Influence of segmental body composition and adiposity hormones on resting metabolic rate and substrate utilization in overweight and obese adults.

PURPOSE: Low resting metabolic rate (RMR) and high carbohydrate reliance at rest are associated with weight gain, but are highly variable in obese individuals. This study determined the relationship of total and segmental body composition and adiposity hormones with RMR and respiratory exchange ratio (RER) in overweight and obese adults. METHODS: In 49 men (n = 23) and premenopausal women (n = 26) [mean ± SD; age = 35.0 ± 8.9 years; body mass index (BMI) = 33.6 ± 5.2 kg·m-2; percent body fat (%fat) = 40.0 ± 8.0%], RMR and RER were evaluated using indirect calorimetry. Total and segmental body composition [fat mass (FM), percent fat (%fat), lean mass (LM), visceral adipose tissue (VAT)] were estimated using dual-energy X-ray absorptiometry. Fasted blood and saliva samples were analyzed for insulin, leptin, estradiol, and cortisol. RESULTS: In men (M) and women (W), RMR significantly correlated (p < 0.05) with FM (M: R = 0.535; W: R = 0.784) and LM (M: R = 0.645; W: R = 0.867). Of the segmental measures, trunk LM (M: R = 0.593; W: R = 0.879; p < 0.05) and leg LM (M: R = 0.664; W: R = 0.821; p < 0.05) had the strongest correlations with RMR. In men, but not women, RER significantly correlated with FM (R = 0.449; p = 0.032), trunk FM (R = 0.501; p = 0.015), and VAT (R = 0.456; p = 0.029). In men, RMR positively correlated with cortisol (R = 0.430, p = 0.040) and estradiol (R = 0.649, p = 0.001) and RER positively correlated with insulin (R = 0.525, p = 0.010). In women, RMR positively correlated with insulin (R = 0.570, p = 0.006), but RER was not significantly correlated with hormones (p > 0.05). CONCLUSIONS: Segmental evaluation of body composition, specifically in the lower extremities and abdomen, may be an effective and efficient way to evaluate metabolic status. Sex-specific evaluations are also imperative.

Prognostic value of angiographic indices of coronary artery disease from the Coronary Artery Surgery Study (CASS).

The Coronary Artery Surgery Study, CASS, enrolled 24,959 patients between August 1975 and June 1979 who were studied angiographically for suspected coronary artery disease. This paper compares the prognostic value for survival without early elective surgery of eight different indices of the extent of coronary artery disease: the number of diseased vessels, two indices using the number of proximal arterial segments diseased, two empirically generated indices from the CASS data, and the published indices of Friesinger, Gensini, and the National Heart and Chest Hospital, London. All had considerable prognostic information. Typically 80% of the prognostic information in one index was also contained in another. Our analysis shows that good prediction from angiographic data results from a combination of left ventricular function and arteriographic extent of disease. Prognosis may reasonably be obtained from three simple indices: the number of vessels diseased, the number of proximal arterial segments diseased, and a left ventricular wall motion score. These three indices account for an estimated 84% of the prognostic information available. 6-yr survival varies between 93 and 16% depending upon the values of these three indices.

Molecular biology of S-layers.

In this chapter we report on the molecular biology of crystalline surface layers of different bacterial groups. The limited information indicates that there are many variations on a common theme. Sequence variety, antigenic diversity, gene expression, rearrangements, influence of environmental factors and applied aspects are addressed. There is considerable variety in the S-layer composition, which was elucidated by sequence analysis of the corresponding genes. In Corynebacterium glutamicum one major cell wall protein is responsible for the formation of a highly ordered, hexagonal array. In contrast, two abundant surface proteins from the S-layer of Bacillus anthracis. Each protein possesses three S-layer homology motifs and one protein could be a virulence factor. The antigenic diversity and ABC transporters are important features, which have been studied in methanogenic archaea. The expression of the S-layer components is controlled by three genes in the case of Thermus thermophilus. One has repressor activity on the S-layer gene promoter, the second codes for the S-layer protein. The rearrangement by reciprocal recombination was investigated in Campylobacter fetus. 7-8 S-layer proteins with a high degree of homology at the 5' and 3' ends were found. Environmental changes influence the surface properties of Bacillus stearothermophilus. Depending on oxygen supply, this species produces different S-layer proteins. Finally, the molecular bases for some applications are discussed. Recombinant S-layer fusion proteins have been designed for biotechnology.

Parvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells.

Disinhibition of cortical excitatory cell gate information flow through and between cortical columns. The major contribution of Martinotti cells (MC) is providing dendritic inhibition to excitatory neurons and therefore they are a main component of disinhibitory connections. Here we show by means of optogenetics that MC in layers II/III of the mouse primary somatosensory cortex are inhibited by both parvalbumin (PV)- and vasoactive intestinal polypeptide (VIP)-expressing cells. Paired recordings revealed stronger synaptic input onto MC from PV cells than from VIP cells. Moreover, PV cell input showed frequency-independent depression, whereas VIP cell input facilitated at high frequencies. These differences in the properties of the two unitary connections enable disinhibition with distinct temporal features.

Calmodulin-activated bacterial adenylate cyclases as virulence factors.

Bordetella pertussis and Bacillus anthracis each produce a virulence-associated, calmodulin-dependent adenylate cyclase toxin, which generates increased levels of cyclic AMP in eukaryotic cells. The two proteins share sequence similarities in their catalytic domains. The remaining regions display different structural and functional organizations that account for the differences both in interaction of the two toxins with target cells and in the resulting disease symptoms.

Changing outcome of angioplasty in the elderly.

OBJECTIVES: This study sought to determine whether in-hospital and intermediate-term posthospital outcomes have changed in elderly patients undergoing percutaneous transluminal coronary angioplasty from the period 1980 through 1989 to the period 1990 through 1992. BACKGROUND: Although elderly patients have a higher incidence of procedure-related deaths and late recurrence of angina after coronary angioplasty, recent complication rates for angioplasty seem to be lower. METHODS: From 1980 to 1989, 982 patients > or = 65 years old underwent nonemergent coronary angioplasty (group A). They were compared with 768 similar patients who had coronary angioplasty from 1990 to 1992 (group B). RESULTS: Patients in group B were older than those in group A and had a higher mean concomitant disease score, a higher proportion of men and a greater proportion of patients with a previous myocardial infarction and previous coronary artery bypass surgery. Despite the increased complexity of the group B cohort, procedural success rates were higher, and rates of important in-hospital complications were much lower than those in group A. For group A versus group B, respectively, the technical success rate was 88.1% versus 93.5% (p < 0.001), in-hospital death rate 3.3% versus 1.4% (p = 0.014), emergency bypass surgery rate 5.5% versus 0.65% (p < 0.001) and incidence of in-hospital death or myocardial infarction 6.3% versus 3.4% (p < 0.005). However, intermediate-term posthospital event-free rates in hospital survivors did not decrease. The rate of death or myocardial infarction at 6 months was 4.7% in group A versus 7.1% in group B (p < 0.05). Survival free of acute myocardial infarction, bypass surgery, repeat coronary angioplasty or severe angina at 1 year was 66.7% in group A versus 54.9% in group B (p < 0.001). The combined in-hospital death/myocardial infarction rate plus that for the first 6 months after hospital dismissal was essentially equivalent for the two groups (10.3% vs. 9.9%, p = NS). CONCLUSIONS: An increase in technical success rates and a reduction in short-term complication rates for coronary angioplasty in the elderly in recent years have not translated into an improved event-free survival rate, which continues to be influenced by important baseline characteristics of these high risk patients.

Percutaneous transluminal coronary angioplasty in the elderly: early and long-term results.

The immediate and long-term efficacy of coronary angioplasty in the elderly was determined by studying 752 patients greater than or equal to 65 years old and comparing patients greater than or equal to 75 years old with those 65 to 74 years old. The oldest patients were more highly symptomatic, were more likely to be in heart failure, had more multivessel disease and were more likely to undergo multivessel dilation. The immediate success rate of angioplasty was higher in the oldest patients (92.8% versus 82%) (p = 0.0003). The hospital mortality rate was also higher (6.2% versus 1.6%) (p less than 0.001). Long-term overall survival was high. However, long-term event-free survival was lowest in the oldest patients, and recurrent severe angina was particularly common. Thus, in very elderly patients, coronary angioplasty is usually successful, but extra caution is warranted; also, long-term relief from angina is less common than in younger patients.

