Observation of edge states derived from topological helix chains.

Introducing the concept of topology has revolutionized materials classification, leading to the discovery of topological insulators and Dirac-Weyl semimetals1-3. One of the most fundamental theories underpinning topological materials is the Su-Schrieffer-Heeger (SSH) model4,5, which was developed in 1979-decades before the recognition of topological insulators-to describe conducting polymers. Distinct from the vast majority of known topological insulators with two and three dimensions1-3, the SSH model predicts a one-dimensional analogue of topological insulators, which hosts topological bound states at the endpoints of a chain4-8. To establish this unique and pivotal state, it is crucial to identify the low-energy excitations stemming from bound states, but this has remained unknown in solids because of the absence of suitable platforms. Here we report unusual electronic states that support the emergent bound states in elemental tellurium, the single helix of which was recently proposed to realize an extended version of the SSH chain9,10. Using spin- and angle-resolved photoemission spectroscopy with a micro-focused beam, we have shown spin-polarized in-gap states confined to the edges of the (0001) surface. Our density functional theory calculations indicate that these states are attributed to the interacting bound states originating from the one-dimensional array of SSH tellurium chains. Helices in solids offer a promising experimental platform for investigating exotic properties associated with the SSH chain and exploring topological phases through dimensionality control.

Conversion of a conventional superconductor into a topological superconductor by topological proximity effect.

Realization of topological superconductors (TSCs) hosting Majorana fermions is a central challenge in condensed-matter physics. One approach is to use the superconducting proximity effect (SPE) in heterostructures, where a topological insulator contacted with a superconductor hosts an effective p-wave pairing by the penetration of Cooper pairs across the interface. However, this approach suffers a difficulty in accessing the topological interface buried deep beneath the surface. Here, we propose an alternative approach to realize topological superconductivity without SPE. In a Pb(111) thin film grown on TlBiSe2, we discover that the Dirac-cone state of substrate TlBiSe2 migrates to the top surface of Pb film and obtains an energy gap below the superconducting transition temperature of Pb. This suggests that a Bardeen-Cooper-Schrieffer superconductor is converted into a TSC by the topological proximity effect. Our discovery opens a route to manipulate topological superconducting properties of materials.

Development of a novel algorithm for detecting glucocorticoid-induced diabetes mellitus using a medical information database.

WHAT IS KNOWN AND OBJECTIVE: Glucocorticoid-induced diabetes mellitus (GIDM) increases the risk of diabetes mellitus (DM)-related complications but is generally difficult to detect in clinical settings. The criteria for diagnosing GIDM have not been established. Recently, medical information databases (MIDs) have been used in post-marketing surveillance (PMS) studies. We conducted a pharmacoepidemiological study to develop an algorithm for detecting GIDM using MID. METHODS: We selected 1214 inpatients who were newly prescribed with a typical glucocorticoid, prednisolone, during hospitalization from 2008 to 2014 from an MID of Hamamatsu University Hospital in Japan. GIDM was screened based on fasting blood glucose (FBG) and haemoglobin A1c (HbA1c) levels according to the current Japan Diabetes Society (JDS) DM criteria, and its predictability was evaluated by an expert's review of medical records. We investigated further candidate screening factors using receiver operating characteristics analysis. RESULTS: Sixty-three inpatients were identified by the JDS DM criteria. Of these, 33 patients were definitely diagnosed as having GIDM by expert's review (positive predictive value = 52·4%). To develop a highly predictive algorithm, we compared the characteristics of inpatients diagnosed with definite GIDM and those diagnosed as non-GIDM. The maximum levels of HbA1c in patients with GIDM were significantly higher than those of patients with non-GIDM (66·9 mmol/mol vs. 58·7 mmol/mol, P < 0·001). The patients with GIDM had significantly higher relative increase in maximum level of HbA1c (RIM-HbA1c) than those with non-GIDM (0·3 vs. 0·03, P < 0·001). However, we did not observe a significant difference in those of fasting blood glucose (FBG) levels. We applied the RIM-HbA1c as a second screening factor to improve the detection of GIDM. It showed that a 13% increase in RIM-HbA1c separated patients with from patients without GIDM. WHAT IS NEW AND CONCLUSIONS: Patients with GIDM had significantly higher RIM-HbA1c than patients with non-GIDM. There was a 13% increase in RIM-HbA1c in patients with GIDM compared to the others. Our detection algorithm for GIDM using an MID achieved high sensitivity and specificity, and was superior to one based only on the current JDS DM criteria. Our results suggest that monitoring changes in HbA1c levels is important for detecting GIDM and adds to current diagnostic criteria for type 2 DM.

