bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo and in vitro hepatic phosphorus-31 magnetic resonance spectroscopy and electron microscopy in chronic ductopenic rejection of human liver allografts
Authors: Taylor-Robinson S D , Sargentoni J , Bell J D , Thomas E L , Marcus C D , Changani K K , Saeed N , Hodgson H J F , Davidson B R , Burroughs A K , Rolles K , Foster C S , Cox I J
Published: June 2010

Background—In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (MRS) provides non-invasive information about phospholipid metabolism.

Aims—To delineate MRS abnormalities in patients with chronic ductopenic rejection (CDR) and to characterise spectral changes by in vitro MRS and electron microscopy.

Patients and methods—Sixteen liver transplant recipients (four with CDR; 12 with good graft function) and 29 controls (23 healthy volunteers; six patients with biliary duct strictures) were studied with in vivo 31P MRS. Peak area ratios of phosphomonoesters (PME) and phosphodiesters (PDE), relative to nucleotide triphosphates (NTP) were measured. In vitro MRS and electron microscopy were performed on biopsy specimens from five patients with CDR, freeze clamped at retransplantation. Phosphoethanolamine (PE), phosphocholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC) concentrations were measured.

Results—The 12 patients with good graft function displayed no spectral abnormalities in vivo; the four patients with CDR showed significantly elevated PME:NTP (p<0.01) and PDE:NTP ratios (p<0.005). Patients with biliary strictures had significant differences in PME:NTP (p<0.01) from patients with CDR, but not in mean PDE:NTP. In vitro spectra from CDR patients showed elevated PE and PC, mirroring the in vivo changes in PME, but reduced GPE and GPC concentrations were observed, at variance with the in vivo PDE findings. On electron microscopy, there was no proliferation in hepatocyte endoplasmic reticulum.

Conclusions—The increase in PME:NTP reflects altered phospholipid metabolism in patients with CDR, while the increase in PDE:NTP may represent a significant contribution from bile phospholipid.
Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours
Authors: Angeletti S , Corleto V D , Schillaci O , Marignani M , Annibale B , Moretti A , Silecchia G , Scopinaro F , Basso N , Bordi C , Delle Fave G
Published: June 2010

Background—Somatostatin receptor scintigraphy (SRS) and octreotide therapy have both changed the management of gastroenteropancreatic endocrine tumours, but very few data are available on the use of SRS and octreotide to visualise and treat somatostatinomas.

Method—The results of SRS and octreotide treatment in three somatostatinoma patients were examined.

Results—SRS was able to detect extensive hepatic involvement in patient 1, one hepatic and one pancreatic lesion in patient 2, and one hepatic lesion in patient 3. Octreotide therapy (0.5 mg/day subcutaneously) was effective in decreasing plasma levels of somatostatin in all three patients. Symptoms (diabetes and diarrhoea) were greatly improved in the two patients with “somatostatinoma syndrome”.

Conclusion—The study shows that somatostatinoma, like most other gastroenteropancreatic endocrine tumours, possesses functioning somatostatin receptors.
Motilin induces gall bladder emptying and antral contractions in the fasted state in humans
Authors: Luiking Y C , Peeters T L , Stolk M F J , Nieuwenhuijs V B , Portincasa P , Depoortere I , van Berge Henegouwen G P , Akkermans L M A
Published: June 2010

Background—Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying.

Aims—To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans.

Methods—After an overnight fast, eight healthy men received increasing intravenous doses of Leu13-motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography.

Results—Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, ,8 and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p<0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p<0.05).

Conclusions—Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further during continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase III activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state.
Chronic intestinal pseudo-obstruction in systemic lupus erythematosus
Authors: Perlemuter G , Chaussade S , Wechsler B , Cacoub P , Dapoigny M , Kahan A , Godeau P , Couturier D
Published: June 2010

Background/Aims—Chronic intestinal pseudo-obstruction (CIPO) reflects a dysfunction of the visceral smooth muscle or the enteric nervous system. Gastrointestinal manifestations are common in systemic lupus erythematosus (SLE) but CIPO has not been reported. Features of CIPO are reported in five patients with SLE.

Methods—From 1988 to 1993, five patients with SLE or SLE-like syndrome were hospitalised for gastrointestinal manometric studies. CIPO was the onset feature in two cases. Antroduodenal manometry (three hours fasting, two hours fed) was performed in all patients, and oesophageal manometry in four.

Results—Intestinal hypomotility associated with reduced bladder capacity and bilateral ureteral distension was found in four patients and aperistalsis of the oesophagus in three. Treatment, which consisted of high dose corticosteroids, parenteral nutrition, promotility agents, and antibiotics, led to remission of both CIPO and urinary abnormalities in all cases. Antroduodenal manometry performed in two patients after remission showed increased intestinal motility. One patient died, and postmortem examination showed intestinal vasculitis.

Conclusions—CIPO in SLE is a life threatening situation that can be reversed by treatment. It may be: (a) a complication or onset feature of the disease; (b) secondary to smooth muscle involvement; (c) associated with ureteral and vesical involvement; (d) the result of intestinal vasculitis.
Reduced susceptibility of mice overexpressing transforming growth factor α to dextran sodium sulphate induced colitis
Authors: Egger B , Carey H V , Procaccino F , Chai N-N , Sandgren E P , Lakshmanan J , Buslon V S , French S W , Büchler M W , Eysselein V E
Published: June 2010

Background—Transforming growth factor α (TGF-α) knockout mice have increased susceptibility to dextran sodium sulphate (DSS) induced colitis.

