bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial flux mapping of Corynebacterium glutamicum during fed‐batch L‐lysine production using the sensor reactor approach
Authors: Drysch A. , El Massaoudi M. , Wiechert W. , de Graaf A. A. , Takors R. 
Published: January 2004

AbstractUsing our recently developed sensor reactor approach, lysine‐producing, nongrowing Corynebacterium glutamicum MH20‐22B cells were subjected to serial 13C‐labeling experiments for flux analysis during the leucine‐limited fed‐batch production phase in a 300‐L bioreactor. Based on two‐dimensional (2D) nuclear magnetic resonance (NMR) measurements of 13C‐labeling patterns of cytoplasmic free metabolites, metabolic flux distributions in the central metabolism were successfully determined. Focusing on the highly concentrated metabolite L‐glutamate, the working hypothesis was validated that the equilibration of labeling patterns in intracellular pools was much faster (up to 9.45 min) than the labeling period (3 h) used in the experiments. Analysis of anaplerotic reactions revealed that highly selective lysine production was accompanied by a significant reduction of decarboxylating reactions from 10 mol% to only 2 mol%, whereas PEP/pyruvate‐carboxylating fluxes remained constant at about 40 mol% of consumed glucose. These results support the conclusion that an optimized C. glutamicum L‐lysine producer should possess increased PEP carboxylase and/or pyruvate carboxylase activity combined with downregulated, decarboxylating fluxes consuming oxaloacetate/malate. The findings also illustrate the usefulness of the sensor reactor approach in the study of industrial fermentations. © 2004 Wiley Periodicals, Inc.
Effect of doxycycline‐regulated calnexin and calreticulin expression on specific thrombopoietin productivity of recombinant chinese hamster ovary cells
Authors: Chung Joo Young , Lim Seung Wook , Hong Yeon Joo , Hwang Sun Ok , Lee Gyun Min 
Published: January 2004

AbstractIn an attempt to increase the specific thrombopoietin (TPO) productivity (qTPO) of recombinant Chinese hamster ovary (rCHO) cells (CHO‐TPO), the effect of expression level of calnexin (CNX) and calreticulin (CRT) on qTPO was investigated. To control both CNX and CRT expression levels simultaneously, the Tet‐Off system was first introduced in CHO‐TPO cells, and stable Tet‐Off cells (TPO‐Tet‐Off) were screened by luciferase assay. The doxycycline‐regulated CNX and CRT expression system in rCHO cells (TPO‐CNX/CRT) was established by cotransfection of CNX and CRT expression vector and pTK‐Hyg vector into TPO‐Tet‐Off cells and subsequent screening by Western blot analysis of CNX and CRT. The expression levels of CNX and CRT in TPO‐CNX/CRT cells could be tightly controlled by adding different concentrations of doxycycline to a culture medium. Compared with the basal level (2 μg/mL doxycyline), a 2.9‐fold increase in CNX expression and a 2.8‐fold increase in CRT expression were obtained in the absence of doxycycline. This, in turn, resulted in a 1.9‐fold increase in qTPO, not inhibiting cell growth or changing in vivo biological activity of TPO. Taken together, these results demonstrate that a simultaneous overexpression of CNX and CRT can increase the qTPO of rCHO cells. © 2004 Wiley Periodicals, Inc.
Experimental comparison of four methods of end-to-side anastomosis with expanded polytetrafluoroethylene
Authors: Trubel W , Schima H , Czerny M , Perktold K , Schimek M G , Polterauer P 
Published: January 2004

Abstract

Background
Four established techniques of distal end-to-side anastomosis (direct anastomosis, Linton patch, Taylor patch and Miller cuff) were compared to investigate the local distribution of anastomotic intimal hyperplasia. The study aimed to elucidate whether mechanical factors or flow alterations are mainly responsible for the improved patency rates reported for vein cuff interposition techniques in infrainguinal arterial reconstructions using prosthetic graft material.