Exposure of phosphatidylserine on the cell surface.

Phosphatidylserine (PtdSer) is a phospholipid that is abundant in eukaryotic plasma membranes. An ATP-dependent enzyme called flippase normally keeps PtdSer inside the cell, but PtdSer is exposed by the action of scramblase on the cell's surface in biological processes such as apoptosis and platelet activation. Once exposed to the cell surface, PtdSer acts as an 'eat me' signal on dead cells, and creates a scaffold for blood-clotting factors on activated platelets. The molecular identities of the flippase and scramblase that work at plasma membranes have long eluded researchers. Indeed, their identity as well as the mechanism of the PtdSer exposure to the cell surface has only recently been revealed. Here, we describe how PtdSer is exposed in apoptotic cells and in activated platelets, and discuss PtdSer exposure in other biological processes.

Evaluation of two Japanese regulatory actions using medical information databases: a 'Dear Doctor' letter to restrict oseltamivir use in teenagers, and label change caution against co-administration of omeprazole with clopidogrel.

WHAT IS KNOWN AND OBJECTIVE: The implementation of appropriate epidemiological methodology using medical information databases (MIDs) to evaluate the effects of regulatory actions has been highly anticipated. To assess scientific methods for active pharmacovigilance using MIDs, we conducted a quantitative assessment of the impact of two regulatory actions by the Japanese government: (i) restriction of use of oseltamivir in teenagers in March 2007 and (ii) caution against the co-administration of omeprazole (OPZ) with clopidogrel (CPG) in April 2010. METHODS: Data were obtained from four hub hospitals in Japan. We measured the seasonal proportion of patients prescribed oseltamivir to those prescribed neuraminidase inhibitors for the 2002/2003 to 2010/2011 seasons. The monthly proportion of patients co-administered OPZ and CPG (OPZ+CPG) to those prescribed CPG was measured from May 2009 to April 2011. We evaluated the changes observed with implementation of the regulatory actions. To estimate the impact of the actions, we conducted segmented regression analysis using interrupted time series data. The impact was assessed by two parameter estimates of the regression model: the change in level for short-term effects and change in trend for long-term effects. RESULTS AND DISCUSSION: The use of oseltamivir in the target 10-19 years age group showed a significant and large decline (63·16%) immediately after the intervention (P = 0·0008). No change was observed in OPZ+CPG, although there was a relative inhibitory trend for OPZ+CPG compared with co-administration of lansoprazole or rabeprazole with CPG as the control group. When restricted to new users of CPG, the stratified results were consistent with the overall results. WHAT IS NEW AND CONCLUSION: The current analysis demonstrates the effectiveness of two regulatory actions. The results of the current study indicate that MID research can contribute to assessing and improving pharmacovigilance activities.

An algorithm for the identification of heparin-induced thrombocytopenia using a medical information database.

WHAT IS KNOWN AND OBJECTIVE: Using effective algorithms for extracting relevant drug and patient information from electronic medical information data systems is likely to form an increasingly important aspect of pharmacovigilance. To this end, we aimed to develop and validate a novel algorithm for detecting heparin-induced thrombocytopenia (HIT) using a medical information database (MID) and for identifying possible risk factors for HIT. METHODS: We developed a new algorithm for detecting HIT based on platelet count at distinct time-points and diagnostic information from patients treated with unfractionated heparin (UFH) from April 2008 through March 2012 at Hospital of Hamamatsu University School of Medicine, Japan. Definitive diagnoses of HIT were made through reviews of the medical records by a skilled haematologist. The performance of the algorithm was assessed using the positive predictive value (PPV). Multivariate logistic regression analysis was used to identify possible risk factors for HIT. RESULTS AND DISCUSSION: This algorithm detected 47 patients with suspected HIT in the source population (n = 2875). Of these, 41 were identified as patients with definitive HIT after review of the medical records. The PPV for the algorithm was 87·2%, and the frequency of definitive HIT was 1·4%. Longer-term treatment (≥4 days) with UFH was identified as a risk factor for HIT, with an odds ratio of 5·38 (95% CI: 2·35-12·32) for definitive HIT. WHAT IS NEW AND CONCLUSION: We developed a novel, high-PPV detection algorithm for HIT and identified longer-term treatment with UFH as a risk factor for HIT. Our results support the utility of MIDs for improving pharmacovigilance.