Aim—To substantiate the findings that TGF-α is a key mediator of colonic mucosal protection and/or repair mechanisms by evaluating the susceptibility of mice overexpressing TGF-α to DSS induced colitis.

Methods—TGF-α overexpression was induced in transgenic mice by ZnSO4administration in drinking water (TG+). Three groups were used as controls: one transgenic group without ZnSO4 administration (TG−), and two non-transgenic littermate groups receiving ZnSO4 (Non-TG+) or only water (Non-TG−). Acute colitis was induced in all groups by administration of DSS (5%, w/v) in drinking water for six days ad libitum.

Results—About 35–39% of the entire colonic mucosa was destroyed in Non-TG−, Non-TG+, and TG− animals compared with 9% in TG+ mice. The crypt damage score was 18.7 (0.9), 18.2 (1.0), 18.9 (0.8), and 6.8 (1.5) (means (SEM)) in Non-TG−, Non-TG+, TG−, and TG+ mice respectively. Mucin and bromodeoxyuridine staining were markedly enhanced in colons of TG+ mice compared with controls, indicating increased mucosal protection and regeneration.

Conclusions—The significantly reduced susceptibility of mice overexpressing TGF-α to DSS further substantiates that endogenous TGF-α is a pivotal mediator of protection and/or healing mechanisms in the colon.
Folate depletion impairs DNA excision repair in the colon of the rat
Authors: Choi S-W , Kim Y-I , Weitzel J N , Mason J B
Published: June 2010

Background/Aims—Diminished folate status appears to promote colonic carcinogenesis by, as of yet, undefined mechanisms. Impaired DNA repair plays a significant role in the evolution of many colon cancers. Since folate is essential for thede novo synthesis of nucleotides and since folate depletion has previously been associated with excessive DNA strand breaks, it was hypothesised that folate depletion may impair DNA repair. Studies were therefore performed to examine whether folate depletion affects the two major categories of DNA repair.

Methods—Study 1: eight weanling male Sprague-Dawley rats were fed on diets containing either 0 or 8 mg folate/kg diet with 1% succinylsulphathiazole for four weeks. After viable colonocytes had been harvested, DNA excision repair was evaluated by a single cell gel electrophoresis assay. Study 2: eighteen animals were fed on similar diets for five weeks. Also in study 2, 18 additional rats were fed on the same defined diet without succinylsulphathiazole for 15 weeks. Weekly injections with the procarcinogen, 1,2-dimethylhydrazine (20 mg base/kg), were administered to the latter group of animals. Five microsatellite loci from different chromosomes were investigated for instability in hepatic and colonic DNA.

Results—In study 1, a significantly retarded rate of DNA excision repair was observed in the folate deficient colonocytes compared with controls (p<0.05). In study 2, there was no evidence of instability at the five microsatellite loci associated with either short or long term folate depletion.

Conclusions—Folate deficiency impairs DNA excision repair in rat colonic mucosa; a similar degree of deficiency, even when administered in conjunction with a colonic carcinogen, did not produce evidence of a widespread defect in mismatch repair.
Systemic and local immune responses againstHelicobacter pylori urease in patients with chronic gastritis: distinct IgA and IgG productive sites
Authors: Futagami S , Takahashi H , Norose Y , Kobayashi M
Published: June 2010

Background—Helicobacter pylori urease is a major target for immune responses among various bacterial components in H pyloriinfected patients.

Aims—To analyse the relation between systemic and local humoral immune responses toH pylori urease and grades of chronic gastritis.

Patients—Seventy five patients with chronic gastritis associated with H pyloriinfection were classified into three groups (grade I, superficial gastritis; II, atrophic gastritis, quiescent; or III, atrophic gastritis, active).

Methods—Anti-H pylori urease specific antibodies in the serum, gastric juice, and biopsy specimens were determined by ELISA or western blotting analysis. The sites for H pylori urease and its specific antibody producing B lymphocytes were confirmed by immunohistochemical analysis.

Results—In the sera of patients with grade I gastritis, weak IgG but relatively strong IgA responses toH pylori urease were observed; dominant strong IgG responses were detected in grade II gastritis. In grade III gastritis, significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG responses was detected in gastric juice and tissue. H pylori urease specific, antibody producing B cells were not found in the gastric mucosa of patients with grade I gastritis despite the presence of such B cells in the duodenal bulb. Specific B cells were observed in the gastric mucosa of patients with grade II and III gastritis with atrophy.

Conclusions—PurifiedH pylori urease, together with localisation of its specific antibody producing B cells, are useful for serological testing and histopathological analysis for determining the stage of chronic gastritis and studying the pathogenesis ofH pylori infection.
Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma
Authors: van Sandick J W , van Lanschot J J B , Kuiken B W , Tytgat G N J , Offerhaus G J A , Obertop H
Published: June 2010

Background—The efficacy of endoscopic biopsy surveillance of Barrett’s oesophagus in reducing mortality from oesophageal cancer has not been confirmed.

Aims—To investigate the impact of endoscopic biopsy surveillance on pathological stage and clinical outcome of Barrett’s carcinoma.