Risk factor profiles of patients with sudden cardiac death and death from other cardiac causes: a report from the Coronary Artery Surgery Study (CASS).

Identification of patients at risk of sudden death is essential if optimal preventive treatment strategies are to be developed. In the Coronary Artery Surgery Study (CASS) Registry, 19,946 patients were analyzed to characterize baseline clinical, hemodynamic and angiographic features of patients dying from sudden cardiac death and to compare them with features of patients dying from other cardiac causes, of those dying from noncardiac causes and of survivors. Of the 11,843 medically treated patients, 1,621 died during a mean follow-up period of 5.0 years: death was sudden in 557 (34%), nonsudden but cardiac in 813 (50%) and noncardiac in 251 (16%). In 8,103 surgically treated patients, 824 deaths occurred during a mean follow-up period of 5.1 years: death was sudden in 204 (25%), nonsudden but cardiac in 390 (47%) and noncardiac in 230 (28%). In general, the patients (both medically and surgically treated) who died of cardiac causes, either suddenly or nonsuddenly, were similar to each other but significantly different from patients who either survived or died of noncardiac causes. Although patients with an increased risk of any type of cardiac death could be identified, there were no measures of angiographic or hemodynamic characteristics that were significantly different between patients with sudden cardiac death and those with nonsudden cardiac death. Identification of patients at high risk for sudden cardiac death will require approaches in addition to clinical, angiographic and hemodynamic assessment, such as electrophysiologic assessment or monitoring techniques to identify triggering mechanisms.

Macrophage interactions.

B. anthracis virulence is the sum of the contributions of factors involved in toxicity, growth and persistence in the host. Recent data has revealed that the interactions between B. anthracis and macrophage is central to the B. anthracis pathogenesis. This review presents and describes tactics by which B. anthracis not only overcomes and avoids macrophages but also perverts the host defense immune system and defense-related products to its advantage. The understanding of the complex network of such interactions is likely to allow new therapeutic and preventative strategies to be developed.

A technique for integrating any DNA fragment into the chromosome of Escherichia coli.

We describe a technique that allows the insertion of any DNA fragment into the EcoRI-site-containing malPpa, the promoter of malPQ, one of the three maltose operons of Escherichia coli. DNA fragments were cloned into the unique EcoRI site of the pBR322-derived plasmid pOM40, which carries malPpa. In the next step these fragments were transposed into the chromosome by homologous recombination events occurring on both sides of malPp. Cells in which such insertion of the entire recombinant plasmid have occurred can be conveniently selected. Excision and curing of the vector plasmid could then occur spontaneously at a high frequency, leaving behind the inserted fragment that can be manipulated as any chromosomal marker. When the inserted fragment contains a properly positioned promoter, its promoting activity can be estimated by assaying amylomaltase, the product of malQ. When required, the inserted fragment can be easily transferred back onto pOM40. As examples of application we have transferred two different fragments into the chromosome of E. coli: one contained the ceaC-ceiC operon, which encodes colicin E3 and its immunity protein, and the other contained the lac promoter of E. coli.

Cloning and expression of the calmodulin-sensitive Bacillus anthracis adenylate cyclase in Escherichia coli.

The adenylate cyclase gene of Bacillus anthracis, encoding the edema factor, a component of anthrax toxin, has been cloned and expressed in Escherichia coli. Clones were selected by their capacity to complement the cyclase deficiency (cya-) of an E. coli strain expressing the eukaryotic protein calmodulin, an essential activator of B. anthracis adenylate cyclase. The protein expressed in E. coli was shown to exhibit adenylate cyclase activity only in the presence of calmodulin. Experiments using a coupled in vitro transcription-translation system revealed that the protein synthesized from the cloned DNA fragment was enzymatically active, upon addition of calmodulin, and could be immunoprecipitated by antibodies directed against purified Bordetella pertussis adenylate cyclase toxin. This indicates that the two calmodulin-dependent adenylate cyclase toxins are immunologically related.

Structural homology between virulence-associated bacterial adenylate cyclases.

