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Effects of sextant transrectal prostate biopsy plus additional far lateral cores in improving cancer detection rates in men with large prostate glands.

PURPOSE: To determine whether additional, far lateral cores improve the diagnostic performance of transrectal sextant biopsy in men with large prostate glands. METHODS: Men with prostate volumes of 50 mL or greater in transrectal ultrasonography who were suspected of prostatic adenocarcinoma were prospectively enrolled. Biopsy criteria were defined as 2.0 ng/mL or greater of serum total prostate-specific antigen and/or abnormal findings on digital rectal examination. Four cores of far lateral biopsies were added to the standard sextant technique. RESULTS: Of 104 patients enrolled in the present study and undergoing biopsy, 14 (13.5%) were diagnosed as having prostate cancer and 27 (26.0%) were diagnosed as having prostatic intraepithelial neoplasia (PIN) or an atypical gland. There were no cases where cancer was only detected in the additional cores, whereas PIN/atypical gland was uniquely detected from the additional, far lateral sites in eight of the 27 patients who were diagnosed with this condition. CONCLUSIONS: Although the number of patients diagnosed as having PIN/atypical gland might increase with the addition of far lateral cores, this additional sampling does not improve cancer detection rates in men with large prostate glands.

Adenocarcinoma↗

Nitric oxide synthase inhibitors reduce sarcomere addition in rat skeletal muscle.

1. Mechanical stimuli are thought to modulate the number of sarcomeres in series (sarcomere number) in skeletal muscle fibres. However, the mechanisms by which muscle cells transduce mechanical signals into serial sarcomere addition have not been explored. In this study, we test the hypothesis that nitric oxide positively modulates sarcomere addition. 2. The soleus muscle was cast-immobilized in a shortened position in 3-week-old female Wistar rats. After 4 weeks, the casts were removed, creating a period of rapid sarcomere addition. During the remobilization period, nitric oxide synthase (NOS) inhibitors or substrate were administered. 3. Rats treated with the non-isoform-specific NOS inhibitor L-nitro-arginine methyl ester during 3 weeks of remobilization had smaller soleus sarcomere numbers than control rats. Rats treated with 1-(2-trifluoromethyl-phenyl)-imidazole, which has greater specificity for the neuronal isoform than for the endothelial isoform of NOS, also had smaller soleus sarcomere numbers than control rats. These results suggest that inhibition of the neuronal isoform of NOS reduces sarcomere addition during remobilization. 4. Rats treated with L-arginine, the substrate for NOS, during 1 week of remobilization had soleus sarcomere numbers for the immobilized-remobilized muscle which were closer to that for the contralateral, non-immobilized muscle than did rats that were not treated with L-arginine. 5. These results support the hypothesis that nitric oxide derived from the neuronal isoform of NOS positively modulates sarcomere addition.

Animals↗

Additional red blood cell alloantibodies after blood transfusions in a nonhematologic alloimmunized patient cohort: is it time to take precautionary measures?

BACKGROUND: Red blood cell (RBC) alloimmunization is common in transfused patients. Most studies report on the rate of alloimmunization in chronically transfused patients, which can be as high as 60 percent. Less is known on the incidence of clinically relevant antibodies in accidentally transfused patients. Because the probability of repeat transfusion increases with longer life expectancy, it was wondered to which extend non-chronically transfused alloimmunized patients are prone to form additional antibodies after repeat transfusion events. STUDY DESIGN AND METHODS: A 20-year retrospective multicenter study was performed analyzing additional alloantibody formation, against the RH, KEL, FY, JK, and MNS blood group systems. RESULTS: After additional transfusions, 21.4 percent of 653 patients produced additional antibodies, resulting in 157 new antibody specificities. At the end of the study 33.4 percent of patients had multiple antibodies. Eighty of 140 patients (57%) who formed additional antibodies did so after one transfusion episode of a median of 2 units of RBCs. Based on the antigen profile of 316 patients, 83 percent of antibodies could have been prevented by extended matching for the C, E, c, K, Fy(a), and Jk(a) antigens. Considering the current available donors in our region, 1 to 10 percent of potential donors would be available for 39 percent of patients and greater than 10 percent of potential donors for 61 percent of patients. CONCLUSION: It has been shown that nonhematooncologic alloimmunized patients are high antibody responders, with a more than 20 times increased risk to form antibodies compared to first-time alloimmunization risk. If extended matching for C, c, E, K, Fy(a), and Jk(a) antigens in the future is considered, this group should be taken into account.

