bluuebunny/crossref_metadata_2025 huggingface dataset:
A high‐grain protein content locus on barley (Hordeum vulgare) chromosome 6 is associated with increased flag leaf proteolysis and nitrogen remobilization
Authors: Jukanti Aravind K. , Fischer Andreas M.
Published: March 2008

Leaf senescence and nitrogen remobilization from senescing tissues are two important factors determining grain protein content (GPC) in cereals. We compared near‐isogenic barley (Hordeum vulgare L.) germplasm varying in the allelic state of a major GPC quantitative trait locus on chromosome 6, delineated by molecular markers HVM74 and ABG458 and explaining approximately 46% of the variability in this trait. High GPC was consistently associated with earlier whole‐plant senescence. SDS–PAGE and immunoblot analysis of flag leaf proteins indicated earlier leaf protein [including ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco)] degradation in high‐GPC germplasm. This was accompanied by enhanced availability of ammonium and glutamine in developing kernels, suggesting increased phloem retranslocation of nitrogen. Based on previous microarray analysis, we performed a detailed expression study of six leaf genes, tentatively involved in plastidial proteolysis, vacuolar proteolysis, intermediary N metabolism and N transport. All of these were upregulated in high‐GPC barley, mostly around 21 to 28 days past anthesis, prior to or around the time demonstrating maximal differences in leaf protein (including Rubisco) levels. Therefore, these genes represent potential targets to manipulate grain protein accumulation. It appears likely that their functional analysis will enhance our understanding of whole‐plant N recycling. Additionally, earlier leaf (photosynthetic) protein degradation may lead to reduced N carbon assimilation in high‐GPC germplasm, explaining past studies demonstrating a negative correlation between GPC and yield.
Boric acid and salinity effects on maize roots. Response of aquaporins ZmPIP1 and ZmPIP2, and plasma membrane H+‐ATPase, in relation to water and nutrient uptake
Authors: Martinez‐Ballesta Maria del Carmen , Bastías Elizabeth , Zhu Chuanfeng , Schäffner Anton R. , González‐Moro Begoña , González‐Murua Carmen , Carvajal Micaela
Published: March 2008

Under saline conditions, an optimal cell water balance, possibly mediated by aquaporins, is important to maintain the whole‐plant water status. Furthermore, excessive accumulation of boric acid in the soil solution can be observed in saline soils. In this work, the interaction between salinity and excess boron with respect to the root hydraulic conductance (L0), abundance of aquaporins (ZmPIP1 and ZmPIP2), ATPase activity and root sap nutrient content, in the highly boron‐ and salt‐tolerant Zea mays L. cv. amylacea, was evaluated. A downregulation of root ZmPIP1 and ZmPIP2 aquaporin contents were observed in NaCl‐treated plants in agreement with the L0 measurements. However, in the H3BO3‐treated plants differences in the ZmPIP1 and ZmPIP2 abundance were observed. The ATPase activity was related directly to the amount of ATPase protein and Na+ concentration in the roots, for which an increase in NaCl‐ and H3BO3+ NaCl‐treated plants was observed with respect to untreated and H3BO3‐treated plants. Although nutrient imbalance may result from the effect of salinity or H3BO3 alone, an ameliorative effect was observed when both treatments were applied together. In conclusion, our results suggest that under salt stress, the activity of specific membrane components can be influenced directly by boric acid, regulating the functions of certain aquaporin isoforms and ATPase as possible components of the salinity tolerance mechanism.
Knockdown of porcine endogenous retrovirus (PERV) expression by PERV‐specific shRNA in transgenic pigs
Authors: Dieckhoff Britta , Petersen Björn , Kues Wilfried A. , Kurth Reinhard , Niemann Heiner , Denner Joachim
Published: March 2008

Abstract:  Background:  Xenotransplantation using porcine cells, tissues or organs may be associated with the transmission of porcine endogenous retroviruses (PERVs). More than 50 viral copies have been identified in the pig genome and three different subtypes of PERV were released from pig cells, two of them were able to infect human cells in vitro. RNA interference is a promising option to inhibit PERV transmission.

Methods:  We recently selected an efficient si (small interfering) RNA corresponding to a highly conserved region in the PERV DNA, which is able to inhibit expression of all PERV subtypes in PERV‐infected human cells as well as in primary pig cells. Pig fibroblasts were transfected using a lentiviral vector expressing a corresponding sh (short hairpin) RNA and transgenic pigs were produced by somatic nuclear transfer cloning. Integration of the vector was proven by PCR, expression of shRNA and PERV was studied by in‐solution hybridization analysis and real‐time RT PCR, respectively.

Results:  All seven born piglets had integrated the transgene. Expression of the shRNA was found in all tissues investigated and PERV expression was significantly inhibited when compared with wild‐type control animals.

Conclusion:  This strategy may lead to animals compatible with PERV safe xenotransplantation.
Stereological Characteristics of the Equine Accessory Nerve
Authors: Matiasek K. , Gais P. , Rodenacker K. , Jütting U. , Tanck J. J. , Schmahl W.
Published: March 2008

Stereological techniques have been increasingly employed for assessment and characterization of neuromuscular diseases in humans and animals. As an adjunct to histopathology, morphometrical algorithms provide quantitative evidence of the peripheral nerve composition, thereby shedding light on its fibre characteristics and basic electrophysiological properties. In the horse, stereological investigations already have focussed on the recurrent laryngeal, deep peroneal and lateral palmar nerves (LPN). Of these, only the latter is suitable for taking biopsies in clinical settings, however, it does not contain any motor fibres and Ia‐afferents. On account of its virtually mixed fibre qualities, most researchers today recommend the cervical branch of the equine accessory nerve (AN) for harvesting diagnostic samples. Thus, the present study was carried out to gain morphometrical proof of the AN composition and to obtain stereological base values in healthy individuals using state‐of‐the‐art technology. All parameters were compared to the common peroneal nerve (CPN), known to harbour all myelinated fibre classes. As this second biopsy site is located farther distally to the neuro‐axis, attention was paid to possible length‐dependent features.

