Discontinuous anchoring transition and photothermal switching in composites of liquid crystals and conducting polymer nanofibers.

We prepared nanocomposites of a nematic liquid crystal and nanofibers of a conducting polymer (polyaniline). All the nanocomposites exhibit a discontinuous surface anchoring transition from planar to homeotropic in the nematic phase on a perfluoropolymer coated surface with a thermal hysteresis (≈ 5.3 °C). We observe a relatively large bistable conductivity and demonstrate a light driven switching of conductivity and dielectric constant in dye doped nanocomposites in the thermal hysteresis (bistable) region. The experimental results have been explained based on the reorientation of the nanofibers driven by the anchoring transition of the nematic liquid crystal. We show a significant enhancement of the bistable temperature range (≈ 13 °C) by an appropriate choice of compound in the binary system.

A clinical decision support system using multilayer perceptron neural network to assess well being in diabetes.

BACKGROUND: Diabetes mellitus is an increasingly common life-style disorder whose management outcomes are measured in symptomatic, biochemical as well as psychological areas. Well being as an outcome of treatment is being increasingly recognized as a crucial component of treatment. There is little published literature on psychosocial outcomes and the factors influencing them. Therefore we have developed a neural network system which is trained to predict the well being in diabetes, using data generated in real life. MATERIAL AND METHODS: We developed a Multi Layer Perceptron Neural Network model, which had been trained by back propagation algorithm. Data was used from a cohort of 241 individuals with diabetes. We used age, gender, weight, fasting plasma glucose as a set of inputs and predicted measures of well-being (depression, anxiety, energy and positive well-being). RESULTS: It was observed that female patients report significantly higher levels of depression than their male counter parts. Some slight high or no significant differences are observed between males and female patients with regard to the number of persons with whom they share their anxieties and fears regarding diabetes. There is not much difference has been observed in energy levels of both males and females. Also, Males have higher pwb value when compared with the female counterparts. Also, this may be due to women tend to react more emotionally to disease and hence experience more difficulty in coping with it. The present sample of women being predominantly house wives may be worrying more about their health and its problems. Also, it is observed that, gender differences are significant with regard to total general well-being. With five inputs (age, sex, weight, fasting plasma glucose, bias), four outputs are four (depression, anxiety, energy and positive well-being) the momentum rate was 0.9, the learning rate 0.7, using a sample of 50. the maximum individual error is 0.001 when the number of iterations were 500, number of hidden layers is 1 and the number of units in the hidden layer are 6, the normalized system error was 470.57. With input samples of 100, 150 and 200, keeping the other variables constant, the normalized system error was 419.61, 359.67 and 332.32 respectively. Similar values are found for the normalized system error when the number of units in the hidden layer have been increased to 7, 8 and 9 respectively. With two hidden layers, and with each hidden layer containing 6,7 ,8, 9, 10, 11 units for the samples 50, 100, 150, and 200, the same values of normalized system error was found. Women having weight between 40 kgs and 85kgs had higher levels of depression than men who had weight between 39kgs and 102 kgs. CONCLUSION: We have developed a prototype neural network model to predict the psychosocial well-being in diabetes, when biological or biographical variables are given as inputs. When greater data was fed to the system, the normalized system error can be reduced.

Effect of perioperative steroid therapy on the postoperative course of patients with oesophageal cancer.

BACKGROUND: Perioperative steroid therapy is often used in oesophageal cancer surgery and we evaluate the effect of this therapy on the secretory leukocyte protease inhibitor levels in the lungs (a major antiprotease in the conducting airways) and postoperative course in oesophageal cancer patients. METHODS: Twenty-one patients operated on for oesophageal cancer in 2003-2004 were treated with perioperative steroid therapy (250 mg of methylprednisolone intravenously 1 h before the operation). Fifteen consecutive patients operated on in 2002 served as a control group. Secretory leukocyte protease inhibitor in bronchoalveolar lavage fluid and the postoperative course in the two groups were compared. RESULTS: The mortality rate was 0% and there was no significant difference in the morbidity rate between the two groups. Days of intubation and systemic inflammatory response syndrome were significantly shorter for the steroid group. The bronchoalveolar lavage fluid secretory leukocyte protease inhibitor level was significantly higher in the steroid group than in the control group on postoperative days 2 and 3. The secretory leukocyte protease inhibitor level on postoperative day 3 was remarkably lower for the patients intubated for > or = 5 days and for those with pulmonary complications. CONCLUSION: Perioperative steroid therapy increased the bronchoalveolar lavage fluid secretory leukocyte protease inhibitor level and reduced the days of intubation and systemic inflammatory response syndrome in patients with oesophagectomy.