Adult↗

Effects of additional and extended acid etching on bonding to caries-affected dentine.

This study evaluated the effects of additional and extended acid etching on microtensile bond strength ( micro TBS) of two adhesive systems to sound (SD) and caries-affected dentine (CAD). Flat surfaces of CAD surrounded by SD of 36 extracted carious third molars were assigned to four treatments (i): self-etching adhesive system (Clearfil SE Bond) applied to dentine surfaces following manufacturer's instructions (MI); (ii) after additional etching for 15 s (35% phosphoric acid, PA); (iii) total-etch one-bottle adhesive (Single Bond) applied to dentine surfaces following MI; or (iv), after etching for 45 s with PA. Composite 'blocks' were built on bonded surfaces and restored teeth were vertically sectioned to obtain bonded slices of 0.7 mm thick. Slices were trimmed to create hourglass-shaped specimens (cross-sectional area of 1 mm(2)), which were tested under tension in a universal testing machine. Additional CAD and SD samples were prepared for scanning electron microscopy observations. Additional and extended etching significantly increased micro TBS to CAD; however, micro TBS of both adhesives to CAD were significantly lower than to SD. Additional and extended etching can improve bonding to CAD; however, adhesives applied on SD showed the best results for bonding.

Acid Etching, Dental↗

Reduction in oral immunogenicity of cholera toxin B subunit by N-terminal peptide addition.

The mucosal adjuvanticity of cholera toxin and the potential of the B subunit of cholera toxin (CtxB) to serve as an oral vaccine carrier have prompted interest in the coupling of immunogenic peptides to this protein. The purpose of this study was to determine how such fusions affect the function of CtxB. Oligonucleotides were genetically fused to the 5' terminus of the ctxB gene to encode additional amino acids of 8, 12, and 24 residues in length. None of these additions affected the ability of CtxB to oligomerize, as determined by nondenaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Circular dichroism revealed no difference in conformation between the modified B subunits, regardless of the length of the addition. However, when compared with native CtxB, additions to the N terminus induced a consistent change in the net conformation of the protein. By using a competitive enzyme immunoassay, the affinity of the modified B subunits for GM1 ganglioside was shown to gradually decrease with increasing length of the N-terminal addition. A similar pattern was observed for the ability of the chimeras to inhibit proliferation of concanavalin A-stimulated spleen cells in vitro, which is a previously described functional property of CtxB that is dependent on its binding to cells. Lastly, the oral immunogenicity of these chimeras was found to be less than that of native CtxB. These results indicate that large fusions to the N terminus of CtxB can significantly affect its biological properties and could reduce its value as a mechanism for effective mucosal immunization.

Administration, Oral↗

Depletion of Saccharomyces cerevisiae tRNA(His) guanylyltransferase Thg1p leads to uncharged tRNAHis with additional m(5)C.

The essential Saccharomyces cerevisiae tRNA(His) guanylyltransferase (Thg1p) is responsible for the unusual G(-1) addition to the 5' end of cytoplasmic tRNA(His). We report here that tRNA(His) from Thg1p-depleted cells is uncharged, although histidyl tRNA synthetase is active and the 3' end of the tRNA is intact, suggesting that G(-1) is a critical determinant for aminoacylation of tRNA(His) in vivo. Thg1p depletion leads to activation of the GCN4 pathway, most, but not all, of which is Gcn2p dependent, and to the accumulation of tRNA(His) in the nucleus. Surprisingly, tRNA(His) in Thg1p-depleted cells accumulates additional m(5)C modifications, which are delayed relative to the loss of G(-1) and aminoacylation. The additional modification is likely due to tRNA m(5)C methyltransferase Trm4p. We developed a new method to map m(5)C residues in RNA and localized the additional m(5)C to positions 48 and 50. This is the first documented example of the accumulation of additional modifications in a eukaryotic tRNA species.

5-Methylcytosine↗

Developmental aspects of uridine addition within mitochondrial transcripts of Trypanosoma brucei.

