bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific in vitro anti‐tumour activity of methotrexate‐monoclonal antibody conjugates prepared using human serum albumin as an intermediary
Authors: Pietersz Geoffrey A , Cunningham Zita , McKenzie Ian FC 
Published: July 2007

SummaryMethotrexate (MTX) is a folic acid antagonist widely used in the treatment of cancer but, like other such agents, has non‐specific toxic side effects. With the aim of reducing these toxic effects, MTX was coupled to monoclonal antibodies (MoAb) in one of two ways; either (a) directly using an active ester derivative or (b) via human serum albumin (HSA), to act as an intermediary and so increase the amount of MTX bound. The MTX coupled directly to anti‐Ly‐2.1 antibody had approximately 10 molecules of MTX per antibody molecule, whereas the HSA coupled material had 24 molecules of MTX per antibody molecule. After coupling MTX directly to antibody there was a loss of potency of the MTX, and MTX‐MoAb conjugates were 30‐fold less potent than free MTX, although the antibody‐coupled material was more specific than free MTX and bound only to the antibody‐reactive target cells. By contrast, the MTX‐HSA‐MoAb conjugates were 3·5 times less potent than free MTX and were 8·5 times more potent than MTX‐MoAb conjugates. Thus, by increasing the amount of drug bound to antibody, more toxic conjugates were made – an important principle for the use of such conjugates for the treatment of cancer in man.
Lymphopenic effects on mice of a component of ammonia caramel, 2‐acetyl‐4(5)‐tetrahydroxybutylimidazole (THI)
Authors: Iscaro Angelina , Mackay Ian R , O'Brien Catherine 
Published: July 2007

SummaryA derivative of ammonia caramel colour (AC) is known to induce a selective lymphopenia in rats. Accordingly, the haematological effects were studied in mice of oral administration in drinking water of 2‐acetyl‐4(5)‐tetrahydroxybutylimidazole (THI), the component of AC responsible for lymphopenia. Initially five groups of BALB/c mice (five mice per group) were given doses of THI ranging from 0 to 200 parts/106 and bled weekly. Doses of THI from 5 to 100 parts/106 had no effect on circulating leucocytes over 6 weeks, but lymphopenia occurred with 200 parts/106. An increase in the concentration of THI to 400 parts/106 in the group on the lowest dose resulted in lymphopenia. An increase in dosagein two groups of mice, to 1000 and 2000 parts/106, resulted in marked lymphopenia. The number of neutrophils, eosinophils and monocytes remained unchanged throughout the experiment. Measurement of the proportions of CD4(L3T4)+ and CD8(Ly2)+ lymphocytes in lymph nodes from mice on high doses of THI did not show a selective depression of either subset, although both were increased relative to non‐T cells. THI causes a selective lymphopenia in mice, as in rats, but at relatively higher doses, and merits investigation in mice as an experimental treatment for states of lymphocyte excess or overactivity.
Association of maturation of the small intestine at weaning with mucosal mast cell activation in the rat
Authors: Cummins AG , Munro GH , Miller HRP , Ferguson A 
Published: July 2007

SummaryMaturation of the small intestine at weaning has some features in common with immunological reactions involving the gut mucosa. Mucosal mast cell (MMC) activation is a prominent feature of both IgE and cell‐mediated mucosal immune responses. MMC activation was therefore studied during the weaning period by measurement of rat mucosal mast cell protease II (RMCPII) release into the systemic circulation as well as MMC counts and jejunal RMCPII content. Maturation of the small intestine was measured by changes in villus and crypt length, and in crypt cell production rate (CCPR). At 3 weeks of age, serum RMCPII increased 17‐fold and MMC showed features of degranulation. At the time of weaning (2–4 weeks), villus and crypt length and CCPR increased progressively to adult values. After weaning, serum RMCPII declined slowly to normal adult levels and MMC regained a normal appearance. This study showed a close association between MMC activation and maturation of the small intestine during the weaning period.
Resistance to cutaneous leishmaniasis in nude mice injected with L3T4+ T cells but not with Ly‐2+ T cells
Authors: Moll H , Scollay R , Mitchell GF 
Published: July 2007

