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PubMed1986

Animal fat effects on nutrient utilization.

Laying hens were employed to study the effects of carrier on the true metabolizable energy (TME) of tallow using corn, milo, soybean meal, wheat bran, and dehydrated alfalfa meal with tallow at 0, 2, 4, or 6%. In addition to bomb calorimetry measurements on feed and excreta samples, tallow TME values were calculated from absorbability data. Estimates of TME for tallow varied with carrier feedstuff from 7.19 kcal/g in soybean meal to 13.62 kcal/g when wheat bran was fed. For the corn, milo, and soybean meal series only fat retentions were significantly affected by tallow supplementation. Calculated tallow absorbabilities were 101.8% with corn, 95.8% with milo, and 107.3% with soybean meal. Highest tallow TME values were obtained with wheat bran and dehydrated alfalfa meal, apparently due to increase protein retention from wheat bran and to both improved protein retention and starch absorption with dehydrated alfalfa meal.

Animal Feed↗

PubMed1976

Transmissible mink encephalopathy. Reduced spongiform degeneration in aged mink of the Chediak-Higashi genotype.

Mink which are 18 months or older and are dying of transmissible mink encephalopathy (TME) have been found to have a marked reduction in spongiform degeneration of the brain if they are homozygous for the Aleutian gene and thus exhibit the autosomal recessive disorder known as the Chediak Higashi (CH) syndrome. CH mink younger than 1 year, and young or old non-CH mink have a typical lesion profile with widespread microvacuolation of the neuropile. Whereas aged CH mink have reduced spongiform degeneration at both the light and electron microscopic level, there is no other apparent alteration in the TME disease process. The length of incubation, clinical signs, astrocytic response, and brain concentration of the TME agent are comparable to those seen in non-CH mink. We conclude that spongiform degeneration is a secondary change in TME and speculate that vacuolation may be the result of lysosomal enzymes causing an increase in ganglioside catabolism.

Age Factors↗

PubMedDate not supplied

[Skills by training. Education and case volume are strong prognostic factors in rectal cancer surgery].

The TME project (TME = total mesorectal excision) demonstrated and probably enhanced a major shift in rectal cancer surgical practice in Stockholm with an increased centralisation and specialisation. As a result, local control and cancer-specific survival has been significantly improved. In addition, the frequency of APR (APR = abdominoperineal resection) declined. TME based surgery demands surgical skill, which can be achieved by participation in education programmes and increased by personal training and experience. Variability in patient outcome is seen also with TME based surgery and is mainly related to case volume, with better results obtained in patients treated by high-volume surgeons. A combined treatment modality approach, integrating the colorectalsurgeon, diagnostic radiologist, pathologist, medical and radiation oncologist is necessary to achieve optimal outcome.

Clinical Competence↗

PubMed2004

[Total mesorectal excision by laparoscopy for rectal cancer].

The treatment of rectal cancer has improved mostly because of the emergence of total mesorectal excision (TME), first described by Heald, and the adjunct of adjuvant therapy in the form of radiotherapy and chemotherapy. Laparoscopy has now been performed for more than a decade with results showing faster return to activity and decreased postoperative pain for intra-abdominal surgery. Laparoscopy is now widely used and is well accepted for the treatment of most intra-abdominal benign pathologies. Furthermore, several authors now report excellent short and medium-term results for the treatment of colorectal cancer. These study tends to show that laparoscopy can be safely applied to digestive malignancies, when oncological principles specific to laparoscopy are respected. The laparoscopic approach is in our opinion a perfect approach for the performance of TME, because of the magnification of structures that it provides, and allows the surgeon to see important structures that need to be identified for the performance of the best oncological and functional procedure possible. This paper describes in a through manner our standardized technique. We also review our own experience with laparoscopic TME, the multimodal treatment of rectal cancer, and provide an analysis of the literature about TME when performed by laparotomy and laparoscopy.

Clinical Trials as Topic↗

PubMedDate not supplied

Identification of hiatal ligament for laparoscopic total mesorectal excision.