Taken together, digital image analysis could be accurately applied on all AN samples. Stereology supported the histological and clinical evidence that the AN contains all myelinated fibre types. The huge range and scatter of fibre counts and density (3351–17 812/mm²) per fascicle were comparable to that measured in the equine common peroneal, deep peroneal, lateral palmar and recurrent laryngeal nerves. Similar to those, fibre diameter distribution was bimodal with slow Aβ‐ and Aγ‐mechanoceptor afferents outnumbering large myelinated Aα‐fibres by a factor of about 1.5. With a g‐ratio at 0.55 ± 0.001, the overall degree of myelination in the AN is highly consistent and insignificantly ranges between that of the equine common peroneal and LPNs. Apart from this subtle deviation, a statistically relevant difference between the more proximal AN and the distal CPN could not be documented. By obtaining morphometrical standard parameters and even more sophisticated distribution indices, stereology is a valuable tool for detection of subtle changes that are likely to escape from the investigators’ eyes. The AN serves as a reliable source for advanced peripheral nerve research and should be accompanied by farther distal nerve probes for assessment of neuropathies that present with a proximodistal gradient.
Use of low carbohydrate, high protein diets in cats with diabetes mellitus
Authors: Hall T. C. , Mahony O. M. , Freeman L. M. , Rozanski E. A.
Published: March 2008

The goal of this randomized, double‐blind study was to compare the effects of feeding a low carbohydrate, high protein diet versus a maintenance diet in a group of cats with diabetes mellitus treated with insulin glargine twice daily. All cats with naturally occurring diabetes mellitus not currently treated with insulin glargine or diabetogenic drugs or being fed a low carbohydrate, high protein diet were eligible for inclusion. Baseline testing included a physical examination, complete blood count, serum biochemistry profile, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were treated with insulin glargine (starting dose of 0.25 U/kg) twice daily. Insulin was adjusted as needed for glucose regulation. Cats were randomized to receive either a low carbohydrate, high protein diet or a feline maintenance diet. Re‐evaluations were performed on all cats at weeks 1, 2, 4, 6 and 10, and included an assessment of clinical signs, physical examination, 12‐h blood glucose curve, and serum fructosamine concentrations. Changes in continuous variables over the course of the study were analyzed using analysis of variance with repeated measures. p < 0.05 was considered statistically significant. Ten cats have completed the study. There were no significant differences between diet groups at baseline for age, gender, weight, body condition score, serum glucose or fructosamine concentrations. Although there was not a significant difference over time in clinical signs, insulin doses, or peak or nadir glucose concentrations between diet groups, diet did have a significant effect on serum fructosamine concentrations (p = 0.01). Six of the 10 cats that have completed the study achieved complete remission by the end of the study period, with no statistical difference between diets. The study's results indicate that diet can have significant effects on glucose regulation in cats receiving insulin glargine for treatment of feline diabetes mellitus.
Detection of serum adiponectin in the cat, bear, and horse using antibody from a commercial ELISA kit
Authors: Lusby A. L. , Kania S. A. , Abd‐Eldaim M. , Bartges J. W. , Kirk C. A.
Published: March 2008

Adiponectin is a hormone secreted from adipose tissue that closely associates with insulin resistance. In contrast to other adipokines, adiponectin levels decrease as fat mass increases. The ability to measure adiponectin in veterinary species will allow researchers to assess hormone function and may lead to improved screening tests and treatments for insulin resistance and type II diabetes. A commercial ELISA kit (B‐bridge International) is available for adiponectin quantification in mice and rats. To test this assay's ability to bind adiponectin in several veterinary species known to develop insulin resistance with obesity, we conducted a Western blot analysis comparing mouse, cat, bear, and horse serum using the antibody provided with the assay. The proteins were subjected to denaturing SDS‐PAGE and transferred to a nitrocellulose membrane. Blocking was performed in 5% milk solution. The membrane was then incubated with the rabbit anti‐mouse adiponectin antibody provided with the ELISA kit, followed by incubation with peroxidase‐labeled goat anti‐rabbit IgG. Detection of bound antibody was performed using enhanced chemoluminescence. Bands corresponding to the adiponectin monomer (30 kDa) were apparent for each sample tested. Therefore, the antibody provided in the ELISA kit appears to bind with adiponectin in all species tested. Our laboratory has previously validated the ELISA mouse/rat adiponectin kit for use in cats. High DNA homology across species and strong antibody binding at the 30 kDa site warrant validation of the kit's accuracy in other species at risk for insulin resistance (eg. horses and bears).
III. Virulence and pathogenicity of Helicobacter pylori
Authors: MARSHALL BARRY J.
Published: March 2008

H. pylori is a highly virulent organism as evidenced by its low infective dose and widespread high prevalence in human populations. Its virulence is achieved through its ability to survive in a moist environment and its massive urease production which allows it to survive in the acidic gastric juice long enough to colonize the gastric mucus.

