bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of Lymphocytes, Granulocytes and Macrophages
Authors: BØYUM A.
Published: February 2009

Abstract. This paper presents the standard procedure for isolating lymphocytes and granulocytes from blood, using the Isopaque‐Ficoll technique. A procedure for isolating granulocytes and macrophages from peritoneal fluid is also described.
Specific Affinity Fractionation of Lymphocytes Using Glass or Plastic Bead Columns
Authors: WIGZELL HANS
Published: February 2009

Abstract. This paper describes column fractionation techniques for separating different lymphocyte subpopulations. For this purpose columns can be coupled with antigen, specific antibodies to membrane determinants on lymphocytes, or immune complexes or aggregated immunoglobulins, which interact with Fc receptors.
Detection of a Third Lymphocyte‐Like Cell Type by Rosette Formation with Erythrocytes Sensitized by Various Anti‐Rh Antibodies
Authors: NATVIG I. B. , FRØLAND S. S.
Published: February 2009

Abstract. Assay systems with erythrocytes sensitized by three different human anti‐Rh isoantibodies, anti‐Rh Ri, Lor and 3360 have been compared for their sensitivity and specificity in detecting Fc receptor‐bearing lymphocyte‐like cells. When carefully standardized, all these test systems detected primarily the ‘third lymphocyte‐like cell type’, different from B and T lymphocytes as detectable by conventional membrane markers.
Use of Mitogens for the Functional Characterization of Human Lymphocyte Subpopulations
Authors: RINGDEN O. , MÖLLER ERNA
Published: February 2009

Abstract. The paper describes the use of mitogens for the functional characterization of human lymphocyte subpopulations with special reference to the activation of human B lymphocytes by antibodies to β2microglobulin.
The Clinical Value of Alpha‐fetoprotein and Human Chorionic Gonadotrophin as Tumour Markers in Patients with Teratoma of the Testis
Authors: CALMAN F. M. B. , PECKHAM M. J. , McELWAIN T. J.
Published: February 2009

The results of serial alpha‐fetoprotein (AFP) and HCG estimations in a group of 66 patients with Stage I and Stage II teratoma of the testis are analysed. AFP levels are elevated (above 25 μg/1) in 61% of patients with active tumour and HCG levels are elevated in 30%. When the two markers are estimated together, 75% of patients with clinically evident tumour are found to have one or the other, or both, markers elevated.

Markers fall to normal levels with a half‐life of five days when tumour is eradicated, and rise again in five out of 12 relapsed patients. The marker elevation was detected two to four months before metastases could be identified by clinical means.

Elevated markers in early‐stage disease do not appear to have any prognostic significance, nor can they be used to predict a group of patients who will later relapse soon after their primary treatment.
Cellular Localization of AFP and HCG in Germ Cell Tumors of the Testis and Ovary
Authors: KURMAN R. J. , SCARDINO P. T. , McINTIRE K. R. , WALDMANN T. A. , JAVADPOUR N. , NORRIS H. J.
Published: February 2009

An immunohistologic study of AFP and HCG in malignant germ cell tumors of the testis and ovary was undertaken to correlate the type of neoplasm with the presence of the markers. Twenty‐one patients with testis tumors and measured serum levels of AFP and HCG and 48 patients with ovarian tumors with no availability of serum were studied utilizing an immunoperoxidase technique. AFP was demonstrated in mononuclear embryonal carcinoma cells and in endodermal sinus tumors. HCG was identified in the syncytiotrophoblastic component of choriocarcinoma and also within syncytiotrophoblastic giant cells in embryonal carcinoma frequently and in endodermal sinus tumor and seminoma rarely. In the testis tumors there was tissue localization of HCG in 13 of 14 patients (93%) with elevated serum HCG while AFP was identified in the tumor of 10 of 14 patients (71%) with elevated AFP. Based on these findings a tentative immunohistologic classification of malignant germ cell tumors utilizing AFP and HCG was proposed. Thus, embryonal carcinoma is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma, dysgerminoma and teratoma are unlikely to be associated with either marker.
Multiple Fetal Antigens in Germ‐cell Tumors
Authors: WAHREN B.
Published: February 2009

Indirect immunofluorescence (IF) on individual malignant teratoma cell populations demonstrated that 1–60% of them stained with anti‐AFP, 0–16% with anti‐ferritin and 0–40% with anti‐CEA antiserum. The proportion of cells containing each antigen varied in the different tumors. In seminoma or normal testicular tissue these antigens were not found.

Raised serum levels of AFP or the ferritin‐like substance were both related to the presence of tumor and furthermore to dissemination of the disease. CEA occurred transiently in serum. HCG levels above normal were obtained in 40% of the patients. AFP, ferritin, CEA and HCG occurred independently. It is therefore concluded that certain germ cell tumors contain subpopulations of cells, differing in the production and release of the antigens studied. The presence of either AFP or ferritin in serum of patients with primary or advanced disease indicated a worse prognosis. In altogether 44 patients with malignant teratomas one or several abnormal serum substances could always be demonstrated.
Clinico‐pathological Aspects of Endodermal Sinus Tumor in Childhood with Reference to PAS‐positive Hyaline Globules observed in Tissue Culture
Authors: TSUCHIDA Y. , KANEKO M. , SAITO S. , ENDO Y. , URANO Y. , OHMI K. , ASAKA T.
Published: February 2009

During the years 1952 through June, 1977, 64 children with tumor of germ cell origin were seen at the Department of Pediatric Surgery, the University of Tokyo Hospital. There were 39 mature, 7 immature and 18 frankly malignant teratomas. Sixteen cases had histological features of endodermal sinus tumor in pure or mixed form, and all of the last eight patients showed elevated serum AFP concentrations ranging from 92,000 ng/ml to 952 ng/ml. Serum AFP concentration declined almost to zero ng/ml with a half life of about 4 days when surgical removal was complete, whereas AFP decreased only to 100–200 ng/ml with radiation therapy and chemotherapy alone. Serum concentrations of prealbumin, albumin, alpha‐1‐antitrypsin and transferrin were almost within normal ranges.

