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PubMedDate not supplied

The role of total mesorectal excision in the management of rectal cancer.

BACKGROUND: Total mesorectal excision (TME) was described 20 years ago and is now being established as the therapeutic gold standard for middle and lower third rectal cancers in a number of countries worldwide. METHODS: The authors reviewed published data regarding TME since its first description in 1982. Emphasis was placed on basic principles, achievable recurrence rates, evidence for use of adjunctive strategies, and the potential of TME. RESULTS: Local recurrence rates following TME approximate 6.6% from published series, accounting for more than 5,000 patients. The available evidence for TME is largely composed of retrospective series, although benefits of TME compare favorably to established conventional controls. Recent studies have clarified the benefit of adjunctive radiotherapy with TME. There is considerable scope for development of TME within the minimal access setting, providing first principles are observed. CONCLUSIONS: Despite initial controversy, TME is now a feasible, reproducible, adjunctive surgical therapy in the management of rectal cancer.

Anastomosis, Surgical↗
PubMed2006

[Effect of total mesorectal excision and preoperative chemoradiotherapy on local recurrence in rectal cancer].

OBJECTIVE: To investigate the effect of total mesorectal excision(TME) and preoperative therapy on local recurrence in rectal cancer. METHODS: Rectal cancer patients who received TME in School of Oncology, Peking University, from January 2000 to August 2004 were enrolled in the study group. Patients who received surgical resection for rectal cancer from January 1996 to December 1999,before the introduction of TME,were chosen as controls. Postoperative complications and local recurrence were compared. Clinicopathological and follow- up data were analyzed. RESULTS: There were 161 patients in the TME group and 173 as controls. The intra- operative blood loss was significant less,hospital stay shorter,and lymph nodes harvested more in TME group than those in the control group,there was no difference in complication rate between the two groups. Local recurrence (LR) rate was 2.5% in TME and 8.0% in the control group, respectively (chi2=5.144; P=0.023). In TME group,the local recurrence rate was 1.8% in the 77 patients with preoperative therapy,and 2.9% in the other patients without preoperative therapy (P=0.182). Logistic regression analysis revealed that TME and vessel cancerous emboli were major risk factors for local recurrence of rectal cancer. CONCLUSION: TME and vessel cancerous emboli are major risk factors for local recurrence of rectal cancer.

Aged↗
PubMed1998

Total mesorectal excision in the treatment of rectal cancer: a view from the USA.

The technique of total mesorectal excision (TME) has sparked much controversy in the surgical community with its reported advantages of reduced local recurrence, improved survival, and reduced need for adjuvant therapy. TME is the total excision of the tumor with precise, sharp dissection to include midrectum and integral mesentery of the hindgut which envelopes the midrectum. In a compiled series of over 10,000 patients treated for rectal cancer, the local recurrence rate for surgery alone was 18.5%. Proponents of TME report local recurrence rates from 3.5% to 7.3% and survival rates greater than 80% at 5 years. Histopathological studies suggest that a proportion of patients will be at increased risk of local recurrence if adequate circumferential and distal mesorectal margins are not achieved as proposed in TME. Unlike any other cancers, there appears to be a great deal of surgeon variability in the treatment of rectal cancer, and local recurrence rates range from 5% to 30%. There is an unanswered question about the high rate of recurrence with the abdominoperineal resection where the principals of TME are followed and a wide excision is performed. Further questions concerning TME include clinical function, anastomotic dehiscence, sexual function, and adjuvant therapy. There are also detrimental functional costs of more distal anastomoses as required by TME, and further, more distal anastomoses are associated with increased leak rates and potentially increased morbidity and mortality. In the hands of its proponents, TME has commendable results and achieves outcomes superior to others that use combined surgery and adjuvant therapy. Unfortunately, experienced surgeons using apparently similar dissection techniques have not been able to reproduce such good results. Potential explanations include variations in technical expertise, patient and tumor selection bias, and differences in the extent of follow-up. The functional costs, increased anastomotic leak rates, and increased need for diversion must be weighed against potential reduced local recurrence rates in patients with mid and upper rectal cancers.

