bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon‐α (IFN‐α) inhibits granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) expression at the post‐transcriptional level in murine bone marrow stromal cells
Authors: Goullner Gerhard , Aman M. Javad , Steffens Hans Peter , Huber Christoph , Peschel Christian , Derigs H. Guunter
Published: March 2008

Summary Recently it has been shown that IFN‐α inhibits expression of GM‐CSF in adherent cells of human long‐term bone marrow cultures (LTBMC) stimulated with interleukin‐1 (IL‐1), tumour necrosis factor‐α (TNF‐α) or endotoxin. The murine bone marrow stromal cell line +/+‐ 1.LDA11 was used to further define regulatory mechanisms of IFN‐α inhibition on GM‐CSF expression. This cell line originated from a murine Dexter type culture and exhibits a pre‐adipocytic phenotype. As in human LTBMC, we could demonstrate a inhibitory effect of IFN‐α co‐incubation on GM‐CSF activity in serum‐free supernatants of +/+‐1.LDA11 stromal cell cultures stimulated with IL‐1 or TNF‐α or the combination of IL‐1 plus TNF‐α. IFN‐α inhibitory effect on GM‐CSF expression was shown to be dose dependent with minimal response at 10U/ml and maximal inhibition at a dose of 500U/ml. Northern blot analysis confirmed these data at the mRNA level. Reprobing of Northern blots for interleukin‐6 (IL‐6) mRNA showed increased expression after IFN‐α incubation, demonstrating specific and differential regulatory effects of IFN‐α on cytokine production in bone marrow stromal cells. Inhibition of GM‐CSF mRNA by IFN‐α was time dependent, starting at about 90–120 min post‐treatment. Cycloheximide (CHX) incubation abolished the inhibitory effect of IFN‐α on GM‐CSF expression, suggesting the requirement of a labile protein. Reporter gene studies were used in order to evaluate the effect of IFN‐α incubation on GM‐CSF mRNA transcription in stromal cells. For this purpose, GM‐CSF promoter fragments were subcloned into a luciferase expression vector. Neither constitutive nor TNF‐α stimulated GM‐CSF transcription was inhibited by IFN‐α co‐incubation. On the other hand, actinomycin‐D chase experiments revealed a reduced GM‐CSF mRNA stability after IFN‐α incubation. The induction of a RNAase, possibly a 2–5A‐dependent RNAase, by IFN‐α may be a possible cause for the increased GM‐CSF mRNA decay. These results show a regulatory role for IFN‐α in the bone marrow microenvironment possibly involved in the myelosuppres‐sive effect of IFN‐α therapy or viral infections.
Quantitative analysis of AML1/ET0 transcripts in peripheral blood stem cell harvests from patients with t(8;21) acute myelogenous leukaemia
Authors: Miyamoto Toshihiro , Nagafuji Koji , Harada Mine , Eto Tetsuya , Fujisaki Tomoaki , Kubota Akira , Akashi Koichi , Mizuno Shin‐Ichi , Takenaka Katsuto , Kanaji Taisuke , Gondo Hisashi , Okamura Takashi , Inaba Shoichi , Niho Yoshiyuki
Published: March 2008

Summary Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic reconstitution after marrow‐ablative chemotherapy in patients with acute leukaemia because of the possibility that there is a lower risk of leukaemic contamination. We have developed a titration assay using a competitive reverse transcriptase polymerase chain reaction (RT‐PCR) which is able to estimate the number of AML1/ETO transcripts so that minimal residual disease (MRD) can be monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia (AML). Using a qualitative RT‐PCR method, AML1/ETO transcripts could be detected in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained from 15 patients with t(8;21) AML. With our competitive RT‐PCR assay, the number of AML1/ETO transcripts was found to be lower in the second PBSC harvest than that in the first in every individual. Furthermore, MRD in PBSC harvests was less than that in the corresponding bone marrow obtained on the day of PBSC collection in the individual patients studied. In 10 patients who received autologous blood stem cell transplantation (ABSCT), we could not find a relationship between the number of AML1/ETO transcripts in the infused PBSC harvests and the clinical outcome after ABSCT. The present study clearly indicates that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukaemic cells, the degree of leukaemic contamination may decrease as chemotherapy is repeated. The mobilization of PBSC by repeated chemotherapy may provide an advantageous source of haemopoietic stem cells for ABSCT.
Large‐cell anaplastic non‐Hodgkin's lymphoma originating in donor cells after allogenic bone marrow transplantation
Authors: Schouten Harry C. , Hopman Anton H. N. , Haesevoets Annick M. , Arends Jan‐Willem
Published: March 2008

Summary .Second neoplasms after allogenic bone marrow transplantation (BMT) occur in donor cells; however, host origin generally cannot be excluded. Using fluorescence in situ hybridization (FISH) the origin of the malignant population can be proven indisputably. In a female patient with CD30+ large‐cell anaplastic non‐Hodgkin's lymphoma (LCAL) after BMT with an HLA‐identical brother donor, FISH using anti‐CD30 immunocytochemistry in combination with anti‐Y‐ and anti‐EBV RNA probes was applied. In pathological lymph nodes the majority of cells were of donor type (Y). CD30‐positive cells were Y‐positive; these cells were also EBV‐positive. Using FISH and immunocytochemistry we have demonstrated convincingly that this, possibly EBV‐induced, LCAC originated in donor cells.
Megakaryopoiesis in patients with cyclic thrombocytopenia
Authors: Nagasawa Toshiro , Hasegawa Yuichi , Kamoshita Masaharu , Ohtani Kouji , Komeno Takuya , Itoh Takayoshi , Shinagawa Atsushi , Kojima Hiroshi , Ninomiya Haruhiko , Abe Tsukasa
Published: March 2008