Total mesorectal excision (TME) based operation is now established as a standard procedure for patients with lower or middle third rectal cancer. Laparoscopic surgery has a great advantage in colorectal surgery, with good operative views, as well as benefit to the patients owing to less invasiveness, early recovery and shorter hospitalization. From April 2001 through March 2002, we assessed the laparoscopic TME for eight consecutive patients with rectal cancer in Kobe University Hospital (median age: 65.3). The procedure included sharp mesorectal dissection with high vascular ligation and preservation of autonomic pelvic nerves. During the laparoscopic TME, the hiatal ligament that is the sequence of anococcygeal raphe body can be identified with the traction of the rectum upward, and this fixes the posterior wall of the rectum to the levator hiatus. Resection of the hiatal ligament enables us to isolate the recto-anal canal up to the level of the internal anal sphincter. We conclude that identification of the hiatus ligament is essential to achieve the appropriate laparoscopic TME.

Adenocarcinoma↗

PubMed2005

Interactions between endothelia of the trabecular meshwork and of Schlemm's canal: a new insight into the regulation of aqueous outflow in the eye.

PURPOSE: To test the hypothesis that trabecular meshwork endothelial cells (TMEs) regulate aqueous outflow by actively releasing ligands that upon binding to Schlemm's canal endothelial cells (SCEs) increase transendothelial flow, thereby facilitating the egress of aqueous. METHODS: We tested our hypothesis by (1) activating the TMEs in vitro using a laser procedure known to increase aqueous outflow in vivo; (2) demonstrating that lasered TMEs become activated at the genome-wide level and synthesize ligands; (3) ascertaining that media conditioned by laser-activated TMEs and ligands therein increase transendothelial flow when added to SCEs; and (4) determining that ligands identified as synthesized by TMEs increase permeability when added to SCEs. RESULTS: We find that adding either media conditioned by lasered TMEs or ligands synthesized by TMEs to naïve control SCEs increases permeability. Adding media boiled, diluted, or conditioned by nonlasered TMEs abrogates these permeability effects. Media conditioned by either lasered TMEs or SCEs (TME-cm/SCE-cm), when added to untreated controls of each cell type, induce congruous gene expression and flow effects: TME-cm induces far more differentially expressed genes (829 in control TMEs and 1,120 in control SCEs) than does the SCE-cm (12 in control TMEs and 328 in control SCEs), and TME-cm also increases flow much more (more than 11-fold in control TMEs and more than fourfold in control SCEs) than does the SCE-cm (fivefold in control TMEs and twofold in control SCEs). CONCLUSIONS: As postulated, the TMEs release factors that regulate SCE permeability. Derangement of this TME-driven process may play an important role in the pathogenesis of glaucoma. Ligands identified, which regulate permeability, have potential use for glaucoma therapy.

Aqueous Humor↗

PubMed1993

Alanine-scanning mutagenesis of the epidermal growth factor-like domains of human thrombomodulin identifies critical residues for its cofactor activity.

Thrombomodulin (TM) is an endothelial cell surface-bound cofactor in thrombin-dependent formation of activated protein C, a potent anticoagulant. Cofactor activity has been localized to the carboxyl-terminal half of the six epidermal growth factor-like (EGF) domains of TM (TME). To identify residues in TME that are critical for activity, 77 alanine point mutants were made between Cys-333 and Cys-462 by site-directed mutagenesis (all residues except Ala, Cys, Gly, and Pro). Mutants were expressed in Escherichia coli and cofactor activity measured directly in periplasmic extracts obtained by osmotic shock. Critical residues were defined as those which when mutated had less than 25% cofactor activity of a reference TME. Western blots of non-reduced samples confirmed that alanine substitutions did not significantly decrease expression levels or result in the formation of multimers. In EGF4, which is essential for protein C activation by the thrombin-TM complex, critical residues were: Asp-349, Glu-357, Tyr-358, and Phe-376. In EGF5-EGF6, critical residues within a proposed acidic thrombin-binding region were: Glu-408, Tyr-413, Ile-414, Leu-415, Asp-416, Asp-417, Asp-423, Ile-424, Asp-425, and Glu-426. A potential Ca(2+)-binding site, which is comprised of residues Asp-423, Asp-425, Glu-426, Asn-439, Leu-440, and Phe-444, was also identified and overlaps the thrombin-binding region. Asp-461, in the C-loop of EGF6 previously shown to be critical for thrombin binding, was also critical. Asp-398, Asp-400, Asn-402, and Asn-429 in EGF5 were also critical. Thus, rapid alanine-scanning mutagenesis of TME has identified 22 critical residues in the region comprising EGF4-6, which is essential for thrombin binding and protein C activation by the thrombin-TM complex.

