Showing papers by "Tufts University published in 1994"
TL;DR: Restricting protein intake and controlling hypertension delay the progression of renal disease in animals and in patients with various chronic renal diseases.
Abstract: Background Restricting protein intake and controlling hypertension delay the progression of renal disease in animals. We tested these interventions in 840 patients with various chronic renal diseases. Methods In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients. Results The mean follow-up was 2.2 years. ...
2,113 citations
TL;DR: It is reaffirm that p53 function is not required for normal mouse development and conclude that p 53 status can strongly influence tumor latency and tissue distribution.
2,034 citations
TL;DR: Findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit and might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.
Abstract: Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF was administered as a single intra-arterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,000 micrograms of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.75 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.
1,071 citations
TL;DR: Direct evidence suggests a crucial role for the fibrinolytic system and its physiological triggers, tissue-type and urokinase-type (u-PA) plasminogen activator, in many proteolytic processes.
Abstract: Indirect evidence suggests a crucial role for the fibrinolytic system and its physiological triggers, tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator, in many proteolytic processes. Inactivation of the t-PA gene impairs clot lysis and inactivation of the u-PA gene results in occasional fibrin deposition. Mice with combined t-PA and u-PA deficiency suffer extensive spontaneous fibrin deposition, with its associated effects on growth, fertility and survival.
1,042 citations
TL;DR: A meta-analysis of 47 studies found externalizing was more strongly linked to parental caregiving for boys than for girls, especially among preadolescents and their mothers, and for mothers than for fathers.
Abstract: A meta-analysis of 47 studies was used to shed light on inconsistencies in the concurrent association between parental caregiving and child externalizing behavior. Parent-child associations were strongest when the measure of caregiving relied on observations or interviews, as opposed to questionnaires, and when the measure tapped combinations of parent behaviors (patterns), as opposed to single behaviors. Stronger parent-child associations were also found for older than for younger children, and for mothers than for fathers. Finally, externalizing was more strongly linked to parental caregiving for boys than for girls, especially among preadolescents and their mothers. The meta-analysis helps account for inconsistencies in findings across previous studies and supports theories emphasizing reciprocity of parent and child behavior.
988 citations
TL;DR: In this paper, optical coherence tomography (OCT) was used for high-resolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo.
Abstract: Objective: To demonstrate a new diagnostic technique, optical coherence tomography, for highresolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo. Optical coherence tomography is a new, noninvasive, noncontact optical imaging modality that has spatial resolution superior to that of conventional clinical ultrasonography ( 90 dB). Design: Survey of intraocular structure and dimension measurements. Setting: Laboratory. Patients: Convenience sample. Main Outcome Measures: Correlation with range of accepted normal intraocular structure profiles and dimensions. Results: Direct in vivo measurements with micrometer-scale resolution were performed of corneal thickness and surface profile (including visualization of the corneal epithelium), anterior chamber depth and angle, and iris thickness and surface profile. Dense nuclear cataracts were successfully imaged through their full thickness in a cold cataract model in calf eyes in vitro. Conclusions: Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens.
958 citations
TL;DR: High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass, strength, and balance in postmenopausal women.
Abstract: Objective. —To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women. Design. —Randomized controlled trial of 1-year duration. Setting. —Exercise laboratory at Tufts University, Boston, Mass. Population. —Forty postmenopausal white women, 50 to 70 years of age, participated in the study; 39 women completed the study. The subjects were sedentary and estrogen-deplete. Interventions. —High-intensity strength training exercises 2 days per week using five different exercises (n=20) vs untreated controls (n=19). Main Outcome Measures. —Dual energy x-ray absorptiometry for bone status, one repetition maximum for muscle strength, 24-hour urinary creatinine for muscle mass, and backward tandem walk for dynamic balance. Results. —Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005±0.039 g/cm 2 (0.9%±4.5%) (mean±SD) and 0.009±0.033 g/cm 2 (10%±3.6%), respectively, in the strength-trained women and decreased by -0.022±0.035 g/cm 2 (-2.5%±3.8%) and -0.019±0.035 g/cm 2 (-1.8%±3.5%), respectively, in the controls ( P =.02 and.04). Total body bone mineral content was preserved in the strength-trained women (+2.0±68 g; 0.0%±3.0%) and tended to decrease in the controls (-33+77 g; -1.2%±3.4%, P =.12). Muscle mass, muscle strength, and dynamic balance increased in the strength-trained women and decreased in the controls ( P =.03 to Conclusions. —High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass, strength, and balance in postmenopausal women. ( JAMA . 1994;272:1909-1914)
957 citations
TL;DR: It is demonstrated that GM- CSF is not an essential growth factor for basal hematopoiesis and an unexpected, critical role for GM-CSF in pulmonary homeostasis is revealed.
