bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy.
Authors: Miguel-Garcia A , Matutes E , Tarin F , Garcia-Talavera J , Miguel-Sosa A , Carbonell F , Catovsky D
Published: June 2007

AIMS--To estimate the proportion and nature of the proliferating (Ki67+) circulating lymphocytes in a series of patients with multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) and to correlate this with other clinical and laboratory parameters, using blood from healthy adults as a control. To investigate the extent to which the B and T lymphoid components are involved in progression and/or control of disease. METHODS--Blood lymphocytes from 15 patients with multiple myeloma, 10 patients with MGUS and 10 healthy adults were analysed using a sequential double immunoenzymatic staining technique. Antibodies directed against Ki67 were used to detect cells in cycle, CD3, CD4, and CD8 to identify T cells, HLA-Dr as a marker for B cells and activated T cells, and CD11b as a marker for natural killer cells. Polyclonal antibodies directed against the kappa and lambda immunoglobulin light chains were also used to detect B cells. RESULTS--The proportion of proliferating (Ki67+) lymphocytes was significantly higher in patients with multiple myeloma (6.8 +/- 2.6) and MGUS (3.5 +/- 1.1) compared with the normal controls (1.69 +/- 0.3); this was also true when multiple myeloma and MGUS cases were compared. In multiple myeloma and MGUS over 50% of the Ki67+ cells were activated T lymphocytes (CD3+/HLA-Dr+); a minority (11%) were non-clonal B lymphocytes. In contrast to controls (6.7 +/- 1.9), in patients with multiple myeloma and MGUS the proportion of proliferating T cells expressing CD8 (23.6 +/- 12.5 and 15.3 +/- 7.7, respectively) and CD11b (13 +/- 8.7 and 11.6 +/- 3.9, respectively) was higher. In multiple myeloma there was a positive correlation between the proportion of Ki67+ lymphocytes, beta-2-microglobulin concentrations and disease stage. CONCLUSIONS--Although the number of patients investigated is small, this study suggests that Ki67 expression in blood lymphocytes from patients with multiple myeloma may be a good prognostic indicator for aggressive disease and may help to distinguish multiple myeloma from MGUS. The activated proliferating T cells in these diseases may represent an immunological reaction against the tumour.
Detection of Helicobacter pylori in gastric biopsy and resection specimens.
Authors: Ashton-Key M , Diss T C , Isaacson P G
Published: June 2007

AIMS: To compare the sensitivity of detecting Helicobacter pylori in gastric biopsy and resection specimens using tinctorial and silver impregnation stains, immunohistochemistry and the polymerase chain reaction (PCR). METHODS: Formalin fixed, paraffin wax embedded tissue from 33 gastric biopsy specimens (26 showing chronic gastritis and seven showing low grade mucosa associated lymphoid tissue (MALT) lymphoma) together with blocks of uninvolved mucosa from gastrectomy specimens for MALT lymphoma (five cases) were studied. Consecutive sections were stained using haematoxylin and eosin, Giemsa, the Warthin-Starry silver stain, and a polyclonal antibody directed against H pylori using an immunoperoxidase technique following heat induced antigen retrieval. PCR analysis of DNA extracted from a further section was carried out using primers which amplified a 411 base pair fragment of the urease A gene. RESULTS: H pylori was detected in 14 (37%) sections stained with haematoxylin and eosin, 21 (55%) with Giemsa, 23 (61%) with Warthin-Starry, and 25 (66%) stained with the antibody. Seventeen (45%) cases were positive on PCR. Immunohistochemistry was positive in all cases in which H pylori was detected by other methods. CONCLUSION: Immunohistochemistry using an immunoperoxidase technique following heat induced antigen retrieval for detecting H pylori in gastric biopsy and resection specimens is highly sensitive and easy to use.
Neuroendocrine differentiation in cervical carcinoma.
Authors: Savargaonkar P R , Hale R J , Mutton A , Manning V , Buckley C H
Published: June 2007

AIMS: To examine neuroendocrine differentiation, as shown by chromogranin A (CGA) expression, in cervical carcinomas. METHODS: Sixty seven cervical carcinomas were studied and were classified as adenocarcinomas, adenosquamous carcinomas or squamous cell carcinomas based on the assessment of haematoxylin and eosin staining and stains for mucin. Where features of glandular differentiation were identified, sections were also stained for evidence of intestinal type mucin. CGA immunostaining was done and the results were graded on a three point scale: 0, + (1-5% of cells positive) and ++ (> 5% of cells positive). These findings were then analysed with respect to lymph node status, tumour differentiation and clinical outcome. RESULTS: There were 32 adenocarcinomas, 18 adenosquamous carcinomas and 17 squamous cell carcinomas. Positive staining was seen in 14 (20.9%) cases, of which four were strongly positive. All but one case were either adenocarcinomas or adenosquamous carcinomas. There was a trend for CGA positivity to be related to intestinal differentiation but this failed to reach statistical significance. No correlation could be demonstrated between CGA staining and lymph node status, tumour differentiation and clinical outcome. CONCLUSIONS: Neuroendocrine differentiation is common in cervical carcinomas where there is evidence of glandular differentiation. Whilst the numbers in this study are relatively small, the presence of neuroendocrine cells in otherwise typical carcinomas does not seem to have any association with clinical behaviour.
Inflammatory pseudotumour of the mouth and maxilla.
Authors: Shek A W , Wu P C , Samman N
Published: June 2007