Gastric colonization is facilitated by cell wall associated lectins which permit the bacterium to bind to gastric mucus and the gastric epithelial cell. Once in this location, H. pylori produces several enzymes which may harm the gastric epithelium, particularly urease (through ammonia generation) and phospholipases A and C. H. pylori also weakens the gastric mucous layer by digesting its glycoproteins and lipids, making the mucus less hydrophobic and more water soluble.

Helicobacter pylori attracts phagocytic cells, inducing both acute and chronic inflammation as well as an antibody response. Persistence of H. pylori in the mucosa may be enhanced by its cytotoxin and catalase production, by which it survives after phagocytosis by neutrophils.
Medical treatment of duodenal ulcer: Acid inhibition or Helicobacter pylori eradication?
Authors: LAI KWOK‐HUNG , CHANG FULL‐YOUNG , TSAY SHYH‐HAW , LU LEE‐CHENG , CHENG JIUNN‐TARNG , JENG SHENG‐SHONG , WU TZEE‐CHUNG , NG WAI‐WAH , JENG JIN‐SHIUNG , LEE SHOU‐DONG , TSAI YANG‐TE
Published: March 2008

To ascertain whether acid inhibition or Helicobacter pylori (HP) colonization is the decisive factor in the healing of duodenal ulcer, we treated 54 patients with famotidine and carried out long‐term follow‐up. Helicobacter pylori colonization was found in 70.4% of patients before treatment. There were no differences in the pre‐treatment characteristics between patients with HP positive or HP negative ulcers. The 4‐week and 8‐week healing rates after famotidine treatment were 72.5% and 82.4% respectively. No difference in HP colonization was found between patients with ulcer healed and those with ulcer not healed (78.4%vs 64.3% at 4th week and 77.3%vs 71.4% at 8th week, P > 0.05). In patients with ulcer healed at 4th week, the intragastric pH was raised significantly and the antral acute inflammation was less severe than those with ulcer not healed. Ulcer recurrence was found in 76.9% of patients within 1 year, but there was no difference in ulcer recurrence between the patients with positive or negative HP colonization at the time of ulcer healing. Our results suggest that duodenal ulcer healing and recurrence are closely related to acid inhibition rather than to HP colonization.
Snake skin pattern gastropathy in cirrhotic patients
Authors: LIN WEN‐JEH , LEE FA‐YAUH , LIN HAN‐CHIEH , TSAI YANG‐TE , LEE SHOU‐DONG , LAI KWOK‐HUNG , HSIA HSIAO‐CHUNG , WANG SUN‐SANG , LO KWANG‐JUEI
Published: March 2008

Gastric mucosal lesions are common in patients with cirrhosis. Among them, snake skin pattern gastropathy (SSPG) is the most distinguishing one. A prospective study was conducted to investigate the incidence of SSPG in cirrhotic patients, the relationship between the degree of portal pressure and SSPG, and the possible association of SSPG with serum levels of gastrin and pepsinogen I. SSPG was found to be significantly more common in 100 cirrhotic patients than in 100 age‐ and sex‐matched healthy controls (41%vs 0%, P < 0.0001). Hepatic venous pressure gradient and serum gastrin and pepsinogen I levels were measured in 21 cirrhotic patients with SSPG and 25 cirrhotics without SSPG. There was no significant difference in hepatic venous pressure gradient (16.1 ± 4.4 mmHg vs 16.1 ± 4.9 mmHg, P > 0.05), serum gastrin level (78.0 ± 26.7 pg/mL vs 80.1 ± 32.5 pg/mL, P > 0.05) and serum pepsinogen I level (69.5 ± 26.6 ng/mL vs 65.2 ± 26.1 ng/mL, P > 0.05) in cirrhotic patients with or without SSPG. In conclusion, SSPG is common in cirrhotic patients. Portal pressure per se may not be the only factor causing SSPG—other aggressive factors may be needed together to cause the gastropathy. There is no evidence of correlation between serum gastrin or pepsinogen I level and SSPG.
Significance of blood flow in the inferior and superior mesenteric veins for the formation of oesophageal varices
Authors: SHIOMI SUSUMU , KUROKI TETSUO , UEDA TADASHI , IKEOKA NAOKO , NISHIGUCHI SHUHEI , NAKAJIMA SHINYA , KOBAYASHI KENZO , MONNA TAKEYUKI , OCHI HIRONOBU
Published: March 2008

The degree of involvement of blood flow in the superior mesenteric vein and inferior mesenteric vein in the formation of oesophageal varices is not known. We have developed a method by which the contributions of these veins to portal blood flow can be evaluated simultaneously in a relatively non‐invasive way. An enteric‐coated capsule containing [123I]iodoamphetamine (IMP) is given by mouth and 3 h later [123I]IMP is instilled into the rectum. The data obtained are treated by computer to calculate the portal shunt index via the inferior and superior mesenteric veins. In chronic hepatitis and cirrhosis, when varices were absent, the difference in these indices was not significant. In the presence of varices, the portal shunt index via the inferior mesenteric vein was significantly higher than that via the superior mesenteric vein. It was suggested that the contribution of blood flow in the inferior mesenteric vein the portal/splenic axis is important in the formation of varices.
Frequency of abnormalities detected by abdominal ultrasound among Japanese adults
Authors: OSHIBUCHI MASAO , NISHI FUMIAKI , SATO MITSUTAKA , OHTAKE HISASHI , OKUDA KUNIO
Published: March 2008