Abstract: The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis.
839 citations
TL;DR: Ten years ago the cloning of IL‐1 resolved the question of whether a single polypeptide could evoke a wide variety of biological effects and opened other avenues of fundamental biological interest.
Abstract: Ten years ago the cloning of two interleukin-1 molecules (IL-1 alpha and IL-1 beta) resolved the question of whether a single polypeptide could evoke a wide variety of biological effects During the past decade, the biology of IL-1 has greatly expanded our understanding of how the host responds to external challenges, such as injury and infection, as well as its role in several diseases We learned of the remarkable potency of IL-1 in the femtomolar range and of its ability to induce a response by triggering only one or two receptors per cell Unexpectedly, the IL-1 family of genes, receptors and associated molecules have been linked to those of Drosophila, nematodes, and microorganisms and IL-1 signal transduction is similar to that observed after cellular stress The cloning of IL-1 opened other avenues of fundamental biological interest For example, in addition to the two agonist molecules IL-1 alpha and IL-1 beta, a third member of the IL-1 gene family is a specific, high affinity receptor antagonist
824 citations
TL;DR: These guidelines are used to review 11 journal articles published from January 1990 through December 1991 whose primary purpose was to assess the accuracy of a diagnostic test against a concurrent reference standard using meta-analysis, and the guidelines are based on current concepts of how to assess diagnostic tests and conduct meta-analyses.
Abstract: Objectives: To introduce guidelines for the conduct, reporting, and critical appraisal of meta-analyses evaluating diagnostic tests and to apply these guidelines to recently published meta-analyses...
772 citations
TL;DR: A mouse strain carrying a germline mutation in the murine homologue of the NF1 gene is constructed in order to study NF1 function and it is shown that homozygosity for the Nf1 mutation leads to abnormal cardiac development and mid–gestational embryonic lethality.
Abstract: Human neurofibromatosis type 1 is a dominant disease caused by the inheritance of a mutant allele of the NF1 gene. In order to study NF1 function, we have constructed a mouse strain carrying a germline mutation in the murine homologue. Heterozygous animals do not exhibit the classical symptoms of the human disease, but are highly predisposed to the formation of various tumour types, notably phaeochomocytoma, a tumour of the neural crest–derived adrenal medulla, and myeloid leukaemia, both of which occur with increased frequency in human NF1 patients. The wild–type Nf1 allele is lost in approximately half of the tumours from heterozygous animals. In addition, homozygosity for the Nf1 mutation leads to abnormal cardiac development and mid–gestational embryonic lethality.
TL;DR: The E-screen test revealed that estrogenic chemicals may act cumulatively; when mixed together they induce estrogenic responses at concentrations lower than those required when each compound is administered alone.
Abstract: Estrogenic pesticides such as DDT and chlordecone generate deleterious reproductive effects. An "in culture" bioassay was used to assess the estrogenicity of several pesticides. The E-screen test uses human breast estrogen-sensitive MCF7 cells and compares the cell yield achieved after 6 days of culture in medium supplemented with 5% charcoal-dextran stripped human serum in the presence (positive control) or absence (negative control) of estradiol and with diverse concentrations of xenobiotics suspected of being estrogenic. Among the organochlorine pesticides tested, toxaphene, dieldrin, and endosulfan had estrogenic properties comparable to those of DDT and chlordecone; the latter are known to be estrogenic in rodent models. The E-screen test also revealed that estrogenic chemicals may act cumulatively; when mixed together they induce estrogenic responses at concentrations lower than those required when each compound is administered alone.