Alanine↗

PubMed1997

Evaluation of a policy of total mesorectal excision for rectal and rectosigmoid cancers.

BACKGROUND: Total mesorectal excision (TME) is advocated for rectal cancer but the indications and extent of resection vary widely between surgeons. METHODS: Seventy-six consecutive patients (61 elective, 15 acute admission) with rectal or rectosigmoid cancer were admitted to a unit where TME was the preferred surgical option for potentially curative cancer at all levels of the rectum. RESULTS: Procedures undertaken were anterior resection (38 patients), abdominoperineal resection (18), Hartmann's procedure (ten) and transanal excision (one). Six patients had proximal faecal diversion alone and surgery was withheld in three. Anastomotic leaks occurred in six of 37 patients who had anterior resection with primary anastomosis, resulting in one early death. The presence of a proximal stoma did not influence the rate or seriousness of anastomotic dehiscence. After potentially curative TME in 45 patients, there have been eight local recurrences, four associated with systemic metastases and four which occurred in isolation (median follow-up 34 months). CONCLUSION: Curative TME was deemed appropriate in 59 per cent of unselected patients with rectal cancer. It was associated with few local recurrences but a morbidity rate that questions its role in treatment of upper third tumours.

Adult↗

PubMed1998

Mesorectal excision for rectal cancer: a view from Europe.

The local recurrence rate after rectal cancer surgery is discussed as related to conventional and total mesorectal excision (TME) techniques. Studies now show that the wide variation in results between centers and among surgeons depends, at least in part, on differences in surgical technique. We conclude that local tumor recurrence rate is lower after TME than after conventional surgery and emphasize the importance of a standardized macroscopic evaluation of the resected specimen. Population-based registration to evaluate the quality of surgery is recommended. It is also suggested that randomized studies on adjuvant treatment for rectal cancer should include a "surgery only" arm when a local tumor recurrence rate of 10% or less is being studied. Until such investigations are performed, we conclude that the role for adjuvant treatment is questionable and that TME surgery is preferred as the treatment option for Stage T1-T3 rectal cancers.

Europe↗

PubMed1997

Paternal transmission of the mouse Thp mutation is lethal in some genetic backgrounds.

Thp is a large deletion on chromosome 17 which includes the maternal lethal gene Tme. Documentation of inheritance patterns suggests that Tme is an imprinted gene which is required for viability; maternal deletion is lethal while paternal deletion is viable. However, paternal transmission of Thp is rarely the expected 50%. We show here that paternally inherited Thp is lethal in some strains, providing evidence of an incompletely penetrant, dosage sensitive lethal allele of a locus that probably maps to the hairpin tail region of chr. 17. Interpretation of the various phenotypes associated with loss of the putative Tme gene, Igf2r, may need to be revised in view of these observations.

Abnormalities, Multiple↗

PubMed2026

Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.

Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patients to define four genomic subtypes (C1, C2, C3, and C4) with divergent survival (C4 worst: median overall survival [OS], 26 months). In parallel, a novel tumor microenvironment (TME) classification based on CD8+T/M2 macrophage ratio stratified patients into High (> 1.5), Intermediate (0.8-1.5), and Low (< 0.8) groups. Unexpectedly, the Intermediate TME group showed the poorest outcomes (5-year OS: 10%). Integration revealed a lethal subgroup (C4 + Intermediate TME; 9.8% of cohort) with a median OS of 3.0 months (hazard ratio = 7.24, p = 0.006). Prognostic nomograms incorporating these subtypes showed promising discriminative performance in internal validation (C-index > 0.78), but external validation is needed. Together, these findings identify a high-risk biological subset and provide a hypothesis-generating framework for future biomarker-driven risk stratification and therapeutic discovery in PCNSL.

Humans↗

PubMed2005

Bladder and sexual function following resection for rectal cancer in a randomized clinical trial of laparoscopic versus open technique.