SummaryThe importance of T cells in resistance to infection with the intracellular protozoan parasite Leishmania major is substantiated by the susceptibility to infection of athymic nude mice of both resistant and susceptible strains. However, the relative roles of different T cell subpopulations remain controversial. In order to address this issue, selected L3T4+ Ly‐2− or L3T4− Ly‐2+ T cell subpopulations from normal mice were adoptively transferred into athymic nude recipients of the same strain, and their capacity to mediate host‐protective immunity against infection with L. major promastigotes was determined. In experiments with mice of different inbred strains, reconstitution with L3T4+ Ly‐2− cells rendered the nude mice completely resistant to cutaneous leishmaniasis, whereas L3T4− Ly‐2+ cells failed to do so. Partial protection in some recipients of large numbers of Ly‐2+ cells could be ascribed to contamination of the transferred inoculum with L3T4+ cells. Thus, resistance to L. major infection in reconstituted nude mice can be promoted by L3T4+ T cells in the absence of detectable Ly‐2+ T cells.
Presence and characterization of lymphocytotoxins in acute and chronic Plasmodium berghei malaria
Authors: Wangoo A , Ganguly NK , Mahajan RC 
Published: July 2007

SummaryThe role of lymphocytotoxic antibodies in elimination of lymphocytes and characterization of these antibodies during Plasmodium berghei infection was examined in BALB/c mice. When assayed at l5°, an increase in lymphocytotoxic levels above base line values was detected in acute infection when parasitaemia exceeded 10%. There was an increase in lymphocytotoxins with increase in parasitaemia to a plateau beyond 25% parasitaemia. When assayed at 37°, lymphocytotoxic activity during acute infection was lower than at 15° but the increase detected was significant. During chronic infection there was a lower increase in the activity detected at 15° and no significant increase in activity assayed at 37° (P>0·05). In addition, peripheral blood lymphocyte counts also dropped during acute infection while there was little change in lymphocyte numbers in the chronic infection group. The lymphocytotoxic antibodies present in sera of infected mice were predominantly of IgM class during acute infection and IgM or IgG class during chronic infection. The relevance of these observations to plasmodium infection is discussed.
Involvement of O2 radicals in ‘autoimmune’ diabetes
Authors: Nomikos IN , Wang Y , Lafferty KJ 
Published: July 2007

SummarySpontaneous diabetes in the non‐obese diabetic (NOD) mice is a CD4 T cell‐dependent process. We have suggested that specific β cell destruction results from free radical production at the site of islet inflammation; oxygen radicals are produced by activated inflammatory cells. We reported here that in vivo treatment of spontaneously diabetic NOD mice with the enzyme superoxide dismutase (2000 U for seven injections) and catalase (40 000 U for seven injections) protects islet tissue from disease recurrence following transplantation into spontaneously diabetic mice. Similar results were obtained when animals were treated with either enzyme alone. This effect was dose‐dependent and little protection was observed when the dose of enzyme was reduced four‐fold. These results indicate that oxygen metabolites, specially superoxide and hydrogen peroxide, are directly involved in the pathogenesis of immunology mediated diabetes.
Localization of a 23 000 MW antigen of Cryptosporidium by immunoelectron microscopy
Authors: Lumb R , Smith PS , Davies R , O'Donoghue PJ , Atkinson HM , Lanser JA 
Published: July 2007

SummaryRabbit antiserum was raised against a 23 000 molecular weight (MW) antigen prepared from Cryptosporidium oocysts by electro‐elution from polyacrylamide gels. The antiserum was tested for specificity by immunoblotting against solubilized oocyst preparations. Several antigens including the 23 000 MW antigen were recognized suggesting that it shared common epitopes with higher MW proteins. The antiserum was then used in conjunction with a protein A‐colloidal gold conjugate to locate antigenic sites within exogenous and endogenous developmental stages of Cryptosporidium. The pellicles of both sporozoites and merozoites exhibited specific labelling, particularly around their anterior ends. No specific labelling was observed for any other membrane determinants or organelles in these or other life cycle stages.
Augmentation of recombinant interleukin‐2‐dependent murine macrophage‐mediated tumour cytotoxicity by recombinant tumour necrosis factor‐α
Authors: Kos FJ 
Published: July 2007