Summary Megakaryopoiesis was examined in 10 patients (eight females and two males) with cyclic thrombocytopenia (CT) to investigate the underlying pathogenesis. Numbers of CFU‐Meg and megakaryocytes and the mean cytoplasmic area (mean area) of megakaryocytes at the peak, nadir, ascent mid phase, and descent mid phase of the platelet cycle were determined. The patients were classified as female cases group I (cases 1–4; previously diagnosed as ITP and CT occurred during remission), female cases group II (cases 5–8; persistent CT from initial diagnosis), and male CT (cases 9 and 10). In three of the four female cases in group I, numbers of CFU‐Meg and megakaryocytes were normal or increased persistently during the platelet cycle, whereas the mean area fluctuated in synchrony with the platelet cycle, suggesting failure of cyclic production rather than platelet destruction. In the female cases in group II and one female case in group I, numbers of CFU‐Meg and megakaryocytes were also normal or increased at four phases of the cycle, but the mean area did not fluctuate, remaining large during the cycle, suggesting cyclic destruction or platelet clearance. In contrast, in the male patients values for numbers of CFU‐Meg, megakaryocytes and mean cytoplasmic area fluctuated during the platelet cycle, indicating that cyclic changes in megakaryopoiesis generated the platelet cycle. These findings indicate that the measurement of cytoplasmic area is useful for distinguishing cyclic platelet production from cyclic destruction or clearance in CT.
Interleukin‐11 enhances gastrointestinal absorption of iron in rats
Authors: Baynes Roy D. , Cook James D. , Keith James
Published: March 2008

Summary The effect of parenteral administration of IL‐11 on gastrointestinal iron absorption was evaluated. A significant increase in the absorption of 59Fe‐tagged food iron fed to fasting rats was observed when two subcutaneous injections of IL‐11 were given 48 and 24 h prior to testing. Relatively similar increases of 25% were observed with IL‐11 doses of 300, 600 and 1000μig/kg for each injection. The increase in absorption did not appear to be related to changes in erythropoiesis. These findings raise the possibility that the enhanced absorption of iron which occurs with ineffective erythropoiesis may in part be mediated by multifunctional haemopoietic growth factors.
Interleukin‐11 (IL‐11) acts as a synergistic factor for the proliferation of human myeloid leukaemic cells
Authors: Lemoli Roberto M. , Fogli Miriam , Fortuna Alessandra , Amabile Marilina , Zucchini Patrizia , Grande Alexis , Martinelli Giovanni , Visani Giuseppe , Ferrari Sergio , Tura Sante
Published: March 2008

Summary. Interleukin‐11 is a stromal cells derived cytokine which stimulates the proliferation of primitive haemopoietic progenitor cells. For this paper we have studied the constitutive expression of IL‐11 mRNA in a panel of well‐known leukaemic cell lines and samples from AML patients at diagnosis. Moreover, the same cellular populations were evaluated for their proliferative response to recombinant‐human‐(r‐hu) IL‐11 alone and combined with r‐hu‐IL‐3, granulocyte‐macrophage colony stimulating factor (GM‐CSF) and stem cell factor (SCF, c‐kit ligand). The colony‐forming ability of HL60, K562, KG1 cells and eight fresh AML cell populations was assessed by a clonogenic assay in methylcellulose. In eight additional AML cases the number of S‐phase leukaemic cells induced by IL‐11 was determined by the bromodeoxyuridine (BRDU) incorporation assay after 3 d of liquid culture.

IL‐11, as single cytokine, did not stimulate the colony formation of the three myeloid cell lines under serum‐containing and serum‐free conditions. In contrast, the proliferation of the leukaemic cells in response to IL‐3, GM‐CSF and SCF was enhanced by co‐incubation with IL‐11, and this effect was reversed in blocking experiments by the anti‐IL‐11 Moab. When tested on primary AML samples, IL‐11 alone showed little, if any, proliferative activity. However, it increased the IL‐3‐dependent blast colony formation in eight out of eight cases and GM‐CSF in seven cases. IL‐11 also augmented synergistically the number of CFU‐L stimulated by SCF in seven cases. A combination of three factors (IL‐11, SCF and IL‐3) yielded optimal colony formation. The BRDU studies showed the significant increase of AML cells in S‐phase when IL‐11 was combined with SCF, whereas the two CSF had no activity on their own. Positive interaction was also observed when IL‐11 was added to IL‐3 supplemented cultures in five out of eight cases tested. Reverse transcriptase‐polymerase chain reaction amplification (RT‐PCR) demonstrated the constitutive expression of IL‐11 mRNA in all the cell lines and 11/12 AML samples studied at diagnosis.

These results indicate that IL‐11 is expressed in leukaemic myeloid cells and that their proliferation is regulated by the cytokine which acts as a synergistic factor.
Pharmacokinetic and pharmacodynamic studies of subcutaneously administered recombinant human interleukin‐3 following chemotherapy for non‐Hodgkin's lymphoma
Authors: Hovgaard D. J. , Mortensen B. T. , Nissen N. I.
Published: March 2008

Summary. The pharmacokinetics and the pharmacodynamic profile of subcutaneously administered recombinant human non‐glycosylated interleukin‐3 (rhIL‐3) was studied in lymphoma patients after standard CHOP chemotherapy. 30 patients received 0.5, 1.0, 5.0, 7.5 and 10/ig/kg (six patients at each dose level) of rhIL‐3 for 14 d. Serum rhIL‐3 samples were obtained regularly during the treatment and serially over a 24 h period on the first (cycle day 2) and the last (cycle day 15) day of rhIL‐3 treatment for pharmacokinetic evaluation. Following s.c. injection on cycle day 2, the maximum rhIL‐3 serum concentration ranged from 289pg/ml (0‐5/ig/kg) to 4690pg/ml (10/xg/kg). Both the maximum serum concentration (R= 0.90, P< 0.0001) and the area under the serum concentration‐time curve (R= 0.95, P< 0.0001) were related to dose.