The primary structure of the calmodulin-sensitive adenylate cyclase toxin from Bacillus anthracis has been determined from the corresponding nucleotide sequence and compared to that of the homologous toxin secreted by Bordetella pertussis. The cya gene of Bacillus anthracis encodes an 800 amino acid (aa) protein beginning with an N-terminal signal peptide. The central part of the B. anthracis adenylate cyclase includes a region of striking homology with the N-terminal part of the B. pertussis enzyme. In this region a particularly well conserved 24-aa peptide and two other less homologous peptides have been identified. These data corroborate the immunological relatedness of the two enzymes and suggest that the two prokaryotic calmodulin-sensitive adenylate cyclases originate from a common ancestor.

The vacuolar ATPase proton pump is required for the cytotoxicity of Bacillus anthracis lethal toxin.

The nature of the cytopathic effect exerted by the lethal factor toxin (LF) of Bacillus anthracis on sensitive cells is unknown. The toxin requires the passage through acidic vesicles in order to exert its effect within the cytosol. Here, we show that bafilomycins and concanamycin A, selective inhibitors of the vacuolar ATPase proton pump, are the most powerful known inhibitors of LF macrophage toxicity. These inhibitors are fully active long after LF addition to macrophages, suggesting that LF enters the cytosol after having reached a late endosomal compartment.

Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha.

The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated protein kinase kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another dual-specificity kinase that phosphorylates and activates p38 MAP kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-alpha induced by lipopolysaccharide/interferon gamma. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.

Spatial arrangement of cerebro-pontine terminals.

Understanding the interaction of the cerebral cortex and cerebellum requires knowledge of the highly complex spatial characteristics of cerebro-cerebellar signal transfer. Cerebro-pontine fibers from one neocortical site terminate in several sharply demarcated patches across large parts of the pontine nuclei (PN), and fibers from different neocortical areas terminate in the same pontine region. To determine whether projections from segregated neocortical sites overlap in the PN, we studied double anterograde tracing of cerebro-pontine terminals from large parts of rat neocortex. In none of these experiments, including double injection into two functionally related areas, were we able to demonstrate overlapping patches, although close spatial relationships were always detected. This non-overlapping distribution is consistent with a compartmentalized organization of the cerebro-pontine projection and may be the basis of the fractured type of maps found in the cerebellar granular layer. The critical distance between two sites on the neocortical surface that project to non-overlapping patches in the PN was found to be 600 microm, by using double injection within the whisker representation of the primary somatosensory area. This matches the diameter of dendritic trees of layer 5 projection neurons, indicating that non-overlapping populations of neocortical projection neurons possess non-overlapping patches of pontine terminals. Estimations based on this critical distance and the pontine volume anterogradely labeled by one injection site indicate that the size of the PN may be well suited to accommodate a complete set of non-overlapping pontine patches from all possible neocortical sites.

Prognostic value of exercise radionuclide angiography in a population-based cohort of patients with known or suspected coronary artery disease.

Five hundred thirty-six residents of Olmsted County, Minnesota, who underwent supine rest and exercise radionuclide angiography because of known or suspected coronary artery disease, were followed for a median of 46 months to determine the prognostic value of exercise radionuclide angiography in a community population who generally did not undergo coronary angiography. There were 71 persons who experienced a new cardiac event (the initial events were cardiac death and nonfatal myocardial infarction in 26 and 45 persons, respectively). A proportional-hazards model identified 4 independent predictors of cardiac events: exercise ejection fraction (p < 0.001), exercise heart rate (p < 0.001), and age (p = 0.04). Four-year infarct-free survival was 98% for the 152 patients with a peak exercise heart rate at or above the median (122 beats/min) and an exercise ejection fraction at or above the median (0.58). In the 150 patients with a peak exercise heart rate < 122 beats/min and an exercise ejection fraction < 0.58, 4-year infarct-free survival was 68%. When this population-based cohort was compared with a referral case series previously reported from our institution, these population-based patients were significantly more likely to be men, to have typical angina, to have higher exercise heart rates and exercise ejection fractions, and were less likely to be receiving beta-receptor antagonist therapy. At each level of exercise ejection fraction, the population-based patients had a slightly but insignificantly greater risk than referral patients for subsequent cardiac events. These population-based data provide strong evidence of the prognostic value of exercise radionuclide angiography in community practice.