SummaryThe activation of murine macrophages by recombinant human interleukin‐2 (rH‐IL‐2) alone or in combination with recombinant human tumour necrosis factor‐α (rH‐TNF) was studied. Mouse peritoneal exudate macrophages were activated in vitro to the tumouricidal state. Macrophage treatment with rH‐IL‐2 alone slightly enhanced cytotoxic activity against B16 melanoma cells. Synergism was observed when macrophages were treated with rH‐IL‐2 and rH‐TNF, either when applied sequentially or when both agents were given at the same time.
Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization
Authors: Chang M C , Uang B J , Tsai C Y , Wu H L , Lin B R , Lee C S , Chen Y J , Chang C H , Tsai Y L , Kao C J , Jeng J H 
Published: July 2007

Background and purpose:Platelet hyperactivity is important in the pathogenesis of cardiovascular diseases. Betel leaf (PBL) is consumed by 200‐600 million betel quid chewers in the world. Hydroxychavicol (HC), a betel leaf component, was tested for its antiplatelet effect.Experimental approach:We tested the effect of HC on platelet aggregation, thromboxane B2 (TXB2) and reactive oxygen species (ROS) production, cyclooxygenase (COX) activity, ex vivo platelet aggregation and mouse bleeding time and platelet plug formation in vivo. The pharmacokinetics of HC in rats was also assessed.Key results:HC inhibited arachidonic acid (AA) and collagen‐induced platelet aggregation and TXB2 production. HC inhibited the thrombin‐induced TXB2 production, but not platelet aggregation. SQ29548, suppressed collagen‐ and thrombin‐induced TXB2 production, but not thrombin‐induced platelet aggregation. HC also suppressed COX‐1/COX‐2 enzyme activity and the AA‐induced ROS production and Ca2+ mobilization. HC further inhibited the ex vivo platelet aggregation of platelet‐rich plasma (>100 nmole/mouse) and prolonged platelet plug formation (>300 nmole/mouse) in mesenteric microvessels, but showed little effect on bleeding time in mouse tail. Moreover, pharmacokinetics analysis found that more than 99% of HC was metabolized within 3 min of administration in Sprague‐Dawley rats in vivo.Conclusions and implications:HC is a potent COX‐1/COX‐2 inhibitor, ROS scavenger and inhibits platelet calcium signaling, TXB2 production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of atherosclerosis and other cardiovascular diseases through its anti‐inflammatory and antiplatelet effects, without effects on haemostatic functions.British Journal of Pharmacology (2007) 152, 73–82; doi:10.1038/sj.bjp.0707367
Antineoplastic activity of 2‐methoxyestradiol in human pancreatic and gastric cancer cells with different multidrug‐resistant phenotypes
Authors: Schumacher Guido , Hoffmann Janine , Cramer Thorsten , Spinelli Antonino , Jacob Dietmar , Bahra Marcus , Pratschke Johann , Pfitzmann Robert , Schmidt Sven , Lage Hermann 
Published: July 2007

AbstractBackground and Aim:  Chemoresistance often leads to loss of the last treatment option for cancer. 2‐Methoxyestradiol (2‐ME2) has been shown to inhibit tumor growth. The aim was to examine the efficacy of 2‐ME2 on multidrug‐resistant human cells from pancreatic and gastric cancer.Methods:  We investigated the impact of 2‐ME2 on multidrug‐resistant cells derived from human pancreatic and gastric cancer cells that were positive or negative for the MDR1‐gene.Results:  In pancreatic cancer cells, growth inhibition was 57% in parental, 72% in MDR1‐negative and 87% in MDR1‐positive cells after 1 μmol/L 2‐ME2. In gastric cancer cells we found a growth inhibition of 75% in parental, 82% in MDR1‐positive and 95% in MDR1‐negative cells. Strong induction of apoptosis was induced after a low dose of 2‐ME2. No significant difference in the amount of apoptotic cells was observed between parental and multidrug‐resistant cells of both tumor types. The number of apoptotic cells after 2‐ME2 ranged from 7.5% in parental gastric cancer cells to 20.1% in MDR1‐negative gastric cancer cells.Conclusion:  2‐ME2 may therefore have clinical application for chemoresistant cancer.
Epidemiological investigation in outpatients with symptomatic gastroesophageal reflux from the Department of Medicine in Zhejiang Province, east China
Authors: Li You‐Ming , Du Juan , Zhang Hong , Yu Chao‐Hui 
Published: July 2007