Methods
Thirty-two expanded polytetrafluoroethylene (ePTFE) femoropopliteal bypass grafts were implanted in 16 sheep using the four anastomotic techniques. After 6 months the grafts were explanted and examined histologically. The local distribution of intimal hyperplasia was determined, particularly for areas of material transition and of high and low shear stress.

Results
The mean amount and distribution of intimal hyperplasia were similar for all anastomotic types. Intimal hyperplasia was greatest along all transitions between ePTFE and venous patches, and between ePTFE and recipient artery. It was lower along the transitions between venous patches and artery, and was lowest at the host artery floor.

Conclusion
Vein interposition did not reduce anastomotic intimal hyperplasia and did not change the distribution patterns of hyperplasia, which were influenced mainly by mechanical factors. The effect of vein interposition is to move areas of maximum intimal hyperplasia away from the small recipient artery up to the more capacious graft-patch anastomosis.
Hyperlipidaemia is positively correlated with lymph node metastasis in men with early gastric cancer
Authors: Kitayama J , Hatano K , Kaisaki S , Suzuki H , Fujii S , Nagawa H 
Published: January 2004

Abstract

Background
Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of serum lipid levels on tumour metastasis is not clearly understood.

Methods
The association between lymph node metastasis and preoperative serum levels of total cholesterol (TC) and triglyceride (TG) as well as various pathological findings for tumours was examined in 353 patients with early gastric cancer who underwent gastrectomy with classical lymphadenectomy.

Results
The rate of lymph node metastasis was significantly higher in patients with early gastric cancer who had hypercholesterolaemia (TC 220 mg/dl or greater) or hypertriglyceridaemia (TG 150 mg/dl or greater). The tendency was more prominent in men, and multivariate analysis showed that hypertriglyceridaemia was an independent risk factor for nodal metastasis in men, in addition to pathological invasion to the submucosal layer or to lymphatic vessels. In contrast, neither hypercholesterolaemia nor hypertriglyceridaemia showed a significant association with nodal status in women with early gastric cancer.

Conclusion
Raised serum lipid levels might favour the development of lymph node metastasis in men with early-stage gastric cancer. In patients with early gastric cancer serum lipid levels should be checked before operation, and the use of minimal local treatments must be considered carefully in male patients with hyperlipidaemia.
Percutaneous radiofrequency ablation of pulmonary metastases in patients with colorectal cancer
Authors: King J , Glenn D , Clark W , Zhao J , Steinke K , Clingan P , Morris D L 
Published: January 2004

Abstract

Introduction
This study aimed to assess the safety and efficacy of imaging-guided percutaneous radiofrequency ablation (RFA) for local control of lung metastases from colorectal cancer (CRC).

Methods
Twenty patients with lung metastases from CRC were treated with a RITA® Starburst XL electrode and RITA® 1500 generator using temperature control and impedance monitoring. Patients received intravenous sedation and analgesia, or local anaesthetic, and stayed in hospital for at least 24 h after treatment. RFA was assessed with computed tomography (CT) at 1 week and 1 month, and then every 3 months.

Results
Forty-four CRC lung metastases in 19 patients were treated successfully at 25 treatment sessions. Five of 19 patients were retreated for new lesions. There were 13 pneumothoraces following the 25 treatments, and six patients required drainage. The median length of follow-up was 730 (range 148–924) days. Six months after treatment CT demonstrated that three lesions had progressed, 25 metastases were stable or smaller, and 11 were no longer visible. At 12 months five metastases had progressed, 11 were smaller or stable, and nine were not visible.

Conclusion
Percutaneous imaging-guided RFA was associated with modest morbidity. RFA can achieve local control of CRC lung metastases: nine of 25 metastases were not visible on CT at 12 months after treatment.
Mechanism of action of botulinum toxin on the internal anal sphincter
Authors: Jones O M , Brading A F , Mortensen N J McC 
Published: January 2004

Abstract

Background
Botulinum toxin is an effective treatment for anal fissure. Manometric studies support an apparent action of botulinum toxin on the internal anal sphincter (IAS). This aim of this study was to establish the underlying mechanism.