TL;DR: Loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-alpha and IL-1 beta modulate energy metabolic and body composition in RA.
Abstract: The cytokines IL-1 beta and TNF-alpha cause cachexia and hypermetabolism in animal models, but their role in human inflammation remains controversial. The relationship between in vitro cytokine production and metabolism was examined in 23 adults with RA and 23 healthy control subjects matched on age, sex, race, and weight. Body composition was measured by multicompartmental analysis of body cell mass, water, fat, and bone mass. Resting energy expenditure (REE) was measured by indirect calorimetry. Cytokine production by PBMC was measured by radioimmunoassay. Usual energy intake, physical activity, disability scores, medication use, and other confounders were also measured. Body cell mass was 13% lower (P < 0.00001), REE was 12% higher (P < 0.008), and physical activity was much lower (P < 0.001) in subjects with RA. Production of TNF-alpha was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1 beta was higher with endotoxin stimulation (P < 0.01). In multivariate analysis, cytokine production was directly associated with REE (P < 0.001) in patients but not in controls. While energy and protein intake were similar in the two groups and exceeded the Recommended Dietary Allowances, energy intake in subjects with RA was inversely associated with IL-1 beta production (P < 0.005). In this study we conclude that: loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-alpha and IL-1 beta modulate energy metabolism and body composition in RA.
TL;DR: Results indicate that certain indirect angiogenic cytokines, such as PDGF-BB or TGF-β1, may act via induction of bFGF and VEGF gene expression in cells resident near endothelial cells in vivo.
Abstract: BACKGROUNDHypoxia and indirect angiogenic factors may stimulate angiogenesis via induction of endothelial cell mitogen(s). To evaluate this hypothesis, we investigated whether low oxygen tension or cytokines known to promote neovascularization in vivo could modulate the expression of either vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in human vascular smooth muscle cells (SMCs).METHODS AND RESULTSSMCs were treated with platelet-derived growth factor BB (PDGF-BB) or transforming growth factor-beta 1 (TGF-beta 1) or exposed to low oxygen tension in serum-free medium. Northern analysis detected low basal levels of VEGF and bFGF mRNA in extracts of unstimulated SMCs. However, both VEGF and bFGF transcripts increased after administration of PDGF-BB (10 or 20 ng/mL) or TGF-beta 1 (0.1 to 10 ng/mL). Hypoxia was a potent stimulus for VEGF gene expression but had no apparent effect on bFGF steady-state mRNA levels.CONCLUSIONSThese results indicate that certain indirect angiog...
TL;DR: This paper described a study of such epistemological beliefs in the context of an introductory physics course and interviewed 6 students, meeting several times with each over one semester, through the development and use of an analytic framework.
Abstract: Students' beliefs about knowledge and learning in a domain may have a significant effect on how they approach the material and on what they learn. This article describes a study of such epistemological beliefs in the context of an introductory physics course. I interviewed 6 students, meeting several times with each over one semester. The interviews involved a variety of conversations and tasks closely tied to the course. Through the development and use of an analytic framework, it was possible to characterize subjects' beliefs. The framework consisted of three dimensions:
TL;DR: Findings indicate that such biases exist and can influence the parser under certain conditions and that P600 amplitude is a function of the perceived syntactic well-formedness of the sentence.
Abstract: Event-related potentials were recorded from 13 scalp locations while participants read sentences containing a syntactic ambiguity. In Experiment 1, syntactically disambiguating words that were inconsistent with the "favored" syntactic analysis elicited a positive-going brain potential (P600). Experiment 2 examined whether syntactic ambiguities are resolved by application of a phrase-structure-based minimal attachment principle or by word-specific subcategorization information. P600 amplitude was a function of subcategorization biases rather than syntactic complexity. These findings indicate that such biases exist and can influence the parser under certain conditions and that P600 amplitude is a function of the perceived syntactic well-formedness of the sentence.