The elimination half‐life T1/2β was 160 min for 0.5 μg/kg and 134 min for 10μg/kg, with no apparent dose relationship. The systemic clearance of 3.0–6.0ml/min/kg was comparable at all dose levels. No significant difference was noted between pharmacokinetic parameters on the first day of rhIL‐3 and the last day of treatment, and no accumulation of the drug was noted throughout the study. The pharmacokinetic parameters correlated poorly to the clinical response of the growth factor, where dose in μg/kg seemed to be the most important single factor.
The glycosylation of red cell autoantibodies affects their functional activity in vitro
Authors: Hadley Andrew G. , Zupanska Barbara , Kumpel Belinda M. , Pilkington Clarissa , Griffiths Helen L. , Leader Katherine A. , Jones Jeff , Booker David J. , Stamps Robert , Sokol Robert J.
Published: March 2008

Summary. Factors governing the functional activity of red cell autoantibodies are poorly defined. Here we report the presence of qualitative differences in the glycosylation of IgG autoantibodies which affect in vitro interactions with FCγRIII. The following antibodies were affinity‐purified by adsorption and elution from normal red cells: IgG eluted from the red cells of 27 haemolysing or non‐haemolysing patients, anti‐D in sera from 11 pregnant women, and IgGl and IgG 3 human monoclonal anti‐D. Monoclonal antibodies with differing levels of agalactosyl IgG were produced by culturing cell lines at high or low cell density. The % IgG with oligosaccharides lacking terminal galactose residues (agalactosyl IgG) of antibodies was designated as low, medium or high according to their reactivity with a monoclonal antibody to terminal N‐acetylglucosamine. FcγRIII‐mediated functional activity was assessed by measuring the K‐cell‐mediated lysis of red cells in eluates diluted to achieve comparable levels of red cell sensitization. All eluates containing allo‐anti‐D were lytic (range 74‐100%). In contrast, lysis by autoantibodies varied from 0 to 100%; 11/13 eluates from red cells of haemolysing patients promoted <5% lysis compared to 2/7 eluates from red cells of non‐haemolysing patients (P<0.02). The ability of autoantibodies to promote K‐cell‐mediated red cell lysis correlated inversely with their level of agalactosyl IgG (r=‐0‐56, P<0.01, n=23). Further, monoclonal anti‐D antibodies with very low levels of agalactosyl IgG were comparatively more lytic than the same antibodies containing more agalactosyl IgG. Analysis of the ratio of κ:λ light chains suggested that autoantibodies from 6/19 patients were monoclonal or oligoclonal in nature. The data indicate that IgG red cell autoantibodies from different patients are functionally heterogenous, and that this may be due, at least in part, to qualitative differences in the Fc region glycosylation reflected by differences in the proportion of agalactosyl IgG. This heterogeneity is consistent with the clonally‐restricted nature of the autoantibodies in some patients.
Heterogenous inhibition of platelet aggregation by monoclonal antibodies binding to multiple sites on GPIIIa
Authors: Lid L.‐X. , Nardi M. A. , Nierodzik M. L. , Karpatkin S.
Published: March 2008

Summary. Six monoclonal IgGl‐k antibodies (LK2, LK3r, LK4‐55, LK5, LK6‐55, LK7r) were raised against platelet membrane GPIIIa in order to study the structure‐function relationship of this molecule. Antibodies were selected on their ability to react with GPIIIa by ELISA on adherent platelets, by immunoblot on platelet lysates and by fluorescence flow cytometry on intact platelets. Fluorescence reactivity varied from 3‐ to 202‐fold greater than isotype control fluorescence. Two MoAbs reacted on immunoblot under reduced conditions (LK7r and LK3r). Two reacted with a 55 kD chymotrypsin/subtilisin digest of GPIIIa which is likely to exclude amino acids 121‐348 (LK4‐55 and LK6‐55). Four of the MoAbs (LK5, LK3r, LK2 and LK4‐55) inhibited tyrosine phosphorylation of one to four distinct bands on immunoblot. LK4‐55 reacted with an N‐terminal 66 amino acid fusion protein of GPIIIa near the PLA epitope (Leu 33). LK7r reacted with a 212‐222 peptide reported to be an RGD fibrinogen binding site. LK2 reacted near a disintegrin‐RGD binding site. Except for LK5, all inhibited ADP, collagen and thrombin‐induced platelet aggregation in a heterogenous fashion. Percentage inhibition of 125I‐fibrinogen binding to platelets varied from 18% to 98%. No correlation was noted between inhibition of fibrinogen binding, location of MoAb binding on GPIIIa, reactivity of MoAb binding with GPIIIa, inhibition of thrombin‐induced tyrosine phosphorylation or inhibition of platelet aggregation induced by ADP, collagen or thrombin. Thus MoAbs, binding to platelet GPIIIa at different sites, inhibit platelet aggregation in a heterogenous manner.
Ferritin excretion and iron balance in humans
Authors: SKIKNE BARRY S. , WHITTAKER PAUL , COOKE ALLEN , COOK JAMES D.
Published: March 2008