Abdominal ultrasound examination was given to 715 (566 male and 149 female) adult non‐manual workers in Tokyo as part of their annually required medical check‐up. Gross abnormalities were found in 44.5% of males and 34.2% of females. The most common finding was fatty liver (15.2%), seen four times as frequently in males as in females. There were 93 elevated lesions in the gall‐bladder in 56 subjects (7.8%); some required follow‐up examinations because malignancy could not be excluded. Small cystic lesions were frequently seen in the kidney (6.4%) and in the liver (4.8%). Gallstones were found in 3.4%. Mild splenomegaly occurred in 3.4%. Ten mass lesions, 8 hyperechoic and 2 hypo‐echoic, were found in the liver, but subsequent imaging studies showed them to be benign haemangiomas. Other changes found included calcific lesions in the liver (2.1%) and in the spleen (0.4%), renal stones (2.0%), thickened wall of the gall‐bladder (3.2%), intramural stones (0.8%) and debris/sludge (0.4%) in the gall‐bladder, dilated pancreatic duct (0.7%) and common bile duct (0.3%), liver cirrhosis (0.4%), hydronephrosis (0.1%), enlarged pancreas (0.1%), small pancreas (0.1%), ovarian tumour (0.1%), uterine tumour (0.1%), abnormally shaped kidney (0.1%) and situs inversus (0.1%). It was concluded that abdominal ultrasound is an important examination for a mass screening or a physical check‐up commonly practised as the ‘human dock’ for adults in Japan.
Dose‐dependent effects of a nitric oxide biosynthesis inhibitor on hyperdynamic circulation in two models of portal hypertension in conscious rats
Authors: PILETTE CHRISTOPHE , KIRSTETTER PHILIPPE , SOGNI PHILIPPE , CAILMAIL STEPHANE , MOREAU RICHARD , LEBREC DIDIER
Published: March 2008

The role of nitric oxide (NO) in the hyperkinetic circulation in portal hypertension has not been clearly elucidated. Different doses of NO inhibitors, haemodynamic values and experimental conditions might explain the discrepant results. The aim of the present study was to investigate the acute effects of a specific biosynthesis inhibitor of NO, Nω‐nitro‐L‐arginine (L‐NNA), on the systemic and splanchnic circulation in normal conscious rats and rats with portal hypertension due to either partial portal vein stenosis or secondary biliary cirrhosis. The administration of L‐NNA (15 to 960 (μg.kg‐1.min‐1) induced a significant dose dependent increase in arterial pressure which was not different among the three groups of rats. Following an acute and maximal vasopressive dose of L‐NNA (1 mg.kg‐1.min‐1) cardiac index decreased more in portal vein stenosed and cirrhotic rats (‐45 ± 3% and ‐45 ± 2%, respectively) than in normal rats (‐31 ± 2%), and systemic vascular resistance increased more in the two groups of portal hypertensive rats than in normals (+161 ± 13% and + 154 ± 10% vs + 85 ± 6%, respectively). L‐NNA caused a greater decrease in portal tributary blood flow in portal vein stenosed and cirrhotic rats (‐63 ± 4% and ‐55 ± 4%, respectively) than in normal rats (‐45 ± 6%). Similarly, the increase in portal territory vascular resistance was significantly more marked in portal vein stenosed and cirrhotic rats (+ 337 ± 62% and +214 ± 24%, respectively) than in normal rats (+153 ± 23%). Portal pressure did not change. Following the acute administration of L‐NNA, no significant difference in splanchnic and systemic haemodynamics were noted between portal vein stenosed and normal rats, except for portal pressure. In cirrhotic rats, splanchnic and systemic values remained different from normal rats. This study confirms that NO plays a role in the haemodynamic changes in portal hypertension, and shows that NO inhibitors have a dose‐dependent effect in conscious portal hypertensive rats.
Plasma cytokine levels and monocyte activation in patients with obstructive jaundice
Authors: PUNTIS MCA , JIANG WG
Published: March 2008

Some monocytic cytokines are important immune regulators. We have investigated cytokine production by monocytes and the blood levels of IL‐1β, IL‐6, TNFα, and TGFβ, in patients with obstructive jaundice. The supernatant from LPS stimulated monocytes from jaundiced patients released significantly increased quantities of TNFα by both bioassay and radioimmunoassay (RIA) (12.4 ± 2.5 fmol/mL and 32.6 ± 8.3 fmol/mL, respectively, for jaundice, compared with 1.6 ± 0.3 fmol/mL and 2.4 ± 0.5 fmol/mL respectively for controls, and also of IL‐6 (54.8 ± 5.0 fmol/mL in jaundice compared with 35.6 ± 5.0 fmol/mL for controls). The production of IL‐1β and TGFβ by stimulated monocytes was unchanged. Jaundiced patients had significantly higher plasma TGFβ, but TNFα and IL‐1β were below the limits of detection. The highest monocyte TNFα and IL‐6 levels were seen in malignant disease patients, especially those with a poor immediate prognosis. We conclude that the production of some cytokines by monocytes is up‐regulated in patients with obstructive jaundice.
Biliary strictures after liver transplantation: Clinical picture, correlates and outcomes
Authors: FELLER RB , WAUGH RC , SELBY WS , DOLAN PM , SHEIL AGR , McCAUGHAN GW
Published: March 2008