Methods—A clinicopathological comparison was made between patients who initially presented with oesophageal adenocarcinoma (n=54), and those in whom the cancer had been detected during surveillance of Barrett’s oesophagus (n=16).

Results—The surveyed patients were known to have Barrett’s oesophagus for a median period of 42 months (range 6–144 months). Prior to the detection of adenocarcinoma or high grade dysplasia, 13 of 16 patients (81%) were previously found to have low grade dysplasia. Surgical pathology showed that surveyed patients had significantly earlier stages than non-surveyed patients (p=0.0001). Only one surveyed patient (6%) versus 34 non-surveyed patients (63%) had nodal involvement (p=0.0001). Two year survival was 85.9% for surveyed patients and 43.3% for non-surveyed patients (p=0.0029).

Conclusions—The temporal course of histological progression in our surveyed patients supports the theory that adenocarcinoma in Barrett’s oesophagus develops through stages of increasing severity of dysplasia. Endoscopic biopsy surveillance of Barrett’s oesophagus permits detection of malignancy at an early and curable stage, thereby potentially reducing mortality from oesophageal adenocarcinoma.
Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain
Authors: Hammer J , Hammer H F , Eherer A J , Petritsch W , Holzer P , Krejs G J
Published: June 2010

Background—Stimulation of sensory nerves with capsaicin regulates ion transport in the small intestine in animal experiments.

Aim—To investigate whether sensory nerves that are stimulated by capsaicin administration influence fluid and electrolyte absorption in the human jejunum in vivo.

Method—Intestinal perfusion studies were performed in 12 healthy subjects using a four lumen tube with a proximal occlusion balloon and a plasma-like electrolyte solution. After an initial control period, 5 (n = 3), 10 (n = 8), or 50 (n = 1) μg/ml capsaicin was added to the perfusate, and this was followed by a final control period. Rates of absorption of water, sodium, potassium, chloride, and bicarbonate were determined in a 30 cm segment of jejunum using a non-absorbable volume marker.

Results—At all three concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared with control periods. Two subjects who received 10 μg/ml and the subject receiving 50 μg/ml experienced crampy abdominal pain.

Conclusion—The results do not support the hypothesis that capsaicin sensitive afferent nerves are involved in the physiological regulation of net absorption or secretion across the human jejunal mucosa. Chemical stimulation of these nerves, however, gives rise to abdominal pain.
HIV enteropathy: comparative morphometry of the jejunal mucosa of HIV infected patients resident in the United Kingdom and Uganda
Authors: Batman P A , Kapembwa M S , Miller A R O , Sedgwick P M , Lucas S , Sewankambo N K , Serwadda D , Pudney J , Moody A , Harris J R W , Griffin G E
Published: June 2010

Aims—To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda.

Patients—Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites.

Methods—Stools and biopsy specimens were examined for enteropathogens. Surface area to volume (S:V) ratio was estimated morphometrically, mean crypt length of jejunal biopsy specimens was measured, and HIV infected cells detected immunohistochemically were quantified.

Results—Enteric pathogens were detected in none of the London patients, and in three Ugandan patients. S:V ratio was lower, and mean crypt length higher, in the specimens of London patients than in normal subjects, but there was no difference in S:V ratio or mean crypt length between Ugandan patients and controls. A negative correlation was present between S:V ratio and mean crypt length in all biopsy specimens analysed. HIV infected cells were detected only in lamina propria.

Conclusion—Infection of cells in the lamina propria of the jejunum with HIV stimulates crypt cell proliferation, and a fall in villous surface area. The mucosal response to HIV is masked by other pathogens in the African environment.
Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis
Authors: Ohba K , Omagari K , Nakamura T , Ikuno N , Saeki S , Matsuo I , Kinoshita H , Masuda J , Hazama H , Sakamoto I , Kohno S
Published: June 2010

Spontaneous regression of hepatocellular carcinoma is a rare phenomenon. Abscopal regression of tumours resulting from the effect of irradiation of a tissue on a remote non-irradiated tissue is also rare. The case of a 76 year old Japanese man with hepatocellular carcinoma that regressed after radiotherapy for thoracic vertebral bone metastasis is described. Serum levels of tumour necrosis factor-α increased after radiotherapy. The findings suggests that such abscopal related regression may be associated with host immune response, involving cytokines such as tumour necrosis factor-α.
Factors affecting splanchnic haemodynamics in Crohn’s disease: a prospective controlled study using Doppler ultrasound
Authors: Maconi G , Parente F , Bollani S , Imbesi V , Ardizzone S , Russo A , Porro G Bianchi
Published: June 2010

Background—Current knowledge on splanchnic haemodynamics in Crohn’s disease is limited.

Aims—To investigate which features of Crohn’s disease affect splanchnic haemodynamics, and to establish whether portal vein (PV) and superior mesenteric artery (SMA) blood supply reflects clinical or biochemical activity of Crohn’s disease.

Methods—Seventy nine patients with Crohn’s disease and 40 controls were evaluated by Doppler ultrasound (US). The mean velocity of PV and SMA flow, the volume of blood flow of the PV and SMA, and the resistance index of SMA were studied. A series of clinical, biochemical, and US variables including Crohn’s disease activity index, serum C reactive protein concentrations, disease duration and its anatomical location, smoking habits, abdominal complications, and current medical therapy, as well as the maximum bowel wall thickness as measured by US, were determined. The relation between PV and SMA blood flow and these variables was assessed by univariate and multivariate analysis.