Summary.Under normal circumstances, most of the lumenal iron taken into the intestinal mucosal cell is stored within the cell as ferritin and subsequently is lost in the faeces when the cell exfoliates at the end of its lifespan. To evaluate whether faecal iron proteins reflect mucosal cell iron as well as whole body iron and to examine further the kinetics of gastrointestinal iron transport, faecal H‐rich and L‐rich ferritin were measured in normal subjects and patients with iron deficiency and genetic haemochromatosis. In normal and iron‐deficient subjects, the concentration of L‐rich but not H‐rich faecal ferritin correlated closely with body iron status. In genetic haemochromatosis, the faecal L‐rich and H‐rich ferritin concentrations were lower than expected for their body iron status. The administration of oral iron to normal subjects led to a rise in L‐rich ferritin. Administration of oral or parenteral iron to patients with iron deficiency led to a prompt rise in both forms of faecal ferritin, although the relative increase of L‐rich ferritin was greater than that of H‐rich ferritin with oral iron administration. Faecal ferritin correlated closely with iron stores in normals and patients with iron deficiency but faecal ferritin levels were lower than expected in genetic haemochromatosis, similar to that previously noted in the duodenal mucosal cells of these patients.
Growth inhibition of leukaemic cells carrying the t(3;21) by the AML1/EVI‐1 ‐specific antisense oligonucleotide
Authors: MITANI KINUKO , OGAWA SEISHI , TANAKA TOMOYUKI , KUROKAWA MINEO , YAZAKI YOSHIO , HIRAI HISAMARU
Published: March 2008

Summary. The t(3;21)(q26;q22) translocation is thought to play an important role in the acute phase transformation of CML. The formation of the AML1/EVI‐1 fusion gene by the translocation leads to expression of the AML1/EVI‐1 fusion protein. Here we demonstrate that the AML1/EVI‐1‐specific antisense oligonucleotide markedly decreases the [H]thymidine incorporation and growth of leukaemic cells carrying the t(3;21) and the t(9;22), but not those of K562 cells. These results indicate that the AML1/EVI‐1 fusion protein could contribute to proliferation of the t(3;21)‐carrying leukaemic cells after entering the blastic crisis phase of CML.
Analysis of the trophy sport fishery for the speckled peacock bass in the Rio Negro River, Brazil
Authors: HOLLEY M. H. , MACEINA M. J. , THOMÉ‐SOUZA M. , FORSBERG B. R.
Published: March 2008

Abstract The middle portion of the Rio Negro River in Brazil near the equator supports a popular recreational sport fishery for speckled peacock bass,Cichla temensis(Humboldt). The objective of this study was to determine the effect of fishing mortality on this population. Fish were collected from sport‐fishing (n = 72) and commercial (n = 103) catches and otoliths were aged to estimate longevity, growth and natural mortality. Recreational anglers in this region seek to catch, then release, larger speckled peacock bass; and fish larger than 62 cm standard length (SL) (about 4.5 kg) served as a bench mark to assess the potential impact of subsistence and commercial harvest on the abundance of larger fish in the sport fishery. Time of opaque band formation on otoliths generally coincided with the dry season (November to April); these bands appeared to form once per year, but formation was highly variable. Speckled peacock bass grew to 62 cm SL on average in 6.4 years, but some fish obtained this size in 4–5 years. Maximum age was 9 years, but most fish were less than 7 years. Instantaneous annual natural mortality (M) estimated from maximum size, longevity and growth ranged from 0.19 to 0.44. Simulation modelling predicted that exploitation rates of fish >25 cm SL similar to the estimated natural mortality rates would reduce the abundance of fish >62 cm by 67–89% compared with no harvest. Even modest exploitation rates of 5% and 10% would result in approximately 30–50% reduction, respectively, of these larger fish. Abundance of large speckled peacock bass that sustains the sport fishery is susceptible to low rates of exploitation in this remote region of Brazil.
Psychometric properties of the Mental Retardation Attitude Inventory‐Revised in Chinese college students
Authors: Hampton N. Z. , Xiao F.
Published: March 2008

Background  This study examines the psychometric properties of the Mental Retardation Attitude Inventory‐Revised (MRAI‐R; Antonak & Harth) in Chinese college students. The research questions included: (1) Is the MRAI‐R a reliable measure for Chinese college student? (2) Is the MRAI‐R related to familiarity with people with intellectual disabilities (PWID) and professional training? and (3) Does the four‐factor model of the MRAI‐R fit the Chinese college student data?

Method  Five hundred and thirty‐four college students from China participated in the study. Descriptive, Pearson product‐moment correlation, Cronbach alpha reliability coefficient and factor analyses were used to examine the reliability and validity of the MRAI‐R in this Chinese college student sample.

Results  The alpha coefficient reliability of the total scale of the MRAI‐R was 0.78. The alpha coefficient reliabilities for the integration–segregation (INSE) subscale, the social distance (SDIS) subscale, the private rights (PRRT) subscale and the subtle derogatory beliefs (SUDB) subscale were 0.50 (INSE), 0.78 (SDIS), 0.50 (PRRT) and 0.21 (SUDB) respectively. Correlation analyses indicated that familiarity with PWID and professional training had a weak correlation with attitudes towards PWID. A confirmatory factor analysis revealed that the standardized factor loadings and goodness‐of‐fit indices were inadequate (the chi‐square/degrees of freedom ratio = 3.24; the goodness‐of‐fit index = 0.85; the comparative fit index = 0.69; the RMSEA* = 0.07). A principal axis factoring analysis (PAF) with oblique rotation identified three factors with 25% of the variance accounted for the sample. However, the results of this PAF were factorial complex and not interpretable in that many items of the scale had double loadings on more than one factor.

Conclusions  The factor structure of the MRAI‐R in this sample of Chinese college students did not replicate the structure found in American adults. Although the SDIS subscale of the MRAI‐R appeared to be a reliable instrument among the four subscales of the MRAI‐R, the reliabilities of the INSE, PRRT and SUDB subscales were low. Continuing investigations of the utility of the MRAI‐R in Chinese culture is needed. Attitude instruments based on Chinese culture may be developed.
Clarification of the memory artefact in the assessment of suggestibility
Authors: Willner P.
Published: March 2008

Aim  The Gudjonsson Suggestibility Scale (GSS) assesses suggestibility by asking respondents to recall a short story, followed by exposure to leading questions and pressure to change their responses. Suggestibility, as assessed by the GSS, appears to be elevated in people with intellectual disabilities (ID). This has been shown to reflect to some extent the fact that people with ID have poor recall of the story; however, there are discrepancies in this relationship. The aim of the present study was to investigate whether a closer match between memory and suggestibility would be found using a measure of recognition memory rather than free recall.

