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PubMed1982

True metabolizable energy of fats at low level dietary inclusion.

When assayed at a 2.5% level of inclusion in a corn-soybean meal basal diet with 40 replications per treatment, no significant differences could be demonstrated between the true metabolizable energies (TME) of corn oil and two samples of tallow varying in stearic acid (18:0) content. All values were in excess of the gross energy of fat, suggesting an improvement in the absorption of other dietary constituents. When assayed at a 15% level in a purified basal diet, the TME of corn oil was significantly higher than that of the tallows; all values were below the gross energy of fat. Use of the practical corn-soybean meal basal improved the TME of the fats by 22.4% (corn oil), 34.9% (low 18:0 tallow), and 43.0% (high 18:0 tallow). A portion of the improvement in the TME of the tallows is presumed to be accounted for by an interaction with fatty acids in the practical basal ingredients that may be obscured at higher levels of inclusion. It is concluded that with adequate replication it is feasible to assay the TME of fats at low levels of dietary inclusion. A comparison of fatty acid absorption in Single Comb White Leghorn roosters during a TME study and in 8 to 9 week broilers on a full-feed regimen suggests that the conditions imposed during a TME assay provide a satisfactory model for evaluating the fat absorption of chickens reared under normal conditions.

Animals↗
PubMed1983

[Application of topographic mapping of electroencephalogram to cerebrovascular diseases].

Not a little difficulties lie in extraction of useful information by visual inspection alone from massive amount of data contained in multichannel polygraphic recordings of electroencephalography (EEG). Therefore, an effort to summarize conventional EEG and to demonstrate it semi-quantitatively has been made by many investigators and recently topographic mapping of EEG (TME), which is able to display equipotential maps of square roots of power spectra over each frequency band on computer-driven color video screen, has been designed. This system was clinically applied to the 16 patients who developed cerebrovascular disease with supratentorial lesions. (1) Slow wave focus was more obviously visualized on delta and/or theta bands of TME compared to visual inspection of conventional EEG in 8 cases out of 16. Also, suppression of alpha wave was beautifully demonstrated in 12 cases out of 16. The fact indicates that TME is useful as a sensitive detector of suppressed neuronal function. (2) Improvement of both TME and clinical signs after oxygenation at high pressure (case 3), carotid endarterectomy (case 1) and bypass surgery (case 6) were well correlated. The fact indicates that TME is one of the acceptable objective parameters for assessment of efficacy of various therapies. (3) TME was employed as a test evaluating effectiveness of bypass operation. This test was performed by compressing anastomosed superficial temporal artery (STA) for 10 minutes and change of TME after compression of STA was observed. In case 2 and 15, suppression of alpha activity was obviously noted in the occipital area ipsilateral to the STA compression following compression of STA, which suggested that these 2 cases depend hemodynamically on the anastomosed STA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Blood loss and transfusion after total mesorectal excision and conventional rectal cancer surgery.

OBJECTIVES: A recent study showed less bleeding and need of transfusion after total mesorectal excision (TME) compared with conventional rectal cancer surgery. The aim of this study was to evaluate this result in more details. PATIENTS AND METHODS: Comparison of transfusion history in rectal cancer resections in two different multicentre-studies. Two hundred and forty-six patients were operated in the period 1991-93 with a conventional technique and 311 patients were operated with TME-technique in the period 1996-98. Peri-operative data, including blood transfusion from one month before until one month after the operation, was recorded prospectively. RESULTS: The median intra-operative blood loss was 1000 ml, range 50-6000 ml, before, and 550 ml, range 10-6000 ml (P < 0.001) after introduction of TME. The overall peri-operative transfusion rate was reduced from 73% to 43% (P < 0.001). When adjusted for blood loss, age, gender, weight, and type of resection, TME significantly reduced the risk of receiving intra or postoperative blood transfusion by 0.4 (CI: 0.3-0.6). The variability in blood loss among 12 TME-centres was more than 400% and not correlated with transfusion requirements within the centres. CONCLUSION: TME results in a reduced blood loss and a reduction of blood transfusion, but additional factors others than blood loss seems to influence the decision of transfusion.