Two endodermal sinus tumors were studied by tissue culture, which demonstrated secretion of diastaseresistant PAS‐positive hyaline globules. PAS‐positive granule is one of the characteristic histologic features of endodermal sinus tumor with demonstrable AFP specific immunofluorescence.
Alpha‐1‐fetoprotein (AFP) and Germ Cell Tumors: Biological and Histological Correlation
Authors: RIMBAUT C. , CAILLAUD J.M. , CAILLOU B. , CARLU C. , RUDANT C. , BUFFE D.
Published: February 2009

The level of α1FP has been evaluated in the sera of 155 children aged 1 month to 16 years with germ cell tumors. Abnormal α1FP levels were found in 63 cases.

Reexamination of histological slides from more than 120 cases, in a double blind study has revealed a close connection between the presence of abnormal α1FP levels in the serum and the presence of vitelline components on the tissue sections: 54 yolk sac tumor out of 60 are α1FP positive (that is 90% and 100% in the acute phase), whatever the site: testis, ovary, vagina, sacrococcygeal, intra‐ or retro‐peritoneal region, mediastinum or intracranium.

Immunohistological localization (immuno‐fluorescence and immuno‐peroxydase) was performed in this study.
The in vitro Production of Alpha‐fetoprotein by Human Embryonic Brain
Authors: MACKIEWICZ A. , HEJDUK W. , BREBOROWICZ J.
Published: February 2009

The presence of AFP in media of 8 central nervous system monolayer cultures and also in 11 liver and in 11 intestine cultures was detected while it was not detected in placental cultures. We consider these findings as an indirect evidence that AFP (or crossreacting substance) is produced by embryonic central nervous system. The production of AFP by embryonic central nervous system may provide new explanation of elevated AFP concentrations in amniotic fluids of conceptuses with neural tube malformations.
An Endogenous Competitor of Estrogen‐rat AFP Interaction Present in Embryo and Adult Rat and Human Sera: Demonstration and Preliminary Characterization
Authors: NUNEZ E. A. , BENASSAYAG C. , VALLETTE G. , DELORME J. , SAVU L. , JAYLE M. F.
Published: February 2009

A highly active competitor of the binding of estrogens to rat alpha‐fetoprotein (AFP) is demonstrated in rat and human sera of various age, sex and hormonal conditions. This new high affinity physiological ligand of the estrophilic AFP is characterized as a low molecular, low polar, non‐phenolsteroid compound with negligible cross‐reactivity towards anti‐estrogen antibodies.
Localization and Some Biological Properties of Pig Alpha‐fetoprotein
Authors: KOVÁR̂Ů F. , POSPÍŜIL M. , TREBICHAVSKÝ I. , HOFMAN J. , KOSTKA J.
Published: February 2009

In studies of the cellular localization of AFP with the use of immunofluorescent, immunochemical and immunoautoradiographic techniques we concentrated in the course of prenatal ontogeny of pigs on the mesenchymal haemopoictic population of lymphatic and haemopoietic organs of these animal species. A marked AFP positivity was demonstrated already in haemopoietic cells of yolk sac, but also in other organs of embryonic and fetal haemopoiesis. In the course of intrauterine development the percentage of AFP‐positive haemopoietic cells decreases and postnatally the AFP positivity of haemopoietic cells does not occur. The decrease in AFP‐positivity of haemopoietic fetal cells is in correlation with the subsequent decrease in the intensity of extramedullary haemopoiesis. In the system in vitro the inhibitory effect of pig AFP on T and B cell mitogen‐induced blast transformation of lymphocytes was demonstrated, similarly as on the mixed lymphocyte reaction. That effect of AFP is dependent on its presence in the first 24 hrs of stimulation and is not species specific. In fetal cell suspensions of lymphatic and haemopoietic organs of pigs their capacity for blastogenic transformation with anti‐AFP serum was demonstrated.
N‐terminal Amino Acid Sequences and C‐terminal Residues of Rat Alpha‐fetoprotein Electrophoretic Variants, ‘Fast’ and ‘Slow’
Authors: PETERS E. H. , LAI P. C. W. , HAY D. M. , LORSCHEIDER F. L.
Published: February 2009

Rat alpha‐fetoproteins ‘fast’ (FRAFP) and ‘slow’ (SRAFP) were prepared to homogeneity from amniotic fluid by preparative polyacrylamide disc gel electrophoresis. Automated Edman degradation revealed that both proteins had the same sequence for residues 1–18. Hydrazinolysis yielded glycine and valine as the C‐termini of FRAFP and SRAFP, respectively. SRAFP was refractile to C‐terminal sequence determination with carboxypeptidases A, B and Y under various enzyme/substrate ratios. S‐carboxyamido methylation and subsequent digestion either in the presence or absence of 6M urea yielded no improvements; these methods work on rat serum albumin.