AIM: To describe the clinicopathological and immunophenotypical findings of two cases of inflammatory pseudotumour in the oral cavity. METHODS AND RESULTS: The patients presented with a short history of swelling in the cheek and the maxilla respectively. Magnetic resonance imaging or computerised tomography scan showed space occupying lesions with infiltrative margins which were interpreted as aggressive malignant neoplasms. Histological examination showed fascicles of spindle cells in a background of chronic reactive inflammatory cells including plasma cells, typical of inflammatory pseudotumour. The spindle cells were positive for vimentin, smooth muscle actin and CD68, but were negative for follicular dendritic cell markers. The lymphocytes showed no light chain restriction. CONCLUSIONS: Inflammatory pseudotumour in the oral cavity is completely benign and simple excision is curative. However, it may be confused with a malignant tumour on clinical and radiographic grounds, and histologically the appearances can also be misinterpreted as those of a more aggressive lesion. Its correct recognition by the surgical pathologist is important to avoid unnecessarily radical and potentially mutilating surgery.
Nosocomial empyema caused by Clostridium difficile.
Authors: Simpson A J , Das S S , Tabaqchali S
Published: June 2007

Pleural infection with Clostridium difficile is extremely rare. A case of nosocomial empyema following chest drain insertion in a 46 year old man is described. The potential of C difficile to cause extra-intestinal infections should be recognised and its isolation from other sites should not be ignored.
Gastroenteritis caused by Aeromonas trota in a child.
Authors: Reina J , Lopez A
Published: June 2007

A case of acute diarrhoea caused by Aeromonas trota (formerly HG 13 group) in a Spanish child is reported. The strain was isolated in the faeces using the CIN agar (cefsulodin-irgasan-novobiocin) culture media. The strain was initially identified as A sobria by the commercial GNI card and API 20E biochemical systems. The strain was, however, VogesProskauer and sucrose negative, so complementary tests of cellobiose fermentation and gluconate oxidation were performed. These tests, together with the strain susceptibility to ampicillin (MIC 1 microgram/ml) and carbenicillin (MIC < 16 micrograms/ml) led to the final identification of A trota. The microbiological characteristics of this new species and the principal tests required for its identification are presented. The isolation, for the first time, of A trota in the Mediterranean area confirms the suspected worldwide distribution of this species.
Accuracy of serology for the diagnosis of Helicobacter pylori infection--a comparison of eight kits.
Authors: Wilcox M H , Dent T H , Hunter J O , Gray J J , Brown D F , Wight D G , Wraight E P
Published: June 2007

AIMS: To determine the accuracy of eight commercially available kits for the serological diagnosis of Helicobacter pylori infection, and hence whether a serology service could be introduced to reduce endoscopy workload. METHODS: Eighty four patients newly presenting to their general practitioners with dyspepsia were recruited. Gold standard diagnosis of H pylori infection was obtained both by a histological examination of gastroduodenal biopsy specimens and by the 14C-urea breath test (UBT). The performance of six quantitative and two qualitative enzyme linked immunosorbent assays for H pylori IgG, used according to the manufacturers' instructions, with serum samples obtained during the endoscopy visit, were compared. RESULTS: The study population had a median age of 45 years, and the prevalence of H pylori infection was 35%. With one exception, where the patient had received a course of anti-H pylori treatment between endoscopy and UBT, there was 100% concordance in the results of the two gold standard techniques. Discordant serology results were more common in patients aged > 50 years (42% of the total) than in younger patients (21%), and this was most noticeable in uninfected patients. The sensitivity of the kits was good (90-100%), but specificity was more variable (76-96%), and the rate of equivocal results was unacceptably high in some cases (0-12%). The overall accuracy of the kits ranged from 83 to 98%. Two kits in particular performed well (Pylori-Elisa II, Bio-Whitaker and Premier, Launch; qualitative) with 98% and 100% accuracy, respectively. CONCLUSIONS: In a symptomatic population with a prevalence of H pylori infection of 35%, particularly in patients aged < 50 years, some but not all serology kits may be used as a highly accurate and inexpensive alternative to the gold standard techniques.
Monocyte activation in patients with non-seminomatous germ cell tumour of the testis before and after tumour eradication.
Authors: Trulson A , Nilsson S , Venge P
Published: June 2007

AIMS: To investigate the kinetics of normalisation of monocyte oxidative activity following tumour eradication. METHODS: Whole blood lucigenin enhanced chemiluminescence was studied in patients with non-seminomatous germ cell tumours. Group 1 comprised 14 patients who had been "cured" of their cancer (the term "cured" as used in this report denotes a relapse free period of at least three years). Group 2 comprised 15 patients who were followed from diagnosis to up to two years after the start of treatment. RESULTS: Lucigenin enhanced chemiluminescence of whole blood in the "cured" patients was similar to that of controls and lower than that in patients who had not yet received chemotherapy (group 2). After treatment, chemiluminescence decreased slowly and did not normalise until 18 months after the start of treatment. Tumour necrosis factor alpha (TNF alpha) concentrations were normal in "cured" patients but were raised in those who had not yet received treatment. TNF alpha was normalised 12 months after start of treatment. Alpha-fetoprotein concentrations were raised in most patients but normalised rapidly after tumour eradication. CONCLUSIONS: The activity of blood monocytes, as measured by whole blood lucigenin enhanced chemiluminescence, is increased in cancer. This activity may be a consequence of the presence of tumour cells. Immunocompetent cells remain active for over a year after eradication of the tumour.
Splenic macrophages in preterm infants: a necropsy study.
Authors: Variend S , Drummond A , Coombs R
Published: June 2007