Anastomosis, Surgical↗
PubMed2004

Upstream stimulatory factors stimulate transcription through E-box motifs in the PF4 gene in megakaryocytes.

Platelet factor 4 (PF4) is expressed during megakaryocytic differentiation. We previously demonstrated that the homeodomain proteins (myeloid ecotropic integration site 1 [MEIS1], Pbx-regulating protein 1 [PREP1], and pre-B-cell leukemia transcription factors [PBXs]) bind to the novel regulatory element tandem repeat of MEIS1 binding element [TME] and transactivate the rat PF4 promoter. In the present study, we investigated and identified other TME binding proteins in megakaryocytic HEL cells using mass spectrometry. Among identified proteins, we focused on upstream stimulatory factor (USF1) and USF2 and investigated their effects on the PF4 promoter. USF1 and 2 bound to the E-box motif in the TME and strongly transactivated the PF4 promoter. Furthermore, physiologic bindings of USF1 and 2 to the TME in rat megakaryocytes were demonstrated by the chromatin immunoprecipitation (ChIP) assay. Interestingly, the E-box motif in the TME was conserved in TME-like sequences of both the human and mouse PF4 promoters. USF1 and 2 also bound to the human TME-like sequence and transactivated the human PF4 promoter. Expressions of USF1 and 2 were detected by reverse-transcriptase-polymerase chain reaction (RT-PCR) in the human megakaryocytes derived from CD34+ cells. Thus, these studies demonstrate that the novel TME binding transcription factors, USF1 and 2, transactivate rat and human PF4 promoters and may play an important role in megakaryocytic gene expression.

Amino Acid Motifs↗
PubMed2025

Tumor microenvironment governs the prognostic landscape of immunotherapy for head and neck squamous cell carcinoma: A computational model-guided analysis.

Immune checkpoint inhibition (ICI) has emerged as a critical treatment strategy for squamous cell carcinoma of the head and neck (HNSCC) that halts the immune escape of the tumor cells. Increasing evidence suggests that the onset, progression, and lack of/no response of HNSCC to ICI are emergent properties arising from the interactions within the tumor microenvironment (TME). Deciphering how the diversity of cellular and molecular interactions leads to distinct HNSCC TME subtypes subsequently governing the ICI response remains largely unexplored. We developed a cellular-molecular model of the HNSCC TME that incorporates multiple cell types, cellular states, and transitions, and molecularly mediated paracrine interactions. Simulation across the selected parameter space of the HNSCC TME network shows that distinct mechanistic balances within the TME give rise to the five clinically observed TME subtypes such as immune/non-fibrotic, immune/fibrotic, fibrotic only and immune/fibrotic desert. We predict that the cancer-associated fibroblast, beyond a critical proliferation rate, drastically worsens the ICI response by hampering the accessibility of the CD8 + killer T cells to the tumor cells. Our analysis reveals that while an Interleukin-2 (IL-2) + ICI combination therapy may improve response in the immune desert scenario, Osteopontin (OPN) and Leukemia Inhibition Factor (LIF) knockout with ICI yields the best response in a fibro-dominated scenario. Further, we predict Interleukin-8 (IL-8), and lactate can serve as crucial biomarkers for ICI-resistant HNSCC phenotypes. Overall, we provide an integrated quantitative framework that explains a wide range of TME-mediated resistance mechanisms for HNSCC and predicts TME subtype-specific targets that can lead to an improved ICI outcome.

Tumor Microenvironment↗
PubMed1981

An evaluation of the true metabolizable energy assay for monitoring the apparent metabolizable energy values of poultry diets.