Interferon-gamma and granulocyte colony-stimulating factor in bronchoalveolar lavage fluid after oesophagectomy.

BACKGROUND: Activated polymorphonuclear leucocytes play a pivotal role in pulmonary complications after oesophagectomy. A lot of inflammatory mediators including interferon-gamma and granulocyte colony-stimulating factor are reported to modify the life span of polymorphonuclear leucocytes. AIMS: In this study we investigated whether interferon-gamma and granulocyte colony-stimulating factor are associated with pulmonary complications after oesophagectomy. PATIENTS AND METHODS: We measured interferon-gamma and granulocyte colony-stimulating factor concentrations in bronchoalveolar lavage fluid of 37 patients who had undergone oesophagectomy and examined the relationship between these mediators and pulmonary complications. RESULTS: Pulmonary complications occurred in nine patients (24%, Pneum(+)). There was no significant difference in age, gender, preoperative comorbid conditions, tumour stage, operation method, operating time or blood loss between the Pneum(+) group and another 28 patients(Pneum(-)). Days until extubation were significantly increased in the Pneum(+) group than in the Pneum(-) group. Interferon-gamma (on postoperative day 2) and granulocyte colony-stimulating factor (on postoperative days 1-3) in bronchoalveolar lavage fluid were significantly increased in the Pneum(+) group than in the Pneum(-) group and granulocyte colony-stimulating factor was significantly correlated with days until extubation. CONCLUSIONS: Our results indicate that bronchoalveolar lavage fluid granulocyte colony-stimulating factor is associated with respiratory conditions after oesophagectomy and assaying it can be useful for predicting pulmonary complications.

An immunohistochemical study of TIMP-3 expression in oesophageal squamous cell carcinoma.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. We have investigated the relationship between TIMP-3 reduction and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 90 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Immunostaining of TIMP-3 was seen in the cytoplasm of cancer cells and normal oesophageal epithelial cells, particularly in cells located in shallow areas of the tumour. TIMP-3 preserved (+), moderate (+/-), and reduced (-) cases accounted for 30, 27, and 33 of the 90 patients, respectively (33, 30, 37%). Significant correlations were observed between TIMP-3 expression and depth of tumour invasion (P=0.001), number of lymph node metastases (P=0.003), infiltrative growth pattern (P=0.003), and disease stage (P=0.005). The survival rates of patients with TIMP-3 (-) cancer were significantly lower than those of patients with TIMP-3 (+) and TIMP-3 (+/-) cancer (P=0.0003). The mean 5-year survival rates of patients with TIMP-3 (+), (+/-), and (-) were 50, 58, and 21%, respectively. In conclusion, decreased expression of TIMP-3 protein correlates with invasive activity and metastasis. This makes the prognosis for patients with cancer that has lost TIMP-3 significantly less favourable than that for patients with cancer that has maintained TIMP-3.

Value of positron emission tomography in the diagnosis of recurrent oesophageal carcinoma.

BACKGROUND: Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) might be useful for staging oesophageal squamous cell carcinoma (SCC). FDG-PET may be more accurate than computed tomography (CT) in diagnosing lymph node metastasis. This retrospective study compared the ability of FDG-PET and CT to diagnose recurrent oesophageal carcinoma. METHODS: Fifty-five patients with thoracic oesophageal SCC who had undergone radical oesophagectomy were studied. The accuracy of FDG-PET and CT in detecting recurrence during follow-up was calculated using data from the first images generated by either modality that suggested the presence of recurrent disease. Lesions deemed to be equivocal on these scans were considered as positive for recurrence. RESULTS: Twenty-seven of the 55 patients had recurrent disease in a total of 37 organs. Locoregional recurrence was observed in 19 patients (35 per cent). Distant recurrent disease occurred in 15 patients (27 per cent) in 18 organs. Six patients had recurrence in the liver, four in the lung, six in bone and two in distant lymph nodes. FDG-PET showed 96 per cent sensitivity, 68 per cent specificity and 82 per cent accuracy in demonstrating recurrent disease. The corresponding values for CT were 89, 79 and 84 per cent. The sensitivity of FDG-PET was higher than that of CT in detecting locoregional recurrence, but its specificity was lower because of FDG uptake in the gastric tube and thoracic lymph nodes. In distant organs the sensitivity of PET in detecting lung metastasis was lower than that of CT, but its sensitivity for bone metastasis was higher. CONCLUSION: FDG-PET has a larger field than CT. Combined PET-CT would appear to be an appropriate modality for the detection of recurrent oesophageal cancer.