AIMS: To study the frequency and nature of histiocytes in the splenic red pulp of infants who died following complicated immaturity/prematurity. METHODS: Twenty four preterm/immature infants were investigated. Frozen sections of formalin fixed splenic tissue were stained with Oil Red O. Paraffin wax sections from the same tissue were conventionally stained with haematoxylin and eosin. Immunohistochemistry was carried out for a number of macrophage markers. The administration of Intralipid was compared with the presence and extent of tissue macrophages. RESULTS: The spleens of 10 infants showed varying degrees of Oil Red O positivity ranging from mild to strong. In all these cases varying numbers of macrophages were confirmed in the splenic parenchyma in ordinary sections. The immunomarkers indicated that the histiocytes belonged to the macrophage phagocytic system. Of the 10 cases with splenic macrophages all had received Intralipid. Of those not receiving Intralipid none showed splenic macrophages. Seven had received Intralipid but did not have splenic macrophages; they had either only received small amounts of Intralipid or Intralipid was discontinued before death. CONCLUSIONS: Splenic macrophages are common at necropsy in immature/preterm infants. The macrophages are most lucidly demonstrated using Oil Red O staining in frozen sections. There is a strong association between the presence of splenic macrophages and Intralipid administration.
Costs and effectiveness of a nurse specialist anticoagulant service.
Authors: Taylor F C , Gray A , Cohen H , Gaminara L , Ramsay M , Miller D
Published: June 2007

AIMS: To determine the costs and effectiveness of an anticoagulant nurse specialist service compared with a conventional consultant service based on two hospital sites in northwest Hertfordshire. METHODS: Sequential design comparing retrospectively the conduct and outcomes of a consultant service with a nurse specialist service over two six month periods. In each of the six month study periods, all new patients consecutively referred for anticoagulation over a three month period (group A) at the start of each study period and a random selection of patients who had already been attending the anticoagulant service for one year or more (group B) were included in the study. Group A patients wre followed for up to three months and group B patients for six months. The main outcome measures were costs of service provision and effectiveness. Costs included those for the use of the anticoagulant service, those related to general practitioner (GP) visits and hospitalisations, and running costs (staff time, laboratory tests, patient transport). Measures of effectiveness were the mean proportion of time patients spend in the therapeutic range, the number of drugs being taken that could interact adversely and/or inhibit haemostatic function, and patient and GP satisfaction with service provision. RESULTS: In the consultant service, for group A there were more patients aged 66-75 years (p = 0.004) and fewer patients aged more than 76 years (p = 0.001); and for group B, there were fewer patients on anticoagulation for cardiac conditions (p = 0.001), but more on anticoagulation for thromboembolic conditions (p = 0.02) than in the nurse specialist service. The clinic running costs of the nurse specialist service were 4.99 Pounds per attendance, compared with 4.75 Pounds in the consultant service. Including all other costs related to treatment, there was no statistically significant difference in cost per patient. There was no significant difference in the proportion of time patients spent in the therapeutic range between the consultant service and the nurse specialist service. In the nurse specialist service, fewer patients in group A were taking drugs that could interact adversely and/or inhibit haemostatic function (p = 0.01) and more patients were satisfied with service provision (p = 0.04) compared with the consultant service. There was no significant variation in GP satisfaction between the two services. CONCLUSION: In the provision of outpatient anticoagulation, the nurse specialist service was no more expensive than the consultant service and, using our primary outcome, at least as effective. The nurse specialist service has some clear advantages compared to the consultant service: provision of domicilliary care for housebound patients, fewer new patients taking drugs that could interact adversely and/or inhibit haemostatic function patients, it is preferred by newly referred patients to the consultant service, and it is as acceptable to their GPs.
Expression of the interleukin 6 receptor in primary renal cell carcinoma.
Authors: Costes V , Liautard J , Picot M C , Robert M , Lequeux N , Brochier J , Baldet P , Rossi J F
Published: June 2007

AIMS: Interleukin 6 (IL-6) is expressed in the majority of renal cell carcinomas and has an important role in the proliferation of some renal cell carcinoma cell lines. This action is mediated by two membrane proteins, gp80 (the IL-6 receptor; IL-6R), which binds IL-6, and gp130, which transduces the signal. The soluble form of gp80 (sIL-6R) is able to activate gp130 when complexed to the IL-6 molecule. These considerations prompted an investigation of IL-6R expression in this malignancy. IL-6, C reactive protein (CRP), and sIL-6R were also measured in serum and correlated to clinical and pathological features. METHODS: Immunostaining was performed on cryostat sections from renal cell carcinoma tumours with M91, an anti-IL-6R monoclonal antibody, using the alkaline phosphatase antialkaline phosphatase technique. The proliferation index was measured using the KI-67 monoclonal antibody. CRP, IL-6, and sIL-6R were measured in serum before nephrectomy, using an immunoenzymatic or immunoradiometric assay. RESULTS: There were significant differences in survival in patients with tumours larger than 8 cm, metastasis at diagnosis, high nuclear grade tumours, detectable serum concentrations of IL-6 (correlated to CRP serum concentration), more than 4% proliferating cells, and the presence of the IL-6R in situ. Furthermore, the serum IL-6 concentration correlated with tumour size and stage. The mean serum sIL-6R concentration was not significantly different from that observed in 40 normal subjects. Tumour IL-6R expression was present in 10 samples. There was a significant association between the presence of the IL-6 receptor in tumours and tumour stage, nuclear grade, proliferation index, and serum IL-6. CONCLUSIONS: This study revealed the importance of IL-6/CRP and IL-6R expression in situ as potential new prognostic factors and opens the way to new therapeutic strategies in renal cell carcinoma.
HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of pleura.
Authors: Kennedy A D , King G , Kerr K M
Published: June 2007