Samples of 35 diets were obtained from five different regions of Canada. The true metabolizable energy (TME) of these diets was measured with mature White Leghorn cockerels. The N-corrected apparent metabolizable energy (MEn) values, calculated from average analysis figures, were supplied by the feed manufacturers. The relationship between TME and MEn was examined in two ways. First, the MEn values were multiplied by 1.097, the factor to convert MEn to TME derived by Sibbald (1977), and the results were compared with the corresponding determined TME values. The percent difference between the estimated and determined TME values were for Alberta from -7.1 to 3.1; for Manitoba from -9.8 to 5.4; for the Maritimes for -.3 to 10.8; for Ontario from -3.9 to 14.7, and for Saskatchewan from -4.2 to 5.7. Second, the ratio of determined TME:MEn for the various diets was calculated. The ratios varied considerably both within a region and between regions, ranging for Alberta from 1.063 to 1.176; for Manitoba from 1.041 to 1.204; for the Maritimes for .990 to 1.102; for Ontario from .957 to 1.141, and for Saskatchewan from 1.036 to 1.144. These data suggest that the TME assay could not be used to accurately monitor the MEn content of diets in commercial practice. However, this may have been due to imprecision in the TME data or in the MEn values or both.

Animal Feed↗
PubMed1981

Influence of an indigestible material on energy excretion by roosters and on true metabolizable energy of corn.

The influence of an indigestible and noncombustible material, silica gel (SG) on the excretion of energy by roosters and on the true metabolizable energy (TME) of corn was determined. Energy excretion by fasted roosters increased linearly with each increment of SG force-fed. The equation, energy excreted (kcal/24 hr) = 9.87 + (.47 x g SG) described this effect of SG. The data also showed that 24 hr was insufficient time for SG to completely clear the digestive tract, irrespective of amount force-fed. The TME of corn was 4.05 kcal/g dry matter when the grain was force-fed alone to roosters, when corn was force-fed in mixtures containing increasing proportions of SG, the TME of corn decreased with each increment of SG in the mixture. It was concluded that the extra energy excreted as a consequence of the presence of SG in mixtures with corn caused an underestimation of corn's TME. The regression coefficient relating energy excretion to amount of SG forced-fed in the previous trial was used to correct energy excretion by roosters fed corn-SG mixtures, and corrected TME's for corn were calculated. The average corrected TME of corn was 3.97 kcal/g dry matter. These data illustrated that an indigestible material passing through the gastrointestinal tract of the chicken changed the amount of fecal metabolic energy excreted and, consequently, influenced the TME value of companion feedstuffs when the conventional TME assay procedure was used.

Animal Feed↗
PubMed2005

[The assessment of curative effect after total mesorectal excision with autonomic nerve preservation for rectal cancer].

OBJECTIVE: To evaluate the impact on sexual function, local recurrence and survival after total mesorectal excision (TME) with autonomic nerve preservation (PANP) of rectal cancer. METHODS: One hundred and five patients after TME with PANP were followed by means of questionnaire on postoperative genital function [TME + PANP(+) group], and the results of 110 patients after TME without PANP [TME + PANP(-) group] were compared with, also their local recurrence and 5-year survival were retrospectively analyzed. RESULTS: TME + PANP(+) group was compared to TME + PANP(-) group: the erection dysfunction, 33.3% vs 63.2%; the ejaculation dysfunction, 43.8% vs 70.0% (P < 0.01), there were significant differences between two groups, but no difference in local recurrent rate and 5-year survival rate (7.6% vs 5.5%; 63.4% vs 59.7%, P > 0.05). CONCLUSION: The TME with PANP of rectal surgery ensure the radical cure of rectal cancer, at the same time reasonably save the postoperative sexual function and obtain satisfactory postoperative survival.

Adult↗
PubMed1997

Ornithine decarboxylase inhibitor lessens the rat gastric carcinogenesis enhancement caused by tyrosine methyl ester.