Development of a detection algorithm for statin-induced myopathy using electronic medical records.

WHAT IS KNOWN AND OBJECTIVE: Demonstration of the utility of electronic medical records (EMRs) for pharmacovigilance (PV) has been highly anticipated. Analysis using appropriately selected EMRs should enable accurate estimation of adverse drug event (ADE) frequencies and thus promote appropriate regulatory actions. Statin-induced myopathy (SIM) is a clinically important ADE, but pharmacoepidemiological methodology for detecting this ADE with high predictability has not yet been established. This study aimed to develop a detection algorithm, highly selective for SIM using EMRs. METHODS: We collected EMRs on prescriptions, laboratory tests, diagnoses and medical practices from the hospital information system of Kobe University Hospital, Japan, for a total of 5109 patients who received a statin prescription from April 2006 to March 2009. The current algorithm for extracting SIM-suspected patients consisted of three steps: (i) event detection: increase in creatine kinase (CK) and subsequent statin discontinuation, (ii) filtration by exclusion factors (disease diagnosis/medical practices) and (iii) refinement by the time course of CK values (baseline, event and recovery). A causal relationship between the event and statin prescription (probable/possible/unlikely) was judged by review of patient medical charts by experienced pharmacists. The utility of the current algorithm was assessed by calculating the positive predictive value (PPV). In a comparative analysis, subjects screened in step 1 were extracted by the diagnostic term/code for 'myopathy/rhabdomyolysis', and the PPV of this diagnostic data approach was also estimated. RESULTS AND DISCUSSION: Five subjects with suspected SIM were identified using our proposed algorithm, giving a frequency of 0·1% for the adverse event. Review of the medical charts revealed that the causal association of SIM with statin use was judged as 'Likely (probable/possible)' for all five suspected patients; thus, the PPV was estimated as 100% (95% confidence interval: 56·6-100%). The higher utility of the current algorithm compared with the diagnostic data approach was also shown by assessing the PPV (100 vs. 33·3%). WHAT IS NEW AND CONCLUSION: We report on a detection algorithm with high predictability for SIM using EMRs. Combined use of exclusion criteria for disease, medical practice data and time course of CK values contributes to better prediction of SIM. The utility of the proposed algorithm should be further confirmed in a larger study.

Effects of prostaglandin E1 on the preparation of platelet concentrates in dogs.

BACKGROUND: Platelet concentrates (PC) are prepared by centrifugation of platelet-rich plasma (PRP) that is prepared by centrifugation of whole blood. The resuspension of the platelet pellet during PC preparation from dogs is difficult because of platelet activation induced by centrifugation. OBJECTIVES: To investigate the efficacy of adding prostaglandin E(1) (PGE(1) ) to prevent platelet activation during PC preparation from dogs. ANIMALS: Fifteen healthy Beagle dogs. METHODS: Prospective, experimental trial: PGE(1) was added to PRP before the high-speed centrifugation during PC preparation. To estimate the effect of this addition, we assessed the platelet aggregability before transfusion, the survival of the platelets after transfusion, and the platelet reactivity after transfusion, which is estimated by the P-selectin expression of the platelets when stimulated by thrombin. RESULTS: The difficulty associated with platelet resuspension was resolved by PGE(1.) PGE(1) strongly inhibited platelet aggregation induced by collagen and ADP; however, it recovered after the platelets were resuspended in plasma without PGE(1) (mean aggregation ratio; collagen: 10.00-80.80%, ADP: 8.20-53.60%). Survival of the platelets after transfusion was not affected by PGE(1) (mean 8.04 and 7.56 days, without and with PGE(1) ), and thrombin-induced P-selectin expression after transfusion in PGE(1) -treated PC was also well maintained (mean positive ratio 53.7 and 47.9%, before and 24 hours after transfusion). CONCLUSIONS AND CLINICAL IMPORTANCE: The addition of PGE(1) in PRP before the centrifugation of PRP can improve the preparation efficiency of PC from dogs, while maintaining the therapeutic efficacy of the platelets.

Gastrin and Helicobacter pylori in low-grade MALT lymphoma patients.