Bypass Angioplasty Revascularization Investigation (BARI): baseline clinical and angiographic data.

This report presents baseline clinical and angiographic data from the Bypass Angioplasty Revascularization Investigation (BARI), a multicenter international trial assessing the relative efficacy of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG) in selected patients with multivessel coronary artery disease. PTCA is commonly performed in patients with multivessel coronary artery disease, yet its long-term efficacy in comparison to CABG is unknown. From August 1988 through August 1991, 1,829 qualifying patients with multivessel disease suitable for either procedure were randomized to PTCA or CABG; sample size estimates were based on anticipated 5-year mortality. Two registry populations were also defined for follow-up: (1) 2,013 patients eligible for randomization but not randomized; and (2) 422 patients considered by angiography as unsuitable for randomization. Patients randomized in BARI were at relatively high risk for subsequent cardiac events: 39% were > or = 65 years old, 55% had prior myocardial infarction, 69% presented with unstable angina or non-Q wave myocardial infarction, and 43% had 3-vessel coronary artery disease. Patients randomized to PTCA and CABG were equally matched in all the important baseline variables. The randomized and the eligible but not randomized groups were similar in most respects. However, the nonrandomized group had a higher proportion with college education; fewer with a history of myocardial infarction, heart failure, diabetes, and smoking; and a somewhat better average ejection fraction. At the 3-month follow-up, PTCA had been performed more commonly in the nonrandomized eligible patients, especially those with 2-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of effects of medical and surgical therapy on survival in severe angina pectoris and two-vessel coronary artery disease with and without left ventricular dysfunction: a Coronary Artery Surgery Study Registry Study.

This nonrandomized study compared the results of early coronary artery bypass grafting to those of initial medical therapy in a group of 2,023 patients with severe angina pectoris and 2 major epicardial coronary arteries having greater than or equal to 70% diameter luminal narrowing. Medical therapy was selected for 706 patients, and 1,317 patients were treated by coronary artery bypass grafting. The 6-year survival rate was 76% for patients treated medically and 89% for patients treated surgically (p less than 0.0001). Cox multivariate analysis showed that surgical treatment was a beneficial independent predictor of survival (p less than 0.001). For patients with 2-vessel coronary artery disease who had Canadian Heart Association class III and IV angina at presentation, surgical therapy provided a survival advantage for patients with impaired left ventricular function and proximal narrowing of 1 or more coronary arteries.

Angiographic changes produced by percutaneous transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is being used with increasing frequency in the treatment of patients with symptomatic coronary artery disease. Balloon inflation results in diverse angiographic findings, reflecting the great variety of anatomic and pathologic changes produced. The long-term effects of inflation on the underlying atherosclerotic lesion and the clinical outcome are unknown but may depend in part on the anatomic changes caused by the dilatation itself. To facilitate communication and evaluation of the results of PTCA, a classification of the angiographic findings and their potential mechanisms is presented. Recognition and analysis of these angiographic findings may be helpful in evaluating the long-term outcome of patients undergoing PTCA.

Employment and recreation patterns in patients treated by percutaneous transluminal coronary angioplasty: a multicenter study.

Employment and recreational patterns were analyzed in 279 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) for treatment of symptomatic coronary artery disease. PTCA was successful in 180 patients (65%). When it was unsuccessful, coronary artery bypass graft surgery was usually performed (80%). Return-to-work rates were high irrespective of the outcome of PTCA. Of patients employed full-time or part-time before treatment, 98.5% of those who had successful PTCA alone and 97% of those whose PTCA was unsuccessful but who underwent uncomplicated coronary artery bypass surgery maintained or improved their work status. In a subgroup of men who had been employed in occupations requiring physical labor, 85% of the men whose PTCA was successful returned to work, compared with 68% of those whose PTCA was unsuccessful. The interval from attempted PTCA to return to work was significantly shorter in the successfully treated group; in patients with successful PTCA, the median time to return to work was 14 days, compared with 60 days in patients in whom PTCA was unsuccessful (p less than 0.001). During follow-up, patients with successful PTCA had less angina and were more active in recreational activities than patients who required alternative treatments.