The mitochondrial respiratory system is absent in slender bloodstream forms of Trypanosoma brucei, incomplete in stumpy bloodstream forms, and complete in procyclic (insect) forms. The steady-state abundance of transcripts of some mitochondrially encoded components of the respiratory system correlates with its differential expression in different life cycle stages. Recently, it was reported that uridines which are not encoded in the genome are added to cytochrome b and cytochrome oxidase II transcripts. We now report that the (U)+ transcripts of both genes are found in procyclic forms and to some degree in stumpy forms but are absent in slender forms. The uridine additions to cytochrome oxidase II correct a frameshift in the gene and presumably allow production of a full-length protein, whereas those added to cytochrome b create an in-frame AUG which extends the N terminus of the predicted protein by 20 amino acids. The stage specificity of uridine additions to these transcripts thus reflects the life cycle stage during which the protein products would be used. Transcripts of MURF2, a gene of unknown function, have additional uridines in both slender and procyclic forms which create two in-frame AUGs. MURF2 transcripts additionally differ from the DNA sequence in ways which cannot be explained by uridine addition alone, implying that other processes alter these transcripts.

Animals↗

Additive effect of unoprostone and latanoprost in patients with elevated intraocular pressure.

AIMS: To assess the additive effect of unoprostone and latanoprost in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) METHODS: 32 patients with POAG or OHT were randomised to receive either latanoprost once daily or unoprostone twice daily for 4 weeks. After 4 weeks, all patients received both latanoprost and unoprostone for another 4 weeks. The IOP was measured at 9 am and 5 pm on the baseline, day 28, and day 56 visits, and at 9 am on day 14 and day 42 visits. The medications were given to the patients in an open label fashion. The observer was masked to the treatment given. The mean of the measurements was calculated. Safety parameters were also recorded. The additive effect of the medications was assessed by the reduction in intraocular pressure (IOP) when both medications were used, compared with when one medication was used. RESULTS: 28 patients completed both treatment periods and had IOP data available for evaluation. After 1 month of treatment, latanoprost significantly reduced IOP (mean by 6.1 (SEM 0.8) mm Hg (p<0.001) and unoprostone by 4.9 (1.0) mm Hg (p<0.001) from the baseline of 24.4 (0.6) mm Hg and 24.4 (1.1) mm Hg respectively (p = 0.18). When latanoprost once daily was given to patients treated with unoprostone, there was additional IOP lowering of 1.9 (0.6) mm Hg (p = 0.012). However, adding unoprostone to those being treated with latanoprost produced an IOP change of +0.4 (0.5) mm Hg (p = 0.42). Ocular symptoms and findings were mild and equally distributed between treatment groups, and after combined therapy. Hyperaemia and ocular irritation were the most frequently reported events. Over a third of patients experienced ocular irritation with the combination of medications. CONCLUSIONS: Latanoprost once daily causes additional IOP lowering in eyes which were being treated with unoprostone twice a day. However, there was no additional IOP lowering when unoprostone was added to eyes which were being treated with latanoprost. Both drugs were well tolerated together with few ocular adverse events.

Adult↗

Subjective perception of additional support requirements of elderly patients discharged from accident and emergency departments.

Fifty per cent of elderly patients discharged from accident and emergency (A&E) departments experience functional deterioration and increased dependence; 5.6% require readmission within 14 days. Discharge is often to inadequate community support. Functional assessment by A&E department staff may identify patients at greatest risk. The predictive ability of 25 patients aged 75 years or over to identify their additional support requirements following discharge from the A&E department was evaluated retrospectively using interview questionnaires 10-20 days after discharge. A total of 23 patients, of mean age 79.3 years, were interviewed. Six patients expressed concern both about coping at home and about needing extra support; four of the nine patients who recruited additional help were in this group (P = 0.239; n.s.). There was no correlation between additional support needed and patients living alone (P = 0.302; n.s.), dependent relative (P = 0.325; n.s.) or existing domiciliary support (P = 0.197; n.s.). All patients were satisfied with their management, and of the six who expressed concern about being able to cope at home, none informed A&E staff. Patients' perception is an unreliable indicator of their need for additional help and their ability to manage at home after discharge from A&E departments. Additional support requirements appear to be unrelated to domestic circumstances.

Aftercare↗

The effects of freeze drying and freeze drying additives on the prothrombin time and the international sensitivity index.