Results—Patients with Crohn’s disease had significantly higher PV and SMA flow and a lower SMA resistance index than controls. Stepwise multiple regression analysis identified bowel wall thickness and location of the disease as the main predictive variables of both PV and SMA blood flow variation, accounting for 36% and 45% of their variability, respectively. No relation was found between splanchnic haemodynamics and disease activity.

Conclusion—A hyperdynamic mesenteric circulation does exist in Crohn’s disease; however splanchnic blood flow does not reflect the clinical or biochemical activity of the disease, but seems to be linked more to other Crohn’s disease characteristics, such as maximum bowel thickness and anatomical location.
Are relatives of patients with multiple HNPCC spectrum tumours at increased risk of cancer?
Authors: Brown S R , Finan P J , Bishop D T
Published: June 2010

Background—Relatives of patients with early onset colorectal cancer, a feature of hereditary non-polyposis colorectal cancer (HNPCC), are at increased risk of colorectal cancer.

Aims—To investigate risk in relatives of patients with multiple primary cancers, another feature of HNPCC.

Methods—Details were obtained on patients from one region who had developed colorectal cancer and a separate primary from the HNPCC tumour spectrum (colorectal, stomach, urinary, ovary, endometrial). Overall, 157 patients had second primaries occurring between 1990 and 1995 and 128 completed family histories were obtained by structured interview (study group). A comparison group of 444 patients with a single colorectal cancer were similarly interviewed.

Results—Fifteen families (13%) from the study group were suggestive of HNPCC compared with three (0.7%, p<0.0001) from the comparison group. Overall risk of colorectal cancer in close relatives of the study group was 3.4 times the general population rate compared with 1.8 times for the comparison group. Bowel cancer risk was even higher for relatives of bowel/ovary and bowel/endometrial subgroups, but was similar to the comparison group for the bowel/bowel subgroup. Finally, extracolonic HNPCC associated cancers were seen twice as frequently as expected in the general population in relatives of the study group.

Conclusion—This study highlights the importance of taking a family history in patients with multiple primary cancers and indicates the risk of malignancy in their relatives.
A UK training programme for nurse practitioner flexible sigmoidoscopy and a prospective evaluation of the practice of the first UK trained nurse flexible sigmoidoscopist
Authors: Duthie G S , Drew P J , Hughes M A P , Farouk R , Hodson R , Wedgwood K R , Monson J R T
Published: June 2010

Background—Flexible sigmoidoscopy is a technical skill that has been successfully performed by suitably trained colorectal nurse practitioners in the USA. However, no recognised training course exists for nurse practitioners in the UK.

Aims—To design and evaluate a training programme for nurse endoscopists.

Methods—A multidisciplinary committee of nurses and clinicians developed a structured programme of study and practice. This involved a staged process of observations, withdrawals, and ultimately, full procedures. Once training had been completed the nurse practitioner was permitted to practice independently. Patients with colorectal symptoms referred for flexible sigmoidoscopy were examined for the final stages of training and independent practice. A prospective evaluation of the training and practice of the first trained nurse flexible sigmoidoscopist was performed. Barium enema, video, clinical follow up, and histology were used to validate the results of the flexible sigmoidoscopies.

Results—The training programme required that 35 observations, 35 withdrawals, and 35 supervised full procedures were performed prior to the development of independent practice. Subsequent to the completion of this programme 215 patients have been examined independently by the nurse practitioner. Ninety three per cent of the examinations were judged successful and pathology was identified in 51%. The nurse endoscopist successfully identified all “significant” pathology whereas barium enema failed to identify pathology in 12.5%. There were no complications.

Conclusion—With suitable training nurse endosocopists are able to perform flexible sigmoidoscopy safely and effectively.
5-Aminosalicylic acid prevents oxidant mediated damage of glyceraldehyde-3-phosphate dehydrogenase in colon epithelial cells
Authors: McKenzie S M , Doe W F , Buffinton G D
Published: June 2010

Background

Reactive oxygen and nitrogen derived species produced by activated neutrophils have been implicated in the damage of mucosal proteins including the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the active inflammatory lesion in patients with inflammatory bowel disease (IBD). This study investigated the efficacy of currently used IBD therapeutics to prevent injury mediated by reactive oxygen and nitrogen derived species.

Methods

GAPDH activity of human colon epithelial cells was used as a sensitive indicator of injury produced by reactive oxygen and nitrogen derived species. HCT116 cells (106/ml phosphate buffered saline; 37°C) were incubated in the presence of 5-aminosalicylic acid (5-ASA), 6-mercaptopurine, methylprednisolone, or metronidazole before exposure to H2O2, HOCl, or NO in vitro. HCT116 cell GAPDH enzyme activity was determined by standard procedures. Cell free reactions between 5-ASA and HOCl were analysed by spectrophotometry and fluorimetry to characterise the mechanism of oxidant scavenging.