Method  Three modifications to the procedure were presented to users of a learning disabilities day service. In all three experiments, a measure of forced‐choice recognition memory was built into the suggestibility test. In experiments 1 and 2, the GSS was presented using either divided presentation (splitting the story into two halves, with memory and suggestibility tests after each half) or multiple presentation (the story was presented three times before presentation of the memory and suggestibility tests). Participants were tested twice, once with the standard version of the test and once with one of the modified versions. In experiment 3, an alternative suggestibility scale (ASS3) was created, based on real events in a learning disabilities day service. The ASS3 was presented to one group of participants who had been present at the events, and a second group who attended a different day service, to whom the events were unfamiliar.

Results  As observed previously, suggestibility was not closely related to free recall performance: recall was increased equally by all three manipulations, but they produced, respectively, no effect, a modest effect and a large effect on suggestibility. However, the effects on suggestibility were closely related to performance on the forced‐choice recognition memory task: divided presentation of the GSS2 had no effect on either of these measures; multiple presentation of the GSS2 produced a modest increase in recognition memory and a modest decrease in suggestibility; and replacing the GSS with the ASS3 produced a large increase in recognition memory and a large decrease in suggestibility.

Implications  The results support earlier findings that the GSS is likely to overestimate how suggestible a person will be in relation to a personally significant event. This reflects poor recognition memory for the material being tested, rather than increased suggestibility per se. People with ID may in fact be relatively non‐suggestible for well‐remembered events, which would include personally significant events, particularly those witnessed recently.
Cytotoxic effects of short‐chain carboxylic acids on human gingival epithelial cells
Authors: Zhang J. , Kashket S.
Published: March 2008

Previous studies showed that foods that are retained on the dentition can accumulate high levels of short‐chain carboxylic acids (acetic, formic, lactic and propionic). Since gingival epithelium is the first periodontal tissue to be challenged by oral factors, a study was undertaken to determine whether short‐chain carboxylic acids can affect epithelial cells in vitro. Immortalized human oral epithelial cells were grown in supplemented keratinocyte growth medium at 37°C, and the effects of short‐chain carboxylic acids were determined with tetrazolium‐based and trypan blue exclusion assays. Low concentrations of short‐chain carboxylic acids inhibited the growth of human oral epithelial cells, while higher concentrations led to cell death. The effects of short‐chain carboxylic acids on the cells were dose‐dependent and varied among the individual acids (propionate >formate >lactate >acetate). Growth inhibition was partly reversible and growth resumed after removal of the acids. However, the time needed for recovery of the cells increased with short‐chain carboxylic acids concentration, consistent with progressively greater damage to the cells at higher short‐chain carboxylic acids concentrations. The observed effects of short‐chain carboxylic acids on gingival cells in vitro supported our hypothesis that short‐chain carboxylic acids can damage the integrity of gingival epithelium in situ.
Lung transplantation in a patient with a thrombophilic disorder
Authors: Elidemir O. , Smith K. J. , Schecter M. G. , Seethamraju H. , Mahoney D. H. , McKenzie E. D. , Mallory G. B.
Published: March 2008

Abstract:  The prothrombin G20210A mutation has been associated with an increased risk of graft failure in renal transplant recipients. Little is known about the potential effect of this mutation on lung transplant recipients. We report the case of bilateral lung transplantation in a patient with cystic fibrosis who was heterozygous for the G20210A mutation of the prothrombin gene.
Propionibacterium acnes lacks the capability to proliferate in platelet concentrates
Authors: Störmer M. , Kleesiek K. , Dreier J.
Published: March 2008

Background and Objectives  Propionibacterium acnes is considered to be one of the most frequent contaminants of platelet concentrates (PCs) when anaerobic culture‐based detection methods are used. But Propionibacteria are often detected too late when blood products have already been transfused. Therefore, its transfusion relevance is still demanding clarification because studies of the outcome of patients transfused with P. acnes‐contaminated PCs are still uncommon. In this study, we monitored clinical effects in patients after transfusion of PCs, which were detected too late in sterility testing. Furthermore, we assessed the bacterial proliferation of Propionibacterium species seeded into PCs to clarify their significance for platelet bacteria screening.

Materials and Methods  In the look‐back process, we followed the route of the putative contaminated PC units from storage to transfusion. In the in vitro study, PCs were inoculated with 1–100 colony‐forming unit (CFU)/ml of clinical isolates of Propionibacteria (n = 10). Sampling was performed during 10‐day aerobic storage at 22 °C. The presence of bacteria was assessed by plating culture and automated BacT/Alert culture system.

Results  Propionibacterium acnes shows slow or no growth under PC storage conditions. Clinical signs of adverse events after transfusion of potentially contaminated PC units were not reported.