We retrospectively examined 154 adults to ascertain the frequency, site of and pre‐disposing factors for biliary strictures after liver transplantation, as well as their management and clinical outcome. Twenty patients (12.5%) were identified with biliary strictures; 16 were non‐anastomotic and four were anastomotic strictures. The median time from transplantation to stricture diagnosis was 17 weeks (range 3–366). Of the 16 non‐anastomotic strictures, six were intrahepatic, eight hilar and two extrahepatic (donor bile duct). A control group (n = 32) of patients transplanted immediately before and after index cases was used to examine for correlates in patients with non‐anastomotic strictures. At the time of diagnosis in the non‐anastomotic index cases, there was a higher incidence of: (i) biliary sludge (63 vs 0%; P< 0.001); and (ii) clinical cholangitis (75 vs 0%; P< 0.001) compared with controls. Primary sclerosing cholangitis was more often the diagnosis in index patients with non‐anastomotic strictures compared with controls (31 vs 9%; P<0.05). There were no differences between index patients and controls (non‐anastomotic group) in ABO blood group non‐identity, cold allograft ischaemia time, use of OKT3 (murine monoclonal antibody to CD3) and hepatic artery thrombosis. Of 15 patients treated with balloon dilatation, seven required stent insertion although none have required surgery. As determined by liver function tests, there was evidence of persisting graft dysfunction in index patients compared with controls (SAP 381 vs 112 U/L, P< 0.001; GGT 529 vs 80 U/L, P< 0.001), but there was no difference in survival during a median follow‐up time of 16 months (range: 3–48 months) from stricture diagnosis. In conclusion, biliary strictures tend to occur within 6 months of transplantation and are an important cause of ongoing graft dysfunction. Non‐anastomotic strictures were more common in patients requiring transplantation for primary sclerosing cholangitis.
Characterization of an animal model of hepatic metastasis
Authors: KURUPPU DARSHINI , CHRISTOPHI CHRIS , BERTRAM JOHN F. , BRIEN PAUL E. O.
Published: March 2008

The experimental study of possible therapies for control of the growth of liver metastases requires the availability of a model which is technically feasible and appears to exhibit growth characteristics similar to human tumours. We report on the development of an intrasplenic injection model of liver metastases, and describe the histology, growth pattern and blood flow demonstrated by light microscopy, stereology and laser Doppler flowmetry. The hepatic metastases were induced in mice by intrasplenic injection of dimethylhydrazine (DMH) induced primary colonic carcinoma cells (106 cells in 1 mL). The growth and development of metastases was studied over a period of 3 weeks at predetermined time points. Tumour cells were visible in the hepatic sinusoids by day 7 by light microscopy. Macroscopically visible tumours with a diameter of 0.18 ± 0.02 cm (mean ± s.d.) were seen by day 10. By this time the tumours had derived a blood supply from the hepatic sinusoids adjacent to the tumour periphery. With further vascularization the tumours reached a diameter of 0.96 ± 0.50 cm by day 22. Metastatic growth was quantitated by stereological analysis of tumour volume in relation to non‐diseased hepatic tissue. Normal mouse liver had a mean volume of 1.13 ± 0.14 cm3. Tumour growth occurred in three phases. During the initial slow phase the volume of metastases increased from 0.03 ± 0.02 cm3 at day 10 to 0.22 ± 0.24 cm3 by day 16. Rapid tumour growth, occurring over the next 3 days, constituted the intermediate phase with metastatic volume reaching 1.21 ± 0.74 cm3 by day 19 (P= 0.0003 compared with day 16). This growth was followed by a plateau phase when the metastatic volume was 1.40 ± 0.55 cm3 at day 22. The volume of total liver and of tumour necrosis followed a similar growth pattern. A necrotic tumour volume of 0.004 ± 0.006 cm3 first seen on day 10 increased to 0.05 ± 0.06 cm3 by day 16, and to 0.25 ± 0.20 cm3 by day 22 (P=0.0022 compared with day 16). The blood flow in metastases measured by laser Doppler flowmetry was lower compared to the non‐diseased liver. Tumour blood flow, expressed as a percentage of normal liver blood flow, was 63.31 ± 26.28% at day 10 and diminished to 27.91 ± 8.99% by day 22, with an increase in tumour size and age. The decrease in flow was significant between days 13 and 16 (P= 0.0015). This intrasplenic mouse model of metastases is reproducible and should prove useful in the study of treatment of hepatic metastases.
The effect of minimum luminal nutrition on bacterial translocation and atrophy of the jejunum during parenteral nutrition
Authors: McCAULEY ROSALIE D. , HEEL KATHRYN A. , CHRISTIANSEN KERYN J. , HALL JOHN C.
Published: March 2008

In situations of catabolic stress, the gut becomes atrophic and may have diminished barrier function as evidenced by an increase in bacterial translocation. The aim of this study was to examine the effect of minimum luminal nutrition during parenteral nutrition on the extent of jejunal atrophy and rate of bacterial translocation. Central venous lines were inserted into 30 rats before they underwent randomization to receive nutritional support with: (a) conventional parenteral nutrition; (b) conventional parenteral nutrition with 3 g/day of rat food (i.e., minimum luminal nutrition); or (c) rat food ad libitum. The rats were assessed after 10 days for nutritional status, extent of jejunal atrophy, caecal flora, as well as the extent of bacterial translocation to the mesenteric lymph nodes, liver and spleen. Rats in the rat food ad libitum group lost the smallest amount of weight and had the least amount of jejunal atrophy, yet had a similar rate of bacterial translocation as the parenterally nourished groups. When compared with the conventional parenteral nutrition group, the minimum luminal nutrition group had better preservation of the weight of the small bowel and its isolated mucosa (P < 0.01), but had a similar rate of bacterial translocation. Minimum luminal nutrition reduced the extent of atrophy of the gut but did not affect the incidence of bacterial translocation. It is inferred that there is no direct relationship between the extent of mucosal atrophy and incidence of bacterial translocation.
Patterns of methane production in a Burmese (Myanmar) population
Authors: BOLIN TD , GENGE JR , DUNCOMBE VM , SOE‐AUNG  , MYO‐KHIN
Published: March 2008