Amino terminal sequences of rat AFP show a high degree of similarity (only seven differences, eight base changes) with the N‐terminal sequence of human AFP. There were few sequence similarities between the N‐termini of rat AFP's and rat or bovine serum albumin or pro‐ or preproalbumin. The C‐terminus of SRAFP is identical to human AFP. The degree of homology between AFP and albumin is discussed.
Interactions of Alpha‐fetoprotein and Other Proteins with Concanavalin A
Authors: DAMBUYANT C. , SIZARET P. , MARTEL N. , BORDES M. , BOURGEAUX C.
Published: February 2009

The chromatography of alpha‐fetoprotein (AFP) containing sera on concanavalin A‐Sepharose 4 B immunoadsorbant (Con A) yields two fractions, one which does and the other which does not bind the Con A. It is thus possible to calculate for various specimens the ratios

Mean ratios of three categories of sera whose AFP titres varied between 14,000 and 430,000 IU/ml were the following: eight cord sera, m = 19.1 ± 4.2%; seven primary liver carcinoma sera (PLC), m = 15.9 ± 2.4%; three teratoblastoma sera, m = 37.5 ± 5.5%. The comparison of mean values by the Wilcoxon test indicated that there were statistically significant differences (p<0.05) between cord sera and teratoblastoma sera on the one hand, and between PLC and teratoblastoma sera on the other hand. It was also found that the ratios did not depend upon levels of AFP in sera. Variations of serum glycoproteins such as those reported in cancer patients are unlikely to account for these differences, especially since they are of much smaller magnitude than those achieved in in vitro experiments. Establishing the existence of patterns of heterogeneity of AFP linked to the origin of serum specimens will however require, in order to eliminate possible interferences by other glycoproteins, the use of purified AFPs. Should the existence of such patterns be confirmed, it will be interesting to see if they are related to differences such as those recently reported between fetal and tumour AFP when inhibition of lymphocyte stimulation was used.
Copper(II)‐Binding Ability of Human Alpha‐fetoprotein
Authors: AOYAGI Y. , IKENAKA T. , ICHIDA F.
Published: February 2009

Our previous sequence study showed that alpha‐fetoprotein (AFP) had one histidyl residue at position 3 or 4 from the N‐terminus (heterogeneous N‐terminus). Since human serum albumin also has a cupric chelate locus histidine at the third position from N‐terminus, copper(II)‐binding ability of AFP was examined by equilibrium dialysis and gel‐filtration method. AFP could bind one mole of copper(II) ion per mole of protein above pH 6.0 and the pH‐dependence of copper(II)‐binding ability of AFP was quite similar to that of albumin. AFP bound 0.5 mole of copper(II) ion at pH 5.4 which is close to the pK value of imidazole of histidine. Photo‐oxidation of AFP in the presence of methylene blue showed that the loss of copper(II)‐binding ability of the protein was parallel to the destruction of histidine. These results indicate that histidyl residues play some important role in this copper(II)‐binding ability of the protein. Reduced and S‐carboxymethylated AFP also had this ability.
The Effect of Alpha‐fetoprotein on the Immune Reponse: Inhibition of the Humoral Response in Adult Mice Antigenically Stimulated with Sheep Red Blood Cells Suspended in Mouse Amniotic Fluid or Alpha‐fetoprotein
Authors: OLINESCU A. , POPESCU D. E. , BABES S. , GANEA D. , DUMITRESCU A.
Published: February 2009

Adult mice of the inbred A2G strain pretreated for four days in a row with mouse amniotic fluid or alpha‐fetoprotein and subsequently antigenically stimulated by an i.p. inoculation of sheep red blood cells suspended in phosphate buffered saline had an unmodified humoral immune response. The number of direct hemolytic plaque forming cells/106 spleen cells and the serum antibody titre were virtually identical to those of the controls.

However, when the antigen was suspended in mouse amniotic fluid or alpha‐fetoprotein and inoculated simultaneously with these proteins, the immune response was depressed.

The antigenicity of red blood cells incubated in alpha‐fetoprotein was not modified.
Immunohistological Studies of CEA, AFP and CPALP in Gastric Cancer
Authors: LEE P. K. , MORI T. , SHIMANO T. , MASUZAWA M. , KOSAKI G.
Published: February 2009

In studying 150 cases of gastric cancer, 93 (62%) were found to be CEA‐positive. Among them, 5 cases had concurrent elevation of serum AFP over 200 ng/ml and appearance of serum CPALP. Further, there were another 2 cases simultaneously positive in serum CPALP. All these 7 cases were of pathologically well‐differentiated adenocarcinoma with liver metastases.

Immunohistologically, CEA was observed on the surface of cancer cells as well as in glandular lumens of cancer tissues, forming a centroglandular pattern, while CPALP was detected in cytoplasm of cancer cells generally but absent in glandular lumens, and no formation of centroglandular pattern was observed. In contrast, most of the cancer cells were found AFP‐negative except for some cancer cells with abundant chromatin in nucleus and acidophilic cytoplasm, in which AFP was detected in cytoplasm. Furthermore, AFP was also scarcely observed in cytoplasm of some normal liver transient cells scattered close to metastatic cancer lesions, suggesting that in gastric cancer, occurrences of CEA, AFP and CPALP originate from cancer cells while mild amounts of AFP are also being synthesized in some normal liver transient cells scattered close to metastatic cancer lesions.
Alkaline Phosphatase Isoenzymes in Carcinoma Tissue of Gastro‐intestinal Tract
Authors: MIKI K. , ODA T. , SUZUKI H. , IINO S. , NIWA H.
Published: February 2009