AIMS: To determine the usefulness of antibodies HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of the pleura. METHODS: Using microwave antigen retrieval and streptavidin-biotin complex horseradish peroxidase immunohistochemistry the above antibodies were used to stain sections of 57 malignant mesotheliomas, 17 reactive pleural hyperplasias, 23 cases of carcinoma metastatic in pleura, 20 primary ovarian cell carcinomas, and 20 primary renal cell carcinomas. RESULTS: Eighty six per cent of mesotheliomas and 82% of reactive mesothelial hyperplasias stained strongly with HBME-1. However, 48% of carcinomas metastatic to pleura also stained, as did all serous ovarian carcinomas. Seventy two per cent of mesotheliomas and 24% of reactive mesothelial hyperplasias stained strongly with the antithrombomodulin antibody; 86% and 88%, respectively, of these cases showed staining of any type. While 26% of metastatic carcinomas showed some staining with antithrombomodulin, only one third of these (9%) showed strong, yet focal, staining. Of 40 ovarian and renal carcinomas only two (5%) showed any staining with antithrombomodulin. CONCLUSIONS: HBME-1, although a sensitive mesothelial marker, is not sufficiently specific to be useful diagnostically, as almost half of carcinomas metastatic to pleura also stained positive. Antithrombomodulin is also a sensitive mesothelial marker and is sufficiently specific to be a useful discriminator, positively identifying, in appropriate circumstances, the mesothelial nature of a cell population.
Micronutrients and immune function: some recent developments.
Authors: Thurnham D I
Published: June 2007

Micronutrient deficiencies probably have few direct effects on the functioning of immune cells. The main effect appears to be a reduction in cell mass that may indirectly affect immune cell function, particularly where T helper cell numbers are reduced. Results of many human studies are contradictory. Some of this contradiction may be accounted for by the fact that disease may lower concentrations of micronutrients in plasma that may be misinterpreted as deficiency. Low plasma vitamin A concentrations however appear to impair immune responsiveness and have deleterious effects on membrane integrity and mucosal function. Zinc may have similar effects on gut integrity and appears to be particularly useful in the treatment of acute diarrhoea. Low concentrations of other nutrients such as ascorbate and iron, may not necessarily impair immune function. Low plasma ascorbate may assist the removal of iron from plasma and low iron concentrations appear to increase the cytotoxicity of macrophages.
Expression of intestinal trefoil factor mRNA is downregulated during progression of colorectal carcinomas.
Authors: Uchino H , Kataoka H , Itoh H , Koono M
Published: June 2007

AIMS: Intestinal trefoil factor is a mucosa associated trefoil peptide expressed predominantly in the goblet cells of the small and large intestine. The aim of this work was to investigate the expression of the intestinal trefoil factor gene in human colorectal cancers. METHODS: The expression of intestinal trefoil factor mRNA was examined by northern blot analysis in 27 cases of surgically resected primary colorectal carcinoma of various stages. RESULTS: Although intestinal trefoil factor mRNA was expressed consistently in the tumours, the levels of expression varied considerably among the cases examined. The levels of expression were low in advanced stage tumours (Dukes's B, C, and D) compared with early stage tumours (Dukes's A) (p < 0.05). In addition, there was a tendency towards a positive correlation, albeit not well defined, between the amounts of intestinal trefoil factor mRNA and the histological differentiation of tumours. CONCLUSIONS: Intestinal trefoil factor mRNA was expressed consistently in the cases of colorectal carcinoma studied and expression was inversely associated with tumour progression.
Possible lethal enhancement of toxins from putative periodontopathogens by nicotine: implications for periodontal disease.
Authors: Sayers N M , Gomes B P , Drucker D B , Blinkhorn A S
Published: June 2007

AIM: To test the hypothesis that lethal synergy in the chick embryo model may occur between nicotine and bacterial products (cell-free extracellular toxins and cell lysates) of five putative periodontopathogens. METHODS: The lethality of cell-free extracellular toxins and cell lysates of five periodontal species was assessed with or without nicotine in the chick embryo assay system. Ten putative periodontopathogens (five species) were studied: Prevotella intermedia (n = 5), Porphyromonas gingivalis (n = 1), Porphyromonas asaccharolytica (n = 1), Fusobacterium nucleatum (n = 2), and Fusobacterium necrophorum (n = 1). RESULTS: Simultaneous testing of cell-free extracellular toxins from isolates W50, PS2, PS3, PS4, and PS5 and nicotine resulted in a percentage kill significantly greater than expected (Fisher's Exact test). Simultaneous testing of cell lysates from isolates W50, PS2, and PS5 and nicotine resulted in a percentage kill significantly greater than expected (Fisher's Exact test). CONCLUSIONS: Lethal synergy in the chick embryo model may occur between nicotine and toxins from putative periodontopathogens (both cell-free extracellular toxins and cell lysates). This may be an important mechanism by which smoking increases the severity of periodontal disease.
Distribution of endogenous tumour necrosis factor alpha in gliomas.
Authors: Maruno M , Kovach J S , Kelly P J , Yanagihara T
Published: June 2007