The effects of combined administration of a catecholamine precursor, tyrosine methyl ester (TME), and an ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the norepinephrine (NE) concentration and ODC activity of the gastric wall, and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received s.c. injections of TME, 512 mg/kg body weight, every other day and drinking water with or without 2.5 g/l of DAP after 25 weeks of oral administration of MNNG. At week 52, administration of TME resulted in significant increases in the incidence of gastric cancers, in the NE concentration and the ODC activity of the antral portion of the gastric wall, and in the labeling index of antral epithelial cells. Administration of both TME and DAP significantly reduced the enhancements by TME of gastric carcinogenesis, NE concentration and ODC activity of the antral wall, and the labeling index of the antral mucosa. Our results suggest that ODC inhibition lessens enhancement by TME of gastric carcinogenesis and that the enhancement by TME of gastric carcinogenesis is mediated in part by polyamine biosynthesis.

Animals↗
PubMed1993

Immunolocalization of scrapie amyloid in non-congophilic, non-birefringent deposits in golden Syrian hamsters with experimental transmissible mink encephalopathy.

Transmissible mink encephalopathy (TME), a naturally occurring subacute spongiform encephalopathy in commercially ranch-reared mink (Mustela vision), is characterized neuropathologically by spongiform changes in the neuropil, intracytoplasmic neuronal vacuolation and astrocytic hypertrophy and hyperplasia. Amyloid deposits have not been observed in brain tissue sections from animals with natural and experimental TME using conventional histochemical stains such as Congo red. To determine if amyloid deposits be visualized by immunocytochemical techniques, we stained formalin-fixed, formic acid-treated brain tissue sections from several animal species with natural and experimental TME, using a rabbit antiserum directed against scrapie amyloid (PrP27-30). Scrapie amyloid-immunoreactive deposits were found in golden Syrian hamsters experimentally infected with TME, but were absent in mink with natural and experimental TME, as well as in ferrets and squirrel monkeys with experimental TME. The scrapie amyloid-immunoreactive deposits, which were non-congophilic and non-birefringent, were distributed in the subependymal, subpial and perivascular regions of the brain, as in hamsters infected with the 263K strain of scrapie. Ultrastructurally, scrapie amyloid-immunoreactive deposits revealed a collection of degenerating neurites with numerous abnormal mitochondria and degenerating synapses. Amyloid fibrils were not observed. Anti-scrapie amyloid antibodies immunoabsorbed with scrapie amyloid abolished immunostaining. Our data indicate the presence of scrapie amyloid lacking the molecular conformation of amyloid fibrils in hamsters with experimental TME.

Animals↗
PubMed2006

The use of biolistic inoculation of cassava mosaic begomoviruses in screening cassava for resistance to cassava mosaic disease.

Inoculation of cassava with infectious clones of cassava mosaic geminiviruses (Geminiviridae: Begomovirus) and total DNA extracts from plants infected with well-characterised viruses was evaluated using the Bio-Rad Helios Gene Gun System. Total DNA extracts from infected plants and cloned viruses were produced for coating gold particles and bombardment onto new cassava genotypes, 96/1089A, 96/1039, 96/0160, 96/0304 and three local landraces TME 117, TME 3 and TME 4. Cloned DNA of a Kenyan isolate of the recombinant variant of East African cassava mosaic virus (EACMV-UG2-[Ka]), was only infectious to TME 117 (7/10 plants), 3 weeks post-inoculation with mild infection symptoms in the newly developing leaves. Biolistic inoculation with a chimeric pseudorecombinant virus between DNA A and B components from EACMV-[Ke-Kilifi] and EACMV-UG2-[Ka], respectively, was infectious to TME 117, 96/1039 and 96/0304 and developed very severe and persistent symptoms. TME 3 and TME 4 also developed symptoms, 12 days post-inoculation (d.p.i.). Total DNA extracts of ACMV and EACMV-[Ke-Kilifi] resulted in serious infections with symptoms already evident, 10d.p.i. In general, biolistic inoculation trials with total DNA extracts resulted in a higher number of infected plants expressing symptoms at a much earlier stage (10-12d.p.i.) compared with trials inoculated with virus clones.

Begomovirus↗
PubMed2005

Novel behavior of O-methylated beta-cyclodextrins in inclusion of meso-tetraarylporphyrins.

