Hypertriglyceridemia Causing Continuous Renal Replacement Therapy Dysfunction in a Patient with End-stage Liver Disease.

Hypertriglyceridemia is infrequently reported as a cause of suboptimal delivery of dialytic therapy in critically ill patients. We report the case of a critically ill liver transplant patient in the Intensive Care Unit who was found to have recurrent filter clotting during continuous renal replacement therapy (CRRT). The patient had increased serum triglycerides (TGs), which was identified approximately 2 weeks into hospitalization and initially believed to be due to prolonged propofol use. The patient's elevated TGs ultimately caused her blood to become lipemic, causing the dialytic circuit to become nonfunctional and placed the patient in imminent danger due to hyperkalemia and metabolic acidosis. Therapeutic plasma exchange was emergently used to lower TG levels, and renal replacement therapy was resumed without any other issues. The patient's persistent hypertriglyceridemia was attributed to a combination of adverse effect of medications and liver graft failure. The high TG level and abnormal liver functions improved after a repeat liver transplantation.

miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase.

hTERT is the catalytic subunit of the telomerase complex. Elevated expression of hTERT is associated with the expansion and metastasis of gastric tumor. In this study, we aimed to identify novel tumor suppressor miRNAs that restrain hTERT expression. We began our screen for hTERT-targeting miRNAs with a miRNA microarray. miRNA candidates were further filtered by bioinformatic analysis, general expression pattern in different cell lines, gain-of-function effects on hTERT protein and the potential of these effects to suppress hTERT 3' untranslated region (3'UTR) luciferase activity. The clinical relevance of two miRNAs (miR-1207-5p and miR-1266) was evaluated by real-time RT-PCR. The effects of these miRNAs on cell growth, cell cycle and invasion of gastric cancer cells were measured with CCK-8, flow cytometry and transwell assays. Finally, the ability of these miRNAs to suppress the transplanted tumors was also investigated. Fourteen miRNAs were identified using a combination of bioinformatics and miRNA microarray analysis. Of these fourteen miRNAs, nine were expressed at significantly lower levels in hTERT-positive cell lines compared with hTERT-negative cell lines and five could downregulate hTERT protein expression. Only miR-1207-5p and miR-1266 interacted with the 3' UTR of hTERT and the expression levels of these two miRNAs were significantly decreased in gastric cancer tissues. These two miRNAs also inhibited gastric tumor growth in vitro and in vivo. Altogether, miR-1207-5p and miR-1266 were determined to be hTERT suppressors in gastric cancer, and the delivery of these two miRNAs represents a novel therapeutic strategy for gastric cancer treatment.

Characterization of cortical potentials evoked by oesophageal balloon distention and acid perfusion in patients with functional heartburn.

Oesophageal visceral hypersensitivity is thought to be important in generating symptoms in functional heartburn (FH). However, the neurophysiological mechanisms involved are poorly understood. The aim of this study was to compare the characteristics of oesophageal cortical evoked potentials (CEPs) induced by balloon distension and acid perfusion in FH and controls. We studied 21 FH patients and 12 healthy volunteers. Oesophageal mechanical stimulation was performed using the specially constructed mechanical pump. CEPs were recorded using the 10-20 international system of electroencephalogram recording. Oesophageal distention elicited recognizable, reproducible and muti-peak CEPs. CEP latencies for N1, P1 and N2 components were significantly shorter (P = 0.016, P = 0.003 and P = 0.031, respectively) in FH than in controls before perfusion. Acid perfusion significantly decreased the latencies of N1, P1 and N2 (P = 0.022, P = 0.007 and P = 0.041, respectively) and significantly increased the amplitude of P1-N2 components (P = 0.020) in FH patients, but not in controls. In conclusion, cortical evoked potential responses evoked by oesophageal distention and acid perfusion were greater in FH than in controls, suggesting that dysfunction of visceral neural pathways and/or alterations in cortical processing may produce and mediate oesophageal hypersensitivity in FH. These findings provide the evidence that central sensitization contributes to the development and maintenance of oesophageal hypersensitivity.

Alterations of MUC1 and MUC3 expression in gastric carcinoma: relevance to patient clinicopathological features.