AIMS: To determine the distribution and cellular origin of endogenous tumour necrosis factor alpha (TNF alpha) in the cellular components of human gliomas. METHODS: Frozen sections of 26 gliomas (four astrocytomas (As); two oligoastrocytomas (OA); one ansplastic astrocytoma (AA); one anaplastic oligoastrocytoma (AOA); 18 glioblastomas (GB)) were examined immunohistochemically using antihuman TNF alpha and anti-Leu-M5 (CD11c) antibodies. Additional studies with double immunohistocchemical procedures were performed with anti-glial fibrillary acidic protein and anti-neurofilament antibodies. RESULTS: Eighty per cent of the AA, AOA, and GB (16 of 20) had a positive reaction for TNF alpha, but only 17% of As and OA (one of six) were positive. Positive cells were seen in both the tumour tissue and adjacent brain tissues. TNF alpha protein was detected not only in the tumour cells but also in the endothelium of tumour vessels as well as reactive astrocytes and neurons. CONCLUSIONS: Endogenous TNF alpha is present in cells of various origins in glial tumours including tumour vessels; however, the role of TNF alpha may be different in different types of cells or altered microenvironment.
Permeability of homotypic and heterotypic gap junction channels formed of cardiac connexins mCx30.2, Cx40, Cx43, and Cx45
Authors: Rackauskas Mindaugas , Verselis Vytas K. , Bukauskas Feliksas F.
Published: June 2007

We examined the permeabilities of homotypic and heterotypic gap junction (GJ) channels formed of rodent connexins (Cx) 30.2, 40, 43, and 45, which are expressed in the heart and other tissues, using fluorescent dyes differing in net charge and molecular mass. Combining fluorescent imaging and electrophysiological recordings in the same cell pairs, we evaluated the single-channel permeability ( Pγ). All homotypic channels were permeable to the anionic monovalent dye Alexa Fluor-350 (AF350), but mCx30.2 channels exhibited a significantly lower Pγthan the others. The anionic divalent dye Lucifer yellow (LY) remained permeant in Cx40, Cx43, and Cx45 channels, but transfer through mCx30.2 channels was not detected. Heterotypic channels generally exhibited Pγvalues that were intermediate to the corresponding homotypic channels. Pγvalues of mCx30.2/Cx40, mCx30.2/Cx43, or mCx30.2/Cx45 heterotypic channels for AF350were similar and approximately twofold higher than Pγvalues of mCx30.2 homotypic channels. Permeabilities for cationic dyes were assessed only qualitatively because of their binding to nucleic acids. All homotypic and heterotypic channel configurations were permeable to ethidium bromide and 4,6-diamidino-2-phenylindole. Permeability for propidium iodide was limited only for GJ channels that contain at least one mCx30.2 hemichannel. In summary, we have demonstrated that Cx40, Cx43, and Cx45 are permeant to all examined cationic and anionic dyes, whereas mCx30.2 demonstrates permeation restrictions for molecules with molecular mass over ∼400 Da. The ratio of single-channel conductance to permeability for AF350was ∼40- to 170-fold higher for mCx30.2 than for Cx40, Cx43, and Cx45, suggesting that mCx30.2 GJs are notably more adapted to perform electrical rather than metabolic cell-cell communication.
Heparin-binding EGF-like growth factor mediates oxyhemoglobin-induced suppression of voltage-dependent potassium channels in rabbit cerebral artery myocytes
Authors: Koide Masayo , Penar Paul L. , Tranmer Bruce I. , Wellman George C.
Published: June 2007

Oxyhemoglobin (OxyHb) can suppress voltage-dependent K+ channel (KV) currents through protein tyrosine kinase activation, which may contribute to cerebral vasospasm following subarachnoid hemorrhage. Here we have tested the hypothesis that shedding of heparin-binding EGF-like growth factor (HB-EGF) and the resulting activation of the tyrosine kinase EGF receptor (EGFR) underlie OxyHb-induced KV channel suppression in the cerebral vasculature. With the use of the conventional whole cell patch-clamp technique, two EGFR ligands, EGF and HB-EGF, were found to mimic OxyHb-induced KV suppression in rabbit cerebral artery myocytes. KV current suppression by OxyHb or EGF ligands was eliminated by a specific EGFR inhibitor, AG-1478, but was unaffected by PKC inhibition. Compounds (heparin and CRM-197) that specifically interfere with HB-EGF signaling eliminated OxyHb-induced KV suppression, suggesting that HB-EGF is the EGFR ligand involved in this pathway. HB-EGF exists as a precursor protein that, when cleaved by matrix metalloproteases (MMPs), causes EGFR activation. MMP activation was detected in OxyHb-treated arteries by gelatin zymography. Furthermore, the MMP inhibitor (GM-6001) abolished OxyHb-induced KV current suppression. We also observed KV current suppression due to EGFR activation in human cerebral artery myocytes. In conclusion, these data demonstrate that OxyHb induces MMP activation, causing HB-EGF shedding and enhanced EGFR activity, ultimately leading to KV channel suppression. We propose that EGFR-mediated KV suppression contributes to vascular pathologies, such as cerebral vasospasm, and may play a more widespread role in the regulation of regional blood flow and peripheral resistance.
Effects of cardiogenic edema fluid on ion and fluid transport in the adult lung
Authors: Gandhi Shephali G. , Rafii Bijan , Harris Michael S. , Garces Alexandra , Mahuran Don , Chen Xi-Juan , Bao Hui-Fang , Jain Lucky , Eaton Douglas C. , Otulakowski Gail , O'Brodovich Hugh
Published: June 2007