The enzymological and immunological properties of alkaline phosphatase (ALP) isoenzymes in carcinoma tissues of the gastro‐intestinal tract were compared with those of purified human intestinal, placental and hepatic ALP's to investigate the gene expression of gastro‐intestinal cancer cells. The results were as follows: ALP obtained from carcinoma tissues of 77 patients was separated into 6 bands (ALPa, ALPb, ALPc, ALPd, ALPe and ALPf) by polyacrylamide‐gel disc electrophoresis. It was concluded that ALPa was similar in its enzymological and immunological properties to hepatic‐type ALP, ALPb was similar to placental‐type ALP (Regan ALP or Nagao ALP), ALPc to intestinal‐type ALP (metaplasia ALP), ALPd to hepatoma‐type ALP (Warnock's variant ALP), ALPe to intestinal‐type ALP except for electrophoretic mobility, and ALPf was similar to hepatic‐type ALP except for neuraminidase sensitivity. ALPb appeared in 16 out of 55 cases (29%) of gastric carcinoma, and 2 out of 21 cases (10%) of colonic carcinoma. ALPd appeared in 4 out of 55 cases (7%). ALPe appeared in 2 out of 55 cases (4%) of gastric, and 3 out o 21 cases (14%) of colonic carcinoma. ALPf appeared in 1 out of 55 cases (2%) of gastric, and 1 out of 21 cases (5%) of colonic carcinoma. These ALP isoenzymes (ALPb, ALPd, ALPe and ALPf) probably originate from the cancer cells themselves and may represent an abnormal gene expression of cancer cells in the process of onco‐developmental differentiation.
Clinical Evaluation of Basic Fetoprotein
Authors: OHKURA H. , MUKOJIMA T. , HATTORI N. , ISHII M.
Published: February 2009

A new antigen, basic fetoprotein (BFP) found by M. Ishii in human fetus and in some cancer tissue of adult, was quantitated in patients' sera by radioimmunoassay. In 167 of 377 patients (44.3%) with malignant diseases, serum BFP exceeded 100 ng/ml and 87 cases (23.0%) were over 200 ng/ml. In contrast, 49 of 230 (21.3%) with benign diseases exceeded 100 ng/ml and 11 cases (4.8%) were over 200 ng/ml. No normal control exceeded 100 ng/ml.

A higher incidence and higher serum‐concentration of BFP were observed in patients with carcinoma of the liver, bile duct, esophagus and kidney, but it was also found in various other malignancies including leukemias and sarcomas. Generally, after a successful operation, BFP fell to normal levels, and with tumor recurrence, BFP levels rose higher particularly with massive metastasis. In the benign group, BFP was higher in patients with acute and chronic active hepatitis.

Although BFP has less organ specificity than other fetal substances, and it appears in some benign diseases too, BFP is a new member of the carcinofetal protein family, which may be a useful marker in cancer pathophysiology.
A single‐staggered dose of calcineurin inhibitor may be associated with neurotoxicity and nephrotoxicity immediately after liver transplantation
Authors: Urbani Lucio , Mazzoni Alessandro , Bindi Lucia , Biancofiore Gianni , Bisà Massimo , Meacci Luca , Esposito Massimo , Mozzo Roberto , Colombatto Piero , Bianco Irene , Grazzini Tiziana , Coletti Laura , De Simone Paolo , Catalano Gabriele , Montin Umberto , Tincani Giovanni , Balzano Emanuele , Petruccelli Stefania , Carrai Paola , Tascini Carlo , Menichetti Francesco , Scatena Fabrizio , Filipponi Franco
Published: February 2009

Abstract:  The aim of the present work was to assess the incidence of neuro‐nephrotoxicity after a single‐staggered dose of calcineurin inhibitors (CI) with different immunosuppressive approaches. From January to December 2006, all liver transplantation (LT) recipients at risk of renal or neurological complications treated with extracorporeal photopheresis (ECP) + mycophenolate mofetil + steroids and staggered introduction of CI (ECP group) were compared with a historical control group on standard CI‐based immunosuppression. The ECP group included 24 patients with a mean model for end‐stage liver disease (MELD) score of 19.9 ± 11.1. The control group consisted of 18 patients with a mean MELD score of 12.5 ± 5.2 (p = 0.012). In the ECP group CI were introduced at a mean of 9.2 ± 6.2 d (4–31 d) after LT. Five patients in the ECP group presented acute neuro‐nephrotoxicity after the first CI administration on post‐transplant d 4, 5, 6, 6, and 14. Overall patient survival at one, six, and 12 months was 100%, 95.8%, and 95.8% in the ECP group vs. 94.4%, 77.7%, and 72.2% in the control group (p < 0.001). In conclusion, we showed that CI toxicity may occur after a single‐staggered dose administration, ECP seems to be a valuable tool for managing CI‐related morbidity regardless of the concomitant immunosuppressive regimen, being associated with a lower mortality rate in the early post‐transplant course.
Liver transplantation for acute liver failure due to toxic agent ingestion in children
Authors: Akman Sezin Asik , Cakir Murat , Baran Masallah , Arikan Cigdem , Yuksekkaya Hasan Ali , Tumgor Gokhan , Saz Ulas Eylem , Zeytunlu Murat , Kilic Murat , Aydogdu Sema
Published: February 2009