Results

GAPDH activity of HCT116 cells was inhibited by the oxidants tested: the concentration that produced 50% inhibition (IC50) was 44.5 (2.1) μM for HOCl, 379.8 (21.3) μM for H2O2, and 685.8 (103.8) μM for NO (means (SEM)). 5-ASA was the only therapeutic compound tested to show efficacy (p<0.05) against HOCl mediated inhibition of enzyme activity; however, it was ineffective against H2O2 and NO mediated inhibition of GAPDH. Methylprednisolone, metronidazole, and the thiol-containing 6-mercaptopurine were ineffective against all oxidants. Studies at ratios of HOCl:5-ASA achievable in the mucosa showed direct scavenging to be the mechanism of protection of GAPDH activity. Mixing 5-ASA and HOCl before addition to the cells resulted in significantly greater protection of GAPDH activity than when HOCl was added to cells preincubated with 5-ASA. The addition of 5-ASA after HOCl exposure did not restore GAPDH activity.

Conclusions

Therapies based on 5-ASA may play a direct role in scavenging the potent neutrophil oxidant HOCl, thereby protecting mucosal GAPDH from oxidative inhibition. These findings suggest that strategies for the further development of new HOCl scavenging compounds may be useful in the treatment of IBD.
Macromolecular transport across the rabbit proximal and distal colon
Authors: Hardin J A , Kimm M H , Wirasinghe M , Gall D G
Published: June 2010

Background

Although many studies have investigated macromolecular uptake in the stomach and small intestine, little is known about macromolecular uptake in the colon.

Aims

To investigate the mechanisms involved in the transport of large antigenically intact macromolecules across the proximal and distal colonic epithelium in the rabbit.

Methods

The mucosal to serosal movement of bovine serum albumin (BSA) was examined in modified Ussing chambers under short circuited conditions. The mucosal surface was exposed to varying concentrations of BSA, and after a 50 minute equilibration period, the mucosal to serosal flux of immunologically intact BSA was determined by ELISA. Total BSA flux was determined by the transport of radiolabelled 125I-BSA.

Results

Intact BSA transport in proximal and distal colonic tissue showed saturable kinetics. Intact BSA transport in the proximal and distal segment was 7% and 2% of the total 125I-BSA flux respectively. Immunologically intact BSA transport in the distal segment was significantly less than that in the proximal segment. Intact BSA transport in the proximal colon was significantly reduced following treatment with sodium fluoride, colchicine, and tetrodotoxin. Cholinergic blockade had no effect on the uptake of intact BSA.

Conclusion

The findings indicate that the transport of intact macromolecules across the proximal and distal large intestine is a saturable process. Further, intact BSA transport in the proximal colon is an energy dependent process that utilises microtubules and is regulated by the enteric nervous system.
A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer
Authors: Yanai H , Noguchi T , Mizumachi S , Tokiyama H , Nakamura H , Tada M , Okita K
Published: June 2010

BACKGROUND/AIMS

Endoscopic ultrasonography is expected to be useful for invasion depth staging of early gastric cancer. A prospective blind study of the staging characteristics of endoscopy and endoscopic ultrasonography for early gastric cancer was performed.

METHODS

Findings of endoscopy and endoscopic ultrasonography using a 20 MHz thin ultrasound probe were independently reviewed and the results of 52 early gastric cancer lesions analysed.

RESULTS

The overall accuracy rates in invasion depth staging of early gastric cancer were 63% for endoscopy and 71% for endoscopic ultrasonography. No statistically significant differences were observed in overall accuracy. Endoscopic ultrasonography tended to overstage, and lesions that were classified as mucosal cancer by endoscopic ultrasonography were very likely (95%) to be limited to the mucosa on histological examination. All 16 lesions staged as mucosal cancer independently but coincidentally by both methods were histologically limited to the mucosa.

CONCLUSIONS

Endoscopic ultrasonography is expected to compensate for the understaging of lesions with submucosal invasion that are endoscopically staged as mucosal cancer.
Vicia faba agglutinin, the lectin present in broad beans, stimulates differentiation of undifferentiated colon cancer cells
Authors: Jordinson M , El-Hariry I , Calnan D , Calam J , Pignatelli M
Published: June 2010

BACKGROUND

Dietary lectins can alter the proliferation of colonic cells. Differentiation is regulated by adhesion molecules which, being glycosylated, are targets for lectin binding.

AIMS

To examine the effects of dietary lectins on differentiation, adhesion, and proliferation of colorectal cancer cells.

METHODS

Differentiation was assessed in three dimensional gels, adhesion by aggregation assay, and proliferation by 3H thymidine incorporation. The role of the epithelial cell adhesion molecule (epCAM) was studied using a specific monoclonal antibody in blocking studies and Western blots. The human colon cancer cell lines LS174T, SW1222, and HT29 were studied.

RESULTS

The cell line LS174T differentiated in the presence of Vicia fabaagglutinin (VFA) into gland like structures. This was inhibited by anti-epCAM monoclonal antibody. Expression of epCAM itself was unaffected. VFA as well as wheat germ agglutinin (WGA) and the edible mushroom lectin (Agaricus bisporus lectin, ABL) significantly aggregated LS174T cells but peanut agglutinin (PNA) and soybean agglutinin (SBA) did not. All lectins aggregated SW1222 and HT29 cells. Aggregation was blocked by the corresponding sugars. Aggregation of cells by VFA was also inhibited by anti-epCAM. VFA, ABL, and WGL inhibited proliferation of all the cell lines; PNA stimulated proliferation of HT29 and SW1222 cells. In competition studies all sugars blocked aggregation and proliferation of all cell lines, except that the addition of mannose alone inhibited proliferation.