Aged↗
PubMed1991

Enhancement by tyrosine methyl ester of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of tyrosine methyl ester (TME) on the incidence, number, and histological types of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in male Wistar rats. Rats were subcutaneously given TME, 512 mg/kg body weight, every other day after 20 weeks of oral treatment with MNNG. Prolonged alternate-day administration of TME caused a significant increase in the incidence and number of gastric cancers of the glandular stomach by week 52. However, it did not affect the histology of the cancers. TME also caused a significant increase in tissue norepinephrine concentrations in the antral portion of the gastric wall and in the labelling indices of the antral epithelial cells. However, TME had no influence on the serum gastrin level and antral pH. These findings indicate that TME enhances gastric carcinogenesis, and this may be related to its effects on increasing norepinephrine levels in the gastric wall and stimulating proliferation of the antral epithelial cells.

Adenocarcinoma↗
PubMed2000

Current status of total mesorectal excision and autonomic nerve preservation in rectal cancer.

Two decades have passed since the late 1970s, which witnessed the introduction of total mesorectal excision (TME)-based operations for rectal cancers on both sides of the Atlantic. Since the introduction of TME, clinical experience has been reported widely in the form of single- and multisurgeon reports from wide geographic regions with multiple participants, and from specialty services with narrow focus and high levels of expertise. All of these published results conclude that in comparison with conventionally practiced blunt surgery for rectal cancer, TME-based (i.e., anatomically correct, sharply performed) operations are associated with significantly lower rates of pelvic (local) recurrences, a significantly higher rate of survival, and significantly lower long-term morbidity. The latter is accomplished through dramatically higher rates of sphincter preservation, and the preservation of both sexual and urinary functions. Overall, there is a remarkable similarity in the clinical results that have been reported from diverse centers. TME now forms the basis of large randomized clinical trials in which the role of adjuvant therapy is being reexamined. The current status of TME is reviewed, and the authors' clinical results of a consecutive series of 544 TME-based operations performed through 1998 are updated.

Autonomic Pathways↗
PubMed2003

[Surgical therapy of rectal carcinoma].

Total mesorectal excision (TME) has gained a revolutionary impact on the surgical therapy of rectal cancer within the last 2 decades, providing superior local tumor control in comparison to conventional resection. Consequently, 85% of rectal carcinomas can be resected by sphincter-preserving surgery without compromising either oncologic radicality or continence. With the introduction of TME, local recurrence rates have been reliably decreased below 10% after curative resection. Surgical dissection along the connective tissue space between rectal and parietal pelvic fascia with complete mesorectal excision results in reliable excision of all relevant lymphatic pathways with preservation of continence and sexual function. Complete removal of a TME specimen is mandatory in carcinomas of the middle and lower third of the rectum. Both removal of the complete TME specimen and careful pathologic examination of the circumferential resection margin have decisive significance. An additional pelvic lymphadenectomy with the potential risk of increased morbidity does not improve prognosis. As a spread of tumor distally along the bowel wall rarely exceeds a few centimeters, a distal resection margin of 1-2 cm is oncologically sufficient in sphincter-saving procedures without compromising prognosis. Taken together, the convincing results of TME provide a rationale for using TME as the dissection policy of choice to resect rectal cancers in the distal two-thirds of the rectum, despite the absence of direct evidence from prospective randomized trials. The question whether laparoscopic curative resection for rectal cancer is oncologically adequate cannot be definitely answered to date, as results of randomized studies are currently missing. However, the preliminary results of laparoscopic resection for rectal cancer provided by centers are promising.

Anal Canal↗
PubMed2007

Acute confusion in patients with systemic cancer.

OBJECTIVE: To determine the incidence, the causes and the prognostic value for survival of acute confusion (delirium) in patients admitted to a general cancer hospital. PATIENTS: Hundred consecutive patients with confusion were examined; 78 had a metastatic disease, 11 had local tumor and 11 had no sign of tumor recurrence at admission. Patients with confusion represented 11.8% (95%CI: 9.7-14.2%) of admissions. Follow-up period lasted 18 months from the inclusion of the last patient. RESULTS: Structural brain lesions (SBL) were mostly metastatic and caused confusion in 36 patients. 57 patients had a toxic or metabolic encephalopathy (TME). The cause remained unexplained in 6 cases, and in one patient the final diagnosis was psychotic state. Most patients with TME had more than one abnormality which could cause confusion. Confusion was reversible in 34 patients, and the odds for its regression was 3-fold higher in patients with TME (P = 0.02). Survival was significantly shorter (P = 0.02) in patients with SBL (median: 3 weeks) than in patients with TME (median: 8 weeks). However, the survival was significantly longer (P = 0.007) in patients with only one toxic or metabolic disorder (median: 20.5 weeks) than in patients with multiple changes (median: 5 weeks). CONCLUSION: Confusion is common in general cancer population. TME is the leading etiology and it is due to multiple causes in most patients. SBL causes confusion in one third of the patients. Patients with TME have a greater chance to recover, and survive longer especially if they have only one toxic or metabolic change.

