

Reduced sympathetic nervous activity. A potential mechanism predisposing to body weight gain.

The sympathetic nervous system is recognized to play a role in the etiology of animal and possibly human obesity through its impact on energy expenditure and/or food intake. We, therefore, measured fasting muscle sympathetic nerve activity (MSNA) in the peroneal nerve and its relationship with energy expenditure and body composition in 25 relatively lean Pima Indian males (means +/- SD; 26 +/- 6 yr, 82 +/- 19 kg, 28 +/- 10% body fat) and 19 Caucasian males (29 +/- 5 yr, 81 +/- 13 kg, 24 +/- 9% body fat). 24-h energy expenditure, sleeping metabolic rate, and resting metabolic rate were measured in a respiratory chamber, whereas body composition was estimated by hydrodensitometry. Pima Indians had lower MSNA than Caucasians (23 +/- 6 vs 33 +/- 10 bursts/min, P = 0.0007). MSNA was significantly related to percent body fat in Caucasians (r = 0.55, P = 0.01) but not in Pimas. MSNA also correlated with energy expenditure adjusted for fat-free mass, fat mass, and age in Caucasians (r = 0.51, P = 0.03; r = 0.54, P = 0.02; and r = 0.53, P = 0.02 for adjusted 24-h energy expenditure, sleeping metabolic rate, and resting metabolic rate, respectively) but not in Pima Indians. In conclusion, the activity of the sympathetic nervous system is a determinant of energy expenditure in Caucasians. Individuals with low resting MSNA may be at risk for body weight gain resulting from a lower metabolic rate. A low resting MSNA and the lack of impact of MSNA on metabolic rate might play a role in the etiology of obesity in Pima Indians.

Adult↗
PubMed1993

Energy cost of arousal: effect of sex, race and obesity.

The basal (BMR) to sleeping metabolic rate (SMR) ratio might represent an estimate of the activation of the nervous system (central/sympathetic) from sleeping to basal state. Since this activation might be influenced by the degree of obesity, and might be different between sexes, we retrospectively analysed energy expenditure data collected for a large number of subjects. Twenty-four hour energy expenditure (24EE), BMR and SMR were measured in a respiratory chamber in 122 Caucasians (63 males/59 females, 32 +/- 10 years, 94 +/- 33 kg, 29 +/- 11% fat) (means +/- s.d.) and in 123 Pima Indians (68 males/55 females, 29 +/- 7 years, 100 +/- 25 kg, 34 +/- 9% fat). The BMR/SMR ratio varied greatly between individuals (1.05 +/- 0.08; range 0.87-1.34). In Pima Indians, BMR/SMR was inversely correlated to both fat mass (r = -0.26; P < 0.01) and BMI (r = -0.22; P < 0.05), whereas, in Caucasians, BMR/SMR was inversely correlated to waist/thigh circumference ratio (r = -0.28; P < 0.01). On average, the BMR/SMR was higher in Pima Indians than in Caucasians (1.06 +/- 0.08 vs. 1.03 +/- 0.07, P < 0.01) and higher in Pima Indian males than in Pima Indian females (1.08 +/- 0.09 vs. 1.04 +/- 0.06, P < 0.05). Studies are needed to investigate whether these differences in the increase in energy expenditure from the sleeping to the basal state are related to differences in the activation of the nervous system and/or to other metabolic factors.

Adolescent↗
PubMed1992

Histone H4 mRNA levels are down-regulated by 3' RNA processing during terminal differentiation of myoblasts.

The capacity for 3' processing of the histone H4 pre-mRNA is lost following differentiation of rat L6 myoblasts to myotubes. Nuclear extracts prepared from proliferating myoblasts, but not differentiated myotubes, actively process histone H4 pre-mRNA in vitro. The activity of two factors required for 3' processing, the heat-labile factor and U7 snRNP, also changes during the differentiation period, concurrent with the loss of 3' processing activity. During myotube formation, the activity of the heat-labile factor decreases significantly while the 5' sequences of the U7 snRNA become progressively resistant to micrococcal nuclease digestion. Thus, the dramatic down-shift in histone H4 mRNA levels which occurs during myoblast differentiation is controlled at both the transcriptional and posttranscriptional level.

Animals↗
PubMed1992

Regulation of U3 snRNA expression during myoblast differentiation.