CONCLUSION

VFA stimulated an undifferentiated colon cancer cell line to differentiate into gland like structures. The adhesion molecule epCAM is involved in this. Dietary or therapeutic VFA may slow progression of colon cancer.
Genetic epidemiology of mutated K-rasproto-oncogene, altered suppressor genes, and microsatellite instability in colorectal adenomas
Authors: Rashid A , Zahurak M , Goodman S N , Hamilton S R
Published: June 2010

BACKGROUND

The genetic epidemiology of colorectal adenomas has not been studied prospectively in colonoscopy patients without cancer.

AIMS

To study genetic alterations in colorectal adenomas and correlate these with patient demographics and adenoma characteristics.

METHODS

Mutations and allelic deletions in 201 adenomas from 60 patients were compared with demographic features, adenoma characteristics, and family history.

RESULTS

The most common alteration was K-ras proto-oncogene mutation, present in 35% of adenomas and 65% of patients. Patients 65 years of age and older had a decreased probability of K-ras mutations (26% versus 45%). Overexpression of p53 gene product was present in only 6% of adenomas but was more frequent in villous or tubulovillous adenomas (19% versus 3%). Allelic loss of chromosome 18q was present in only 2% of adenomas and was significantly less frequent than p53 overexpression. DNA replication errors (RER) were present in 7% of adenomas and 15% of patients, including multiple adenomas in four patients (two with hereditary non-polyposis colorectal cancer syndrome). Only 36% of RER positive adenomas had alteration of BAT-26 alleles, none had alteration of BAT-25, and only one (8%) had mutation in the transforming growth factor β type II receptor gene. RER positive adenomas were more likely to have a K-ras mutation. In patients with multiple adenomas, there was concordance of p53 overexpression and RER but not of K-ras mutations.

CONCLUSIONS

Genetic progression in colorectal adenomas is heterogeneous, involving factors related to patient age and the presence of RER for the occurrence of ras mutations, but different intraindividual characteristics for the occurrence of p53 alterations and RER.
High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis
Authors: Sobajima J , Ozaki S , Uesugi H , Osakada F , Inoue M , Fukuda Y , Shirakawa H , Yoshida M , Rokuhara A , Imai H , Kiyosawa K , Nakao K
Published: June 2010

BACKGROUND

High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 have been identified as novel antigens of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), and the existence of anti-HMG1 and anti-HMG2 antibodies in a population of patients with ulcerative colitis has been reported.

AIMS

To investigate whether HMG1 and HMG2 are target antigens for p-ANCAs in autoimmune hepatitis (AIH).

PATIENTS

Serum samples from 28 patients with AIH, 44 patients with primary biliary cirrhosis (PBC), 27 patients with chronic hepatitis C, and 23 patients with chronic hepatitis B were tested.

METHODS

ANCAs were detected by routine indirect immunofluorescence (IIF). Anti-HMG1 and anti-HMG2 antibodies were assayed by enzyme linked immunosorbent assay.

RESULTS

p-ANCAs were detected in 89% (25/28) of patients with AIH, 36% (16/44) of patients with PBC, 11% (3/27) of patients with chronic hepatitis C, and 13% (3/23) of patients with chronic hepatitis B. Anti-HMG1 and/or anti-HMG2 antibodies were detected in 89% (25/28) of patients with AIH, 70% (31/44) with PBC, 26% (7/27) with chronic hepatitis C, and 9% (2/23) with chronic hepatitis B. In AIH, anti-HMG1 and/or anti-HMG2 antibodies were detected in 96% (24/25) of p-ANCA positive patients. The p-ANCA staining pattern detected by IIF using sera from patients with AIH disappeared or decreased in titre after preincubation with a mixture of HMG1/HMG2. The presence and titres of those antibodies in AIH correlated significantly with those of p-ANCA, but not with those of anti-nuclear antibody or anti-smooth muscle antibody.

CONCLUSIONS

HMG1 and HMG2 are significant target antigens of p-ANCA in AIH.
The Stamp-in-Safety programme, an intervention to promote better supervision of children on childcare centre playgrounds: an evaluation in an urban setting
Authors: Chelvakumar Gayathri , Sheehan Karen , Hill Amy L , Lowe Danita , Mandich Nicole , Schwebel David C
Published: June 2010

Using a non-equivalent control group design, this report evaluated a previously studied behavioural intervention, the Stamp-in-Safety programme, which is designed to reduce the injury risk for young children on playgrounds at childcare centres by increasing the quality of adult supervision and rewarding children for safe play. In an urban, commercial childcare centre, 71 children aged 3–5 years and 15 teachers participated. Primary outcome measures were teacher verbalisations (warnings, explanations, redirects), teacher location (core, outskirt, or fringe of playground), child risk-taking behaviours (using equipment appropriately) and the number of injuries on the playground. Analyses revealed that the intervention had a modest positive effect in promoting safer teacher and child playground behaviours. This study reaffirms previous results that the Stamp-in-Safety programme is an effective method to decrease the risk of playground injuries at childcare centres.
Application of a novel and low cost technique to construct paraffin tissue microarrays out of paraffinised needle biopsy specimens from patients with breast cancer
Authors: Vogel Ulrich Felix , Bültmann Burkhard
Published: June 2010

Background

Paraffin tissue microarrays (TMAs) are a well accepted tool in pathology for high throughput molecular profiling, quality control and clinicopathological trials. No reports on TMAs constructed from paraffinised needle biopsy specimens (PNBSs) derived from patients with breast cancer can be found in the literature. PNBSs are sometimes the only source for tumour characterisation important for treatment.