Adult↗
PubMed2004

Anion binding to a ferric porphyrin complexed with per-O-methylated beta-cyclodextrin in aqueous solution.

5,10,15,20-Tetrakis(4-sulfonatophenyl)porphinato iron(III) (Fe(III)TPPS) forms a very stable 1:2 complex with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD), whose iron(III) center is located at a hydrophobic cleft formed by two face-to-face TMe-beta-CD molecules. Various inorganic anions (X(-)) such as F(-), Cl(-), Br(-), I(-), N(3)(-), and SCN(-) coordinate to Fe(III)TPPS(TMe-beta-CD)(2) to form five-coordinate high-spin Fe(III)TPPS(X)(TMe-beta-CD)(2), while no coordination occurs with ClO(4)(-), H(2)PO(4)(-), NO(3)(-), and HSO(4)(-). Except for F(-), none of the anions investigated coordinate to Fe(III)TPPS in the absence of TMe-beta-CD due to extensive hydration to the anions as well as to Fe(III)TPPS. The present system shows a high selectivity toward the N(3)(-) anion. The thermodynamics suggests that Lewis basicity, hydrophilicity, and shape of an X(-) anion are the main factors to determine the stability of the Fe(III)TPPS(X)(TMe-beta-CD)(2) complex.

Anions↗
PubMed2001

Quality of life after low anterior resection with total mesorectal excision and temporary loop ileostomy for rectal carcinoma.

BACKGROUND: Low anterior resection (LAR) with total mesorectal excision (TME) may be the optimal operation for carcinoma of the mid or lower rectum. Routine formation of a temporary defunctioning stoma has been recommended with TME. The impact of this strategy on health-related quality of life (HRQOL) has not been addressed. METHODS: A prospective longitudinal study was conducted among 24 patients undergoing LAR with TME and loop ileostomy for rectal cancer. Clinical outcomes were documented. HRQOL was assessed using Short Form 36 (SF-36). Twenty-three patients undergoing high anterior resection (HAR) for rectosigmoid cancer were studied concurrently to determine the effects of major colorectal resection without a stoma. RESULTS: Time to resume normal diet, length of stay in hospital and time to return to non-work activities were similar after HAR or LAR with TME and loop ileostomy. Twelve weeks after HAR SF-36 scores were stable or improved compared with preoperative levels. In contrast, 12 weeks after LAR + TME patients had a reduction in physical functioning scores on SF-36. SF-36 scores improved after ileostomy closure. Ileostomy closure increased total hospital stay and time off non-work activities. CONCLUSION: LAR with TME and temporary loop ileostomy for rectal cancer results in a long total hospital stay and impairs aspects of HRQOL. Prompt stoma closure should be a priority in these patients.

Aged↗
PubMed2003

Managing rectal cancer: the Dutch experience.

One of the major problems in the treatment of rectal cancer has been the inability to achieve local control. Traditional surgery, now outmoded, involves blunt digital dissection and was associated with a high incidence of local recurrence. In an attempt to improve local control and survival, many adjuvant treatment modalities have been investigated. In the context of conventional nonstandardized surgical procedures, pre-operative radiotherapy has been shown to improve local control and overall survival. In recent years treatment outcome has been extensively improved by the introduction of the TME technique first described by Heald. This has resulted in such low recurrence rates and improved survival that the question had to be answered whether pre-operative short-term radiotherapy is still beneficial in TME treated patients. The question was answered in the TME trial set up by the Dutch ColoRectal Cancer Group that randomised between standardized and quality-controlled TME surgery alone and TME surgery preceded by short-term pre-operative radiotherapy. This paper reviews the developments in the treatment of resectable rectal cancer, highlights the results from the Dutch TME trial, and considers future directions in improving outcome.

Humans↗
PubMed2003

Strain-specific kinetics of prion protein formation in vitro and in vivo.

