Lung adenocarcinoma presenting with enlarged and multiloculated cystic lesions over 2 years

We report a case of lung adenocarcinoma in which cystic lesions enlarged and multiloculated over 2 years. Histological examination of the resected specimen found proliferation of nonmucinous adenocarcinoma cells along the alveolar walls, revealing bronchioloalveolar cell carcinoma type extension. In cystic lesions, particularly those not associated with inflammation, lung adenocarcinoma, particularly bronchioloalveolar cell carcinoma type, should be a diagnostic consideration. .     

Rapid diagnostic system of bacterial infection

Approach to develop genetic detection system for bacterial infection in blood is a demanding subject because number of bacteria in blood stream is very few and in most cases the number of bacteria is less than the detection limit of gene amplification methods. At the first stage of blood sampling, we only applied gene amplification method against fastidious organisms to culture and organisms causes severe infection. Organisms which are usually found very few in blood are subjected to blood culture. After monitoring system of blood culture gave positive signal of bacterial growth, DNA or RNA in culture media were extracted and amplified with universal primers for bacteria and fungi. Amplicons were applied to a rapid sequencer. However, in case of mixed infection, the sequencing is not successful. In such cases, the amplicons are analized with DNA microarray, immobilized 16S rDNA and 28S rDNA of 1,000 human pathogenic bacteria and fungi.     

Antecedent hypertension interacts with adverse ventricular remodeling after myocardial infarction

BACKGROUND: Ventricular remodeling is an independent predictor of left ventricular function in patients with myocardial infarction (MI). Accelerated ventricular remodeling is a probable contributor to the increased mortality observed after MI in hypertensive patients. The purpose of this study is to assess the relationship of antecedent hypertension to ventricular remodeling after MI. METHODS: Seventy-nine patients presenting with a first acute MI (AMI) who were treated and attained Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 with re-perfusion therapy within 12 hours of their symptom onset were enrolled in this study. All of them underwent left ventriculography (LVG) immediately after re-perfusion therapy and again at 6 months after the occurrence of MI. Patients were divided into two groups; hypertensive group and normotensive group. End-diastolic volume index (EDVI), end-systolic volume index (ESVI), and EF were compared between acute phase and 6 months after AMI in each group. RESULTS: The hypertensive group showed a significant increase in both EDVI and ESVI after 6 months, whereas the normotensive group did not. In addition, there was no change in EF in the hypertensive group, whereas EF increased significantly after 6 months in the normotensive group. As a result, percent change in ESVI and EF showed significantly differences between the hypertensive group and normotensive group, whereas percent change in EDVI showed no significant difference between the two groups. CONCLUSIONS: Antecedent hypertension interacts with ventricular remodeling after MI.     

Relationships between brachial-ankle pulse wave velocity and conventional atherosclerotic risk factors in community-dwelling people

BACKGROUND: A simple instrument has been developed to measure brachial-ankle pulse wave velocity (baPWV). The aim of the present study was to use this instrument to study the relationship between baPWV and conventional atherosclerotic risk factors. METHODS: Community-dwelling Japanese (632) living in a rural area (234 men and 398 women) participated in a municipal medical health survey that included baPWV measurement and a traditional clinical examination, conducted in June, 2002. RESULTS: Men had a significantly higher baPWV than women. No interaction between gender and age on baPWV was identified. Multiple linear regression analysis indicated that age, hemodynamic factors (diastolic blood pressure, pulse pressure, and heart rate), hemoglobinA1c, current drinking and smoking status, and mild retinal changes had significant independent influences on higher baPWV. CONCLUSIONS: In this rural population, age, gender, and hemodynamic factors were independently associated with baPWV, along with traditional atherosclerotic risk factors, although no significant associations between baPWV and histories of atherosclerotic diseases or subclinical atherosclerosis except for mild retinal changes were demonstrated.     