[structure: see text] The mechanism for formation of extremely stable 1:2 inclusion complexes of water-soluble meso-tetraarylporphyrins with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD) in aqueous solutions has been studied by means of NMR spectroscopy and isothermal titration calorimetry. To simplify the system, 5,10,15-tris(3,5-dicarboxylatophenyl)-20-phenylporphyrin (1) was used as a guest porphyrin, because 1 forms only a 1:1 inclusion complex with cyclodextrin (CD). As host compounds, native beta-CD and the O-methylated-beta-CDs such as heptakis(2,3-di-O-methyl)- (2,3-DMe-beta-CD), heptakis(2,6-di-O-methyl)- (2,6-DMe-beta-CD), and TMe-beta-CDs were used. The thermodynamic parameters for complexation such as binding constants (K) and enthalpy (DeltaH degrees ) and entoropy changes (DeltaS degrees ) were determined by means of isothermal titration calorimetry. The K value for complexation of 1 with CD increases in the order beta-CD (K = (1.2 +/- 0.1) x 10(3) M(-)(1)) < 2,6-DMe-beta-CD ((1.2 +/- 0.1) x 10(4) M(-)(1)) << TMe-beta-CD ((6.9 +/- 0.4) x 10(6) M(-)(1)) < 2,3-DMe-beta-CD ((8.5 +/- 0.5) x 10(6) M(-)(1)), indicating participation of the secondary OCH(3) groups in extremely strong complexation of 1 with CD. Complex formation of 1 with beta-CD and 2,6-DMe-beta-CD is an enthalpically and entropically favorable process, while that with TMe-beta-CD and 2,3-DMe-beta-CD is an enthalpically much more favorable but an entropically less favorable process. The thermodynamic parameters suggest that inclusion of 1 into the cavities of TMe-beta-CD and 2,3-DMe-beta-CD is promoted by van der Waals interactions, which are stronger than those in the cases of beta-CD and 2,6-DMe-beta-CD. (13)C NMR spectra show that the conformations of both TMe-beta-CD and 2,3-DMe-beta-CD are altered upon inclusion of 1, while those of beta-CD and 2,6-DMe-beta-CD are mostly retained. On the basis of these results, it can be concluded that induced-fit type complexation of 1 with TMe-beta-CD and 2,3-DMe-beta-CD causes extremely strong binding of the host to the guest.

Binding Sites↗
PubMed2000

Determination of r-7,t-8,9,c-10-tetrahydroxy-7,8,9, 10-tetrahydrobenzo[a]pyrene in human urine by gas chromatography/negative ion chemical ionization/mass spectrometry.

r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (trans-anti-BaP-tetraol) is the major hydrolysis product of r-7, t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), the principal ultimate carcinogen of the environmental pollutant benzo[a]pyrene (BaP). As part of a program to establish activation/detoxification profiles of urinary metabolites of BaP in humans, we developed a method for quantifying trans-anti-BaP-tetraol. Urine was collected from three groups of individuals exposed to BaP: psoriasis patients treated with a coal tar-containing ointment, steel workers, and smokers. [(2)H(12)]-trans-anti-BaP-tetraol was added to the urine as an internal standard. The urine was treated with beta-glucuronidase and sulfatase, and then the BaP-tetraols were enriched by reverse-phase and phenylboronic acid solid-phase extraction. The resulting fraction was treated with sodium hydride and methylmethane sulfonate to convert BaP-tetraols to the corresponding tetramethyl ethers (BaP-TME). The mixture was purified by normal-phase HPLC and analyzed by gas chromatography/negative ion chemical ionization/mass spectrometry with selected ion monitoring. [(13)CH(3)](4)-trans-anti-BaP-TME was used as an external standard. Ions at m/z 376, 380, and 388 were monitored for quantitation of trans-anti-BaP-TME, [(13)CH(3)](4)-trans-anti-BaP-TME, and [(2)H(12)]-trans-anti-BaP-TME, respectively. The instrumental detection limit was approximately 1 fmol of trans-anti-BaP-TME. trans-anti-BaP-tetraol (as trans-anti-BaP-TME) was detected in 20 of 20 individuals receiving coal tar therapy (mean, 16 fmol/mL of urine), 13 of 13 exposed steel workers (mean, 4.1 fmol/mL of urine), and nine of 21 cigarette smokers (mean, 0.5 fmol/mL of urine). The means in these groups were significantly different (P < 0.0001). The urine of steel workers was also analyzed for cis-anti-BaP-tetraol and cys-syn-BaP-tetraol, but neither was found. The results of this study provide a quantitative method for determination of parts per trillion levels of trans-anti-BaP-tetraol in human urine. Ultimately, this method can be employed as part of a phenotyping approach for assessing BaP metabolites in human urine.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters.