Conclusion  Propionibacteria do not proliferate under PC storage conditions and therefore may be missed or detected too late when blood products have already been transfused.
Indomethacin‐induced changes in canine gastric mucosal haemodynamics and haemoglobin oxygenation, and the effects of topical anti‐ulcer agents
Authors: INATOMI NOBUHIRO , SATO NOBUHIRO , SATOH HIROSHI , MAKI YOSHITAKA , NAKAMURA NOBUTO , KAMADA TAKENOBU
Published: March 2008

Abstract Changes in gastric mucosal haemoglobin concentration (mucosal blood volume), mucosal haemoglobin oxygenation, mucosal blood flow and gastric arterial blood flow caused by indomethacin, an ulcerogenic agent, and anti‐ulcer agents were investigated in the stomach flap of anesthetized dogs. Indices of mucosal haemoglobin concentration and haemoglobin oxygenation, mucosal blood flow and arterial blood flow to the stomach flap were measured simultaneously. The intravenous injection of indomethacin (10 mg/kg) caused an immediate decrease in mucosal haemoglobin concentration with a gradual decrease in mucosal and arterial blood flow, and a slight decrease in mucosal haemoglobin oxygenation. The topical application of prostaglandin E2 (10 μg/ml) and spizofurone (a new anti‐ulcer agent, 1 mg/ml) to the mucosa significantly increased these parameters, and remedied the decreases of these parameters caused by indomethacin. Cimetidine (20 mg/ml), pirenzepine (10 mg/ml) and proglumide (40 mg/ml) given topically did not significantly increase these parameters in the resting state or the indomethacin‐induced ischaemic state. This study indicates that: indomethacin decreases gastric haemodynamics, and that improvement occurred with application of mucosal protective agents (i.e. prostaglandin E2 and spizofurone) and changes in mucosal blood concentration were closely correlated with those in mucosal blood flow and arterial blood flow, but correlated less well with those in the case of haemoglobin oxygenation.
Favourable outcome in sclerotherapy for bleeding oesophageal varices in schistosomiasis: Results in 30 patients
Authors: KARAWI MOHAMED AL , MOHAMED ABDELRAHMAN ELSHEIKH , HANID M. ANWAR , OTAIBI RAJI AL , SHAHED MAIE
Published: March 2008

Abstract Thirty consecutive patients with bleeding oesophageal varices secondary to schistosomal liver disease received injection sclerotherapy. These formed a part of a prospective study, to evaluate the role of sclerotherapy in the treatment of bleeding oesophageal varices due to different aetiological factors in patients seen at the Gastroenterology Unit, Riyadh Armed Forces Hospital, Saudi Arabia, between December 1980 and July 1984.

Schistosomiasis is endemic in parts of Saudi Arabia. Sclerotherapy has a special place in schistosomal liver disease as liver function is well preserved in this disease. The new antischistosomal drugs are effective and may halt the progress of the disease. However, in many patients portal hypertension with bleeding oesophageal varices is found at diagnosis. Of the patients with schistosomiasis, 63.3% were Group A Child's Classification. Oesophageal varices have been eradicated in 11 cases during the mean follow‐up period of 28 months (range 3‐44 months). Four patients were referred for surgery because of bleeding gastric varices, two of whom died following operation. One patient, who was also hepatitis B surface antigen positive, died due to re‐bleeding from gastric varices. The remaining 25 patients had no recurrence of bleeding and their liver function remained satisfactory.

Surgical procedures for oesophageal varices in schistosomiasis carry the risk of peri‐operative and postoperative morbidity and mortality. In contrast, complications following sclerotherapy are minor compared to surgical procedures and none of our patients had any serious sclerotherapy complications.
Depressed lymphocyte responses to wheat germ agglutinin and other mitogens in treated coeliac disease patients
Authors: DREW P. A. , KWITKO A. O. , SHEARMAN D. J. C.
Published: March 2008

Abstract This report investigates the possibility that inappropriate lymphocyte responses to wheat germ agglutinin (WGA), a mitogen found in wheat which influences proliferation of and immunoglobulin (Ig) synthesis by peripheral blood mononuclear cells (PBMC), may account for some of the immunological dysfunction noted in coeliac disease. The PBMC were prepared from healthy controls and 16 patients with coeliac disease who had received a gluten‐free diet for periods of 1 month to over 20 years. There was no difference in the proliferative responses of PBMC from the patients and normal subjects to optimal mitogenic concentrations of phytohaemagglutinin (PHA) or Concanavalin A (Con A), but the responses of the cells of the patients to pokeweed mitogen (PWM) and to a suboptimal concentration of Con A were reduced. The proliferative response induced by WGA in PBMC from treated coeliac patients was significantly depressed compared with controls. The synthesis of Ig by PWM‐stimulated PBMC, and the Con A induced suppression of this synthesis, was the same in cultures of PBMC from the patients or the controls. There was no difference in the effect of WGA on Ig synthesis between the patients and controls. It is concluded that there is no difference in the effect of WGA on Ig synthesis by PBMC from coeliac disease patients or controls, but that lymphocytes from coeliac disease patients proliferate poorly in response to WGA.
Repeated endoscopic sclerotherapy of oesophageal varices due to non‐cirrhotic portal fibrosis using intravariceal polidocanol
Authors: BHARGAVA D. K. , ATMAKURI S. P.
Published: March 2008

Forty patients with variceal bleeding due to non‐cirrhotic portal fibrosis have been treated by repeated endoscopic injection sclerotherapy using intravariceal polidocanol (1%). This has decreased re‐bleeding as evidenced by a decrease in mean bleeding risk factor (BRF) and transfusion requirement; difference between presclerotherapy and postsclerotherapy parameters were significant (P < 0.001). Low doses of polidocanol (mean 13.2 ml per session) were effective in the obliteration of varices. The mean sclerotherapy sessions required for obliteration were 8.04 (s.d. = 2.24). Complications were infrequent. Cumulative survival for 4 years was 92.5%. Based on these results endoscopic sclerotherapy is recommended for managing variceal bleeding due to non‐cirrhotic portal fibrosis and is a reasonable alternative to surgery.
Inhibitory effect of sera from patients with liver cirrhosis on natural killer activity
Authors: MORIZANE T. , NAKAMURA T. , INAGAKI Y. , TSUCHIMOTO K. , WATANABE T. , SAITO H. , KAWAMURA N. , SATOH I. , TSUCHIYA M.
Published: March 2008