The molecular basis of prion strain diversity is proposed to be encoded by distinct conformations of the abnormal scrapie isoform of the prion protein (PrP(Sc)). PrP(Sc) formation for the hyper (HY) and drowsy (DY) strains of the transmissible mink encephalopathy (TME) agent was investigated using the cell-free PrP conversion reaction to determine the role of distinct PrP(Sc) conformations in the rate of in vitro conversion of cellular PrP into protease-resistant PrP. PrP conversion increased at an exponential rate for both TME strains until peak levels were reached at 72-96 h of reaction time. The amount and rate of PrP conversion for HY TME was greater than those for DY TME between 48 h and the peak level of PrP conversion. Between 96 and 120 h, there was a negative rate of PrP conversion; and between 120 and 168 h, the net rate of HY and DY PrP conversion approached zero. These findings suggest that PrP conversion can occur in three distinct stages: an elongation phase, a depolymerization phase, and a steady-state phase. Strain-specific properties between the TME strains were identified only during the elongation phase. The steady-state phase could be disrupted by the addition of PrP(Sc) to, or by sonication of, the cell-free PrP conversion reaction. These treatments resulted in an increase in the amount of PrP conversion that was equal to or greater than that found during the peak level of PrP conversion for both TME strains, indicating that the steady-state phase was in dynamic equilibrium. In a related study, the rate of accumulation of HY and DY PrP(Sc) in hamster brain exhibited a strain-specific pattern that had similarities to the strain-specific PrP conversion reaction during the elongation phase. These results suggest that strain-specific conformations of PrP(Sc) have the ability to influence the rate of additional PrP(Sc) formation from cellular PrP both in vitro and in vivo.

Animals↗
PubMed1998

Linear model of nitrogen balance and examination of the nature of true metabolisable energy and its nitrogen corrected form.

1. The nature of nitrogen (N) corrected true metabolisable energy (TMEN) was derived using a linear model of N balance, constructed from the relationship between excreted and ingested N. 2. TME was described in terms of a regression line, formed from 'fed' points relating energy voided to energy ingested (GE), as GE - (afed + bGE) + afast. On assignment of theoretical excreta and ingested energy components, a deviation from conceptual metabolisable energy (MEc), equal to the difference between afed and afast, was established and attributed to metabolic urinary energy (UmE). 3. The N balance model is based on the form of relationship between N excreted and N ingested (NI) that exhibits a linear deviation at 'initial' rates of N ingestion. The model postulates the following: The deviation is the result of a sparing effect of ingested N on the N component of UmE, viz. metabolic urinary N (UmN); The magnitude of UmN, through 'initial' values of fed N, is described by an intercept component, aNp, and a slope quantity, -(bNr - bNna) NI, where bNna and bNr are respectively the slopes of N excretion through 'initial' and 'subsequent' rates of ingested food N; The magnitude of the deviation from zero nitrogen balance (ZNB) through 'initial' and 'subsequent' rates of ingested N is the sum of the previous terms and aNm - (1 - bNr) NI, where aNm is the intercept component representing maintenance losses of N at fasting and (1-bNr) NI is the quantity of fed N retained to replace maintenance N loss. 4. Application of the appropriate energetic forms of UmN and aNm, viz. Et aNp - Et (bNr - bNna) NI and EuaNm, to the expression for obtaining TME, demonstrated that TME exceeded MEc by the quantities Et (bNr - bNna) NI and Et aNp, for test food intakes resulting in 'initial' and 'subsequent' rates of food N, respectively. 5. Application of appropriate energetic components of the model to simulate correction of TME to ZNB, demonstrated TMEZNB to be a biased quantity, deviating from MEc by the amount -Eu (1 - bNr) NI or expressed as an excreta energy slope component, [formula: see text] where Eu is an appropriate energy coefficient. An alternative perspective is that ZNB correction removes the energetic form of UmN as a source of bias, but introduces one related to EuaNm. Its nature may be perceived by regarding TME as a function of a regression line relating energy excreted (EE) to energy ingested that has been corrected for UmN energetic bias and is pivoting on a fulcrum vertically aligned with the position of ZNB on the GE (x) axis. The regression line rotates anti-clockwise in response to ZNB correction by an amount equal to the magnitude of EuaNm measured on the EE (y) axis from the point of interception. 6. The study identified processes that may be employed to remove bias and improve precision of TME.

Animals↗
PubMed1990

A rapid and economical method of preparing radioiodinated cyclic nucleotide derivatives for use in radioimmunoassays.