AIMS: Several studies have reported conflicting and inconclusive results concerning the clinical relevance of mucin expression in gastric carcinoma. This study investigated the correlations between aberrant expression of mucins in gastric carcinoma and patient clinicopathological features. METHODS: The expression of MUC1, MUC2, MUC3, MUC5AC, and MUC6 was investigated immunohistochemically in gastric carcinoma (n = 46) in relation to patient clinicopathological features. RESULTS: All normal gastric mucosa samples expressed MUC1, MUC5AC, and MUC6. MUC1, MUC2, MUC3, MUC5AC, and MUC6 were expressed in 29, 31, 30, 18, and 21 of the 46 cases of gastric carcinoma, respectively. The number of cases expressing MUC1 was significantly higher (p < 0.01) in patients with a small tumour size (>/= 5 cm) and in patients in clinical stages I-II, compared with clinical stages III-IV (p < 0.05). Expression was significantly lower (p < 0.05) in patients exhibiting metastasis. The number of cases expressing MUC3 was significantly higher in patients in clinical stages III-IV (p < 0.05), and in those with serosal invasion (p < 0.05) or metastasis (p<0.01). No significant relations were found between MUC2, MUC5AC, MUC6, and clinical stage, metastasis, or tumour size. CONCLUSIONS: Membrane bound mucins MUC1 and MUC3 appear to be associated with the development of gastric carcinoma. Patients who maintained high immunoreactivity for anti-MUC1 antibody had a better prognosis, whereas those with an increase in anti-MUC3 immunoreactivity had a poorer prognosis, as judged by tumour size, serosal invasion, and metastasis. However, no correlation was found between MUC2, MUC5AC, or MUC6 and clinical prognosis.

Theoretical studies on cycloaddition reactions between keteniminium cations and olefins.

The mechanisms of seven reactions between keteniminium cations and olefins have been theoretically explored at BHandHLYP/6-31G level. It is found that these seven reactions always form a relatively stable hydrogen-bonded type of ion-molecule complex first except for reactions 1d+2a and 1e+2a, which have no hydrogen atom attached to nitrogen atom in keteniminium cations. Some reactions take place via a concerted but unsynchronous mechanism, and the others are stepwise processes. The substituent effects are also studied. The data reveal that the electron-pushing substituents on keteniminium cations disfavor the reaction, and the electron-attracting substituents on keteniminium cations favor the reactions. The substituent effects on ethene are contrary to the former case.

Alterations of telomerase activity and terminal restriction fragment in gastric cancer and its premalignant lesions.

AIMS: In order to explore the role of alterations of telomerase activity and terminal restriction fragment (TRF) length in the development and progression of gastric cancer. METHODS: Telomerase activity was detected in 176 specimens of gastric mucosa obtained through an operation or endoscopical biopsy by using the telomeric repeat amplification protocol (TRAP) assay. Meanwhile, the mean length of TRF was measured with the use of a Southern blot in part of those samples. RESULTS: Telomerase activity was detected in 14 of 57 (24.6%) chronic atrophy gastritis patients, six of 18 (33.3%) intestinal metaplasia patients, three of eight (37.5%) dysplasia patients and 60 of 65 (92.3%) gastric cancer patients, respectively. Normal gastric mucosa revealed no telomerase activity. No association was found between telomerase activity and any clinicopathological parameters. The mean TRF length was decreased gradually with age in normal mucosa and in gastric cancer tissue. Regression analysis demonstrated that the reduction rate in these tissues was 41 +/- 12 base pairs/year. Among 35 gastric cancers, TRF length was shown to be shorter in 20 cases (57.1%), similar in 12 cases (34.3%) and elongated in three cases (7.6%), compared to the corresponding adjacent tissues. The mean TRF length tended to decrease as the mucosa underwent chronic atrophy gastritis, intestinal metaplasia, dysplasia and into gastric cancer. The mean TRF length in gastric cancer was not statistically correlated with clinicopathological parameters and telomerase activity. CONCLUSIONS: Our results suggest that telomerase is expressed during the early stage of gastric carcinogenesis, and that the clinical significance of TRF length appears to be limited in gastric cancer.

Telomere erosion is independent of microsatellite instability but related to loss of heterozygosity in gastric cancer.

AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. METHODS: Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-betaRII and BAX genes were analyzed by PCR-based methods. RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-betaRII and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (> or = 2 loci, n = 8), but none was found in those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters. No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P<0.01). This tendency was also observed in APC and MCC genes, although there was no statistical significance. CONCLUSION: The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either low MSI or MSS, multiple deletions may represent the LOH pathway. Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.

A direct transition state theory based analysis of the branching in NH2 + NO.

A combination of high-level quantum-chemical simulations and sophisticated transition state theory analyses is employed in a study of the temperature dependence of the N2H + OH-->HNNOH recombination reaction. The implications for the branching between N2H + OH and N2 + H2O in the NH2 + NO reaction are also explored. The transition state partition function for the N2H + OH recombination reaction is evaluated with a direct implementation of variable reaction coordinate (VRC) transition state theory (TST). The orientation dependent interaction energies are directly determined at the CAS + 1 + 2/cc-pvdz level. Corrections for basis set limitations are obtained via calculations along the cis and trans minimum energy paths employing an approximately aug-pvtz basis set. The calculated rate constant for the N2H + OH-->HNNOH recombination is found to decrease significantly with increasing temperature, in agreement with the predictions of our earlier theoretical study. Conventional transition state theory analyses, employing new coupled cluster estimates for the vibrational frequencies and energies at the saddlepoints along the NH2 + NO reaction pathway, are coupled with the VRC-TST analyses for the N2H + OH channels to provide estimates for the branching in the NH2 + NO reaction. Modest variations in the exothermicity of the reaction (1-2 kcal mol-1), and in a few of the saddlepoint energies (2-4 kcal mol-1), yield TST based predictions for the branching fraction that are in satisfactory agreement with related experimental results. The unmodified results are in reasonable agreement for higher temperatures, but predict too low a branching ratio near room temperature, as well as too steep an initial rise.

Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability.

AIM: To investigate the role of DNA microsatellite instability (MSI) in gastric carcinogenesis by studying associations between MSI status, clinicopathological features, and loss of genetic loci. METHODS: Six microsatellite loci and loss of heterozygosity at APC, DCC, and MCC were analysed by polymerase chain reaction based methods in 53 cases of advanced gastric cancer. RESULTS: MSI was observed in 32.1% of gastric carcinomas (17/53) and 20% of foci of intestinal metaplasia (3/15). Seven gastric carcinomas (13.7%) were MSI-high (MSI-H) (three loci or more) and 10 (18.9%) were MSI-low (MSI-L) (one or two loci). The frequency of MSI-H was higher in intestinal (25.0%) than in diffuse carcinomas (3.7%) (p < 0.05). None of the MSI-H tumours showed loss of heterozygosity at APC, MCC, or DCC loci. CONCLUSIONS: MSI may have an important and early role in a subset of gastric cancers, particularly the intestinal type. The MSI-H subset of gastric cancer has features in common with its colorectal counterpart, whereas MSI-L and microsatellite stable cancers appear to develop through the loss of heterozygosity pathway.

Detection of telomerase activity in biopsy samples of colorectal cancer.

BACKGROUND: Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends. The expression of telomerase is thought to be required for cellular immortality and oncogenesis. METHODS: To investigate the role of telomerase in the pathogenesis of colorectal cancer, we analysed telomerase activity in biopsy samples of colorectal cancer and colonic adenomas. Using a polymerase chain reaction-based assay, we examined telomerase activity in 52 samples of colorectal cancer, 12 colonic adenomas and 30 normal colonic mucosa samples obtained by endoscopic biopsy. RESULTS: Telomerase activity was detectable in 88.5% (46/52) of colorectal carcinomas, in 50% (6/12) of colonic adenomas but not in normal colorectal mucosa. There was no correlation between telomerase activity and tumour location, type, size and differentiation (P > 0.05). CONCLUSIONS: It was concluded that telomerase activation plays a role in the evolution of colorectal cancer, and that measurement of telomerase activity in biopsied colorectal mucosa samples may provide information both as a diagnostic marker to detect small numbers of cancer cells, and as a screening method for patients at high risk for colorectal carcinoma.

Loss of heterozygosity and loss of expression of the DCC gene in gastric cancer.

AIM: To investigate the role of DCC gene inactivation in the development and progression of gastric cancer. METHODS: Loss of heterozygosity and loss of expression of the DCC gene was studied in 51 surgical specimens of gastric cancer using detection based on polymerase chain reaction. RESULTS: Loss of heterozygosity was found in 35.3% (18 of 51) of specimens and was detected more often in stage III and IV (50%) than in stage I and II cancers (14.3%) (p < 0.05). Occurrence of loss of heterozygosity was not correlated with histological type, tumour size, depth of invasion, or lymph node metastasis. Loss of expression was found in 49% of cases (25 of 51). Loss of expression was not significantly correlated with any clinicopathological variable. CONCLUSIONS: Loss of heterozygosity and loss of expression of the DCC gene are often encountered in gastric cancer. Loss of heterozygosity of the DCC gene is a late event and associated with malignant progression.

Studies on the relationship between the point mutation of ras oncogenes and the prognosis of patients with gastric cancer.

AIM: To study the relationship between the point mutation of ras oncogenes and the prognosis of patients with gastric cancer. METHODS: The point mutations at codon 12 and 61 of c-Ha-ras, at codon 12 and 13 of K-ras, and at codon 12 of N-ras were studied with PCR-RFLP in 88 formalin fixed and paraffin embedded specimens of gastric cancer. RESULTS: It was found that the overall rate of point mutation of ras oncogenes was 18.2% and the positivity of the point mutation of ras oncogenes was related to the cancerous invasion of the serosa, the status of lymph node metastasis, the stage of cancer and the survival time after surgery. CONCLUSION: The findings suggest that the determination of point mutations of ras oncogenes can be used to determine the prognosis of patients with gastric cancer.

Loss of heterozygosity and mRNA expression at deleted in colorectal cancer gene locus in gastric cancer.