While up to 50% of Western populations produce methane, this is less than that of rural black Africans and there is no information on methane production in populations from Asian developing countries. Females consistently produce methane more commonly than males, and methane production in children under the age of five years, except in Nigeria, is unusual. Breath methane was sampled in 1426 subjects from Myanmar ranging in age from 1 month to 88 years, with a mean age of 26.2 years. Half (49.8%) of the Myanmar population produced methane, this figure comprising 53% of females and 46% of males sampled. Methane production increases with age and reaches adult levels after 10 years of age. A high prevalence of methane production was found in children under 3 years of age (15.8%). Methane production was absent in 13 solely breast‐fed children and increased as other food was introduced into the diet. There was an association of methane production within families and with smoking. The prevalence of methane production increased in male and female smokers, with 75% of smokers producing methane. Methane production was not associated with occupation, education, income, water source, latrine type, previous diarrhoea, antibiotic usage or socio‐economic status.
Clinicopathological study of colorectal mucinous carcinoma in Taiwan: A multivariate analysis
Authors: WU CHENG‐SHYONG , TUNG SHUI‐YI , CHEN PANG‐CHI , KUO YOW‐CHII
Published: March 2008

The clinicopathological significance of colorectal mucinous carcinoma is controversial, although some authors feel mucinous carcinoma has a worse prognosis than that of non‐mucinous carcinoma. To clarify the significance of this type of carcinoma in Taiwan, a retrospective review of patients with colorectal carcinoma treated at Chang Gung Memorial Hospital between 1984 and 1988 was undertaken. During this period, 53 mucinous carcinomas and 401 non‐mucinous carcinomas fulfilling the inclusion criteria were analysed. Mucinous carcinomas were more common in patients 39 years of age or under (P < 0.005). Most mucinous carcinomas were located in the rectum/rectosigmoid, followed by the right colon; however, the right colon had a higher relative incidence (38 vs 8%, respectively; P < 0.005). Mucinous carcinomas presented at a significantly more advanced stage (23 vs 8%, respectively, stage D disease; P < 0.005) and had a markedly lower curative resection rate (68 vs 84%, respectively; P < 0.05). Following curative resection, mucinous carcinomas tended to have an increased incidence of subsequent distant metastasis (27.8 vs 18.8%, respectively; P < 0.005). The overall survival rate of patients with mucinous carcinoma was worse than that of non‐mucinous carcinoma (P < 0.005). Multivariate analysis showed that clinically important predictive factors were stage of disease on diagnosis and subsequent distant metastasis. The mucinous histological type itself was not an independent prognostic factor in colorectal cancer.
Sulindac and indomethacin inhibit formation of aberrant crypt foci in the colons of dimethyl hydrazine treated rats
Authors: CHARALAMBOUS DORA , FARMER CHIP , O'BRIEN PAUL E.
Published: March 2008

Aberrant crypt foci are microscopic lesions found in the colons of rodents treated with carcinogens, and in patients with premalignant colorectal conditions. They consist of single or multiple abnormal crypts and show cellular changes ranging from dysplasia to microscopic adenomacarcinoma. It is thought that these lesions represent the initial stages of the adenomacarcinoma path that results in the development of colorectal neoplasia. We have examined the effect of sulindac and indomethacin on the formation of aberrant crypt foci in rats treated with dimethylhydrazine (DMH). Aberrant crypt foci were induced in male Sprague‐Dawley rats with two oral doses of dimethyl hydrazine at 25 mg/kg per dose. Rats were randomized to receive sulindac at 3 mg/kg (n= 20) or 10 mg/kg (n=18) b.d., indomethacin at 1 mg/kg per day (n=18) or 2 mg/kg per day (n=19) or control (n= 37). Drug treatment was started on the day following the first dose of carcinogen and continued for 3 weeks. Colons were fixed flat overnight in 10% formalin and stained with 0.2% Methylene Blue solution before being studied. There was a significant reduction in the number of aberrant crypt foci in rats treated with 10 mg/kg b.d. sulindac (P= 0.001) and indomethacin at 2 mg/kg per day (P= 0.0002). Sulindac, at 3 mg/kg b.d., and indomethacin, at 1 mg/kg per day, did not have a statistically significant effect (P= 0.089 and P= 0.052, respectively). None of the drug treatments affected the relative frequency of single crypt vs multiple crypt foci. Previous studies have shown that sulindac and indomethacin will significantly inhibit the growth and development of tumours in DMH treated rats. The current data suggest that one of the pathways of action of NSAID is to inhibit the formation of early preneoplastic lesions.
Pancreatic calculi superimposed upon slow growing pancreatic cancer
Authors: NODA A. , TAKEUCHI K. , IBUKI E. , MURAYAMA H. , KOBAYASHI T. , NONOGAKI T.
Published: March 2008