Abstract:  ALF is characterized by sudden onset, impaired liver function, jaundice and encephalopathy, without previous liver disease. We analyzed the patients who underwent LT due to toxic agent induced ALF to raise community awareness about preventing the toxic agent induced ALF. Five children (three boys, two girls) underwent LT due to toxic agent ingestion. Toxic agents were mushroom poisoning (n = 2), Datura stramonium (n = 1), yellow phosphorous (n = 1) and INH (n = 1). On admission, one patient had stage IV, two had stage III and two had stage II hepatic encephalopathy but worsened during the follow‐up. One patient had renal failure, and three patients required mechanical ventilation. Three patients underwent LRLT and others from a DD. Post‐operative complications were managed by supportive managements successfully, and overall all the patients are alive (100% survival) without any organ sequelae. Although outcome of these patients are excellent, ALF may be prevented in these cases by educating the public about consuming mushrooms and toxic effects of wild plants, prohibiting fireworks and serial liver enzyme measurements after initiating INH.
Percutaneous liver biopsy: retrospective study over 15 years comparing 287 inpatients with 428 outpatients
Authors: Weigand Kilian , Weigand Kurt
Published: February 2009

Background and Aim:  Liver histology still represents the gold standard for the assessment of liver inflammation, necrosis, and fibrosis. The least cumbersome way of obtaining liver tissue is percutaneous liver biopsy. The aim of this retrospective study was to compare the complications following liver biopsy in in‐ and outpatients and to evaluate for which patients the benefit from liver biopsy is highest.

Methods:  All patients undergoing percutaneous liver biopsy at a teaching hospital between January 1990 and April 2005 were evaluated for indications, complications and impact of histology.

Results:  Liver biopsy was performed in 287 inpatients and 428 outpatients with a success rate of 99.4%. The total complication rate was 6.3% in inpatients and 11% in outpatients. Only two major complications, but no deaths occurred. Pain was the main complication, especially in young patients with chronic viral hepatitis. Despite normal alanine aminotransferase (ALT) levels advanced liver fibrosis was found in 9.3%, 2.6%, and 5.4% of all patients with HBV‐, HCV infection, and non viral liver diseases, respectively. In 3% of all patients evaluated a previously unrecognized second liver disease was found. In 21.4% of the patients alkaline phosphatase (AP) levels were elevated, and in more than 90% of these patients liver biopsy led to the final diagnosis.

Conclusion:  Liver biopsy is safe in in‐ and outpatients. Biopsy is particularly helpful in patients suspected of having liver disease in spite of normal ALT levels or in patients exhibiting unexplained elevated AP levels.
Stephania tetrandra prevents and regresses liver fibrosis induced by carbon tetrachloride in rats
Authors: Chor Josette S Y , Yu Jun , Chan Ka Kui , Go Yin Yin , Sung Joseph J Y
Published: February 2009

Background and Aim:  There is currently no safe and effective treatment for liver fibrosis. We have previously shown that Stephania tetrandra (ST) and Salvia miltiorrhiza (SM) suppress cell proliferation and enhance apoptosis of hepatic stellate cell (HSC) in vitro. In this study, we aimed to investigate the anti‐fibrotic effect of these two herbs in vivo.

Methods:  Liver fibrosis was induced by carbon tetrachloride (CCl4) injection in rats for 5 weeks. SM, ST or SM + ST was gavaged on day 1 of CCl4 administration to study the preventive effects of herbs on hepatic fibrosis. In a separate study designed to assess possible fibrosis regression, rats were randomly allocated to be treated with SM, ST or SM + ST when fibrosis was established. Liver injury and collagen content were assessed. HSC activation and apoptosis were determined.

Results:  As compared with the CCL4‐only rats, serum ALT was significantly lower in CCl4‐treated rats that received either SM (P < 0.01) or ST (P < 0.01). Administration of ST significantly prevented (P < 0.01) or reversed the hepatic fibrosis (P < 0.01) induced by CCL4. Moreover, rats treated with ST had reduced protein expression of α‐SMA both in prevention (P < 0.05) and in regression (P < 0.01) experiments. The double‐color staining of α‐SMA and TUNEL showed that ST increased HSC apoptosis. However, co‐treatment of SM + ST did not increase the antifibrotic effect of ST.

Conclusions:  Stephania tetrandra safely and effectively prevents and reverses hepatic fibrosis through activating HSC apoptosis in rats.
Therapeutic effects of rectal administration of muscovite on experimental colitis in rats
Authors: Chen Yan , Chen Yi , Liu Wei‐li , Zhou Tian‐hua , Cai Jian‐ting , Du Qing , Wang Liang‐jing , Wu Jia‐Guo , Si Jian‐min
Published: February 2009

Background and Aims:  The aim of this study was to investigate whether rectal administration of muscovite can ameliorate colonic inflammation in a rat model of experimental colitis, and its possible mechanism.

Methods:  Female Sprague‐Dawley (SD) rats with trinitrobenzene sulfonic acid (TNBS)‐induced colitis were treated with rectal administration of muscovite or 5‐aminosalicylic acid (5‐ASA) daily for 14 days. The changes in body weight, macroscopic damage and histologic scores were subsequently evaluated. Gene expression of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), mucin2 (MUC2) and trefoil factor 3 (TFF3) in the colonic tissues was assessed by semiquantitative reverse transcription polymerase chain reaction (RT‐PCR) while protein levels of TNF‐α and IL‐1β were detected by ELISA. Mucin2 expression in colonic mucosa was detected by immunohistochemistry. The capacity of muscovite to adsorb cytokines in vitro was determined by the changes in the amount of TNF‐α, IL‐1β secreted by lipopolysaccharide (LPS)‐stimulated THP‐1 cells and IL‐8 secreted by LPS‐stimulated HT‐29 cells.