AbstractBackground and Aim:  To elucidate the epidemiology of gastroesophageal reflux disease (GERD) symptoms in outpatients from the Department of Medicine in 10 hospitals in Zhejiang Province, east China.Methods:  A cross‐sectional survey in the cluster random sample was conducted from November 2004 to June 2005 using a validated Chinese version of the reflux disease questionnaire and other items recording the demographic characteristics for GERD symptoms. The statistical analysis was performed with SPSS 13.0 programs.Results:  A total of 15 283 outpatients from the Department of Medicine were investigated. The prevalence of GERD symptoms was 7.28% (95% confidence interval [CI], 6.87%, and 7.69%) with the prevalence rate increasing with age (P < 0.001), which was higher in men (7.79%, 95% CI: 7.20%, 8.38%) than in women (6.73%, 95% CI: 6.18%, 7.28%; χ2 = 5.81, P < 0.05). The prevalence rate of the gastrointestinal symptoms in GERD symptoms, including epigastric discomfort, nausea, retrosternal pain, belching, globus sensation, loss of appetite, excessive salivation, vomiting, wheezing cough, weight loss, and dysphagia were all higher than the non‐GERD patients (P < 0.0001). In the GERD patients, the prevalence of diseases, such as pharyngolaryngitis, snoring, bronchitis, liver disease, and gallbladder disease were all higher than the non‐GERD patients (P < 0.01). The multiple logistic regression analysis showed that old age, night‐shift work, heavy work burdens, single or divorced people, increase intake of greasy or sweet foods, excessive eating, and constipation were independent risk factors associated with GERD symptoms.Conclusion:  GERD has a high prevalence in China and its main associated factors include respiratory, laryngopharyngeal and dental disorders, sex, anthropometrical variables, and social–psychological characteristics.
Primary biliary cirrhosis in Singapore: Evaluation of demography, prognostic factors and natural course in a multi‐ethnic population
Authors: Wong Reuben‐Km , Lim Seng‐Gee , Wee Aileen , Chan Yiong‐Huak , Aung Myat‐Oo , Wai Chun‐Tao 
Published: July 2007

AbstractBackground and Aim:  Primary biliary cirrhosis (PBC) is infrequent in Asians. Among Asian patients with PBC, information on natural course is scarce. The aim of this study was to study the clinical course and prognosticators among Asians with PBC.Methods:  During 1990–2005, patients diagnosed with PBC at the National University Hospital, Singapore, constituted the retrospective cohort. Their demographic characteristics were evaluated. To evaluate the prognostic factors and natural course, two outcome measures were assessed: hepatic decompensation and death or liver transplant. Multivariate analysis was undertaken to identify factors associated with hepatic decompensation and terminal event (death or liver transplantation).Results:  Thirty‐four PBC patients aged 56.8 ± 1.8 years (mean ± SEM) of whom 32 (94%) were women were included. Thirty‐two (94%) of them were of Chinese origin. At presentation, 18 (53%) were symptomatic in the form of jaundice (n = 9, 26.5%), pruritus (n = 6, 17.6%) and fatigue (n = 5, 14.7%). During 4.80 ± 0.7 (range 0.02–15.03) years follow up, 6/16 (37.5%) asymptomatic patients developed symptoms. After 5 years, 17.6% (n = 6) and 8.8% (n = 3) had hepatic decompensation and terminal event, respectively. Sicca syndrome was present in 26% (n = 9) of patients. Multivariate analysis revealed that serum bilirubin level at presentation was the sole determinant of decompensation. Rate of change of laboratory indices did not predict either event.Conclusion:  In Singapore, Chinese women constitute most of the PBC patients. Elevated serum bilirubin level at presentation was the sole predictive marker associated with dismal outcome.
Low‐dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients
Authors: Oh Jung‐Hwan , Choi Myung‐Gyu , Dong Mi‐Sook , Park Jae‐Myung , Paik Chang‐Nyol , Cho Yu‐Kyung , Jeong Jeong‐Jo , Lee In‐Seok , Kim Sang‐Woo , Han Sok‐Won , Choi Kyu‐Yong , Chung In‐Sik 
Published: July 2007