BACKGROUND: Bladder and sexual dysfunction are recognized complications of mesorectal resection. Their incidence following laparoscopic surgery is unknown. METHODS: Bladder and sexual function were assessed in patients who had undergone laparoscopic rectal, open rectal or laparoscopic colonic resection as part of the UK Medical Research Council Conventional versus Laparoscopic-Assisted Surgery In Colorectal Cancer (CLASICC) trial, using the International Prostatic Symptom Score, the International Index of Erectile Function and the Female Sexual Function Index. Sexual and bladder function data from the European Organization for Research and Treatment of Cancer QLQ-CR38 collected in the CLASICC trial were used for comparison. RESULTS: Two hundred and forty-seven (71.2 per cent) of 347 patients completed questionnaires. Bladder function was similar after laparoscopic and open rectal operations for rectal cancer. Overall sexual function and erectile function tended to be worse in men after laparoscopic rectal surgery than after open rectal surgery (overall function: difference - 11.18 (95 per cent confidence interval (c.i.) -22.99 to 0.63), P = 0.063; erectile function: difference -5.84 (95 per cent c.i. -10.94 to -0.74), P = 0.068). Total mesorectal excision (TME) was more commonly performed in the laparoscopic rectal group than in the open rectal group. TME (odds ratio (OR) 6.38, P = 0.054) and conversion to open operation (OR 2.86, P = 0.041) were independent predictors of postoperative male sexual dysfunction. No differences were detected in female sexual function. CONCLUSION: Laparoscopic rectal resection did not adversely affect bladder function, but there was a trend towards worse male sexual function. This may be explained by the higher rate of TME in the laparoscopic rectal resection group.

Aged↗

PubMed2006

Radiological findings do not support lateral residual tumour as a major cause of local recurrence of rectal cancer.

BACKGROUND: The aim of this study was to determine the sites of local recurrence following radical (R0) total mesorectal excision (TME) for rectal cancer in an effort to elucidate the reasons for recurrence. METHODS: Thirty-seven patients with recurrence following curative resection for rectal cancer were identified from a population of 880 patients operated on by surgeons trained in the TME procedure. Two radiologists independently examined 33 available computed tomograms and magnetic resonance images taken when the recurrence was detected. RESULTS: Twenty-nine of the 33 recurrences were found in the lower two-thirds of the pelvis. Two recurrent tumours appeared to originate from lateral pelvic lymph nodes. Evidence of residual mesorectal fat was identified in 15 patients. Fourteen of the recurrent tumours originated from primary tumours in the upper rectum; all of these tumours recurred at the anastomosis and 12 of the 14 patients had evidence of residual mesorectal fat. CONCLUSION: Lateral pelvic lymph node metastases are not a major cause of local recurrence after TME. Partial mesorectal excision may be associated with an increased risk of local recurrence from tumours in the upper rectum.

Adenocarcinoma↗

PubMed2005

Rapid differentiation of Fusarium oxysporum isolates using PCR-SSCP with the combination of pH-variable electrophoretic medium and low temperature.

Differentiation of Fusarium oxysporum is significantly important for unraveling the pathogenetic mechanism of Fusaria wilts. In this study, isolates of F. oxysporum were screened from the soils in the rhizosphere of watermelon plant by Komada medium and differentiated by SSCP approach with the combination of pH-variable electrophoretic medium (Tris-MES-EDTA (TME), pH 6.1) and low temperature (9 degrees C). We found that TME was a good electrophoretic medium and its pH value was variable over the course of electrophoresis in our apparatus. The pH-variable electrophoretic medium made more contribution for the better differentiation of F. oxysporum isolates than low temperature. The combination of TME pH 6.1 and low temperature showed an improved effect on resolution of ssDNAs. Leaving partial nondenatured dsDNA for SSCP was advantageous for differentiation of F. oxysporum isolates. The SSCP patterns of F. oxysporum isolates proved to be highly reproducible. Sequencing data confirmed that this SSCP method could detect one single base change within the 550 bp PCR fragment from the ribosomal internal transcribed spacer region of F. oxysporum.

Base Sequence↗

PubMed2002

Tropomyosin isoforms present in the sea anemone, Anthopleura japonica (Anthozoa, Cnidaria).

