bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐apoptotic functions of granzymes
Authors: Romero V. , Andrade F. 
Published: March 2008

AbstractGranzymes (granule enzymes) are proteases released from cytotoxic lymphocyte granules into target cells to protect mammals from virus infection and transformed cells. Once released into the cytoplasm of the target cell, granzymes activate specific pathways to induce cell death. Although the induction of target cell death has been considered the central function for these proteases, accumulating evidence suggests that granzymes also possess additional non‐death‐related functions. Thus, some granzymes can achieve direct antiviral activities through the cleavage of proteins encoded by viruses as well as host factors required for the viral life cycle. The presence of elevated concentrations of circulating granzymes in various inflammatory processes and granzyme‐mediated cleavage of extracellular substrates suggest that these proteases may have extracellular effects relevant to virus and tumor rejection and the pathogenesis of chronic inflammatory diseases. Here, we discuss the current knowledge of the substrates and the proposed non‐apoptotic functions of granzymes, with special interest in non‐death‐related functions of granzymes inside the target cell.
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

SummaryStereological 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.
III. Virulence and pathogenicity of Helicobacter pylori
Authors: MARSHALL BARRY J. 
Published: March 2008

Abstract 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

AbstractTo 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

AbstractGastric 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

AbstractThe 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

AbstractAbdominal 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

AbstractThe 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

AbstractSome 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

AbstractWe 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

AbstractThe 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

AbstractIn 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

AbstractWhile 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.