BACKGROUND: This study of patients with Helicobacter pylori infection and low-grade MALT lymphoma aimed to investigate: 1) the effect of H. pylori eradication therapy on the serum gastrin level, 2) whether changes of the serum gastrin level after therapy could predict the prognosis of patients with this tumour, and 3) the relationship between the gastric H. pylori load, the serum gastrin level and the status of MALT lymphoma. METHODS: Thirteen patients with documented low-grade MALT lymphoma and H. pylori infection were enrolled and received H. pylori eradication therapy as the sole initial treatment. The presence of H. pylori, the serum gastrin level, the endoscopic findings, the pathologic features of the biopsies and resected specimens, and the endoscopic ultrasonography findings were evaluated before and after therapy. Follow-up was carried out every 3-6 months. RESULTS: H. pylori eradication was eventually achieved in all 13 patients. The pretreatment fasting serum gastrin level decreased from 177.1 +/- 107.4 pg/ml to 129.2 +/- 78.1, 96.4 +/- 66.6 and 80.1 +/- 42.7 pg/ml after 0-3, 3-6 and 6-9 months, respectively (all P < 0.05). Successful eradication of H. pylori was followed by a decrease of the fasting serum gastrin level and complete regression of initial low-grade MALT lymphoma was observed in all patients. However, two patients subsequently developed recurrent high-grade MALT lymphoma or high-grade lymphoma. In one of them, the serum gastrin level rose again above the pretreatment value. In the other, however, the fasting gastrin level fell throughout the study period. The median fasting serum gastrin level before H. pylori eradication therapy was higher in the patients with tumours of the gastric body (203.4 +/- 108.9 pg/ml) than in those with tumours of the antrum and angulus (89.3 +/- 28.0 pg/ml) (P = 0.06). CONCLUSIONS: Hypergastrinaemia may be associated with an increased risk of gastric MALT lymphoma.

Bilateral massive pleural effusions caused by uremic pleuritis.

A 61-year-old man was started on hemodialysis in June 1998. Just after the commencement of dialysis, a chest X-ray film revealed bilateral pleural effusions. The effusions were hemorrhagic and exudative, and did not respond to dialysis. He was transferred to our university hospital on October 8,1998. Repeated thoracentesis demonstrated hemorrhagic and exudative characteristics without any diagnostic evidence. Pleural biopsies showed fibrosis and lymphocyte infiltration. The effusions were massive and did not respond to treatments including hemodialysis, repeatedly performed pleurodesis and the administration of antituberculous drugs. He died of respiratory failure on December 30, 1998. The autopsy confirmed bilateral fibrinous pleuritis without any underlying infections or malignancy. We diagnosed this case as uremic pleuritis from this clinical course and the autopsy findings. The clinical entity of uremic pleuritis was recognized as a complication of patients with hemodialysis in 1969. Uremic pleuritis generally responds to continued hemodialysis and the prognosis is usually good. However, some case reports demonstrated that surgical decortication is only indicated in cases with a severe clinical course. The clinical course of the present case was progressive and fatal. Uremic pleuritis is a serious complication of hemodialysis, which may lead to death.

Adrenomedullin inhibits the pressor effects and decrease in renal blood flow induced by norepinephrine or angiotensin II in anesthetized rats.

Adrenomedullin (AM), a hypotensive peptide originally isolated from human pheochromocytoma, has been reported to regulate renal functions. In patients with glomerulonephritis, the serum levels of AM are elevated as well as hypertensive agents norepinephrine (NE) and angiotensin II (AII). The effects of AM on the NE- or AII-induced pressor effects and renal blood flow responses, however, are not well clarified. We examined the effects of AM on blood pressure and renal blood flow induced by NE or AII in anesthetized rats. Arterial blood pressure and renal blood flow were measured using a calibrated pressure transducer and a laser Doppler flowmeter, respectively. Drugs were injected into the tail vein with a syringe. Intravenous administration of AM (1-3 nmol/kg) decreased the arterial blood pressure in anesthetized rats in a dose-dependent manner, whereas it did not affect the renal blood flow. NE or AII administration in anesthetized rats caused both increases in blood pressure and decreases in renal blood flow. Simultaneous administration of AM with NE or All prevented the increasing effects of blood pressure and inhibited the decreases in renal blood flow caused by NE or AII. These findings suggest that AM may have a protective role against the pressor effects and decrease in renal blood flow caused by NE or AII.