We have previously shown that cardiogenic pulmonary edema fluid (EF) increases Na+ and fluid transport by fetal distal lung epithelia (FDLE) (Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM and O'Brodovich H. J Physiol 544: 537–548, 2002). We now report the effect of EF on Na+ and fluid transport by the adult lung. We first studied primary cultures of adult type II (ATII) epithelium and found that overnight exposure to EF increased Na+ transport, and this effect was mainly due to factors other than catecholamines. Plasma did not stimulate Na+ transport in ATII. Purification of EF demonstrated that at least some agent(s) responsible for the amiloride-insensitive component resided within the globulin fraction. ATII exposed to globulins demonstrated a conversion of amiloride-sensitive short-circuit current ( Isc) to amiloride-insensitive Isc with no increase in total Isc. Patch-clamp studies showed that ATII exposed to EF for 18 h had increased the number of highly selective Na+ channels in their apical membrane. In situ acute exposure to EF increased the open probability of Na+-permeant ion channels in ATII within rat lung slices. EF did increase, by amiloride-sensitive pathways, the alveolar fluid clearance from the lungs of adult rats. We conclude that cardiogenic EF increases Na+ transport by adult lung epithelia in primary cell culture, in situ and in vivo.
Transgenic RNA Interference in Mice
Authors: Gao Xue , Zhang Pumin
Published: June 2007

The discovery that small interfering RNA duplexes (siRNA) can silence gene expression in mammalian cells has revolutionized biomedical research. The most successful application of the discovery has been to study gene function in cultured human or mouse cells. However, the knockdown effect of siRNA is only transient. To achieve a more sustained gene-silencing effect, shRNA (small hairpin RNA) expressed from a vector is preferred. An additional benefit of shRNA is that RNA interference (RNAi) can now be applied in vivo through delivering shRNA-expressing vectors by transgenic technology. Transgenic RNAi not only allows the study of biological processes not present in cultured cells but also offers chronic therapeutic potentials. In this review, we will summarize the developments in the generation of transgenic RNAi mice.
A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases
Authors: Luyendyk James P. , Piper J. Daniel , Tencati Michael , Reddy K. Veera , Holscher Todd , Zhang Rong , Luchoomun Jayraz , Chen Xilin , Min Wang , Kunsch Charles , Mackman Nigel
Published: June 2007

Objective—

Oxidative stress contributes to the pathogenesis of many diseases, including atherosclerosis and sepsis. We have previously described a novel class of therapeutic compounds with antioxidant and antiinflammatory properties. However, at present, the intracellular targets of these compounds have not been identified. The purpose of this study was to elucidate the mechanism by which 2 structurally-related antioxidants (AGI-1067 and AGI-1095) inhibit LPS induction of tissue factor (TF) expression in human monocytic cells and endothelial cells.

Methods and Results—

We found that succinobucol (AGI-1067) and AGI-1095 inhibited LPS induction of TF expression in both monocytic cells and endothelial cells. These compounds also reduced LPS induction of nuclear AP-1 and expression of Egr-1 without affecting nuclear translocation of NF-κB. Importantly, these antioxidants inhibited LPS activation of the redox-sensitive kinase, apoptosis signal-regulating kinase-1 (ASK1) and the mitogen-activated protein kinases (MAPKs) p38, ERK1/2, and JNK1/2.

Conclusions—

AGI-1067 and AGI-1095 inhibit TF gene expression in both monocytic cells and endothelial cells through a mechanism that involves the inhibition of the redox-sensitive MAP3K, ASK1. These compounds selectively reduce the activation/induction of MAPK, AP-1, and Egr-1 without affecting NF-κB nuclear translocation.
The Extracellular Matrix in Wound Healing: A Closer Look at Therapeutics for Chronic Wounds
Authors: Agren Magnus S. , Werthen Maria
Published: June 2007

Disappointing results with the use of exogenous recombinant growth factors in chronic wounds have redirected the focus to the extracellular matrix (ECM). Newer research has clearly changed our view on the role of the ECM in tissue repair and dismissed the dogma that the sole function of ECM is a passive physical support for cells. It is now clear that intact or fragmented ECM molecules are capable of transducing signals pivotal for cell processes in wound healing primarily via integrin interactions in concert with growth factor activation. In addition, our knowledge about ECM molecules in minute concentrations with biological activity, but devoid of significant structural influence, is increasing. This article reviews the multifaceted molecular roles of ECM in the normal wound-healing process and some molecular abnormalities in chronic wounds, and touches on potential therapies based on the developments of tissue biology.
Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants
Authors: Imanishi Daisuke , Miyazaki Yasushi , Yamasaki Reishi , Sawayama Yasushi , Taguchi Jun , Tsushima Hideki , Fukushima Takuya , Yoshida Shinichiro , Sasaki Hiroshi , Hata Tomoko , Tomonaga Masao
Published: June 2007