TL;DR: The demonstrated relation between the presence of the receptors and the absence of atherosclerosis in premenopausal women suggests that these receptors may play a functional role in coronary atheroprotection.
Abstract: BACKGROUNDThe relative absence of coronary atherosclerosis in premenopausal women has been established. Estrogen is presumed to play a role in the protection of coronary arteries from atherosclerosis, and part of this protective effect appears to be mediated by amelioration of serum lipid profiles. However, all of the atheroprotective effect of estrogen is not explained by alteration of serum lipids. In this study, we attempt to identify evidence of estrogen receptors in coronary artery specimens of female patients and in human vascular smooth muscle cells.METHODS AND RESULTSPostmortem coronary artery specimens were obtained from premenopausal (n = 18) and postmenopausal (n = 22) women who died with significant coronary artery disease (n = 19) and from noncardiac causes with normal coronary arteries (n = 21). Sections were examined for evidence of estrogen receptor expression using a monoclonal antibody stain. Radioligand binding assays for estrogen receptors were performed on human vascular smooth muscle...
TL;DR: It is demonstrated for the first time that human VSMCs express E2-receptor mRNA and protein and that the E2 receptor inVSMCs is capable of estrogen-dependent gene activation, suggesting a mechanism by which estrogen may directly alter VSMC function.
Abstract: BACKGROUND The decreased incidence of coronary artery disease observed in postmenopausal women given estrogen (E2) replacement demonstrates an atheroprotective effect of E2 that is generally believed to be mediated by indirect, E2-induced changes in cardiovascular risk factor profiles We hypothesized that the atheroprotective effect of E2 may be in part mediated by a direct effect of E2 on vascular smooth muscle cells (VSMCs) Therefore, a series of experiments was performed to determine whether human VSMCs contain a competent E2 receptor, a ligand-activated transcription factor known to mediate E2-induced effects in nonvascular cells METHODS AND RESULTS Ribonuclease protection assays, with a probe derived from the human E2 receptor, were used to demonstrate E2-receptor mRNA in human saphenous vein VSMCs To show that VSMCs contain E2-receptor protein as well as message, immunoblotting and immunofluorescence studies with a monoclonal anti-E2-receptor antibody were performed, and E2-receptor protein was detected by both methods Transient transfection assays using a specific E2-responsive reporter system were used next to determine whether the VSMC E2 receptor is capable of E2-induced transcriptional transactivation Initial studies using mammary artery-derived VSMCs resulted in a 24-fold increase in reporter activity in response to 10(-7) mol/L E2 Subsequent studies using saphenous vein VSMCs demonstrated increasing levels of reporter activation as the concentration of E2 was increased from 10(-9) mol/L (13-fold increase; SEM, 007; P = 05, n = 3) to 10(-7) mol/L (16-fold increase; SEM, 004; P = 002, n = 6) The specificity of the E2-induced transactivation of the reporter gene was shown by dose-dependent inhibition of transactivation by the pure E2 antagonist ICI 164,384 and by enhancement of the transactivation by simultaneous overexpression of the E2 receptor CONCLUSIONS We have demonstrated for the first time that human VSMCs express E2-receptor mRNA and protein and that the E2 receptor in VSMCs is capable of estrogen-dependent gene activation These data suggest a mechanism by which estrogen may directly alter VSMC function
TL;DR: It is shown that the diffusion‐collision model of protein folding is supported by a growing body of experimental and theoretical evidence, and future directions for developing the model and its applications are outlined.
Abstract: The diffusion-collision model of protein folding is assessed. A description is given of the qualitative aspects and quantitative results of the diffusion-collision model and their relation to available experimental data. We consider alternative mechanisms for folding and point out their relationship to the diffusion-collision model. We show that the diffusion-collision model is supported by a growing body of experimental and theoretical evidence, and we outline future directions for developing the model and its applications.