Methods
Porcine IAS strips were suspended in a superfusion organ bath and allowed to equilibrate. Electrical field stimulation (EFS) was applied with parameters that induced nitrergic relaxation followed by noradrenaline-mediated contraction. These responses were compared before and after addition of botulinum toxin.

Results
All strips developed myogenic tone, which was slightly increased following the addition of botulinum toxin. EFS-induced nitrergic relaxation was unaffected by toxin treatment. However, EFS-induced contraction was significantly reduced by toxin treatment. 1,1-Dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, caused muscle strip contraction, which was blocked by guanethidine, implying the presence of sympathetic ganglia within the IAS. Botulinum toxin significantly attenuated DMPP-induced contraction.

Conclusion
In the treatment of anal fissure the major effect of botulinum toxin on the IAS is blockade of sympathetic (noradrenaline mediated) neural output. This is probably a postganglionic action, involving a reduction in noradrenaline release at the neuromuscular junction. Botulinum toxin has no significant effect on nitrergic transmission, which is probably not vesicular in nature.
Differential effect of nitric oxide synthase inhibition on sigmoid colon longitudinal and circular muscle responses to nicotine and nerve stimulation in vitro
Authors: McKirdy H C , Richardson C E , Green J T , Rhodes J , Williams G T , Marshall R W 
Published: January 2004

Abstract

Background
Nicotine has been shown to release nitric oxide from nerves in human sigmoid colon. This effect has been used to investigate the innervation and functional relationship of the longitudinal and circular muscle layers.

Methods
Strips of longitudinal and circular muscle were obtained from 19 patients with colorectal cancer. The strips from ten patients were subjected to electrical field stimulation (EFS) in vitro using stimulus parameters for selective stimulation of nerves. The effect of nicotine 1–10 μmol/l on EFS responses was then measured in the presence and absence of a nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME) 200 μmol/l. The effect of nicotine on spontaneous activity was investigated in the muscle strips from the other nine patients.

Results
Both longitudinal and circular strips responded to EFS with contraction. The time to achieve a peak contractile response (time to peak; TTP) was significantly longer (P &lt; 0·001) in circular strips. l-NAME reduced the mean(s.e.m.) TTP in circular muscle from 23·3(2·0) to 17·2(1·5) s (P = 0·007) and altered its pattern of response to resemble that of longitudinal muscle. Nicotine 10 μmol/l reduced the contraction to EFS in circular (P &lt; 0·001) but not in longitudinal (P = 0·347) muscle. The nicotine-induced reduction in circular muscle contraction was blocked by l-NAME 200 μmol/l (P = 0·005).

Conclusion
These findings suggest that nitric oxide release on neural stimulation is greater in circular than in longitudinal muscle.
Population-based study of carotid endarterectomy in Western Australia
Authors: Laurvick C L , Norman P E , Semmens J B , Hobbs M S T 
Published: January 2004

Abstract

Background
Previous studies reported an increase in the rates of operation following the publication of major trials that demonstrated the benefit of carotid endarterectomy in reducing stroke. The aim of this study was to determine whether carotid endarterectomy rates have continued to rise despite the reducing trend in most manifestations of atherosclerotic cardiovascular disease.

Methods
Record linkage was used to select patients who had a carotid endarterectomy during the interval from 1988 to 2001. Incidence rates were age-standardized and trends were examined with Poisson regression.

Results
The rate increased by 13·8 per cent per year between 1988 and 1998; however, from 1999 onwards the rate of carotid surgery fell by 15·8 per cent per year. In octogenarians, the rate increased steadily from 0·9 to 5·1 per 100 000 person-years between 1992 and 2000. The proportion of octogenarians also increased significantly from 0·9 per cent in 1988–1990 to 19·5 per cent in 2000–2001 (χ2 = 60·11, 4 d.f., P &lt; 0·001).