To examine whether donor-derived cells could exist in nonhematopoietic tissues of recipients after allogeneic hematopoietic stem-cell transplantation, we examined the patterns of the short tandem repeat (STR) of DNA extracted from fingernail clippings of recipients so that the contamination of blood cells was excluded. All 21 patients reached donor-derived hematopoiesis after transplantation and 20 of them were in remission of the primary diseases at the time of sampling. Compared with the STRs of donor cells, among 9 of 21 patients, DNA extracted from fingernail samples showed coexistence of the donor pattern of the STRs, sharing from 8.9% to 72.9% of total STR areas. Time from transplantation to sampling was from 305 to 2399 days among positive cases. These results demonstrate for the first time the existence of stable contribution of donor cells in fingernails among recipients of allogeneic hematopoietic stem cells.
Expression of LIM kinase 1 is associated with reversible G1/S phase arrest, chromosomal instability and prostate cancer
Authors: Davila Monica , Jhala Darshana , Ghosh Debashis , Grizzle William E , Chakrabarti Ratna
Published: June 2007

Background

LIM kinase 1 (LIMK1), a LIM domain containing serine/threonine kinase, modulates actin dynamics through inactivation of the actin depolymerizing protein cofilin. Recent studies have indicated an important role of LIMK1 in growth and invasion of prostate and breast cancer cells; however, the molecular mechanism whereby LIMK1 induces tumor progression is unknown. In this study, we investigated the effects of ectopic expression of LIMK1 on cellular morphology, cell cycle progression and expression profile of LIMK1 in prostate tumors.

Results

Ectopic expression of LIMK1 in benign prostatic hyperplasia cells (BPH), which naturally express low levels of LIMK1, resulted in appearance of abnormal mitotic spindles, multiple centrosomes and smaller chromosomal masses. Furthermore, a transient G1/S phase arrest and delayed G2/M progression was observed in BPH cells expressing LIMK1. When treated with chemotherapeutic agent Taxol, no metaphase arrest was noted in these cells. We have also noted increased nuclear staining of LIMK1 in tumors with higher Gleason Scores and incidence of metastasis.

Conclusion

Our results show that increased expression of LIMK1 results in chromosomal abnormalities, aberrant cell cycle progression and alteration of normal cellular response to microtubule stabilizing agent Taxol; and that LIMK1 expression may be associated with cancerous phenotype of the prostate.
Depression, Immunity, and Survival in Patients With Hepatobiliary Carcinoma
Authors: Steel Jennifer L. , Geller David A. , Gamblin T. Clark , Olek Marion C. , Carr Brian I.
Published: June 2007

Purpose

The aims of the present study were to assess the prevalence of depressive symptoms at diagnosis, test the association between depressive symptoms and survival, and preliminarily test a mediational model of depression, immunity, and survival in patients with hepatobiliary carcinoma (HBC).

Patients and Methods

One hundred one patients diagnosed with HBC were prospectively studied. Depressive symptoms were measured at diagnosis using the Center for Epidemiological Studies Depression Scale (CES-D). Sociodemographic and disease-specific data were gathered from the patients' charts. In a subsample of patients, stress; alcohol, tobacco, and drug use; sleep quality; physical activity; social support; natural killer (NK) cell number and cytotoxicity; and plasma levels of interleukin (IL) -4, IL-5, tumor necrosis factor alpha, and interferon gamma were measured. Survival was measured from date of diagnosis to death.

Results

At diagnosis, 37% of patients reported a CES-D score of ≥ 16 (clinical range). Using Cox regression analysis, sociodemographic and disease-specific variables and CES-D score significantly predicted survival (Breslow χ2= 32.4, P = .006). Only vascular invasion (P = .001) and CES-D score ≥ 16 (P = .03) were significant predictors. In a subsample of 23 patients, patients who reported a CES-D score of ≥ 16 were found to have significantly lower NK cell numbers than patients who reported a CES-D score of less than 16 (F1,21= 9.39, P = .003). A robust trend was found in which NK cell number was associated with survival. A mediational model linking depressive symptoms and survival, with NK cell number as a mediator, was preliminarily supported.

Conclusion

Secondary to the high prevalence of depressive symptoms and impact on survival, psychological and pharmacologic interventions should be designed and implemented in patients diagnosed with HBC.
Book Reviews
Authors: Stohlman Sarah Michelle , Szczepaniková Alice , Ignaczak Ewa , Visser Oane , Scholliers Peter , van der Geest Sjaak , Vermeulen Hans , Płonka Tomasz , TImmer Jaap , Salemink Oscar
Published: June 2007

Sarah Ahmed, Claudia Castañeda, Anne-Marie Fortier, and Mimi Sheller (eds.), Uprootings/regroundings: questions of home and migration

Susanne Binder and Jelena Tošič (eds.), Refugee studies and politics: human dimensions and research perspectives, and Philomena Essed, Georg Frerks, and Joke Schrijvers (eds.), Refugees and the transformation of societies: agency, policies, ethics and politics

Paul John Eakin (ed.), The ethics of life writing

Chris Hann and the ‘Property Relations’ group, The postsocialist agrarian question: property relations and the rural condition

Anne J. Kershen (ed.), Food in the migrant experience

Michael Lambek and Paul Antze (eds.), Illness and irony: on the ambiguity of suffering in culture

Cristóbal Mendoza, Labour immigration in Southern Europe: African employment in Iberian labour markets

Thomas Carl Patterson, Marx’s ghost: conversations with archaeologists

Adam Reed, Papua New Guinea’s last place: experiences of constraint in a postcolonial prison

Shinji Yamashita and J. S. Eades (eds.), Globalization in Southeast Asia: local, national and transnational perspectives
Comments on Reyna
Authors: Friedman Jonathan
Published: June 2007