CT is useful for identifying patients with complicated appendicitis.

BACKGROUND AND AIMS: We often come across patients with complicated appendicitis (perforation, abscess formation, or peritonitis) and it is essential to get accurate and detailed information on these patients preoperatively. In this study, we investigated whether or not preoperative computed tomography is useful for identifying these patients. PATIENTS AND METHODS: Plain and intravenously-contrasted helical computed tomography was obtained preoperatively in 94 (75%) of 125 patients who underwent appendectomy. Twenty-eight (30%) of the 94 patients had complicated appendicitis (Compli(+) group). We compared clinical factors and computed tomography findings of the Compli(+) group with those of 66 other patients (Compli(-) group). RESULTS: There was no significant difference between the Compli(+) and Compli(-) groups in gender, white blood cell count, the present rate of an enlarged appendix, or appendicolith. Fat stranding and free fluid on computed tomography were significantly associated with complicated appendicitis by both univariate and multilogistic regression analysis. Fourteen (70%) of the 20 patients with fat stranding and free fluid on computed tomography had complicated appendicitis and only 1 (4%) of the 28 Compli(+) patients had neither fat stranding nor free fluid on computed tomography. CONCLUSION: Our study has indicated that fat stranding and free fluid on computed tomography are significant for complicated appendicitis and helical computed tomography is a powerful tool for identifying patients with complicated appendicitis preoperatively.

FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma.

Focal adhesion kinase (p125(FAK); 'FAK') is a tyrosine kinase that is localised to cellular focal adhesions and is associated with a number of other proteins, such as integrin adhesion receptors. We performed an immunohistochemical analysis of FAK protein expression to determine the relationship between FAK overexpression and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 91 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Seven human ESCC cell lines-TE-1, TE-2, TE-8, TE-13, TE-15, TT, and TTn-and one immortalized human keratinocyte cell line-HaCaT-were used in Western blot analysis. Immunostaining of FAK was seen in the cytoplasm of cancer cells, particularly in cells located in the invasive fronts of cancer nests. FAK overexpression was detected in 54 of the 91 patients (59.3%). Significant correlations were observed between FAK overexpression and cell differentiation (P=0.0057), depth of tumour invasion (P=0.0023), presence of regional lymph node metastasis (P=0.0097), number of lymph node metastases (P=0.0026), and disease stage (P=0.012). The survival rates of patients with FAK-overexpressing cancer were significantly lower than those of patients without FAK-overexpression cancer (P=0.006). The 5-year survival rate of patients without FAK overexpression was 69%, whereas that of patients with FAK overexpression was 38%. On Western blot analysis, FAK was expressed at a high level in TE-1, TE-8, TE-15, and TT cells, at a moderate level in TE-2 and TTn cells, and at a low level in TE13 and HaCaT cells. FAK phosphorylation at tyrosine 397 was demonstrated in proportion to the intensity of FAK in all cell lines except TE15 and HaCaT. In conclusion, FAK overexpression of ESCC was related to cell differentiation, tumour invasiveness, and lymph node metastasis. Consequently, patients with ESCC who had FAK overexpression had a poor prognosis.

Seven-day triple therapy with omeprazole, amoxycillin and clarithromycin for Helicobacter pylori infection in haemodialysis patients.