2'-O-succinyladenosine 3':5'-cyclic monophosphate tyrosyl methyl ester (ScAMP-TME) and 2'-O-succinylguanosine 3':5'-cyclic monophosphate tyrosyl methyl ester (ScGMP-TME) were radioiodinated using chloramine T and Na125I. The resulting radiolabeled cyclic nucleotide derivatives, ScAMP-125I-TME and ScGMP-125I-TME, were subsequently purified by reverse-phase chromatography on Sep-Pak C18 cartridges (Waters Associates, Milford, MA) and tested as tracers in sensitive radioimmunoassays for cAMP and cGMP, respectively. Purified ScAMP-125I-TME and ScGMP-125I-TME functioned in the respective radioimmunoassays for up to 12 weeks when suspended in a 1:1 (v:v) mixture of n-propanol and 20 mM sodium acetate, pH 6.0. Thus, this purification method enables rapid and economical preparation of tracers for cyclic nucleotide radioimmunoassays. Furthermore, our findings suggest that reverse-phase chromatography may be applicable to the purification of other small polar molecules to which tyrosyl groups have been added for the purpose of radioiodination.

Cyclic AMP↗
PubMed2002

Preoperative radiotherapy improves survival for patients undergoing total mesorectal excision for stage T3 low rectal cancers.

OBJECTIVE: To examine the effect of preoperative radiotherapy (PRT) on patients who undergo rectal resection with total mesorectal excision (TME) for stage T3 low rectal cancers. SUMMARY BACKGROUND DATA: Evidence for the value of PRT before rectal cancer surgery is weakened by variability in the use of TME. Many surgeons have concluded that PRT is unnecessary for small rectal tumors if TME is performed, but there are no prospective data to support this opinion. METHODS: Since 1980, 2,200 patients with rectal cancer have been enrolled in a prospective database. Of these, 259 underwent curative anterior or abdominoperineal resection with TME for pathologically confirmed T3 lesions within 8 cm of the anal verge. Patients were grouped by receiving PRT (n = 92) or not receiving PRT (n = 167). Five-year overall survival and 5-year local recurrence rates were evaluated. RESULTS: Overall survival was increased from 52% in patients not receiving PRT to 63% in those receiving PRT. PRT increased overall survival for node-negative patients from 58% to 82%, with no benefit for node-positive patients. There was no significant difference in local recurrence rates. When categorized by tumor size, there was no difference in overall survival or local recurrence for 0- to 2-cm tumors or those larger than 5 cm, but PRT increased overall survival from 50% to 72% for patients with 2- to 5-cm tumors. Similar results were observed for patients with tumors staged as T3 on preoperative endoluminal ultrasound. CONCLUSIONS: Patients with pT3 low rectal cancers undergoing resection with TME have an improved survival with PRT. The effect is most beneficial for patients with node-negative and 2- to 5-cm tumors, although this group may include larger and node-positive tumors that have been downstaged by PRT. PRT should be advocated for all patients with T3 rectal cancers less than 8 cm from the anal verge, even if the surgery includes a properly performed TME.

Adenocarcinoma↗
PubMed2006

Laparoscopic sphincter-preserving total mesorectal excision with colonic J-pouch reconstruction: five-year results.

OBJECTIVE: To prospectively evaluate the oncologic and functional outcomes of laparoscopic total mesorectal excision (TME) with colonic J-pouch reconstruction. BACKGROUND: TME is considered the established gold standard in rectal cancer surgery. However, data on laparoscopic sphincter-preserving TME are limited. METHODS: Patients with mid or low rectal cancer underwent laparoscopic TME with colonic J-pouch reconstruction by a single surgical team. Clinical and oncologic data were prospectively recorded and analyzed. RESULTS: From March 1999 to September 2004, 105 patients underwent laparoscopic TME with colonic J-pouch reconstruction. The mean operating time was 170.4 minutes and mean blood loss was 91.5 mL. The mean anastomotic distance from the anal verge was 3.9 cm. Conversion was required in 2 cases. The mean circumferential and distal margins were 17.1 mm and 3.4 cm, respectively. There was 1 case of microscopic circumferential margin involvement and 1 case of microscopic distal margin involvement. There was no 30-day mortality, and 6 patients underwent reoperation for major complications. There was no port-site metastasis. The mean follow-up time was 26.9 months (range, 1.3-65.6 months). The actuarial 5-year cancer-specific survival and local recurrence rates were 81.3% and 8.9%, respectively. Erectile dysfunction occurred in 13.6% of males, while 2 patients developed incomplete bladder denervation. Bowel function after ileostomy closure was satisfactory, with an average bowel motion of less than 3 times per day at 2 years after ileostomy closure. CONCLUSIONS: Laparoscopic TME with colonic J-pouch reconstruction is a safe procedure with reasonable operating time and does not appear to pose any threat to the oncologic and functional outcomes.