Conclusion
For the first time a recent decline has been observed in the rate of carotid endarterectomy, most likely owing to a combination of the deceasing incidence of atherosclerosis and more widespread use of effective drugs in the treatment of cardiovascular disease. The rate and proportion of operations in patients aged 80 years or older has increased steadily.
Serum vascular endothelial growth factor as a tumour marker in soft tissue sarcoma
Authors: Hayes A J , Mostyn-Jones A , Koban M U , A'Hern R , Burton P , Thomas J M 
Published: January 2004

Abstract

Background
Vascular endothelial growth factor (VEGF) is a potent tumour-produced angiogenic factor. In this study serum levels of VEGF were measured before treatment and during follow-up in patients undergoing primary treatment for suspected soft tissue sarcoma (STS) to assess the value of serum VEGF as a tumour marker.

Methods
Between April 2001 and September 2002, serum VEGF levels were analysed prospectively in 144 patients undergoing primary treatment (surgery, 123; cytotoxic chemotherapy, ten; oral imatinib, eight; radiotherapy, three) for suspected soft tissue sarcoma. Serum VEGF was measured by immunoassay before treatment, in the immediate postoperative interval in patients undergoing surgery, and during follow-up. Serum VEGF concentrations were also measured in 15 healthy volunteers.

Results
Median pretreatment serum VEGF levels were significantly raised in patients with grade 2 and grade 3 sarcomas compared with concentrations in patients with benign lesions (413 and 467 versus 233 pg/ml respectively; P = 0·007 and P = 0·003 respectively). In patients with tumours that had a high level of VEGF expression before treatment, follow-up measurements reflected disease status after treatment.

Conclusion
Serum VEGF expression correlated with grade in soft tissue sarcoma and reflected response to treatment.
Electrolytic liver ablation is not associated with evidence of a systemic inflammatory response syndrome
Authors: Teague B D , Court F G , Morrison C P , Kho M , Wemyss-Holden S A , Maddern G J 
Published: January 2004

Abstract

Background
Local ablation has been proposed for treatment of liver tumours. Cryoshock, a variant of the systemic inflammatory response syndrome (SIRS), is a potentially fatal complication of cryoablation caused by systemic release of necrotic breakdown products from ablated liver. The proinflammatory cytokines tissue necrosis factor (TNF) α and interleukin (IL) 1 are important mediators of this response. This study assessed the risk of SIRS complicating electrolytic liver ablation by measuring circulating levels of inflammatory cytokines, other inflammatory markers and clinical markers of organ function.

Methods
Electrolytic liver ablation was performed in 16 pigs and four pigs served as controls. Platelet count, and serum levels of urea, creatinine, liver enzymes, C-reactive protein (CRP), TNF-α and IL-1β were measured before treatment and for 72 h after the procedure.

Results
There were significant dose-related increases in CRP and alanine aminotransferase levels with liver electrolysis. There was no significant derangement in renal function or platelet count following ablation. A rise in serum TNF-α and IL-1β levels was not associated with liver electrolysis.

Conclusion
There was no evidence of organ failure or significantly raised levels of proinflammatory cytokines as a result of liver electrolysis, suggesting that this is a safe procedure for liver ablation.
The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia–reperfusion injury
Authors: Ninomiya M , Shimada M , Harada N , Soejima Y , Suehiro T , Maehara Y 
Published: January 2004

Abstract

Background
Oxidative stress contributes to hepatic ischaemia–reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury.

Methods
After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs–Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) α were measured in the perfusate.

Results
Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P &lt; 0·050), hepatic enzyme release into the perfusate (P = 0·038), total bile production (P = 0·029) and malondialdehyde concentration (P = 0·038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P = 0·032). TNF-α levels were not affected.

Conclusions
MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.
Surgical revision after failure of laparoscopic adjustable gastric banding
Authors: Weiss H G , Kirchmayr W , Klaus A , Bonatti H , Mühlmann G , Nehoda H , Himpens J , Aigner F 
Published: January 2004

Abstract

Background
This paper reports the outcome of surgical revision for complications following laparoscopic placement of an adjustable silicone gastric band (AGB) to treat morbid obesity.

Methods
Seventy-three (19·1 per cent) of 382 patients who underwent laparoscopic AGB placement between January 1996 and March 2001 presented with complications within 6 years after operation. Revision was carried out with the intention of reinstating the functional device in all patients.