AIM: To determine whether freezing, freeze drying protective additives, or freeze drying of plasma samples from patients on coumarin treatment and from normal individuals affects prothrombin times or the international sensitivity index (ISI) calibration. METHODS: The effect of the addition of the protective additives singly and combined on the prothrombin time of coumarin samples and normal samples before and after freeze drying was observed using high and low ISI reference thromboplastins. ISI values were also determined. RESULTS: Freezing caused a prolongation of prothrombin time in the normal plasma samples with both reagents, which was significant with the low ISI human. Prolongation (non-significant) of the prothrombin time in coumarin plasma samples occurred with the human reagent only. Significant prolongation of normal prothrombin time by some of the protective additives before and after freeze drying was observed with both thromboplastins but to a greater extent with the human. Significant prolongation of prothrombin time in coumarin plasma samples was observed, but again was more marked with human thromboplastin. An approximate ISI was determined on the 20 coumarin samples. The only marked ISI change was with the WHO human thromboplastin after freeze drying of plasma, where a decrease from 0.95 to 0.90 was observed, corresponding to a marked prothrombin ratio increase. CONCLUSIONS: Freeze drying additives and the freeze drying procedure prolong normal and coumarin prothrombin times, with low ISI thromboplastin. Less marked prolongations occurred with a high ISI rabbit reagent, coumarin samples showing more significant prolongations. Marked ISI change in freeze dried plasma was only recorded with the low ISI ECAA human reagent. Frozen normal plasma samples cannot be used with confidence for ISI calibrations.

Animals↗

Adverse effect of additional weight on exercise against gravity in patients with chronic obstructive airways disease.

The effects of an acute, artificially simulated increase in body weight on exercise performance were examined in 14 patients of normal weight (mean (SD) body mass index 22.3 (2.7)), age 61 (8) years) with chronic obstructive airways disease (FEV1 1.2 (0.5) 1; vital capacity (VC) 2.9 (0.6) 1), and in six normal subjects with similar age and sex distribution. The patients performed a six minute walking test and a symptom limited step climbing test both with and without an additional 10 kg weight (two leaded aprons). The normal subjects performed a step test with and without the additional weight. Ventilation (VE) and oxygen consumption (VO2) were measured during step climbing. Resting spirometric values were not altered by the additional weight. In the patients the median number of steps climbed fell from 67.5 when they were unweighted to 44.5 when they were weighted. Mean VE and VO2 were increased during weighted step climbing by 14% and 13% but the maximum levels of VE and VO2 achieved were similar during unweighted and weighted exercise (VE 36.8 (8.6) and 37.3 (10.2) 1 min-1, VO2 1.35 (0.3) and 1.41 (0.4) 1 min-1 respectively). The normal subjects were readily able to complete 150 steps both with and without the additional weight. In the patients the six minute walking distance fell only slightly with the extra weight, from 554 (SD 61) to 540 (62) m. A subsidiary study was carried out in six healthy younger subjects in which VE and VO2 were measured during a 5.6 km/h six minute treadmill walk at zero incline. The additional weight did not alter VE or VO2 during exercise. In conclusion, a small acute increase in body weight substantially worsened the already reduced "uphill" exercise performance in patients with chronic obstructive airways disease because of its effect on ventilation and oxygen consumption. These results suggest that modest weight loss might benefit patients with chronic obstructive airways disease even though they may be only slightly above their ideal body weight.

Body Weight↗

Molecular cytogenetic characterization of Aegilops biuncialis and its use for the identification of 5 derived wheat-Aegilops biuncialis disomic addition lines.