Mobility of the doped holes and the antiferromagnetic correlations in underdoped high- Tc cuprates.

The emergence and the evolution of the metallic charge transport in the La2-xSrxCuO4 system from lightly to optimally doped samples (x = 0.01-0.17) are studied. We demonstrate that in high-quality single crystals the in-plane resistivity shows a metallic behavior for all values of x at moderate temperatures and that the hole mobility at 300 K changes only by a factor of 3 from x = 0.01 to 0.17, where its x dependence is found to be intriguingly similar to that of the inverse antiferromagnetic correlation length. We discuss an incoherent-metal picture and a charged-stripe scenario as candidates to account for these peculiar features.

Transport anomalies and the role of pseudogap in the 60-K phase of YBa(2)Cu(3)O(7-delta).

We report the result of our accurate measurements of the a- and b-axis resistivity, Hall coefficient, and the a-axis thermopower in untwinned YBa(2)Cu(3)O(y) single crystals in a wide range of doping. It is found that both the a-axis resistivity and the Hall conductivity show anomalous dependences on the oxygen content y in the 60-K phase below the pseudogap temperature T(*). The complete data set enables us to narrow down the possible pictures of the 60-K phase, with which we discuss a peculiar role of the pseudogap in the charge transport.

Clinical significance of natriuretic peptides and cyclic GMP in hemodialysis patients with coronary artery disease.

BACKGROUND: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) are suitable markers of 'dry body weight' (DW) in hemodialysis (HD) patients. However, it is still unknown whether these markers can be applied to patients with renal failure and coronary artery disease (CAD). We examined the reliability of these peptides as volume markers in HD patients with CAD. We also assessed the relationship between natriuretic peptides and indices of left ventricular (LV) function. METHODS: Plasma concentrations of ANP, BNP and cGMP were determined before and after HD in patients with CAD (group 1, n = 19, mean age 63 +/- 12 years) and were compared with those of patients without cardiac disease (group 2, n = 20, age 61 +/- 15 years). Using data obtained by cardiac catheterization, we examined the relationship between natriuretic peptides and indices of LV function in HD patients with CAD. RESULTS: Baseline ANP (244 +/- 205 pg/ml), BNP (713 +/- 928 pg/ml) and cGMP (29.6 +/- 21.6 pmol/ml) were significantly higher in group 1 than in 11 healthy volunteers (18.6 +/- 9.9 pg/ml, 7.7 +/- 7.6 pg/ml, cGMP 8.9 +/- 4.9 pmol/ml, respectively). HD significantly reduced plasma ANP (87 +/- 75 pg/ml) and BNP (477 +/- 702 pg/ml) although they were still above normal control. HD reduced plasma cGMP (7.2 +/- 4.5 pmol/ml) to normal values, suggesting the elimination of cGMP across the dialyzers. Baseline levels of ANP, BNP and cGMP in group 2 were less than those of group 1 but higher than the control. HD reduced natriuretic peptides in group 2 to levels lower than those in post-HD group 1. After HD, there was no significant correlation between reductions in body weight and changes in ANP or BNP. Baseline ANP and BNP levels closely correlated with pulmonary artery pressure, pulmonary artery wedge pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction. A significant correlation was observed between BNP levels and the severity of CAD. CONCLUSION: ANP, BNP and cGMP seem to be a useful markers for fluid overload but not for DW in HD patients with CAD. Plasma ANP and BNP might be useful markers for left ventricular function.

Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway.

We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K(ATP)) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 microM to 1 mM inhibited [(3)H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 microM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K(ATP) mediators. Cromakalim, a K(ATP) activator, and glibenclamide, a K(ATP) inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.

Both of the N-terminal and C-terminal regions of human papillomavirus type 16 E7 are essential for immortalization of primary rat cells.