The effect of sera from patients with liver cirrhosis (LC) and from healthy donors on natural killer (NK) activity of normal peripheral blood mononuclear cells (PBMC) was investigated. PBMC from a healthy donor were pre‐incubated for 3 h at 37°C in media containing 50% test sera and washed twice with phosphate‐buffered saline (PBS). Cytotoxic activity was determined using 51Cr‐labelled K‐562 cells as target. It was demonstrated that sera from both healthy donors and patients with LC suppressed the NK activity of normal PBMC compared with a PBS control. But the level of inhibition caused by patients’ sera (n= 30) was significantly higher than that caused by normal sera (n= 30; P < 0.001, Wilcoxon rank sum test). Sera from a patient with LC and a healthy subject were fractionated by a Sephacryl S‐300 column and the effect of five fractions on NK activity of normal MNC was assessed. Fractions 3 and 4 from both sera had inhibitory effects although Fraction 5 revealed an enhancing effect. These results suggest that human sera contain factors which both inhibit and enhance NK activity and that their net effects are inhibition. Since it is known that IgG is eluted in Fraction 4, IgG was separated from sera with a DEAE‐Sephacel column and its effect on NK activity was examined. IgG from patients’ sera was observed to suppress NK activity more often than those from healthy donors at the same concentrations.
Serum auto‐antibodies in patients with hepatocellular carcinoma: The clinical significance of antinuclear antibody
Authors: KIYOSAWA KENDO , IMAI HARUHIKO , SODEYAMA TAKESHI , FURUTA KIYOSHI , GIBO YUKIO , KUMAGAI TOSHIKO , KAMEKO MITSUAKI , KANAI MASAMITSU , FURUTA SEIICHI
Published: March 2008

Auto‐antibodies including antinuclear antibody (ANA), antismooth muscle antibody, antimitochondrial antibody, rheumatoid factor, lupus erythematosus factor, antimicrosomal antibody and antithyroglobulin antibody were assayed in sera from 84 patients with hepatocellular carcinoma, 70 with liver cirrhosis, 50 with chronic hepatitis, 30 with cancer of the alimentary tract and 100 normal subjects. A significantly higher incidence and higher titre of ANA was found in patients with hepatocellular carcinoma, and the patterns of nuclear fluorescence detected by the indirect immunofluorescent test using cultured baby hamster kidney cells were predominantly speckled and nucleolar. In 16 patients with this disease, serial assays of ANA were done in sera obtained before and after development of hepatoma and/or after resection of the hepatic tumour. Antinuclear antibodies evolved in six patients in conjunction with the progression from cirrhosis to hepatoma, and two of three ANA‐positive patients who had the hepatic tumour resected lost ANA from their sera after resection.

The significance of ANA in the sera of patients with malignant neoplasms is yet to be clarified, but it may be closely associated with the evolution of hepatocellular carcinoma.
Cerebral function in unoperated patients with non‐cirrhotic portal fibrosis: A comparison with compensated non‐alcoholic cirrhotics
Authors: SARIN S. K. , BEHARI M. , GUPTA M.
Published: March 2008

Cerebral functions were studied in 22 unoperated patients with non‐cirrhotic portal fibrosis (NCPF), 23 patients with compensated non‐alcoholic cirrhosis of the liver and 45 healthy controls. In each patient electroencephalography (EEG) and psychometric tests were performed. Neither EEG nor any psychometric test was abnormal in patients with NCPF, whereas in patients with cirrhosis of the liver, EEG was abnormal in 9%, the number connection in 35%, five point star construction in 13% and reverse counting test in 39%. These results suggest that subclinical hepatic encephalopathy is not common in non‐cirrhotic portal fibrosis seen in India.
Intestinal absorption, metabolism and effects of bacterial chemotactic peptides in rat intestine
Authors: WOODHOUSE A. F. , ANDERSON R. P. , MYERS D. B. , BROOM M. F. , HOBSON C. H. , CHADWICK V. S.
Published: March 2008

N‐formylated chemotactic peptides are produced by intestinal bacteria in vitro and Can be detected in intestinal luminal fluids. The healthy intestine must have mechanisms for preventing absorption of such peptides which can induce an inflammatory response when introduced systemically. Synthetic formyl‐methionyl‐leucyl‐phenylalanine (F‐met‐leu‐3H‐phe) has been used as a model bacterial chemotactic peptide to investigate intestinal absorption and metabolism of such peptides in the rat. Disappearance of tritium‐activity was rapid from jejunal and ileal loops and substantial hydrolysis of peptide occurred with only labelled metabolites appearing in portal blood. Less absorption and less metabolism occurred in the colon. Degradation of F‐met‐leu‐phe was due to a mucosal carboxypeptidase and was inhibited by benzylsuccinate, a potent inhibitor of the enzyme. In the presence of inhibitor, luminal disappearance from ileal loops was abolished and F‐met‐leu‐3H‐phe was not detected in portal blood indicating that healthy gut mucosa is ‘impermeable’ to intact peptide. The intestinal ‘barrier’ preventing mucosal penetration and the inflammatory effects of luminal bacterial peptides have two components: restricted mucosal permeability and a carboxypeptidase capable of hydrolysing such peptides with loss of their bioactivity.
Pathogenesis of distal renal tubular acidosis (incomplete form) in cirrhosis: Normal urinary Pco2 after bicarbonate loading
Authors: SAKAI HIDEKI , HASUMURA YASUSHI , TAKEUCHI JUGORO
Published: March 2008