AIM: To assess the effects of the deleted in colorectal cancer (DCC) gene changes on the development and progression of gastric cancer. METHODS: The loss of heterozygosity (LOH) and mRNA expression DCC gastric cancer using a PCR-based detection method. RESULTS: LOH was found in 35.3% (18/51) of the specimens, and the LOH was more frequently detected in tumors from patients with stage III or IV cancer (50.5%) than those in stages I or II (14.3%) (P < 0.05). The occurrence of LOH was not found to correlate with the histological type, tumor size, invasion depth and lymph node metastasis of gastric cancer. The mRNA expression of the DCC gene was studied in 26 of the 51 cases, of which LOE was found in 30.8% (8/26). LOE was not significantly correlated to LOH or other clinicopathological parameters. CONCLUSION: LOH and LOE of DCC gene are frequently encountered in gastric cancer, and the LOH of DCC gene is a late event associated with progression of gastric cancer.

[Some immune functions of patients with carcinoma].

To evaluate efficiency of LAK cells from patients with cancer a number of immune functions of patients with advanced carcinoma was investigated. The results showed that: from patients with cancer, lymphocyte transformation (32.83 +/- 52.59), responses of lymphocytes to IL-2 (5.94 +/- 9.31), and to IL-2/PHA (32.25 +/- 43.05), and NK activity (11.18 +/- 6.98), LAK activity (17.86 +/- 9.57) were significantly suppressed (In the healthy donors, the data were 75.70 +/- 52.65, 24.59 +/- 28.25, 125.47 +/- 74.11 respectively, P < 0.001); sIL-2R and TNF concentrations (241.9 +/- 172.5 pmol/L and 1.86 +/- 1.52 ng/ml respectively) in serum from patients with cancer were significantly higher than that of healthy control (134.2 +/- 73.5 pmol/L and 0.63 +/- 0.20 ng/ml respectively, P < 0.05-0.001). Since patients with cancer had suppressed responses of lymphocytes to IL-2, low NK and LAK cell activity, LAK cells from patients with cancer might be less effective than those from healthy donor in the treatment of cancer.

[Transplantation of pedicled gastric wall flaps to the intestines in Wistar rats].

The pedicled gastric wall flaps of Wistar rats were transplanted to their duodenum, jejunum and colon respectively. After the operation the rats were killed at the 3rd, 6th, 9th and 12th month respectively. Intestinal metaplasia (IM) was observed in all the gastric grafts transplanted to the intestines under photomicroscope, TEM and SEM. Alkaline phosphatase positive IM was seen in the gastric graft mucosa transplanted to the duodenum and jejunum. The results showed that the formation of IM of the gastric mucosa may be related to a change of the microenvironment around the tissues and that gastric mucosa may differentiate into intestinal mucosa by the increase of pH value.

AN-132 block of cardiac sodium channels: a gate-related receptor analysis.

Based on the gate-related receptor hypothesis, an analysis of kinetics of AN-132, a new antiarrhythmic agent, blockade of cardiac sodium channels and the gate-related receptor which is bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of AN-132 (30 mumol/L) blocking were 0.051, 0.038, and 0.034 AP-1 at stimulation frequencies of 1.0, 2.0 and 3.0 Hz, respectively. The time constant of recovery from block by AN-132 at resting potential -90 mV was 39.5 s. These findings are in agreement with those experimental data documented. The analysis of gate-related receptor shows that AN-132 binds the inactivation gate-related receptor, and the binding and unbinding are modulated by the inactivation process.

Mechanisms of action of sodium channel blocker: gate-related receptor hypothesis.

A new hypothesis on mechanisms of action of the sodium channel blocker, the gate-related receptor hypothesis, has been proposed in this paper. Furthermore, a mathematic model and parameter estimation procedure for the kinetics analysis have also been given. Using the model and procedure, modeling and analyzing of cardiac sodium channel blockade by lidocaine and dauricine have been performed. The model-estimated results were not only coincident with those documented, but also provided some new information which may be helpful for understanding mechanism of blocking action of both drugs on sodium channels. The studies suggested that the gate-related receptor hypothesis is good for the elucidation of mechanisms of action of the sodium channel blocker.

Computer simulation of metoclopramide block of cardiac sodium channels.

Based on the gate-related receptor hypothesis, a quantitative study on kinetics and state-dependency of metoclopramide (Met) blockade of cardiac sodium channels was performed by computer simulation. The characteristics of Met, a sodium channel blocker modulated simultaneously by both activation and inactivation gates were described and analyzed for the first time. The time constant of recovery from blocking for Met at resting potential -85 mV was 2.82 s, which was increased during depolarization or hyperpolarization. Its apparent rate of onset of blocking was 0.49 AP-1 at a stimulation frequency of 2.0 Hz. A concentration-dependent shift of h infinity curve was found at doses higher than 100 mumol/L Met. This study provides a new test and verification for our gate-related receptor hypothesis.