Aim

To develop a novel and low cost technique to construct TMAs from PNBSs (PNBSs–TMAs) in order to close this gap in TMA technology.

Methods

Using a skin biopsy punch, tumour-bearing parts of 84 PNBSs were punched out of the donor blocks, freed from the surrounding paraffin by melting and manually transferred into the preformed holes in the recipient block. After filling the holes, the PNBSs–TMA was fixed to a double sided adhesive tape and completely melted. Quality assessment of this new technique was performed comparing the HER2 status (synonym: cerbB2) of the PNBSs–TMA with the results of the original PNBSs and a TMA harbouring the tumour in corresponding resection and mastectomy specimens (RM–TMA).

Results

A 187-hole PNBSs–TMA with 84 PNBSs was successfully constructed. About 1% of the included PNBSs displayed signs of rolling and folding or of floating off the slide during the staining procedure. The results of immunohistochemistry, fluorescence in situ hybridisation and automated brightfield double in situ hybridisation showed high quality standard of the PNBSs–TMA, suitable for precise tumour profiling.

Conclusions

PNBSs–TMAs are suitable for clinicopathological trials, especially those in which PNBSs are the only tumour source.
Method and developer characteristics for effective agile method tailoring
Authors: Conboy Kieran , Fitzgerald Brian
Published: June 2010

It has long been acknowledged that software methods should be tailored if they are to achieve optimum effect. However comparatively little research has been carried out to date on this topic in general, and more notably, on agile methods in particular. This dearth of evidence in the case of agile methods is especially significant in that it is reasonable to expect that such methods would particularly lend themselves to tailoring. In this research, we present a framework based on interviews with 20 senior software development researchers and a review of the extant literature. The framework is comprised of two sets of factors—characteristics of the method, and developer practices—that can improve method tailoring effectiveness. Drawing on the framework, we then interviewed 16 expert XP practitioners to examine the current state and effectiveness of XP tailoring efforts, and to shed light on issues the framework identified as being important. The article concludes with a set of recommendations for research and practice that would advance our understanding of the method tailoring area.
Computational rephotography
Authors: Bae Soonmin , Agarwala Aseem , Durand Frédo
Published: June 2010

Rephotographers aim to recapture an existing photograph from the same viewpoint. A historical photograph paired with a well-aligned modern rephotograph can serve as a remarkable visualization of the passage of time. However, the task of rephotography is tedious and often imprecise, because reproducing the viewpoint of the original photograph is challenging. The rephotographer must disambiguate between the six degrees of freedom of 3D translation and rotation, and the confounding similarity between the effects of camera zoom and dolly.

We present a real-time estimation and visualization technique for rephotography that helps users reach a desired viewpoint during capture. The input to our technique is a reference image taken from the desired viewpoint. The user moves through the scene with a camera and follows our visualization to reach the desired viewpoint. We employ computer vision techniques to compute the relative viewpoint difference. We guide 3D movement using two 2D arrows. We demonstrate the success of our technique by rephotographing historical images and conducting user studies.
Transcriptome profiling and network analysis of genetically hypertensive mice identifies potential pharmacological targets of hypertension
Authors: Puig Oscar , Wang I-Ming , Cheng Ping , Zhou Pris , Roy Sophie , Cully Doris , Peters Mette , Benita Yair , Thompson John , Cai Tian-Quan
Published: June 2010

Hypertension is a condition with major cardiovascular and renal complications, affecting nearly a billion patients worldwide. Few validated gene targets are available for pharmacological intervention, so there is a need to identify new biological pathways regulating blood pressure and containing novel targets for treatment. The genetically hypertensive “blood pressure high” (BPH), normotensive “blood pressure normal” (BPN), and hypotensive “blood pressure low” (BPL) inbred mouse strains are an ideal system to study differences in gene expression patterns that may represent such biological pathways. We profiled gene expression in liver, heart, kidney, and aorta from BPH, BPN, and BPL mice and determined which biological processes are enriched in observed organ-specific signatures. As a result, we identified multiple biological pathways linked to blood pressure phenotype that could serve as a source of candidate genes causal for hypertension. To distinguish in the kidney signature genes whose differential expression pattern may cause changes in blood pressure from those genes whose differential expression pattern results from changes in blood pressure, we integrated phenotype-associated genes into Genetic Bayesian networks. The integration of data from gene expression profiling and genetics networks is a valuable approach to identify novel potential targets for the pharmacological treatment of hypertension.
On the Abstract Subordinated Exit Equation
Authors: Mejri Hassen , Mliki Ezzedine
Published: June 2010

Let ℙ = (Pt) t>0 be a C0‐contraction semigroup on a real Banach space ℬ. A ℙ‐exit law is a ℬ‐valued function t∈]0, ∞[→φt ∈ ℬ satisfying the functional equation: Ptφs = φt+s, s, t > 0. Let β be a Bochner subordinator and let ℙβ be the subordinated semigroup of ℙ (in the Bochner sense) by means of β. Under some regularity assumption, it is proved in this paper that each ℙβ‐exit law is subordinated to a unique ℙ‐exit law.
Serum Interleukin‐4 and Total Immunoglobulin E in Nonatopic Alopecia Areata Patients and HLA‐DRB1 Typing
Authors: Attia Enas A. S. , El Shennawy Dina , Sefin Ashraf
Published: June 2010