BACKGROUND: Triple therapy is accepted as the treatment of choice for Helicobacter pylori eradication, but there is no consensus on how long the therapy should be maintained in haemodialysis (HD(+)) patients. Our aims in this study were to evaluate the safety and efficacy of the 7-day triple therapy in HD(+) patients. METHOD: Forty-seven HD(+) and 55 HD(-) patients with dyspepsia underwent endoscopy. The prevalence of H. pylori was detected by Giemsa stain, followed by the urea breath test (UBT). H. pylori(+) patients were scheduled to undergo 7-day triple therapy and the success of eradication was investigated by UBT. RESULTS: Forty-five (44%) patients were positive for H. pylori. Forty of them underwent triple therapy and 39 (98%) patients completed the treatment. Eradication was successful in 32 (82%) and unsuccessful in 7 (18%) patients. There was no significant difference between these groups in age, gender, endoscopic findings or HD, and only previous treatment was significant for eradication failure by univariate and multivariate logistic regression analysis. Side effects were observed in 2 (15%) of 13 HD(+) and 3 (11%) of 27 HD(-) patients, and one HD(-) patient had to stop medication because of severe nausea and vomiting. The eradication rate was 93% (28/30) in patients without previous treatment. The triple therapy was unsuccessful in 7 patients, and 4 of them again underwent 7-day triple therapy, but all resulted in failure. CONCLUSIONS: Seven-day triple therapy is safe and effective for primary treatment of H. pylori infection in both HD(+) and HD(-) patients, but a new treatment is necessary for patients with previous treatment.

Genetic alterations and expression of the protein phosphatase 1 genes in human cancers.

Recent studies have revealed that genetic alterations of the protein phosphatase genes, including PTEN, PPP2R1A, PPP2R1B and PPP1R3, are involved in human carcinogenesis. In the present study, we examined the genetic and expression status of nine protein phosphatase 1 (PP1) genes in 55 human cancer cell lines, consisting of 10 small cell lung cancers, 22 non-small cell lung cancers, 11 colorectal cancers, 7 gastric cancers and 5 ovarian cancers. The PP1 genes examined were three catalytic subunit genes, PPP1CA, PPP1CB and PPP1CC, and six regulatory subunit genes, PPP1R1A, PPP1R2, PPP1R5, PPP1R6, PPP1R7 and PPP1R8. Three catalytic subunit genes and three regulatory subunit genes, PPP1R2, PPP1R7 and PPP1R8, were ubiquitously expressed in the 55 cell lines, while PPP1R1A, PPP1R5, and PPP1R6 were differentially expressed. Possible missense mutations of the PPP1R5, PPP1R7 and PPP1R8 genes were detected in one (2%), two (4%) and one (2%) cell line, respectively. A rare, non-synonymous polymorphism was also identified in the PPP1R5 gene. Four of the 55 cell lines carried genetic alterations of several protein phosphatase genes, including PTEN, PPP1R3, PPP1R7 and PPP1R8. Ubiquitous expression as well as a lack of genetic diversity of catalytic subunit genes suggested the essential role of these genes for the growth of cancer cells. In contrast, differential expression, somatic mutations and/or genetic polymorphisms of several regulatory subunit genes indicate the involvement of these genes in multistep carcinogenesis.

Differential expression of the LAMB3 and LAMC2 genes between small cell and non-small cell lung carcinomas.

To identify genes differentially expressed between small cell lung carcinoma (SCLC) cells and non-SCLC cells, mRNA differential display was applied to 3 SCLC cell lines and 6 non-SCLC cell lines. The LAMB3 gene was identified as being expressed only in non-SCLC cells and not in SCLC cells. The LAMB3 gene encodes the laminin beta3 chain, which is a unique component of laminin-5. Laminin-5 is a heterotrimer protein consisting of the alpha3, beta3, and gamma2 chains, and another unique component of laminin-5 is the gamma2 chain encoded by the LAMC2 gene. RT-PCR analysis of the LAMB3 and LAMC2 genes in 45 lung cancer cell lines revealed that both the LAMB3 and LAMC2 genes were co-expressed in 21 of 32 non-SCLC cell lines (66%) but only in one of 13 SCLC cell lines (8%). Coexpression of the LAMB3 and LAMC2 genes was also observed in all 4 cases of primary non-SCLC cells examined but not in the corresponding non-cancerous lung cells. Since alpha6beta4 integrin, the specific laminin-5 binding receptor, is known to be expressed only in non-SCLC cells and not in SCLC cells, it was indicated that laminin-5 is a critical microenvironmental factor for the growth of non-SCLC cells but not of SCLC cells. The differences in the expression of integrins and laminins would be critical factors to distinguish SCLC and non-SCLC cells, and such differences might be associated with the unique biological properties of SCLC cells, including metastatic potential and drug sensitivity.

Absence of hSNF5/INI1 mutation in human lung cancer.