How refreshing to see this piece after so much language poured onto the pages of journals and books to demonstrate that we are in an entirely new universe, a millennial capitalism where globalization finally reigns supreme. Reyna is old-fashioned for many. He uses Marx and even, God help us, Lenin, whom he attempts to rescue by finding another route to the same conclusions concerning the highest stage of capitalism or at least the inevitability of imperialist wars.
Glarner Waldwirtschaft im letzten Viertel des 20. Jahrhunderts | Glarner Forest Management in the last quarter of the 20th Century
Authors: Marti Fritz
Published: June 2007

Looking back on the last quarter of the 20th century, we see that the most striking changes in forest management have come about following large and frequent catastrophes. Management– concerned solely with wood production in former times – is oriented more towards retaining stability of the stands nowadays. In addition, the aspect of tending and improving the environment continues to gain ground. The growing gap between expenditure and profit is particularly acute in Glarner mountain forest areas. The extension of promotional silvicultural measures, which widely determines today's management, is to be seen as a logical consequence.
Risikoanalyse und Kostenwirksamkeit bei der Massnahmenplanung – Beispiel Diesbach | Risk analysis and cost efficiency of measure planning – the example of Diesbach
Authors: Gächter Markus , Bart Rolf
Published: June 2007

The region under survey around Diesbach takes in an area of approx. 11.7 km2. Along the perimeter are former rubble and refuse heaps, as well as a number of the typical side channels arising from the protrusions of debris of more recent times. In keeping with the high water flows, along a stretch of about 300 m the Diesbach is channelled along a plaster-coated basin. An integral project, set up in 2000, had the aim of producing a concept for measures to be taken to reduce risk based on a comprehensive hazard and risk analysis. In addition, the project called for the cost efficiency of measures.

The elaboration of the project followed guideline set out by the Canton for the protection from natural hazards. Risk analysis,as an instrument of projects aimed at natural hazards, lies at the centre of these guidelines, because it is inadequate to merely identify changes in danger levels. The risk posed by the Diesbach is expressed in an annual expected damage value of approx. 120 000 Swiss francs. The measure concept will cost approx. 1.6 million Swiss francs and takes into account the problem of loose deposit as well as driftwood with a cost/earning ratio of about 2. The project shows the advantages of a risk-based solution in an exemplary way.
Forstliche Betriebsabrechnung im Kanton Glarus | Forest enterprise accounts in the canton of Glarus
Authors: Rast Fridolin
Published: June 2007

The economic development of forest enterprises in the canton of Glarus can be illustrated using more or less complete accounts, which go back for more than 10 years and clearly demonstrate the need for subsidies. Losses, of wood production and protective function, (300–400 Swiss francs per ha,without subsidies) remained unchanged following the damage caused by hurricane Vivian in 1992, albeit with diminishing yield and lower subsidies. This means that, since 1996,owners have carried considerable losses themselves. The concentration process towards large-scale forest enterprises has begun and financial problems could force communities to accelerate this process. The main goal is to maintain the protective function of the forest and boost the regional forest economy if wood, as a product, is not to be relegated to the background.
Kantonale Ausführungsgesetzgebungen zum eidgenössischen Waldgesetz – ein Überblick | Cantonal execution regulations of the Federal Forest Law – an overview
Authors: Seitz Andreas , Zimmermann Willi
Published: June 2007

Ten years after the Federal Forest Law came into force all cantons have adjusted their execution regulations to fit the new Federal Laws. The legislative steps taken by the cantons have led to a considerable standardisation of Forest Law, in both formal and material procedures. In the near future there are no major legislative activities to be expected at the cantonal level. In future the emphasis will lie in the implementation and execution of Cantonal and Federal Forest Law.
A statistical approach to logical inference in endocrine physiopathology
Authors: Thiry S. , Bouckaert A.
Published: June 2007

A combined logical‐statistical approach is suggested here for endocrine physiopathological inference. The prior knowledge of the endocrine system is formalized by a Boolean model. Boolean equations are solved to estimate prior probability distributions. A Bayesian strategy, taking into account the observational errors, is used to solve a specific endocrine problem.
Condorcet — a man of the avant‐garde
Authors: Michaud Pierre
Published: June 2007

In 1785 Condorcet proposed a method to aggregate qualitative data, but until very recently this method was attributed to contemporary authors and its importance completely neglected.
Diagnosing departures from stability in a multidimensional multivariate system
Authors: Gheva David
Published: June 2007

This paper deals with a system containing n m‐variable elements measured at p points of time. The data matrices for each point of time are represented by the biplot technique. Each biplot provides a map of the system which can be used to determine visually the relations between the elements and variables. The biplots are then compared by superimposing them to obtain an ‘aggregate’ graph. Differences between the biplots indicate departure from stability of the system. An example drawn from the Israeli banking system is provided.
Subjective probability and causality assessment
Authors: Lane David A.
Published: June 2007

Serious adverse reactions to a drug usually occur too rarely to be identified in the clinical trials required to demonstrate efficacy before the drug can be put on the market. Instead, they are generally first encountered in the uncontrolled world of everyday clinical practice, and the industrial and national regulatory agencies that are responsible for drug safety must rely for their first indications of a possible drug‐adverse event connection on case reports submitted to them by practitioners who observe an occurrence of the event in one of their patients taking the drug. A typical situation in the work of these agencies finds a group of experts assembled around a table reviewing a small series of case reports (perhaps as small as one!) that link a particular drug with a particular type of adverse event. The experts want to determine whether, for each case in their series, the available evidence indicates that the drug caused the adverse event to occur. How are they to proceed? This paper outlines an approach to this problem, based on the use of subjective probability.