The aim of the experiments was to produce and identify different Triticum aestivum-Aegilops biuncialis disomic addition lines. To facilitate the exact identification of the Ae. biuncialis chromosomes in these Triticum aestivum-Ae. biuncialis disomic additions, it was necessary to analyze the fluorescence in situ hybridization (FISH) pattern of Ae. biuncialis (2n = 4x = 28, U(b)U(b)M(b)M(b)), comparing it with the diploid progenitors (Aegilops umbellulata, 2n = 2x = 14, UU and Aegilops comosa, 2n = 2x = 14, MM). To identify the Ae. biuncialis chromosomes, FISH was carried out using 2 DNA clones (pSc119.2 and pAs1) on Ae. biuncialis and its 2 diploid progenitor species. Differences in the hybridization patterns of all chromosomes were observed among the 4 Ae. umbellulata accessions, the 4 Ae. comosa accessions, and the 3 Ae. biuncialis accessions analyzed. The hybridization pattern of the M genome was more variable than that of the U genome. Five different wheat-Ae. biuncialis addition lines were produced from the wheat-Ae. biuncialis amphiploids produced earlier in Martonvásár. The 2M, 3M, 7M, 3U, and 5U chromosome pairs were identified with FISH using 3 repetitive DNA clones (pSc119.2, pAs1, and pTa71) in the disomic chromosome additions produced. Genomic in situ hybridization (GISH) was used to differentiate the Ae. biuncialis chromosomes from wheat, but no chromosome rearrangements between wheat and Ae. biuncialis were detected in the addition lines.

Cytogenetic Analysis↗

The improvement of lipase secretion and stability by addition of inert compounds into Acinetobacter calcoaceticus cultures.

Acinetobacter calcoaceticus BD413 produces variable amounts of an exocellular lipase that becomes rapidly inactivated upon secretion. To achieve high yield and protect the enzyme, we assayed the addition of several inert compounds to cell-free supernatants, cell fractions, and whole cultures. Glass beads, poly(ethylene glycol) 600, Triton X-100, saccharose, gum arabic, and beta-cyclodextrin were among the compounds tested. beta-Cyclodextrin and gum arabic (and saccharose to a lesser extent) were effective enzyme stabilizers in cell-free supernatants, while gum arabic, glass beads, and Triton X-100 improved lipase secretion from cells, and, therefore, total lipase yield (30-50%, according to the additive). In whole cultures, beta-cyclodextrin was the most effective additive, particularly in combination with glass beads or gum arabic. Indeed, cultures containing beta-cyclodextrin plus gum arabic were able to maintain 95% (+/- 1.5%) of the initial lipase activity for more than 16 h, while control cultures with no additives maintained only 10% (+/- 4%) of the enzyme activity after the same period. In conclusion, the addition of inert compounds in cultures may be considered a useful approach for achieving increased yield and lipase stabilization, amenable for downstream processing.

Acinetobacter calcoaceticus↗

Evaluation of experimental combined toxicity by use of dose-frequency curves: comparison with theoretical additivity as well as independence.

Dose-frequency curves of toxic effects of a substance A were evaluated in the absence and in the presence of a fixed dose of a second substance B. Data were fitted by the curve-fitting program ALLFIT. Observed combined frequencies of A + B were compared statistically with the expected frequencies of additivity and (or) independence by the phi 2-square goodness-of-fit test. The theoretical dose-frequency curves expected for an additive response were obtained by a solely graphical procedure and the theoretical curves for independent effects were calculated from the effects of B and A at certain doses. In rotarod tests with trained mice, the combined deteriorating effect of ethanol and benzodiazepines were significantly over-additive. However, their lethal interaction appeared underadditive in mice. The lethal underadditive interaction of ethanol and phencyclidine (PCP) can be ascribed largely to independent actions of these compounds. Loss of righting reflex was additively enhanced by PCP, whereas PCP overadditively enhanced the effect of ethanol. The insecticidal action of the cholinesterase inhibitors malathion and parathion appeared additive and significantly different from independent interaction. A comparison of results from dose-response curves with isoboles showed good agreement. The method appears as an attractive alternative or as a complementary procedure to the isobolographic analysis. Combination experiments as described can be carried out and evaluated rather simply, with a minimum of expenditure and a maximum of information.

Animals↗

Rate of compliance with recommendations for additional mammographic views and biopsies.

All recommendations for immediate additional studies and biopsies following routine mammography during a 6-month period were reviewed retrospectively to establish compliance rates and determine the time intervals for completion of the recommendations. During this period, 5,693 mammograms were obtained. Additional mammographic studies and biopsies were recommended for 364 (6.4%) and 180 (3.2%) of all patients, respectively. The compliance rates were 99.7% (n = 363) for additional studies and 98.9% (n = 178) for biopsies. Additional studies and biopsies were completed within 30 days of the recommendations in 98.4% (n = 358) and 91.7% (n = 165) of the patients, respectively. Compliance with recommendations for additional studies within relatively short periods can be maximized by having the mammographic facility schedule examinations directly with the patients. Compliance with biopsy recommendations can be optimized by directly contacting the referring physician. Follow-up written reports should specifically state that a biopsy is recommended and that this has been discussed directly with the referring physician.