We report on a 59 year old male patient with cancer of the head of the pancreas, upon which pancreatic calculi were superimposed during the 3 year clinical course. Pancreatic calculi were noted in the main pancreatic duct (MPD) on both computed tomographic scans and ultrasonographs of the abdomen approximately 10 months after the recognizable dilatation of the MPD. Existence of the calculi was confirmed by autopsy. Elemental analysis and infrared spectrophotometry of the calculi demonstrated that the main constituent of the calculi was calcium carbonate. Histopathological examination showed that the pancreatic cancer was moderately differentiated adenocarcinoma. Immunohistochemical studies revealed that pancreatic stone protein (lithostathine) was present in the cytoplasm of tumour cells. In this case, pancreatic cancer progressed to obstruct the MPD unusually slowly, resulting in stagnation of pancreatic secretion and subsequent formation of the calculi.
Vagal hyperactivity in stress induced gastric ulceration in rats
Authors: CHO CH , QIU BS , BRUCE IC
Published: March 2008

Indirect evidence suggests that stress ulceration is provoked by vagal hyperactivity. However, direct evidence of hypervagal activity during stress conditions is lacking. Experiments were designed to directly measure vagal activity under different stress conditions in rats. Starvation stress for 48 h did not change the mean amplitude of action potentials, but their frequency was significantly decreased. Restraint stress at 22°C increased vagal activity, both amplitude and frequency, in the first 60 min; these responses were markedly enhanced by cold (4°C) and persisted for at least 2 h. Starvation for 48 h did not induce any gastric mucosal lesions. Restraint alone produced petechiae in the gastric mucosa, but cold restraint induced severe haemorrhagic ulcers. It is concluded that cold restraint stress provokes a prolonged vagal hyperactivity, which is one of the causative factors for gastric ulceration.
Effects of transforming growth factors on the wound repair of cultured rabbit gastric mucosal cells
Authors: KOBAYASHI OSAMU , WATANABE SUMIO , HIROSE MIYOKO , SATO NOBUHIRO
Published: March 2008

We have evaluated the role of two different transforming growth factors in the restoration of rabbit primary cultured gastric mucosal cells using a new wound repair model. After forming confluent monolayer cell sheets, a wound with a constant size (2 mm2) was made using a rotating silicon tip. Either TGFα (0.1–100 ng/mL) or TGFβ1 (0.1–10 ng/mL) was added to the medium and the process of wound repair was monitored and analysed quantitatively by an image analyser. Cell proliferation was examined by BrdU staining. After wounding, the cells fronting the wound formed lamellipodia and migrated towards the centre of the wound. In the control group, the wound healed completely 48 h after wounding. TGFα promoted wound healing and the wound healed within 36 h in the presence of TGFα. TGFα increased the number of proliferative cells and they appeared in an earlier phase of healing than in controls. TGFβ did not have any effect on the wound repair process. In conclusion, TGFα promotes mucosal cell repair processes in the rabbit primary cultured gastric mucosal wound repair model in a dose‐dependent manner by accelerating migration and proliferation. TGFα may modulate the healing process of a gastric ulcer or erosion in vivo.
Role of endotoxaemia in hyperdynamic circulation in rats with extrahepatic or intrahepatic portal hypertension
Authors: LEE FA‐YAUH , WANG SUN‐SANG , YANG MAY CHUEN‐MAY , TSAI YANG‐TE , WU SHWU‐LING , LU REI‐HWA , CHAN CHO‐YOU , LEE SHOU‐DONG
Published: March 2008

This study investigated the role of endotoxaemia in the development of hyperdynamic circulation observed in rats with extrahepatic (high collateralization) or intrahepatic (low collateralization) portal hypertension. Compared with sham‐operated rats, decreased mean arterial pressure and systemic vascular resistance were detected on days 1, 4 and 14 following partial portal vein ligation. By day 1, the cardiac index of portal vein‐ligated rats was similar to that of sham‐operated rats and progressively increased, thereafter, reaching statistically higher values on days 4 and 14. No differences in plasma endotoxin levels were found between portal vein‐ligated and sham‐operated rats throughout the observation period. Both carbon tetrachloride‐induced cirrhotic rats with and without ascites had a higher cardiac index and lower systemic vascular resistance than those of control rats, and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma endotoxin levels were higher in cirrhotic rats with ascites (8.6±2.0 pg/mL; P < 0.01) than those of control rats (2.2±0.3 pg/mL) and cirrhotic rats without ascites (2.4±0.6 pg/mL). These results suggest that factors other than endotoxaemia play a role in the development of hyperdynamic circulation observed in rats with extrahepatic portal hypertension and cirrhotic rats without ascites, but that endotoxaemia may contribute to the maintenance of hyperdynamic circulation found in cirrhotic rats with ascites. The severity of liver disease may be a more important factor than the presence of portosystemic shunting for the development of endotoxaemia in portal hypertensive states.
Long‐term administration of natural interferon‐α in patients with chronic hepatitis C: Relationship to serum RNA concentration, HCV‐RNA genotypes, histological changes and hepatitis C virus
Authors: KUMADA TAKASHI , NAKANO SATOSHI , TAKEDA ISAO , SUGIYAMA KEIICHI , OSADA TOSHIMASA , KIRIYAMA SEIKI , TOYODA HIDENORI , SASA TOSHI , SHIBATA MOTOHIRO , MORISHIMA TSUNEO , NAKANO ISAO , FUKUDA YOSHIHIDE , KOSAKA YOSHITANE , TAMEDA YUKIHIKO , NAKASHIMA MITSUYOSHI
Published: March 2008