Results:  Rectal administration of muscovite improved the loss of body weight, macroscopic and histologic scores of TNBS‐induced colitis in a dose‐dependent manner. Trinitrobenzene sulfonic acid‐induced expression of TNF‐α and IL‐1β was reduced by muscovite and 5‐ASA treatment. Reduction of MUC2 expression in colitis rats was reversed by muscovite and 5‐ASA treatment. However, the expression of TFF3 mRNA in colonic mucosa was not affected. In addition, we found muscovite inhibited the expression of TNF‐α, IL‐1β secreted by THP‐1 and IL‐8 secreted by HT‐29 cells in a dose‐dependent manner.

Conclusions:  Our study demonstrated for the first time that rectal administration of muscovite can ameliorate colonic inflammation of TNBS‐induced colitis. Further confirmatory studies are needed to prove that muscovite might be a potential therapeutic agent for the treatment of ulcerative colitis.
Stochastic and deterministic processes jointly structure tropical arthropod communities
Authors: Farnon Ellwood M. D. , Manica Andrea , Foster William A.
Published: February 2009

The question of whether ecological assemblages are structured by stochastic and deterministic (e.g. interspecific competition) processes is controversial, but it is difficult to design sampling regimes and experiments that can dissect the relative importance of stochastic and deterministic processes in natural assemblages. Using null models, we tested communities of arthropod decomposers in tropical epiphytes for patterns of species co‐occurrence, while controlling for habitat gradients, seasonal variations and ecological succession. When environmental conditions were controlled, our analysis showed that the communities were structured stochastically. However, analysing mixed sets of communities that were deliberately created either from two distinct heights or two successional stages revealed that communities were structured deterministically. These results confirm that habitat gradients and dispersal/competition trade‐offs are capable of generating non‐random patterns within decomposer arthropod communities, but reveal that when such effects are accounted for, species co‐occurrence is fundamentally random.
Effect of PCR amplicon size on assessments of clone library microbial diversity and community structure
Authors: Huber Julie A. , Morrison Hilary G. , Huse Susan M. , Neal Phillip R. , Sogin Mitchell L. , Mark Welch David B.
Published: February 2009

PCR‐based surveys of microbial communities commonly use regions of the small‐subunit ribosomal RNA (SSU rRNA) gene to determine taxonomic membership and estimate total diversity. Here we show that the length of the target amplicon has a significant effect on assessments of microbial richness and community membership. Using operational taxonomic unit (OTU)‐ and taxonomy‐based tools, we compared the V6 hypervariable region of the bacterial SSU rRNA gene of three amplicon libraries of c. 100, 400 and 1000 base pairs (bp) from each of two hydrothermal vent fluid samples. We found that the smallest amplicon libraries contained more unique sequences, higher diversity estimates and a different community structure than the other two libraries from each sample. We hypothesize that a combination of polymerase dissociation, cloning bias and mispriming due to secondary structure accounts for the differences. While this relationship is not linear, it is clear that the smallest amplicon libraries contained more different types of sequences, and accordingly, more diverse members of the community. Because divergent and lower abundant taxa can be more readily detected with smaller amplicons, they may provide better assessments of total community diversity and taxonomic membership than longer amplicons in molecular studies of microbial communities.
ARE RECENT DEFENCES OF THE BRAIN DEATH CONCEPT ADEQUATE?
Authors: JOFFE ARI
Published: February 2009

Brain death is accepted in most countries as death. The rationales to explain why brain death is death are surprisingly problematic. The standard rationale that in brain death there has been loss of integrative unity of the organism has been shown to be false, and a better rationale has not been clearly articulated. Recent expert defences of the brain death concept are examined in this paper, and are suggested to be inadequate. I argue that, ironically, these defences demonstrate the lack of a defensible rationale for why brain death should be accepted as death itself. If brain death is death, a conceptual rationale for brain death being equivalent to death should be clarified, and this should be done urgently.
Estimation and model adequacy checking for multivariate seasonal autoregressive time series models with periodically varying parameters
Authors: Ursu Eugen , Duchesne Pierre
Published: February 2009

We introduce a class of multivariate seasonal time series models with periodically varying parameters, abbreviated by the acronym SPVAR. The model is suitable for multivariate data, and combines a periodic autoregressive structure and a multiplicative seasonal time series model. The stationarity conditions (in the periodic sense) and the theoretical autocovariance functions of SPVAR stochastic processes are derived. Estimation and checking stages are considered. The asymptotic normal distribution of the least squares estimators of the model parameters is established, and the asymptotic distributions of the residual autocovariance and autocorrelation matrices in the class of SPVAR time series models are obtained. In order to check model adequacy, portmanteau test statistics are considered and their asymptotic distributions are studied. A simulation study is briefly discussed to investigate the finite‐sample properties of the proposed test statistics. The methodology is illustrated with a bivariate quarterly data set on travelers entering in to Canada.
Improvement in lipid profiles over 6 years of follow‐up in adults with AIDS and immune reconstitution
Authors: Williams PL , Wu JW , Cohn SE , Koletar SL , McCutchan JA , Murphy RL , Currier JS ,   for the AIDS Clinical Trials Group 362 Study Team
Published: February 2009

Objectives

The aim of the study was to evaluate long‐term changes in lipids and to assess other coronary heart disease (CHD) risk factors in highly experienced AIDS patients with immune reconstitution, and to examine their association with antiretroviral therapy (ART).

Methods

We evaluated 433 AIDS patients with prior severe immunosuppression and ART‐based immune reconstitution, followed in a multicentre prospective observational study between 2000 and 2006. We estimated the prevalence at entry of hypercholesterolaemia and metabolic syndrome, and 10‐year CHD risks. Trends in total cholesterol (TC), triglycerides (TG) and high‐density lipoprotein (HDL) cholesterol were evaluated over time, and use of specific ART drugs at each study visit was assessed using mixed effect models, adjusting for CHD risk factors and use of lipid‐lowering agents.