In liver cirrhosis, an associated defect in urinary acidification is well known but its pathophysiologic nature is not well defined. Recent studies suggest that the urine Pco2 during maximal alkalinization of the urine is an adequate index of distal hydrogen ion secretion. To evaluate the nature of distal renal tubular acidosis (distal RTA) in cirrhosis, the urine minus blood Pco2 gradient [(U – B)Pco2] in alkaline urine was determined in four patients with cirrhosis and distal RTA, and compared with that in four patients without distal RTA (control subjects), as well as with that in one patient with Sjögren's syndrome and distal RTA (subject with impaired distal acidification). As expected, the (U – B)Pco2 after sodium bicarbonate loading was low (10.6 mmHg) in the subjects with impaired distal acidification and normal (32.5 mmHg, s.e.m. = 4.8) in control subjects. By contrast, all four patients with cirrhosis and distal RTA were able to achieve a normal (U – B)Pco2 gradient (33.8 mmHg, s.e.m. = 4.0) after sodium bicarbonate loading, even in the presence of the defect in urinary acidification under acid loading. These results suggest that the pathophysiology of the urinary acidification defect in liver cirrhosis is distinct from that in ordinary distal RTA; the latter signifies a defect in H+ secretion (secretory or voltage‐dependent RTA), whereas, in cirrhosis, an increased permeability for H+ may cause the inability to acidify the urine.
Monoclonal antibodies to human pancreatic carcinoma
Authors: YUAN SHI‐ZHEN , MCINTYRE LAURENCE J. , KIM YOUNG S.
Published: March 2008

Hybridoma cultures were produced by the fusion of SP2 mouse myeloma cells with spleen cells from mice immunized with human pancreatic carcinoma cells. After limiting dilutions, three monoclonal antibodies, YPan1, YPan2, and YPan3, which bound to immunizing cells but not to normal human skin fibroblasts, were further characterized. The three monoclonal antibodies were found to bind to all seven pancreatic carcinoma cell lines but not to other carcinoma cell lines tested except some colon carcinoma cell lines. When human tissue sections were examined using immunohistochemical techniques, the three monoclonal antibodies identified antigens in the pancreatic carcinomas and some normal pancreases, but only YPan1 showed strong positive staining. No cross‐reactivity was seen in sections of other carcinomas tested except some colon carcinomas. The results suggest that these monoclonal antibodies may be usefully applied to the detection of pancreatic carcinomas.
Response of the gastric mucosa to manipulation of gastric acid output in the cervical cord transected rat
Authors: MACLELLAN DONALD G. , SHULKES ARTHUR , HARDY KENNETH J.
Published: March 2008

The role played by gastric acid in stress ulceration following acute quadriplegic injury was examined in the C7 cord transected rat. Gastric acid output was manipulated by intraperitoneal administration of cimetidine (50 mg/kg), pentagastrin (5μg/kg) or saline in equal volumes. In comparison with control values (78 μEq/h per 200 g rat weight), cimetidine significantly decreased (16 μEq/h per 200 g) and pentagastrin increased (156 μEq/h per 200 g) the median gastric acid output. However, while cimetidine also significantly reduced the resultant ulceration, pentagastrin did not significantly enhance the ulceration compared with the control values. Furthermore, there was no correlation between gastric acid output and total ulcer length in any of the groups. It is concluded that while acid plays a permissive role in ulcerogenesis, factors other than acid define the quantity of gastric stress ulceration following acute spinal injury.
Pathogenetic role of Campylobacter pyloridis in gastric ulcer
Authors: HUI WAI‐MO , LAM SHIU‐KUM , CHAU PAT‐YIM , HO JOANA , LAU WAN‐YEE , POON KAR‐PANG , LAI CHING‐LUNG , ANNA SUK‐FONG LOK , LUI IRENE OI‐LIN , NG MATTHEW MA‐TAI
Published: March 2008

Recent reports of the occurrence of Campylobacter pyloridis in the stomach of patients with gastric ulcer have revived interest in the possible aetiological role of bacteria in this condition. To study the pathogenetic role of C. pyloridis in gastric ulcer, endoscopic biopsies, at least four from antrum, four from fundus and four, where appropriate, from the ulcer site, were taken from 28 non‐ulcer controls and 67 patients with gastric ulcer before and after complete healing of ulcer, following treatment with either enprostil or cimetidine for up to 8 weeks. The activity of gastritis as assessed by the degree of polymorph infiltration was graded blindly, by two independent pathologists, as nil, mild, moderate or severe. The presence of C. pyloridis was determined by smear and culture, and by Warthin Starry stain, and the bacterial density after staining was scored. The occurrence of C. pyloridis in the gastric antrum was not significantly different in gastric ulcer than in controls but was significantly (P < 0.005) more frequent in gastritic than in non‐gastritic mucosa. With gastric ulcer healing the activity of antral gastritis improved significantly (P < 0.05). Despite ulcer healing and improvement of gastritis, the frequency of occurrence and the density of C. pyloridis remained unchanged. It seems that C. pyloridis occurs frequently in gastritic mucosa, and does not affect the healing of gastric ulcer or improvement of gastritis, suggesting that it is unlikely to play a major pathogenetic role.
Nutritional factors in the aetiopathogenesis of amoebic liver abscess in man
Authors: RAINA N. , GANDHI B. M. , SHARMA M. P. , MITHAL S. , ACHARYA S. K. , TANDON B. N.
Published: March 2008

Thirty‐seven patients with amoebic liver abscess and 20 controls were studied for their nutritional status. Their dietary history suggested deficient intake of total calories, protein, fat, Vitamin A and β carotene. No significant difference was observed in the levels of iron intake in patients and controls.

Biochemical parameters suggested a hypoproteinemic state associated with low levels of cholesterol, VLDLc, HDLc, Vitamin A, β carotene, iron and TIBC in the patients in comparison to controls. The protein electrophoresis pattern showed an increase in α1, α2, and γ fractions in patients compared with controls, whereas the albumin fraction was reduced.

On the basis of these findings and previously published experimental studies, it is suggested that amoebic liver abscess in human subjects is associated with undernutrition due to a poorly balanced diet. Thus, undernutrition may facilitate invasive amoebiasis in man.