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon‐α (IFNα) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR‐SR), as evidenced by the absence of serum hepatitis C virus (HCV)‐RNA during the administration period and at 6 months after the final administration of IFNα and a normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR‐SR cases, significant improvements (P <0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR‐SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type Ib. A comparison by virus concentration revealed that CR‐SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 105 copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 105 copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre‐administration virus concentration (P=0.0061) and genotype (P=0.0015). These results suggest that the preadministration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.
Monoclonal antibodies to rabbit hepatocyte myosin that cross‐react with human liver myosin
Authors: UENO TAKASHI , WATANABE SUMIO , HIROSE MIYOKO , NOZAWA RYUSHI , YASUURA SHINICHI , EGAWA HISAYO , SATO NOBUHIRO , KOMINAMI EIKI
Published: March 2008

We prepared polyclonal and monoclonal antibodies against myosin purified from rabbit hepatocytes. Immunoblotting analyses revealed that the polyclonal antibody and four (HM1, HM2, HM3 and HM4) of five monoclonal antibodies reacted with myosin heavy chain. Chymotryptic cleavage of myosin yielded a 130 kDa fragment comprising the tail portion of the myosin heavy chain and a 67 kDa fragment comprising the ATP‐binding active site of the myosin head. All active antibodies reacted with epitopes localized in the 130 kDa fragment. Monoclonal antibodies HM3 and HM4 and the polyclonal antibody reacted strongly with myosin heavy chains from a human liver homogenate prepared from a surgically resected liver specimen. Immunocytochemical analyses showed that myosin is localized along the plasma membrane as well as around the bile canaliculi in both rabbit and human hepatocytes. Immunocytochemical analyses on liver blocks obtained from those patients who suffered various types of diseases accompanying cholestasis clearly indicated a marked increase in pericanalicular myosin. This altered myosin localization is analogous to that observed in phalloidin‐treated liver. Thus, myosin localization, determined using these antibodies, can provide a valid morphological basis for diagnosing the pathological state of the patient liver.
Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis
Authors: KIRSTETTER PHILIPPE , PILETTE CHRISTOPHE , MOREAU RICHARD , CAILMAIL STEPHANE , SAFKA VACLAV , SOUPISON THIERRY , LEBREC DIDIER
Published: March 2008

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 μg/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414±25vs290±26 dyn.s/cm5per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98±6vs79±7 mmHg), systemic vascular resistance (318±30vs207±10 dyn.s/cm5per 100 g), portal pressure (14.0±1.0vs11.3±0.9 mmHg) and portal territory vascular resistance (1362±163vs1031±182 dyn.s/cm5per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.
Adaptation of the gastric epithelium to injury is maintained in vitro and is associated with increased TGF‐α expression
Authors: DOLJANIN KATRINA , SKELJO MARYANNE V. , YEOMANS NEVILLE D. , GIRAUD ANDREW S.
Published: March 2008

Adaptation is the name given to the progressive decrease in gastric mucosal damage following repeated dosing with damaging agents. This study aimed to determine whether adaptation is an intrinsic property of the gastric epithelium and the role in the development of this process of TGFα. Rats were given either one or six daily doses of 10 mg/kg diclofenac or six daily doses of vehicle only (1% methylcellulose). On the 7th day, antral mucosa was taken for organ culture and loaded with [51Cr]. Explants were challenged with ethanol and damage quantified by [51Cr] release. In a separate experiment, rats were dosed as above and the gastric mucosa was extracted and TGFα quantified by RIA. The rate of [51Cr] release was significantly lower after ethanol injury in explants from rats previously adapted to diclofenac (9.2±2.5%) compared with those exposed to a single damaging dose of diclofenac (25.9±3.5%) or vehicle only (26.4±3.3%; P < 0.01; anova). The concentration of TGFα was significantly higher in the gastric epithelium of rats adapted to diclofenac than other groups (P < 0.05; t‐test). Cross adaptation of the gastric mucosa to injury has therefore been demonstrated in antral mucosal explants in organ culture while TGFα peptide expression is elevated in the adapted gastric mucosa. These findings suggest that adaptation is an inherent property of the gastric epithelium and it is likely that TGFα may play a role in its maintenance.
Mental retardation and colorectal disease: Colonoscopic mass screening to determine whether the risk of adenomatous polyposis syndrome is increased in the mentally retarded
Authors: UNO YOSHIHARU
Published: March 2008

Adenomatous polyposis syndrome (APS) is often associated with mental retardation, but whether there is a causal relationship between the two is unknown. This study was initiated to determine colorectal disease rates among mentally retarded subjects and whether they are at risk of developing colorectal cancer. Colonoscopic mass screenings were conducted to detect the presence of colonic neoplasms in 134 patients housed at an institution for the mentally retarded. The ages of these subjects ranged from 32 to 69 years (mean: 44 years) and their IQ scores ranged from 35 to 63. Screening presented no difficulties and the colonic regions up to the caecum were inspected in all patients. Polyps were found in 24 patients (17.9%), an abnormal fixation in two (1.5%), melanosis coli in two (1.5%) and haemorrhoids in two (1.5%). Thirteen subjects had a single polyp (54%), five had two polyps (21%), three had three polyps (12.5%) and three had four polyps (12.5%). Twenty one polyps were less than 5 mm in diameter, 14 were 5–9 mm and nine were 10 mm or larger. No cases of APS were detected during this mass screening programme. The mentally retarded patients in this study were not found to be at a high risk of developing either APS or colon cancer.