Effects of TAK-802, a novel acetylcholinesterase inhibitor, on distension-induced rhythmic bladder contractions in rats and guinea pigs

In the present study, we investigated the effects of 8-[3-[1-[(3-fluorophenyl)methyl]-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (TAK-802), a novel acetylcholinesterase inhibitor, on distension-induced rhythmic bladder contractions in urethane-anesthetized rats and guinea pigs. TAK-802 potently inhibited human-erythrocyte-derived acetylcholinesterase activity with an IC(50) value of 1.5 nM, which represented a potency 30 and 250 times greater than that of the two carbamate acetylcholinesterase inhibitors, neostigimine and distigmine, respectively. Unlike the carbamate acetylcholinesterase inhibitors, TAK-802 exhibits high selectivity for acetylcholinesterase inhibition over butyrylcholinesterase inhibition. In an assay conducted to measure the muscarinic and nicotinic actions, TAK-802 was found to exhibit higher selectivity for muscarinic actions over nicotinic actions in comparison to distigmine. Both TAK-802 and distigmine increased isovolumetric bladder contractions in rats and guinea pigs in a dose-dependent manner, with a minimum effective dose (MED) of 0.01 and 0.03 mg/kg i.v., respectively, in rats, and 0.01 and 0.1 mg/kg i.v., respectively, in guinea pigs. The effects of both the drugs were completely abolished by atropine. These results suggest that TAK-802 and other acetylcholinesterase inhibitors can effectively increase reflex bladder contractions by increasing the efficacy of acetylcholine released by nerve impulses. On the other hand, bethanechol, a muscarinic agonist, markedly changed the pattern of distension-induced bladder contractions when administered at the dose of 1 mg/kg i.v., and it did not necessarily augment well-coordinated bladder contractions. Thus, considering that it has some selectivity for muscarinic action, TAK-802 might be expected to be useful in the treatment of voiding dysfunction caused by impaired detrusor contractility.     

Effects of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice

The present study was designed to investigate the effect of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice. Mice were immunized subcutaneously at the base of the tail with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0) and were treated daily with oral administration of various doses of rolipram from days 0 to 20. On day 21, production of anti-OVA IgG and proliferative responses to the antigen were determined. Anti-OVA IgG2a and interferon-gamma (IFN-gamma), as indicators of Th1 responses, and anti-OVA IgG1 and interleukin-10 (IL-10), as indicators of Th2 responses, were also measured. The results showed that treatment with rolipram failed to affect the production of OVA-specific IgG but decreased the proliferation of spleen cells to the antigen. Its inhibitory effect on these immune responses was correlated with a marked decrease in IFN-gamma but not IL-10 production, although neither anti-OVA IgG2a nor IgG1 production was affected by rolipram. These results suggest that rolipram may preferentially inhibit Th1 responses more effectively than Th2 responses. Administration of rolipram resulted in suppression of antigen (OVA)-induced arthritis in mice. The suppression of joint inflammation by rolipram was associated with the inhibition of the OVA-specific proliferative responses of spleen cells and IFN-gamma secretion. These results indicate that rolipram may be effective in regulating Th1-mediated diseases such as rheumatoid arthritis.     

In vitro inhibition of recombinant ligand-gated ion channels by high concentrations of milnacipran

Rationale Tricyclic antidepressants are known to inhibit various ligand-gated ion-channel (LGIC) receptors, and some of their clinical features may be associated with this activity. The effects of milnacipran, a selective inhibitor of the reuptake of serotonin and noradrenaline, on LGIC receptors have not yet been investigated on such ion-channel receptors.Objectives To determine the in vitro effect of milnacipran on four recombinant LGIC receptors, nicotinic acetylcholine, N-methyl-d-aspartate, -amino butyric acid (GABA) and 5-hydroxytryptamine_3A receptors.Methods Receptors were expressed in Xenopus oocytes and LGIC activity measured using a two-voltage clamp technique.Results There was no interaction at the GABA receptor. The results at the other LGIC receptors showed that they could be inhibited by high concentrations of milnacipran.Conclusions At high concentrations, milnacipran can inhibit certain LGICs. It is, however, unlikely that these interactions have any clinical consequence under normal therapeutic conditions, since the concentrations required are considerably higher than those achieved in plasma of treated patients.     

Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia

Antipsychotic polypharmacy has been empirically used and a recent trend in favour of that mode of therapy has been suggested for the treatment of schizophrenia. The clinical efficacy, however, still remains to be clarified. In order to critically evaluate the usefulness of such kind of psychopharmacotherapy, antipsychotic combination regimen (polypharmacy) was switched to a treatment with the single main antipsychotic (monotherapy) in cross-tapered fashion, while approximately maintaining the total amount, for patients with chronic schizophrenia. Patients had been treated with an average of three antipsychotics and maintained with the same antipsychotic polypharmacy regimen for more than 6 months before the entry. They were followed up with an antipsychotic monopharmacy and evaluated at 24 wk after completion of switching. Forty-seven patients were recruited for this study. Of 44 patients for whom evaluation was possible, 24 (54.5%) remained stable, while 10 (22.7%) showed improvement and the same number of patients ended in a deleterious status. Twenty-two patients were converted to antipsychotic monotherapy, while another 12 needed minimal dosing of low-potency agents. Overall, social functioning, evaluated by the Global Assessment of Functioning and the Clinical Global Impression, remained unchanged. Eighteen of 34 successful patients showed adverse effects of the main antipsychotic medication, which necessitated a significant dose reduction. Nine out of 10 deteriorating patients had been treated with a combination of low- and high-potency antipsychotics. It is suggested that many instances of antipsychotic polypharmacy is avoidable. The result is compatible with the current treatment recommendations, which dictate the use of a single antipsychotic agent.     

Frequent downregulation of 14-3-3 sigma protein and hypermethylation of 14-3-3 sigma gene in salivary gland adenoid cystic carcinoma

14-3-3 sigma:, a target gene of the p53 tumour suppressor protein, has been shown to regulate the cell cycle at the G2/M checkpoint. Recent studies have demonstrated that 14-3-3 sigma is downregulated by hypermethylation of the CpG island in several types of cancer. In this study, we investigated the expression and methylation status of 14-3-3 sigma in human salivary gland adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Immunohistochemical analysis revealed that the positive expression rate of 14-3-3 sigma in ACC (one out of 14) was markedly lower than that in MEC (ten out of 10). Since most of the ACCs carried the wild-type p53 protein, downregulation of 14-3-3 sigma in ACC may not be due to the dysfunction of p53 pathway. Microdissection-methylation-specific PCR revealed that frequent hypermethylation of the 14-3-3 sigma gene was observed in ACC when compared to that in MEC. In cultured-ACC cells, we confirmed the downregulation of 14-3-3 sigma via hemimethylation of the gene by sequencing analysis after sodium bisulphite treatment. Furthermore, re-expression of 14-3-3 sigma in the ACC cells was induced by the treatment with DNA demethylating agent, 5-aza-2'-deoxycytidine. Irradiation apparently induced the enhanced expression of 14-3-3 sigma and G2/M arrest in normal salivary gland cells; however, in the ACC cells, neither induction of 14-3-3 sigma nor G2/M arrest was induced by irradiation. These results suggest that downregulation of 14-3-3 sigma might play critical roles in the neoplastic development and radiosensitivity of ACC.     

alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis

BACKGROUND: Serum alpha1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries alpha(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains. METHODS: Serum AGP levels in patients with various types of malignancies (n=214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody. RESULTS: A significant difference (P <0.001) in serum AGP levels was observed in preoperative patients compared with levels in the healthy control group, but the levels in individual patients did not reflect their clinical status. Conversely, it was found not only that the patterns of AGP glycoforms differed widely in the patient group compared with the healthy control group, but they also changed depending on each patient's clinical status. Furthermore, AGP glycoforms seemed to be appropriate markers of disease progression and prognosis according to follow-up studies of 45 patients during prolonged preoperative and postoperative periods. CONCLUSIONS: Patients with advanced malignancies who had AGP glycoforms that contained highly fucosylated triantennary and tetraantennary sugar chains for long periods after surgery were likely to have a poor prognosis. However, patients who had AGP glycoforms without such changes were expected to have a good prognosis.