Differentiation of proliferating rat L6 myoblasts to syncytial multinucleated myotubes results in a significant downshift in the rate of U3 snRNA gene transcription, paralleling the decrease in rRNA synthesis previously documented. Coordinate production of U3 snRNA and rRNA during the differentiation process adds further support for a role of U3 snRNA in ribosome biogenesis. Despite the dramatic decrease in U3 snRNA transcription during differentiation, a corresponding drop in the cellular level of U3 snRNA does not occur. In myotubes, the amount of U3 snRNA is regulated at the post-transcriptional level in which there is a significant accumulation of U3 snRNA in the cytoplasm of myotubes. This intracellular redistribution of U3 snRNA may significantly affect the entire process of rRNA maturation or result from the decrease in ribosome production accompanying terminal differentiation of myoblasts.

Animals↗
PubMed1992

Predictors of outcome after percutaneous endoscopic gastrostomy: a community-based study.

Percutaneous endoscopic gastrostomy (PEG) is used to provide nutrition for patients who are unable to eat but have a functionally intact gut. Clinical guidelines for PEG are uncertain and have been derived mainly from referral practices. We performed a population-based cohort study in 97 residents of Olmsted County, Minnesota, referred for PEG between January 1982 and December 1988 to determine complications, duration of tube feeding, and survival. Follow-up continued until death or February 1990. Inpatient and outpatient records were reviewed to determine indications, comorbid conditions, level of consciousness, and limitations in activities of daily living. Outcomes determined after referral for PEG included type and number of complications, tube removal, and survival. Statistical methods used included Kaplan-Meier and proportional hazards regression analyses. PEG placement was successful in 94% of patients. Although complications occurred in 70% of patients, they usually were minor (88%) and most occurred within 3 months. In 24 patients, tubes were removed because eating was resumed. The probability of surviving 30 days, 1.5 years, and 4 years after referral for PEG was 78%, 35%, and 27%, respectively. The major causes of death within and after 30 days were pneumonia, heart disease, and vascular disease of the central nervous system. An increased risk of death after referral for PEG placement was associated with older age, male gender, diabetes, and specific indications for PEG. If validated in other population-based studies, these predictors of survival after referral for PEG placement could be used to identify patients with a low probability of survival who may not benefit from PEG.

Adolescent↗
PubMed1992

Visualization of a mammalian transcription initiation complex.

Various proteins required for the initiation of eukaryotic gene transcription by RNA polymerase II have been identified and characterized, but little is known about their organization into a functional unit. Here, we describe the appearance of the murine ribosomal protein (rp) L32 gene transcription initiation complex as determined by transmission electron microscopy. Using a fractionated nuclear extract enriched for transcription factors necessary for rpL32 gene transcription in vitro and a DNA fragment containing the rpL32 gene promoter, the transcription initiation complex was imaged by standard transmission electron microscopy. Quantitative image analysis demonstrated that the complex is a multilobed structure whose two-dimensional projections are approximately 24 x 34 nm in size. Looping of the DNA seen in these images suggests that the proteins residing at the promoter region associate with proteins several hundred base pairs distant to the RNA start site, with bending of the DNA allowing these interactions to occur.

Animals↗
PubMed1991

Control points in eucaryotic ribosome biogenesis.

Ribosome biogenesis in eucaryotic cells involves the coordinated synthesis of four rRNA species, transcribed by RNA polymerase I (18S, 28S, 5.8S) and RNA polymerase III (5S), and approximately 80 ribosomal proteins translated from mRNAs synthesized by RNA polymerase II. Assembly of the ribosomal subunits in the nucleolus, the site of 45S rRNA precursor gene transcription, requires the movement of 5S rRNA and ribosomal proteins from the nucleoplasm and cytoplasm, respectively, to this structure. To integrate these events and ensure the balanced production of individual ribosomal components, different strategies have been developed by eucaryotic organisms in response to a variety of physiological changes. This review presents an overview of the mechanisms modulating the production of ribosomal precursor molecules and the rate of ribosome biogenesis in various biological systems.

Cell Nucleolus↗
PubMed1990

Characterization of a mammalian ribosomal protein gene promoter.

The presence of specific promoter elements, notably the TATA and GC boxes, has been useful for categorizing genes transcribed by RNA polymerase II. The gene for the murine ribosomal protein (r-protein) L32 lacks both of these elements, although it has GC-rich regions. The conditions required for its optimal synthesis in vitro, however, resemble the properties of promoters containing TATA (adenovirus major late promoter) rather than GC boxes (dihydrofolate reductase). To further investigate the relationship of the r-protein gene to different promoter elements, transcription competition analyses were used to distinguish the presence of common protein-binding sequences. The low levels of competition observed by either the adenovirus major late promoter or dihydrofolate reductase promoter with the r-protein gene promoter resulted from general transcription factors present in each initiation complex. Competition by factors binding to common sequence elements was not observed, indicating the r-protein L32 gene possesses elements distinct from those present in the other genes examined.

Adenoviridae↗