Results
Successful surgical revision or gradual balloon deflation was performed in 53 patients (29 port-related complications, 14 pouch dilatations, 12 band leakages, three oesophageal dilatations, two symptomatic hernias, one late migration, one intracerebral bleed). Of these patients, 51 (96·2 per cent) had a successful outcome according to the Bariatric Analysis and Reporting Outcome System following significant additional postinterventional weight loss. AGB removal was carried out in 20 patients (13 early or late migrations, five pouch dilatations, three port-related complications, two psychiatric disorders, one band leakage). The final failure rate for complicated AGB procedures was 30·1 per cent.

Conclusion
AGB placement is associated with a variety of complications. In most cases surgical complications can be treated with minimally invasive surgery, which should allow further weight loss and improvement of quality of life during long-term follow-up. Alternative bariatric procedures should be reserved for patients with poor outcome after surgical revision of the AGB.
Randomized clinical trial of virtual reality simulation for laparoscopic skills training
Authors: Grantcharov T P , Kristiansen V B , Bendix J , Bardram L , Rosenberg J , Funch-Jensen P 
Published: January 2004

Abstract

Background
This study examined the impact of virtual reality (VR) surgical simulation on improvement of psychomotor skills relevant to the performance of laparoscopic cholecystectomy.

Methods
Sixteen surgical trainees performed a laparoscopic cholecystectomy on patients in the operating room (OR). The participants were then randomized to receive VR training (ten repetitions of all six tasks on the Minimally Invasive Surgical Trainer—Virtual Reality (MIST-VR)) or no training. Subsequently, all subjects performed a further laparoscopic cholecystectomy in the OR. Both operative procedures were recorded on videotape, and assessed by two independent and blinded observers using predefined objective criteria. Time to complete the procedure, error score and economy of movement score were assessed during the laparoscopic procedure in the OR.

Results
No differences in baseline variables were found between the two groups. Surgeons who received VR training performed laparoscopic cholecystectomy significantly faster than the control group (P = 0·021). Furthermore, those who had VR training showed significantly greater improvement in error (P = 0·003) and economy of movement (P = 0·003) scores.

Conclusion
Surgeons who received VR simulator training showed significantly greater improvement in performance in the OR than those in the control group. VR surgical simulation is therefore a valid tool for training of laparoscopic psychomotor skills and could be incorporated into surgical training programmes.
Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy
Authors: Brown W A , Thomas J , Gotley D , Burmeister B H , Lim K-H , Martin I , Walpole E T , Thomson D B , Harvey J A , Smithers B M 
Published: January 2004

Abstract

Background
Approximately 25 per cent of patients with oesophageal cancer who undergo neoadjuvant chemoradiotherapy have no evidence of tumour in the resected specimen (complete pathological response). Those who do not respond have a poor 5-year survival compared with complete responders, regardless of whether or not they undergo surgery. Selecting for surgery only those who have a response to neoadjuvant therapy has the potential to improve overall survival as well as to rationalize the management of non-responders. This study assessed the accuracy of oesophagogastroscopy in this setting.

Methods
A prospective database of 804 patients undergoing oesophageal resection for carcinoma was reviewed. Endoscopic assessment of the response to neoadjuvant therapy in 100 consecutive patients was compared with the pathological assessment of response. The survival for each level of response was compared.

Results
At endoscopy 30 patients were considered to have had a complete response. This was confirmed pathologically in 15 patients. Survival was improved in those with a pathologically confirmed complete response (3-year survival rate 62·4 (s.e. 12·9) per cent) compared with non-responders (16·3 (s.e. 6·6) per cent). Those with microscopic residual disease also had an improved 3-year survival rate (46·3 (s.e. 12·2) per cent); however, oesophagogastroscopy failed to identify this subset.

Conclusion
Oesophagogastroscopy may be useful in the assessment of tumour response to neoadjuvant therapy. However, owing to its poor accuracy patients should not be excluded from further therapeutic intervention on the basis of this assessment alone.