Experimental transmission of the Stetsonville, Wisconsin, U.S.A. source of transmissible mink encephalopathy (TME) to outbred Syrian golden hamsters resulted in two distinct syndromes, termed hyper (HY) and drowsy (DY), that diverge by the third hamster passage. The syndromes differed with respect to clinical signs, incubation period, brain titre, brain lesion profile and pathogenicity in mink. HY hamster TME had an incubation period of 65 +/- 1 days and was characterized by clinical signs of hyperaesthesia and cerebellar ataxia. Lethargy and the absence of hyperexcitability or cerebellar ataxia were representative of DY hamster TME which had an incubation period of 168 +/- 2 days. At endstage, HY and DY infected animals had brain titres of 10(9.5) LD50/g and 10(7.4) LD50/g of tissue, respectively, indicating that the replication kinetics of these two strains is different. Hamster TME passaged back into mink revealed that only DY retained mink pathogenicity. This suggests that the DY agent is the major mink pathogen in the Stetsonville TME source that is also pathogenic in hamsters after a long incubation period. The HY agent is likely to be a minor component of the original TME mink brain that replicates more rapidly than DY agent in hamsters, but alone is non-pathogenic in mink. The presence of the HY and DY strains of agent that retain their biological characteristics on repeated hamster passage in the Stetsonville TME source requires that the informational molecule encoding these transmissible agents has the capacity to account for this biological diversity.

Animals↗
PubMed2002

Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial.

PURPOSE: Total mesorectal excision (TME) surgery in the treatment of rectal cancer has been shown to result in a reduction in the number of local recurrences in retrospective studies. Reports on improved local control after preoperative, hypofractionated radiotherapy (RT) have led to the introduction of a prospective randomized multicenter trial, in which the effect of TME surgery with or without preoperative RT were evaluated. Any benefit in regard to a reduced local recurrence rate and possible improved survival must be weighed against potential adverse effects in both the short-term and the long-term. The present study was undertaken to assess the acute side effects of short-term, preoperative RT in rectal cancer patients and to study the influence of five doses of 5 Gy on surgical parameters, postoperative morbidity and mortality in patients randomized in the Dutch TME trial. PATIENTS AND METHODS: We analyzed 1,530 Dutch patients entered onto a prospective randomized trial, comparing preoperative RT with five doses of 5 Gy followed by TME surgery with TME surgery alone, of which 1,414 patients were assessable. Toxicity from RT, surgery characteristics, and postoperative complications and mortality were compared. RESULTS: Toxicity during RT hardly occurred. Irradiated patients had 100 mL more blood loss during the operation (P <.001) and showed more perineal complications (P =.008) in cases of abdominoperineal resection. The total number of complications was slightly increased in the irradiated group (P =.008). No difference was observed in postoperative mortality (4.0% v 3.3%) or in the number of reinterventions. CONCLUSION: Preoperative hypofractionated RT is a safe procedure in patients treated with TME surgery, despite a slight increase in complications when compared with TME surgery only.

Adult↗
PubMed2005

Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients--a Dutch colorectal cancer group study.