TL;DR: This paper found that racial environment has a strong and consistent effect on racial-political attitudes, but little-to-no effect on measures of prejudice, and that this racial environment effect is pronounced among those most affected by black political progress (southern Democrats evaluating Jesse Jackson).
Abstract: In this study, I look at the relationship of black population and white racial attitudes in the contemporary South. Merging county-level census data with individual-level N.E.S. data from the 1980s to create a variable tapping "racial environment," I also use this study to test the validity of a group conflict theory of racial-political attitudes. I find that racial environment has a strong and consistent effect on racial-political attitudes, but little-to-no effect on measures of prejudice. Moreover, this racial environment effect is pronounced among those most affected by black political progress (southern Democrats evaluating Jesse Jackson). Contrary to a symbolic racism approach to the study of racial-political attitudes, these three findings support the contention that threat, in the form of group conflict, influences political positions on racial issues.
Book•
30 Apr 1994TL;DR: A Framework for the Study of Creativity by David Henry Feldman, Mihaly Csikszentmihalyi, and Howard Gardner as mentioned in this paper is a framework for the study of creativity.
Abstract: Acknowledgments Preface A Framework for the Study of Creativity by David Henry Feldman, Mihaly Csikszentmihalyi, and Howard Gardner The Fruits of Asychrony: A Psychological Examination of Creativity by Howard Gardner and Constance Wolf The Creators' Patterns by Howard Gardner Creativity: Proof that Development Occurs by David Henry Feldman Creativity: Dreams, Insights, and Transformations by David Henry Feldman The Domain of Creativity by Mihaly Csikszentmihalyi Memes versus Genes: Notes from the Culture Wars by Mihaly Csikszentmihalyi Conclusion: Creativity Research on the Verge Bibliography Index
TL;DR: It is shown that a physically reasonable spacetime that is eternally inflating to the future must possess an initial singularity.
Abstract: It is shown that a physically reasonable spacetime that is eternally inflating to the future must possess an initial singularity.
TL;DR: Comparing regional activities of 201Tl and 99mTc-sestamibi after resting injections in patients with coronary artery disease and regional or global left ventricular dysfunction found the two agents comparably predict reversibility of significant regional wall motion abnormalities after revascularization in such patients to a similar degree.
Abstract: BACKGROUNDRegional 201Tl activity after resting injection, imaged early and after redistribution, reflects viable myocardium and can predict improved isotope uptake as well as regional and global ventricular function after revascularization. 99mTc-sestamibi, a perfusion tracer with favorable imaging characteristics, has distinct kinetics compared with 201Tl, demonstrating minimal redistribution; this property may give 201Tl an advantage for detecting viable myocardium, particularly in segments with resting hypoperfusion. The purpose of this study was to compare regional activities of 201Tl and 99mTc-sestamibi after resting injections in patients with coronary artery disease and regional or global left ventricular dysfunction and to assess their comparative abilities for predicting recovery of severe regional ventricular dysfunction after revascularization.METHODS AND RESULTSQualitative and quantitative comparisons of rest and redistribution 201Tl activity and sestamibi activity 1 hour after rest injection...
TL;DR: The merits of dual-coding and context-availability theories were investigated by examining the topographic distribution of event-related brain potentials in 2 experiments and different scalp distributions of an N400-like negativity were elicited by concrete and abstract words.
Abstract: Dual-coding theory argues that processing advantages for concrete over abstract (verbal) stimuli result from the operation of 2 systems (i.e., imaginal and verbal) for concrete stimuli, rather than just 1 (for abstract stimuli). These verbal and imaginal systems have been linked with the left and right hemispheres of the brain, respectively. Context-availability theory argues that concreteness effects result from processing differences in a single system. The merits of these theories were investigated by examining the topographic distribution of event-related brain potentials in 2 experiments (lexical decision and concrete-abstract classification). The results were most consistent with dual-coding theory. In particular, different scalp distributions of an N400-like negativity were elicited by concrete and abstract words.