E7 oncoproteins of mucosal high-risk human papillomavirus type 16 and 18 (HPV16 and HPV18) immortalize primary rodent cells and transform them in collaboration with the activated ras, possibly by interaction with retinoblastoma gene product RB and its related p107. On the other hand, E7 of the cutaneous epidermodysplasia verruciformis-associated HPV5 and HPV8 possess ras-collaborative transformation but not immortalization activity. By using polymerase chain reaction, we constructed chimeric E7 from immortalizing HPV16 E7 and nonimmortalizing HPV5 E7, which have boundaries at the 37/39th, 61/62th, or 79th codon of the HPV16 E7. These chimeric E7 were cloned into the expression vectors to examine their ras-collaboration and immortalization activities. Chimeric E7 that contained N-terminal 39 amino acid residues (R), 61R and 79R of HPV16 E7, showed ras-collaboration activity in primary rat embryo fibroblast and primary baby rat kidney (BRK) cells as efficiently as HPV16 E7. Meanwhile, only the chimeric E7 containing N-terminal 79R of HPV16 E7 was able to immortalize primary BRK cells without second oncogenes. Co-transfection of two chimeric E7 carrying HPV16 N-terminus and HPV16 C-terminus induced immortalization of primary BRK cells. These results suggest that (i) in addition to the N-terminal RB-binding domain, the C-terminal region of HPV16 E7 is essential for immortalization of primary BRK cells, and (ii) two different immortalization functions are present in the two regions of HPV16 E7. By using a yeast two hybrid system, we searched for the HeLa cDNA whose products can bind the C-terminal region of HPV16 E7.

A clinicopathologic study of gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: It is still unclear which patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma will benefit from the eradication of Helicobacter pylori. METHODS: The authors studied a total of 34 patients. Twenty-three patients had primary gastric lymphoma and underwent gastric resection as initial treatment. Eleven patients with gastric MALT lymphoma who received antibiotics against H. pylori as initial treatment were also included. In all 34 patients, the presence of H. pylori, endoscopic findings, and pathologic features were evaluated. Immunohistochemical expression of Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) was classified as follows: (-), no reactive cells; (+), scattered positive cells; (2+), nests of positive cells; (3+), diffuse positive cells. RESULTS: Patients with low grade MALT lymphoma (LG) tended to be positive for H. pylori (6 of 9), to localize within the submucosa (7 of 9), not to have lymph node involvement (7 of 8), and to have lower tumor stage compared with patients with high grade MALT components (HG). Bcl-2 protein was expressed with high frequency by LG (7 of 9). Strong expression of p 53 was more common in the HG tumors (4 of 14), and strong expression of PCNA showed a significant difference between LG (1 of 8) and HG patients (12 of 13). Investigation of the patients with long term follow-up (n = 4) revealed that LG remained superficial for a long time and showed gradual progression. Most of these tumors were Bcl-2+/p53-approximately+/-/ PCNA- approximately +. There were two patients whose superficial LG (sm/Bcl-2+/p53-/PCNA- approximately +) regressed after the disappearance of H. pylori. On the other hand, one patient developed ulcerated LG (sm/Bcl-2 /p53+/PCNA3+) after disappearance of H. pylori. The authors found complete regression of MALT lymphoma in 9 of 11 patients after H. pylori eradication. Initial tumors of these 9 patients were superficial/sm/n(-)/low grade/Bcl-2+approximately +/-/p53-approximately+ (n = 9), /PCNA-approximately+(n = 6), /PCNA 2+ (n = 3). Two local recurrence and one non-Hodgkin lymphoma in other sites were observed after initial therapy. CONCLUSIONS: Gastric MALT lymphoma with (H. pylori positive/superficial/sm/low grade/Bcl-2 +/p53- approximately +/PCNA- approximately +) pattern will disappear after a patient is cured of H. pylori infection.

A new bioactive steroidal saponin, furcreastatin, from the plant Furcraea foetida.

Microbial and plant secondary metabolites were screened for compounds that are selectively cytotoxic to mutant p53-expressing mouse fibroblasts. As a result, furcreastatin, a novel steroidal saponin, was isolated from an EtOH extract of the leaves of Furcraea foetida. Furcreastatin consisted of hecogenin as the aglycone and a hexasaccharide containing D-galactose, L-rhamnose and four D-glucose residues. The structure was determined to be (3 beta,5 alpha,25R)- 3-hydroxyspirostan-12-one 3-O-[alpha-L-Rhap-(1-->4)-beta-D-Glcp-(1-->3)-¿beta-D-Glcp-(1-->3) -beta-D- Glcp-(1-->2)¿-beta-D-Glcp-(1-->4)-beta-D-Galp] by extensive NMR spectroscopic studies. Furcreastatin decreased the viability of mutant p53-over-expressing cells with an ED50 of 4.0 micrograms/mL, and decreased that of the parental cell-line with an ED50 of 9.6 micrograms/mL.