Results

At entry to observational follow‐up, 28% of the 433 subjects had hypercholesterolaemia and 15% had a predicted 10‐year CHD risk above 20%. Average TC and fasting TG levels declined over the follow‐up period (median=5.8 years), and these declines were associated with increased use of physician‐prescribed lipid‐lowering agents and changes in ART regimens. After adjustment for CHD risk factors, TC and TG levels were significantly higher for those on ritonavir‐boosted protease inhibitors and those on nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly efavirenz, than for other patients.

Conclusions

Abnormalities in serum lipids were common at baseline but became less so over time, and this improvement was associated with increased use of lipid‐lowering agents and selection of ART agents with less deleterious effects on lipids.
Risk factors for incident diabetes mellitus among HIV‐infected patients receiving combination antiretroviral therapy in Taiwan: a case–control study
Authors: Lo Y‐C , Chen M‐Y , Sheng W‐H , Hsieh S‐M , Sun H‐Y , Liu W‐C , Wu P‐Y , Wu C‐H , Hung C‐C , Chang S‐C
Published: February 2009

Objectives

Recent studies suggest that patients with HIV infection are at increased risk for incident diabetes mellitus (DM). We investigated the incidence and risk factors of DM among HIV‐infected patients receiving combination antiretroviral therapy (CART) in Taiwan.

Methods

Incident cases of DM were identified among HIV‐infected patients at the National Taiwan University Hospital between 1993 and 2006. A retrospective case–control study was conducted after matching cases with controls for sex, age at HIV diagnosis, year of HIV diagnosis, mode of HIV transmission and baseline CD4 lymphocyte count. A multivariate analysis was performed to identify risk factors for incident DM among HIV‐infected patients.

Results

In 824 HIV‐infected patients eligible for analysis, 50 cases of incident DM were diagnosed, resulting in an incidence of 13.1 cases per 1000 person‐years of follow‐up. In total, 100 matched controls were identified. Risk factors for incident DM were a family history of DM [odds ratio (OR) 2.656; 95% confidence interval (CI) 1.209–5.834], exposure to zidovudine (OR 3.168; 95% CI 1.159–8.661) and current use of protease inhibitors (OR 2.528; 95% CI 1.186–5.389).

Conclusions

Incident DM was associated with a family history of DM, exposure to zidovudine and current use of protease inhibitors in HIV‐infected patients receiving CART in Taiwan.
Restraint, Seclusion and PRN Medication in English Services for People with Learning Disabilities Administered by the National Health Service: An Analysis of the 2007 National Audit Survey
Authors: Sturmey Peter
Published: February 2009

Background  There is much interest in the use and prevention of unnecessary restrictive behavioural procedures; however, accurate estimates of their use are lacking. The Healthcare Commission and Commission for Social Care Inspection (2007) recently reported such data from a large sample of units administered by the National Health Service (NHS).

Materials  This study analysed data from The Healthcare Commission on the use of personal and mechanical restraint, PRN (as needed) medication and other restrictive procedures were analysed from 509 service units and 3902 service users.

Results  Approximately 80% of service units reported using PRN medication and approximately half of service units used personal or mechanical restraints. A small number of services units used restrictive procedures much more than most service units. A small number of service users experience a very large number of applications of restrictive procedures.

Conclusion  Contemporary English services administered by the NHS and independent health care use restrictive behaviour management procedures commonly, including non‐evidence‐based practices, such as PRN medication. These services should focus resources on the small proportion of services units and service users and adopt evidence‐based practices to safely reduce these restrictive procedures, enhance service user quality of life and ensure value for money from commissioned services.
A novel mutation (p.Thr198Ser) in the 1A helix of keratin 5 causes the localized variant of Epidermolysis Bullosa Simplex
Authors: Bowden Paul E. , Knight Arthur G. , Liovic Mirjana
Published: February 2009

Abstract:  A novel missense mutation (p.Thr198Ser) in the 1A helix of keratin 5 (K5) has been identified in a four‐generation family with a history of the localized variant of epidermolysis bullosa simplex (EBS‐loc), a genetic skin fragility disorder caused by K5 or K14 mutations. Genomic DNA was isolated from blood samples of patients and their healthy relatives, and all exons of the genes encoding K5 and K14 (KRT5 and KRT14) were amplified by PCR and directly sequenced. The identified mutation was confirmed by mismatch allele‐specific (MM‐AS)‐PCR and restriction enzyme digestion with RsaI. K5 p.Thr198Ser lies at the C‐terminal end of the 1A helical domain and is considered to be outside of the main mutation hotspot region. This is the first reported mutation to affect position 30 of the 1A helix (1A:T30S) in any of the 54 known keratins.
Defining chronodisruption
Authors: Erren Thomas C. , Reiter Russel J.
Published: February 2009