Frequent occurrence of chromosome 22q deletions in lung cancer indicates the presence of a tumor suppressor gene on this chromosome arm. The hSNF5/INI1 gene at chromosome 22q11.2 has recently been shown to act as a tumor suppressor in rhabdoid tumors. To investigate whether the hSNF5/INI1 gene located on chromosome 22q is involved in lung carcinogenesis, mutation analysis of the hSNF5/INI1 gene was performed using 50 lung cancer cell lines. No mutations causing amino acid substitutions or frameshifts were found by PCR-SSCP analysis of the entire coding region. The results indicated that the hSNF5/INI1 gene is not inactivated in lung cancers and suggested the presence of another tumor suppressor gene on chromosome 22q. Thus, further studies are necessary to identify the target lung tumor suppressor gene(s) on chromosome 22q.

Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display.

mRNA differential display was applied to three small cell lung carcinoma (SCLC) cell lines, six non-small cell lung carcinoma (NSCLC) cell lines, and three normal lung tissues to identify genes differentially expressed between lung carcinoma cells and normal lung tissues and between SCLC cells and NSCLC cells. We isolated five differentially expressed genes, two that were novel and three that were already known. DIL-1 (differentially expressed in cancerous and noncancerous lung cells; HGMW-approved symbol SPON2) and pulmonary surfactant apoprotein A were expressed in normal lung tissues but not in lung carcinoma cell lines, whereas DIL-2 (HGMW-approved symbol C20orf2) and nm23-H1 were expressed in lung carcinoma cell lines but not in normal lung tissues. The remaining gene, Annexin II, was expressed at a lower level in SCLC than in NSCLC and normal lung tissues. These genes were also differentially expressed in primary lung cancers. One of the two novel genes, DIL-1, encodes a secreted protein homologous to the Mindin/F-spondin family. The other, DIL-2, encodes a protein with a putative ATP/GTP binding site motif. These data provide basic information necessary to understand the differences in gene expression profiles between lung carcinoma and normal lung and between SCLC and NSCLC. Further characterization of these genes will help to clarify the molecular mechanisms of human lung carcinogenesis.

Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers.

The PTEN/MMAC1/TEP1 gene has been isolated as a tumor suppressor gene that is altered in several types of human tumors including brain, breast, and prostate cancers. In the present study, we report PTEN/MMAC1/TEP1 alterations in human lung cancers. Intragenic homozygous deletions were detected in 6 (40%) of 15 small cell lung carcinoma (SCLC) cell lines and in 2 (8%) of 25 non-small cell lung carcinoma (NSCLC) cell lines. A nonsense mutation and a missense mutation were detected in 2 (8%) NSCLC cell lines. An intragenic homozygous deletion, a 1-bp frameshift mutation, and a nonsense somatic mutation were also detected in three (6%) of 47 surgical specimens. All the lung tumors with PTEN/MMAC1/TEP1 mutations were homozygous for the mutant alleles. These findings suggest that PTEN/MMAC1/TEP1 plays a role as a tumor suppressor gene in the genesis and/or progression of human lung cancer.

Catalytic properties of mouse carbonic anhydrase V.

A cDNA encoding the mouse carbonic anhydrase V gene was isolated by reverse transcription and polymerase chain reaction from BALB/c mouse liver mRNA. Vectors containing the full coding sequence as well as two different NH2-terminal truncated genes expressed enzymatically active protein in Escherichia coli. The carbonic anhydrase V produced by a vector containing the full coding sequence, which includes a possible NH2-terminal mitochondrial targeting signal, was proteolytically processed by E. coli and contained several amino-terminal ends. The two NH2-terminal truncated vectors deleted, respectively, 1) the 29-amino acid putative targeting sequence and 2) 51 amino acids, yielding a protein equivalent to a carbonic anhydrase (CA) V isolated from mouse liver mitochondria; and both vectors produced homogeneous protein fractions. These latter two forms of CA V had identical steady-state constants for the hydration of CO2, with maximal values of kcat/Km at 3 x 10(7) M-1 s-1 and kcat at 3 x 10(5) s-1 with an apparent pKa for catalysis of 7.4 determined from kcat/Km. In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, ethoxzolamide, and cyanate, CA V is very similar to CA II. Mouse CA V has a tyrosine at position 64, where the highly active isozyme II has histidine serving as a proton shuttle in the catalytic pathway. Investigation of a site-specific mutant of CA V containing the replacement Tyr64-->His showed that the unique kinetic properties of CA V are not due to the presence of tyrosine at position 64.