TL;DR: The results in 35 men suggest that aging may be associated with a significant impairment in the ability to control food intake following overeating or undereating, which may help to explain the vulnerability of older persons to unexplained weight gain and weight loss.
Abstract: Objective. —To investigate the effects of aging on mechanisms of body energy regulation and thereby determine the causes of unexplained weight loss in older persons, a factor predisposing to premature death and disability. Design. —Dietary intervention study. Setting. —Metabolic ward and outpatient. Participants. —The subjects were 35 healthy younger and older men of normal body weight consuming a diet of typical composition and performing usual activities. Main Outcome Measures. —Subjects were either overfed by a mean (±SD) of 4.09 (±0.26) MJ/d (n=17) or underfed by 3.17 (±0.68) MJ/d (n=18) for 21 days. Measurements were made of changes in body weight, body composition, and energy expenditure during overfeeding or underfeeding, and of subsequent voluntary nutrient intakes and changes in body weight. Results. —There was no significant effect of aging on changes in body composition, body weight, or energy expenditure with overfeeding or underfeeding. However, following overfeeding, younger men exhibited spontaneous hypophagia, whereas the older men did not (mean [±SD] changes in energy intake relative to control values were -2.11 [±2.18] and 1.55 [±2.11] MJ/d, respectively;P=.006). As a result, the younger men lost the excess body weight gained during overfeeding but the older men did not. Similarly, following underfeeding, the younger men exhibited hyperphagia while the older men did not (mean [±SD] changes in energy intake relative to control values were 1.88 [±2.31]and -0.52 [±1.54] MJ/d, respectively;P=.02), and as a result the older men failed to regain the weight lost during underfeeding. Conclusions. —These results in 35 men suggest that aging may be associated with a significant impairment in the ability to control food intake following overeating or undereating. Since overeating and undereating occur routinely as part of the normal pattern of energy regulation, the findings reported herein may help to explain the vulnerability of older persons to unexplained weight gain and weight loss. (JAMA. 1994;272:1601-1606)
TL;DR: The phenotypic effects of combined germline mutations in these two tumour suppressor genes Rb and p53 are described to indicate that mutations in Rband p53 can cooperate in the transformation of certain cell types in the mouse.
Abstract: The tumour suppressor genes Rb and p53 are mutated in several types of human cancer, and many tumour types carry mutations in both genes. To study how these genes normally function, we and others have created mouse strains with Rb and p53 mutations. Here we describe the phenotypic effects of combined germline mutations in these two tumour suppressor genes. Mice mutant for both genes have reduced viability and exhibit novel pathology including pinealoblastomas, islet cell tumours, bronchial epithelial hyperplasia and retinal dysplasia. These data indicate that mutations in Rb and p53 can cooperate in the transformation of certain cell types in the mouse.
TL;DR: Findings indicate that the spectral and photochemical properties of curcumin are strongly influenced by solvent and in biological systems, singlet oxygen, superoxide and products of photodegradation may all participate inCurcumin phototoxicity depending on the environment of the dye.
Abstract: Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, is a natural yellow-orange dye derived from the rhizome of Curcuma longa, an East Indian plant. In order to understand the photobiology of curcumin better we have studied the spectral and photochemical properties of both curcumin and 4-(4-hydroxy-3-methoxy-phenyl)-3-buten-2-one (hC, half curcumin) in different solvents. In toluene, the absorption spectrum of curcumin contains some structure, which disappears in more polar solvents, e.g. ethanol, acetonitrile. Curcumin fluorescence is a broad band in acetonitrile (lambda max = 524 nm), ethanol (lambda max = 549 nm) or micellar solution (lambda max = 557 nm) but has some structure in toluene (lambda max = 460, 488 nm). The fluorescence quantum yield of curcumin is low in sodium dodecyl sulfate (SDS) solution (phi = 0.011) but higher in acetonitrile (phi = 0.104). Curcumin produced singlet oxygen upon irradiation (lambda > 400 nm) in toluene or acetonitrile (phi = 0.11 for 50 microM curcumin); in acetonitrile curcumin also quenched 1O2 (kq = 7 x 10(6) M-1 s-1). Singlet oxygen production was about 10 times lower in alcohols and was hardly detectable when curcumin was solubilized in a D2O micellar solution of Triton X-100. In SDS micelles containing curcumin no singlet oxygen phosphorescence could be observed. Curcumin photogenerates superoxide in toluene and ethanol, which was detected using the electron paramagnetic resonance/spin-trapping technique with 5,5-dimethyl-pyrroline-N-oxide as a trapping agent. Unidentified carbon-centered radicals were also detected.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: AmpG and ampD, genes essential for beta‐lactamase regulation, are here shown to be required for recycling as well and it is suggested that AmpG is the permease for a large muropeptide and AmpD is a novel cytosolic N‐acetylmuramyl‐L‐alanine amidase that cleaves anhMurNAc‐tripeptid to release tripeptides, which is then recycled.