Abstract:  When the International Agency for Research on Cancer (IARC) classified shift‐work that involves circadian disruption as probably carcinogenic to humans in 2007, this was the prelude to extensive experimental and epidemiological research in coming years. Indeed, with some 20% of people worldwide being engaged in some type of work at unusual times, including the night, it is a must to investigate, and to clarify as soon as possible, the biologically plausible links via circadian disruption with epidemic cancers such as of the breast or prostate. Surprisingly, neither the IARC information available so far nor the general literature provides a clear definition of what the critical component in the postulated chain of causation, namely circadian disruption, is. Here we offer our definition of chronodisruption (CD), a concept which we proposed in 2003 and which we operationalized recently in research which addressed the putative links between shift‐work, time‐zone‐travel and human cancers independently of the IARC and led to similar causal interpretations. As a basis for further research in this area with possible high relevance for public health, we: (i) elaborate our definition of CD, with melatonin being a key biological intermediary, by putting critical disruptions, and the resulting disorder, of circadian clocks, biological rhythms and circadian organization into thematic and historical context with Colin Pittendrigh’s insights almost half a century ago; (ii) provide material on ‘what are chronodisruptors?’ and (iii) pose a key question which needs to be answered by and for experimental and epidemiological CD research. We hope that defining CD can contribute to studies which may help to find clues to a background incidence of epidemic internal cancers for which – so far in many cases – we lack causal explanations.
Physics-Based Modeling and Control of Residual-Affected HCCI Engines
Authors: Shaver Gregory M. , Gerdes J. Christian , Roelle Matthew J.
Published: February 2009

Homogeneous charge compression ignition (HCCI) is a novel combustion strategy for IC engines that exhibits dramatic decreases in fuel consumption and exhaust emissions. Originally conceived in 1979, the HCCI methodology has been revisited several times by industry but has yet to be implemented because the process is difficult to control. To help address these control challenges, the authors here outline the first generalizable, validated, and experimentally implemented physics-based control methodology for residual-affected HCCI engines. Specifically, the paper describes the formulation and validation of a two-input, two-state control-oriented system model of the residual-affected HCCI process occurring in a single engine cylinder. The combustion timing and peak pressure are the model states, while the inducted gas composition and effective compression ratio are the model inputs. The resulting model accurately captures the system dynamics and allows the simultaneous, coordinated control of both in-cylinder pressure and combustion timing. To demonstrate this, an H2 optimal controller is synthesized from a linearized version of the model and used to dictate step changes in both combustion timing and peak pressure within about four to five engine cycles on an experimental test bed. The application of control also results in reductions in the standard deviation for both combustion timing and peak pressure. The approach therefore provides accurate mean tracking, as well as a reduction in cyclic dispersion. Another benefit of the simultaneous coordination of both control inputs is a reduction in the control effort required to elicit the desired response. Instead of using a peak pressure controller that must compensate for the effects of a combustion timing controller, and vice versa, the coordinated approach optimizes the use of both control inputs to regulate both outputs.
Effects of Jet Obliquity on Hydraulic Jumps Formed by Impinging Circular Liquid Jets on a Moving Horizontal Plate
Authors: Kate R. P. , Das P. K. , Chakraborty Suman
Published: February 2009

The present work attempts to investigate the effects of jet obliquity on the spatial patterns formed as a consequence of hydraulic jumps due to the impingement of circular liquid jets on continuously moving but nonaccelerating horizontal flat plates. Both the normal and the oblique impinging jets are considered, in order to characterize the contrasting features of the associated hydraulic jump mechanisms. Theoretical calculations are executed to obtain the locations of the jump, for different jet and plate velocities and jet inclination angles, using a depth-averaged momentum integral equation for shallow-free surface flows. Comparisons are subsequently made between the theoretical predictions and experimental observations reported in the literature, and a good agreement between these two can be observed. Special cases of a circular hydraulic jump when the target plate is stationary and the impinging jet is vertical, and elliptic hydraulic jumps when the target plate is stationary and the impinging jet is obliquely inclined, are also discussed. It is conjectured that flow due to impinging jets on a horizontal moving plate can be modeled as an equivalent flow due to an inclined impinging jet on stationary horizontal flat plates, with appropriate alterations in the jet velocity and the jet inclination angles.
Modeling the Onset of Gas Entrainment in a Single Downward Discharge From a Stratified Gas-Liquid Region With Liquid Crossflow
Authors: Bowden R. C. , Hassan I. G.
Published: February 2009

The critical height at the onset of gas entrainment, in a single downward oriented discharge from a stratified gas-liquid region with liquid crossflow, was modeled. The assumptions made in the development of the model reduced the problem to that of a potential flow. The discharge was modeled as a point-sink while the crossflow was said to be uniform at the main pipe inlet. The potential function was determined from a superposition of known solutions for a point-sink and uniform flow. The resulting system of three equations demonstrated that the flow field was dominated by the discharge and crossflow Froude numbers. The system was solved numerically and provided a relationship between the geometry, flow conditions, dip location, and critical height. The model predicted that the critical height increased with the discharge Froude number and decreased with the crossflow Froude number. With no imposed crossflow, the model prediction demonstrated agreement with transient and quasisteady experimental data to within ±30%. Existing experimental correlations showed inconsistent crossflow effects on the critical height and disagreed with the model predictions at high discharge Froude numbers.
Vowel-to-vowel coarticulation in Japanese: The effect of consonant duration
Authors: Löfqvist Anders
Published: February 2009

This paper examines vowel-to-vowel lingual coarticulation in sequences of vowel-bilabial consonant-vowel, where the duration of the oral closure for the consonant is either long or short. Native speakers of Japanese served as subjects. The linguistic material consisted of Japanese word pairs that only differed in the duration of the labial consonant, which was either long or short. Recordings were made of lip and tongue movements using a magnetometer system. It was hypothesized that there would be greater vowel-to-vowel coarticulation in the context of a short consonant, since a long consonant would allow the tongue more time to move. The overall results do not show any strong support for this hypothesis, however. Subjects modulate the speed of the tongue movement between the two vowels, making it slower during the long than during the short consonant.