Five isoforms of tropomyosin, designated as TMa, TMb, TMc, TMd, and TMe, were detected in the sea anemone, Anthopleura japonica. The apparent molecular weights of these isoforms were estimated to be approximately 30 kD to 37.5 kD, and their pI values were approximately 4.55 (TMa and TMb) and 4.65 (TMc, TMd, and TMe). Although sea anemone tropomyosin isoforms have the ability to bind to rabbit skeletal muscle actin, they preferably bind to actin at higher concentrations of Mg(2+) (10-20 mM) and slightly lower pH (6.2-7.2) than those used in conventional conditions. Antigenic properties of sea anemone tropomyosin seemed to be considerably specific to each isoform. Distribution of tropomyosin isoforms in the sea anemone body was somewhat portion-specific. TMa, TMb, and TMe were detected similarly in the extracts from tentacle, oral disc, column, mouth, and pedal disc. Although TMc and TMd were detected abundantly in the tentacle extract and moderately in the column and mouth extracts, these components were not contained in the pedal disc extract and detected only faintly in the oral disc extract.

Actins↗

PubMed2026

Impact of Genomic Mutations on the Transcriptional Pathways and Tumor Microenvironment Landscape of Localized Early Prostate Cancer.

BACKGROUND: The management of intermediate-risk early prostate cancer (PCa) is challenging due to the difficulty in distinguishing indolent from aggressive tumors. This study explores the association between genomic alterations and the tumor and its microenvironment (TME) and implications for disease progression. METHODS: We performed multi-omic profiling in a cohort of 53 localized PCa using targeted sequencing, transcriptional, and proteomic spatial profiling. RESULTS: Somatic mutations and copy number alterations in RB1 (21%), PTEN (18%), and TP53 (9%) were identified. Kaplan-Meier analysis revealed that alterations in the RB and Cell Cycle pathways, particularly aberrations in PTEN, TP53, or RB1, were associated with shorter biochemical recurrence-free survival (p < 0.001). Spatial proteomic analysis demonstrated a complex immune landscape in patients with mutations. The tumor compartment demonstrated higher expression of immune checkpoint markers, T-cell activation proteins, and proliferation markers; and a TME that is enriched with CD8 + T cells and antigen-presenting cells, but also with immunosuppressive M2 macrophages, suggesting adaptive immune resistance. CONCLUSIONS: Our analysis demonstrates that genomic alterations in PTEN, TP53, or RB1 are not only prognostic for poor outcomes but are also associated with a unique, immunologically complex TME in this Brazilian cohort.

Humans↗

PubMed2000

Laparoscopic total mesorectal excision with autonomic nerve preservation.

Laparoscopy has greatly influenced abdominal surgery. We hypothesize that the benefits of minimally invasive surgery are applicable to rectal cancer. A cadaver model of laparoscopic rectal resection with total mesorectal excision (TME) and autonomic nerve preservation was utilized to explore this hypothesis. The principles of TME were followed, including high vascular ligation, sharp mesorectal dissection, and identification and preservation of the autonomic pelvic nerves. After proving feasibility in the cadaver model, a clinical study was performed on patients with mid to low rectal cancers. We observed acceptable morbidity with this minimally invasive technique of rectal resection and TME. We conclude that there is growing evidence that laparoscopic methods can be applied to patients with rectal cancer.

Adenocarcinoma↗

PubMed2005

Urinary and sexual function after total mesorectal excision.

The autonomous pelvic nerves are in close contact to the visceral pelvic fascia that surrounds the mesorectum. The concept of total mesorectal excsion (TME) in rectal cancer treatment has led to a substantial improvement of autonomous pelvic nerve preservation. Consecutively, this highly precise and sharp dissection technique under direct vision reduces the problem of accidental bladder denervation from 50-60% with conventional rectal cancer surgery to less than 20% with TME and the problem of postoperative impotence from 70-100% to less than 30%. The learning curve in this technically demanding procedure plays a major role with regard to a satisfying nerve preservation. The laparoscopic approach for TME allows to obtain similarly favorable results with regard to postoperative urogenital function, at least for tumors situated in the middle and upper third of the rectum, compared with open surgery. The present paper describes and depictures in detail the anatomy and the pathophysiology of autonomic pelvic nerves, the surgical technique for nerve preservation and gives a short overview of the results in the literature including own data.

Autonomic Nervous System↗