Abstract: A mechanism for bacteria to monitor the status of their vital cell wall peptidoglycan is suggested by the convergence of two phenomena: peptidoglycan recycling and beta-lactamase induction. ampG and ampD, genes essential for beta-lactamase regulation, are here shown to be required for recycling as well. Cells lacking either AmpG or AmpD lose up to 40% of their peptidoglycan per generation, whereas Escherichia coli normally suffers minimal losses and instead recycles 40 or 50% of the tripeptide, L-alanyl-D-glutamyl-meso-diaminopimelic acid, from its peptidoglycan each generation. The ampG mutant releases peptidoglycan-derived material into the medium. In contrast, the ampD mutant accumulates a novel cell wall muropeptide, 1,6-anhydro N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (anhMurNAc-tripeptide), in its cytoplasm. This work suggests that AmpG is the permease for a large muropeptide and AmpD is a novel cytosolic N-acetylmuramyl-L-alanine amidase that cleaves anhMurNAc-tripeptide to release tripeptide, which is then recycled. These results also suggest that the phenomenon of beta-lactamase induction is regulated by the level of muropeptide(s) in the cytoplasm, since an ampD mutation that results in beta-lactamase expression even in the absence of a beta-lactamase inducer coincides with accumulation of anhMurNAc-tripeptide. The transcriptional regulator AmpR is presumably converted into an activator for beta-lactamase production by sensing the higher level of muropeptide(s). This may be an example of a general mechanism for signaling the progress of external events such as cell wall maturation, cell division or cell wall damage.
Journal Article•
TL;DR: This review will focus on IL-1 as a cytokine of primary and strategic importance to the initiation and progression of inflammatory and infectious diseases.
Abstract: Interleukin-1 (IL-1) is primarily an inflammatory cytokine Biologically, IL-1 is more closely related to tumor necrosis factor (TNF) than any other cytokine or interleukin, although the structure and receptors for IL-1 and TNF are clearly distinct IL-1 is active in the low pM and fM range and IL-1 receptors (IL-1R) are expressed in most cells, although less than 100 receptors per cell is not an uncommon finding Based on short-term blockade of IL-1 receptors in humans and animals and IL-1 beta knock-out mice, there is no evidence that IL-1 beta plays a role in development, or normal homeostasis such as metabolism, hematopoiesis, renal and hepatic function or regulation of blood pressure On the other hand, IL-1 alpha is found constitutively produced by various epithelial cells, keratinocytes of the skin and in the brain In these locations, IL-1 may contribute to cell growth and repair functions During inflammation, injury, immunological challenge or infection, IL-1 is produced and because of its multiple biological properties, IL-1 must contribute to disease Most studies on IL-1 are derived from experiments in which humans or animals are injected with IL-1 or IL-1 is added to cells in vitro The biological properties of IL-1 suggest that its effects often mimic host responses to infection, inflammation, injury or immunologic challenge Using specific IL-1 blockade, it is clear IL-1 is playing a critical role in some disease processes This review will focus on IL-1 as a cytokine of primary and strategic importance to the initiation and progression of inflammatory and infectious diseases