Adenocarcinoma↗
PubMed1992

Molecular cloning of a mink prion protein gene.

Transmissible mink encephalopathy (TME) is a rare disease which is presumably transmitted to ranch-raised mink from scrapie-infected sheep offal or bovine spongiform encephalopathy-infected cattle products. Although the infectious agent of TME has not been isolated, there is circumstantial evidence that TME is caused by prions. The experimental host range of TME includes sheep, cattle, monkeys and hamsters. However, TME has never been transmitted to mice. Since experiments in transgenic animals have shown that the prion protein (PrP) gene modulates the susceptibility, incubation time and neuropathology of prion-induced disease, we have started to analyse the mink PrP gene. PrP, as deduced from a genomic DNA sequence, consists of 257 amino acids and overall shows similarity of 84 to 90% with the sequences of the PrPs of other mammalian species. It remains to be determined whether these differences in the primary structure of PrP will explain the peculiar host range of TME.

Amino Acid Sequence↗
PubMed2002

Prospective evaluation of anorectal function after total mesorectal excision for rectal carcinoma with or without preoperative radiotherapy.

OBJECTIVE: Anorectal function is greatly disturbed after rectal surgery with or without radiotherapy (RT). To clarify the underlying mechanisms, we designed a prospective study to evaluate the effect of RT and surgery on anorectal function and clinical outcome of patients with a rectal carcinoma. METHODS: Thirty-four patients with a rectal carcinoma participated in this study. They filled out a symptom questionnaire and underwent anal manometry, anal and rectal mucosal electrosensitivity testing, and a rectal barostat, before surgery, 4 and 12 months postoperatively. Thirteen patients were lost to follow-up, 14 underwent surgery alone (total mesorectal excision [TME]), and seven also received RT (RT + TME). RESULTS: Functional outcome was disappointing in both groups, with at 4 months a significantly higher defecation frequency after RT + TME as compared with TME. Anal sphincter function and rectal sensitivity to pressure-controlled distention were not affected by either treatment. Rectal compliance, however, was significantly reduced after RT + TME at 4 and 1 2 months, resulting in lower rectal volumes at the thresholds for first sensation and desire to defecate. Rectal but not anal mucosal electrosensitivity was higher after TME + RT. CONCLUSIONS: Anorectal function after rectal surgery with or without RT is greatly hampered because of a decreased rectal compliance. After 12 months, partial improvement is shown, especially in the absence of RT.

Adult↗
PubMed2005

Extraneural prion neuroinvasion without lymphoreticular system infection.

While prion infection of the lymphoreticular system (LRS) is necessary for neuroinvasion in many prion diseases, in bovine spongiform encephalopathy and atypical cases of sheep scrapie there is evidence to challenge that LRS infection is required for neuroinvasion. Here we investigated the role of prion infection of LRS tissues in neuroinvasion following extraneural inoculation with the HY and DY strains of the transmissible mink encephalopathy (TME) agent. DY TME agent infectivity was not detected in spleen or lymph nodes following intraperitoneal inoculation and clinical disease was not observed following inoculation into the peritoneum or lymph nodes, or after oral ingestion. In contrast, inoculation of the HY TME agent by each of these peripheral routes resulted in replication in the spleen and lymph nodes and induced clinical disease. To clarify the role of the LRS in neuroinvasion, the HY and DY TME agents were also inoculated into the tongue because it is densely innervated and lesions on the tongue, which are common in ruminants, increase the susceptibility of hamsters to experimental prion disease. Following intratongue inoculation, the DY TME agent caused prion disease and was detected in both the tongue and brainstem nuclei that innervate the tongue, but the prion protein PrP(Sc) was not detected in the spleen or lymph nodes. These findings indicate that the DY TME agent can spread from the tongue to the brain along cranial nerves and neuroinvasion does not require agent replication in the LRS. These studies provide support for prion neuroinvasion from highly innervated peripheral tissues in the absence of LRS infection in natural prion diseases of livestock.

Animals↗