Background. Interleukin‐4 (IL‐4), a Th2 cytokine, can stimulate immunoglobulin E (IgE) transcription. No previous studies evaluated the genetic mechanisms in nonatopic AA patients with elevated serum IgE. Objective. To compare serum IL‐4 and total IgE levels between Egyptian nonatopic AA patients and healthy subjects and to investigate a possible relation to HLA‐DRB1 alleles. Results. Serum IL‐4 and total IgE were measured by ELISA in 40 controls and 54 nonatopic AA patients. Patients′ HLA‐DRB1 typing by sequence specific oligonucleotide probe technique was compared to normal Egyptian population. We found significantly elevated serum IL‐4 and total IgE in AA patients (particularly alopecia universalis, AU, and chronic patients) (P < .01). HLA‐DRB1*11 is a general susceptibility/chronicity allele. DRB1*13 is a protective allele. DRB1*01 and DRB1*07 are linked to chronicity. Localized AA showed decreased DRB1*03 and DRB1*07. Extensive forms showed increased DRB1*08 and decreased DRB1*04. Elevated IL4 and IgE were observed in patients with DRB1*07 and DRB1*11 not DRB1*04. Conclusion. Serum IL‐4 and IgE are elevated in nonatopic AA patients, particularly AU and chronic disease. Relevant susceptibility, chronicity, and severity HLADRB1 alleles may have a role in determining type, magnitude, and duration of immune response in AA favouring increased IL4 and IgE.
Cell-Permeable Peptide DEPDC1-ZNF224 Interferes with Transcriptional Repression and Oncogenicity in Bladder Cancer Cells
Authors: Harada Yosuke , Kanehira Mitsugu , Fujisawa Yoshiko , Takata Ryo , Shuin Taro , Miki Tsuneharu , Fujioka Tomoaki , Nakamura Yusuke , Katagiri Toyomasa
Published: June 2010

Bladder cancer is the second most common genitourinary cancer worldwide, yet its oncogenic origins remain poorly understood. The cancer-testis antigen DEPDC1 was shown recently to contribute to bladder cancer oncogenesis. In this study, we examined the biological functions of DEPDC1 and defined a potential therapeutic strategy to target this molecule. Coimmunoprecipitation and immunocytochemistry revealed that DEPDC1 interacted and colocalized with zinc finger transcription factor ZNF224, a known transcriptional repressor. Inhibiting this interaction with a cell-permeable peptide corresponding to the ZNF224-interacting domain in DEPDC1 induced apoptosis of bladder cancer cells in vitro and in vivo. By inhibiting DEPDC1-ZNF224 complex formation, this peptide triggered transcriptional activation of A20, a potent inhibitor of the NF-κB signaling pathway. Our findings indicate that the DEPDC1-ZNF224 complex is likely to play a critical role in bladder carcinogenesis. Cancer Res; 70(14); 5829–39. ©2010 AACR.
Epigenetic Regulation of Vitamin D 24-Hydroxylase/CYP24A1 in Human Prostate Cancer
Authors: Luo Wei , Karpf Adam R. , Deeb Kristin K. , Muindi Josephia R. , Morrison Carl D. , Johnson Candace S. , Trump Donald L.
Published: June 2010

Calcitriol, a regulator of calcium homeostasis with antitumor properties, is degraded by the product of the CYP24A1 gene, which is downregulated in human prostate cancer by unknown mechanisms. We found that CYP24A1 expression is inversely correlated with promoter DNA methylation in prostate cancer cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) activates CYP24A1 expression in prostate cancer cells. In vitro methylation of the CYP24A1 promoter represses its promoter activity. Furthermore, inhibition of histone deacetylases by trichostatin A (TSA) enhances the expression of CYP24A1 in prostate cancer cells. Quantitative chromatin immunoprecipitation-PCR (ChIP-qPCR) reveals that specific histone modifications are associated with the CYP24A1 promoter region. Treatment with TSA increases H3K9ac and H3K4me2 and simultaneously decreases H3K9me2 at the CYP24A1 promoter. ChIP-qPCR assay reveals that treatment with DAC and TSA increases the recruitment of vitamin D receptor to the CYP24A1 promoter. Reverse transcriptase-PCR analysis of paired human prostate samples revealed that CYP24A1 expression is downregulated in prostate malignant lesions compared with adjacent histologically benign lesions. Bisulfite pyrosequencing shows that CYP24A1 gene is hypermethylated in malignant lesions compared with matched benign lesions. Our findings indicate that repression of CYP24A1 gene expression in human prostate cancer cells is mediated in part by promoter DNA methylation and repressive histone modifications. Cancer Res; 70(14); 5953–62. ©2010 AACR.
NF1 Inactivation Revs Up Ras in Adult Acute Myelogenous Leukemia
Authors: Mullally Ann , Ebert Benjamin L.
Published: June 2010

Mutations in the Ras pathway are common in myeloid malignancies. NF1, a tumor suppressor and negative regulator of Ras, is inactivated in a subset of adult acute myelogenous leukemia (AML) cases. Loss of NF1 function sensitizes cells to inhibition of mammalian target of rapamycin (mTOR), a downstream effector of Ras activation, highlighting a potential therapeutic opportunity for some AML patients. Clin Cancer Res; 16(16); 4074–6. ©2010 AACR.