Biopsy↗

Hepatocellular carcinoma: are combined CT during arterial portography and CT hepatic arteriography in addition to triple-phase helical CT all necessary for preoperative evaluation?

PURPOSE: To determine whether the combination of CT during arterial portography (CTAP) and CT hepatic arteriography (CTHA) provides an added benefit to triple-phase helical CT (THCT) alone in the preoperative evaluation of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-two consecutive patients with pathologically proved HCC underwent THCT (hepatic arterial, portal venous, and delayed phases) and combined CTAP and CTHA. Two radiologists reviewed the images in three sessions: first the THCT images alone, then with the CTAP images, and finally all three sets of images. RESULTS: There were 73 pathologically confirmed HCCs. Among 72 lesions considered as HCC at THCT, 69 were proved to be HCCs. Of the additional 37 nodules interpreted as HCC at CTAP, only one was confirmed as such. Among the additional 20 lesions presumed to be HCC at combined CTAP and CTHA, only two were proved to be HCCs. The sensitivity was 94% (69 of 73 lesions) at THCT, 96% (70 of 73) with additional CTAP, and 97% (71 of 73) with all three modalities. The positive predictive value was 96% (69 of 72) at THCT, 65% (70 of 107) with additional CTAP, and 80% (71 of 89) with all three modalities. CONCLUSION: The use of CTAP and CTHA, in addition to being invasive and costly, resulted in an unacceptably high false-positive rate without a substantial increase in sensitivity. Therefore, CTAP and CTHA are not recommended for preoperative evaluation of HCC; THCT alone is preferred.

Adult↗

Ileal mucosal cyclic AMP and Cl secretion: serosal vs. mucosal addition of cholera toxin.

Changes in ion transport and cyclic AMP (cAMP) concentration produced by addition of cholera toxin to the serosal side of isolated rabbit ileal mucosa (CTs) were compared to the changes produced by addition to the mucosal side (CTm). CTs increased short-circuit current (SCC) as did CTm but it did so more slowly. CTs, unlike CTm, did not significantly decrease electrical conductance. Inhibition of the SCC response to theophylline, a measure of preexisting secretion, was almost complete 180 min after CTm but was not yet significant 180 min after CTs. Longer (280 min) after CTs, the SCC response to theophylline was reduced by 59%, a significant reduction but less than that caused by CTm. A statistically significant change in net Cl flux could not be demonstrated after CTs, although at 280 min the measured flux was halfway between the fluxes for control and CTm tissues. Cyclic AMP concentrations were determined at 190 min, 10 min after addition of theophylline. CTs, despite little or no effect on ion transport, increased cAMP to the same level as did CTm, and the effect on cAMP of adding toxin to both sides was additive. We conclude that 1) active secretion is probably stimulated by cholera toxin added on the serosal side, although more slowly than after addition to the mucosal side and 2) much of the toxin-stimulated cAMP content of the mucosa is not coupled to secretion.

Animals↗

Additive regulation of hepatic gene expression by dwarfism and caloric restriction.

Disrupted growth hormone/insulin-like growth factor-1 signaling (DF) and caloric restriction (CR) extend life span and delay the onset of age-related diseases in rodents. In combination, these interventions additively extend life span. To investigate the molecular basis for these effects, we performed genome-wide, microarray expression analysis of liver from homozygous and heterozygous Ames dwarf mice fed ad libitum or CR. CR and DF additively affected a group of 95 genes. Individually and together, DF and CR independently affected the expression of 212 and 77 genes, respectively. These results indicate that DF and CR affect overlapping sets of genes and additively affect a subset of genes. Together, the interventions produced changes in gene expression consistent with increased insulin, glucagon and catecholamine sensitivity, gluconeogenesis, protein turnover, lipid beta-oxidation, apoptosis, and xenobiotic and oxidant metabolism; and decreased cell proliferation, lipid and cholesterol synthesis, and chaperone expression. These data suggest that the additive effects of DF and CR on life span develop from their additive effects on the level of expression of some genes and from their independent effects on other genes. These results provide a novel and focused group of genes closely associated with the regulation of life span in mammals.

Animals↗