PURPOSE: Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision (TME). This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 x 5 Gy radiotherapy and TME. Also, hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment. PATIENTS AND METHODS: Long-term morbidity was assessed in patients from the prospective randomized TME trial, which investigated the efficacy of 5 x 5 Gy before TME surgery for mobile rectal cancer. Dutch patients without recurrent disease were sent a questionnaire. RESULTS: Results were obtained from 597 patients, with a median follow-up of 5.1 years. Stoma function, urinary function, and hospital treatment rates did not differ significantly between the treatment arms. However, irradiated patients, compared with nonirradiated patients, reported increased rates of fecal incontinence (62% v 38%, respectively; P < .001), pad wearing as a result of incontinence (56% v 33%, respectively; P < .001), anal blood loss (11% v 3%, respectively; P = .004), and mucus loss (27% v 15%, respectively; P = .005). Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone. CONCLUSION: Although preoperative short-term radiotherapy for rectal cancer results in increased local control, there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone. Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME. Future strategies should be aimed at selecting patients for radiotherapy who are at high risk for local failure.

Adult↗
PubMed2006

First and second cattle passage of transmissible mink encephalopathy by intracerebral inoculation.

To compare clinicopathologic findings of transmissible mink encephalopathy (TME) with other transmissible spongiform encephalopathies (TSE, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie and chronic wasting disease [CWD]), two groups of calves (n = 4 each) were intracerebrally inoculated with TME agents from two different sources (mink with TME and a steer with TME). Two uninoculated calves served as controls. Within 15.3 months postinoculation, all animals from both inoculated groups developed clinical signs of central nervous system (CNS) abnormality; their CNS tissues had microscopic spongiform encephalopathy (SE); and abnormal prion protein (PrP(res)) as detected in their CNS tissues by immunohistochemistry (IHC) and Western blot (WB) techniques. These findings demonstrate that intracerebrally inoculated cattle not only amplify TME PrP(res) but also develop clinical CNS signs and extensive lesions of SE. The latter has not been shown with other TSE agents (scrapie and CWD) similarly inoculated into cattle. The findings also suggest that the diagnostic techniques currently used for confirmation of bovine spongiform encephalopathy (BSE) would detect TME in cattle should it occur naturally. However, it would be a diagnostic challenge to differentiate TME in cattle from BSE by clinical signs, neuropathology, or the presence of PrP(res) by IHC and WB.

Animals↗
PubMed2004

Mechanoenergetic estimation of multiple cross-bridge steps per ATP in a beating heart.

The efficiency from the ventricular O(2) consumption (VO(2)) to the total mechanical energy (TME) generated by ventricular contraction has proved relatively constant at approximately 35%, independent of the loading and contractile conditions in a canine heart. TME is the sum of the external mechanical work for ejecting a stroke volume against the afterload and of the mechanical potential energy for developing ventricular pressure in each beat. The approximately 35% VO(2)-to-TME efficiency indicates an also constant approximately 60% ATP-to-TME efficiency in a beating heart, based on the nominal approximately 60% VO(2)-to-ATP efficiency in the myocardial oxidative phosphorylation. I newly attempted to explain the load-independent approximately 60% ATP-to-TME efficiency by the recently reported approximately 7-10 nm unitary step size and approximately 0.8-1.5 pN unitary force of a cross-bridge (CB) at the molecular level in in vitro motility assays. This single CB behavior suggests that its unitary cycle could generate a mechanical energy of approximately 0.6-1.5x10(-20) J at most. From the nominal free energy of approximately 10x10(-20) J per ATP, the efficiency from one ATP to the CB unitary cycle would then be approximately 6-15%. This low efficiency is only approximately 1/10-1/4 of the approximately 60% ATP-to-TME efficiency at the heart level. This discrepancy suggests that each CB would repeat the unitary cycle at least approximately 4-10 times per ATP to achieve the high constant ATP-to-TME efficiency in a beating heart. This seems to represent a considerable mechanoenergetic advantage of the heart at the integrative heart level as compared to the molecular CB level.

Adenosine Triphosphate↗