AbstractBackground and Aim:  Proton‐pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non‐Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients.Methods:  A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high‐dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed.Results:  Pantoprazole 40 mg b.i.d. and high‐dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high‐dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers.Conclusion:  A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes.
Inhibition of TXA2synthesis with OKY‐046 improves liver preservation by prolonged hypothermic machine perfusion in rats
Authors: Xu Hongzhi , Lee Charles Y , Clemens Mark G , Zhang Jian X 
Published: July 2007

AbstractBackground and Aim: We previously reported that hypothermic machine perfusion (HMP) for liver preservation is feasible, but hepatic microcirculatory dysfunction and significant liver damage remain major obstacles in its application when the preservation is extended to 24 h. The underlying injury mechanism is not well understood. The present study sought to investigate the role of thromboxane A2(TXA2) in the pathogenesis of liver injury after prolonged HMP.Methods: Livers isolated from Sprague–Dawley rats were subjected to continuous machine perfusion with University of Wisconsin (UW) solution at a flow rate of 0.4 mL/min/g liver at 4°C for 24 h. A specific TXA2synthase inhibitor, OKY‐046 (OKY), was added to UW solution during the preservation period and to the Krebs–Henseleit buffer during reperfusion. The performance of the livers after preservation was evaluated using an isolated liver perfusion system with Krebs–Henseleit buffer at a flow rate of 15 mL/min at 37°C for 30 min.Results: Prolonged HMP induced a significant release of TXA2into the portal circulation as indicated by markedly increased levels of TXB2in the perfusate during reperfusion (at 30 min, 1447.4 ± 163.6 pg/mLvs50.91 ± 6.7 pg/mL for control). Inhibition of TXA2synthesis with OKY significantly decreased releases of TXA2(69.8 ± 13.4 pg/mL) concomitant with reduced lactate dehydrogenase (LDH) releases (at 30 min, HMP + OKY: 144.9 ± 27.9 U/L; HMP: 369.3 ± 68.5 U/L; simple cold storage or SCS: 884.4 ± 80.3 U/L), decreased liver wet/dry weight ratio (HMP + OKYvsSCS and HMP: 3.6 ± 0.3vs4.4 ± 0.1 and 3.9 ± 0.2, respectively) and increased hyaluronic acid uptake (at 30 min, HMP + OKYvsSCS, HMP: 33.1 ± 2.9%vs13.9 ± 3.6%, 18.6 ± 2.4%, respectively). Liver histology also showed significant improvement in tissue edema and hepatocellular necrosis with OKY compared with HMP without OKY.Conclusion: The results demonstrate that TXA2is involved in the development of hepatocellular injury induced by HMP, and inhibition of TXA2synthesis during preservation and reperfusion protects liver hepatocytes and sinusoidal endothelial cells from injuries caused by prolonged HMP.
Pulsed dye laser: what's new in non‐vascular lesions?
Authors: Karsai S , Roos S , Hammes S , Raulin C 
Published: July 2007

AbstractBackground and objective  In dermatology, the pulsed dye laser (PDL) is the therapeutic instrument of choice for treating most superficial cutaneous vascular lesions. In addition, clinical experience over the last decade allowed us to treat patients with an ever increasing number of non‐vascular indications. The purpose of this report is to summarize and critically appraise the scientific evidence that support the role of PDL in treating non‐vascular skin lesions.Methods  A literature‐based study has been conducted, including the review of publications over the period January 1995 to December 2006, using the Medline Database. We also included our own experience in managing non‐vascular lesions with the PDL. Four sets of preoperative and postoperative photos are presented.Results  For viral skin lesions, PDL proved to be an alternative to other therapy options. This applies particularly to periungual warts and mollusca contagiosa. The mechanism of PDL with inflammatory dermatoses has not yet been elucidated. The effect seems to be better if there is a vascular component to the disease. With most of these indications (such as psoriasis and acne), PDL currently plays a rather minor or complementary role. Regarding collagen remodelling (hypertrophic scars, keloids, stretch marks, and skin rejuvenation), the question of whether a therapy makes sense or not has to be decided from case to case.Conclusion  With PDL, it is possible to achieve good results with numerous, partly less well‐known indications (i.e. lupus erythematosu). With other diseases, PDL has so far been considered to be a complementary therapy method or to be in an experimental state.