Total Syntheses of Marrubiin and Related Labdane Diterpene Lactones.

Total syntheses of the labdane diterpene lactones marrubiin, marrulibacetal, desertine, marrulibacetal A, marrubasch F, cyllenine C, marrulanic acid, and marrulactone are described. The trans-decalin moiety of these molecules was constructed in a stereoselective manner by a Pauson-Khand reaction, and the resultant cyclopentenone was oxidatively cleaved for formation of the lactone ring. Elongation of the side chain at C9 was achieved by an epoxide-opening reaction with a variety of nucleophiles, and the functional group manipulations completed the syntheses of these natural products. Stereochemistries of desertine could be established by the transformations.

Comparison of single-stapling and hemi-double-stapling methods for intracorporeal esophagojejunostomy using a circular stapler after totally laparoscopic total gastrectomy.

BACKGROUND: Laparoscopic total gastrectomy is not widely performed because of the difficulty of esophagojejunal reconstruction. This study analyzed complication rates of two different methods for reconstruction by a circular stapler after totally laparoscopic total gastrectomy (TLTG). METHODS: Between 2010 and 2014, clinical data of 19 patients who underwent TLTG for gastric adenocarcinoma were collected retrospectively. There were two methods to fix the anvil of a circular stapler into the distal esophagus: In the single-stapling technique (SST) group, Endo-PSI(II) was used for purse-suturing on the distal esophagus for reconstruction, and in the hemi-double-stapling technique (hemi-DST) group, the esophagus was cut by linear stapler with the entry hole of the anvil shaft opened after inserting the anvil tail. In both groups, surgical procedures were the same, except for the reconstruction. RESULTS: All TLTGs were performed securely without mortality. Intracorporeal laparoscopic esophagojejunal anastomosis was performed successfully for all the patients. In the hemi-DST group, four patients experienced anastomotic stenosis, three of whom required endoscopic balloon dilation. In contrast, no stenosis was seen in the SST group (p = 0.033). CONCLUSIONS: Anastomosis with SST is preferred to that with hemi-DST to minimize postoperative complications.

Construction of Bridged Polycyclic Systems by Polyene Cyclization.

A stereoselective construction of bridged tri- and tetracyclic systems embedded in some 3,5-dimethylorsellinic acid (DMOA)-derived meroterpenoids was achieved by exploiting a polyene cyclization of suitably functionalized epoxyallylsilanes. Both the olefinic substituent on the epoxide and allylic trimethylsilyl (TMS) group were found to play pivotal roles in the success of the present reaction. The fact that the cyclization of monocyclized byproducts did not proceed strongly suggests that the reaction could be a concerted transformation.

Glycosylation with 2-Acetamido-2-deoxyglycosyl Donors at a Low Temperature: Scope of the Non-Oxazoline Method.

A direct construction of 1,2-trans-ß-linked 2-acetamido-2-deoxyglycosides was investigated. The 3,4,6-tri-O-benzyl- and 3,4,6-tri-O-acetyl-protected glycosyl diethyl phosphites and 4,6-O-benzylidene-protected galactosyl diethyl phosphite each reacted with a variety of acceptor alcohols in the presence of a stoichiometric amount of Tf2NH in CH2Cl2 at -78 °C to afford the corresponding ß-glycosides in good to high yields with complete stereoselectivity. Some experiments provided strong evidence that the corresponding oxazolinium ions are not responsible for the reaction. We demonstrated that glycosylations with the corresponding glycosyl imidate and thioglycoside also proceeded at a low temperature, indicating the possibility of these donors being attractive alternatives to the phosphite. A plausible reaction mechanism, which features glycosyl triflimide and contact ion pair as reactive intermediates, is proposed on the basis of the results obtained with 2-acetamido-2-deoxymannosyl donors.

Synthesis of the Tetrasaccharide Repeating Unit from Acinetobacter baumannii Serogroup O18 Capitalizing on Phosphorus-Containing Leaving Groups.

The first convergent synthesis of the tetrasaccharide repeating unit of the polymeric O antigen isolated from Acinetobacter baumannii serogroup O18 has been achieved. The ManNAcß1→4Gal and GalNAcß1→3Gal units were successfully obtained through ß-selective glycosylation with 2-azido-4,6-O-benzylidene-2-deoxymannosyl diphenyl phosphate and Tf2NH-promoted glycosylation with 2-acetamido-2-deoxygalactosyl diethyl phosphite, respectively. The disaccharide units could be coupled with the aid of TMSClO4 as an activator of the diphenyl phosphate leaving group, and global deprotection completed the synthesis of the tetrasaccharide.

Synthesis of chiral building blocks for oxygenated terpenoids through a simultaneous and stereocontrolled construction of contiguous quaternary stereocenters by an Ireland-Claisen rearrangement.

Methods for highly stereocontrolled syntheses of chiral building blocks with a triad of contiguous stereocenters, including two quaternary ones, have been developed. Ireland-Claisen rearrangement of the (Z)-silyl ketene acetal generated stereoselectively from the (R)-3-methylcyclohex-2-enyl ester derived from an acyclic carboxylic acid proceeded through a chairlike transition state to give the rearranged product with an S configuration at the position α to the carboxyl group. Introduction of a cyclic conformational constraint in the acid component completely switched the transition state of the rearrangement to a boatlike one, leading to the predominant formation of a product with an R configuration, from which pseudodiastereomeric α-hydroxy esters were obtained in a four-step sequence. The enyne obtained through a base-mediated double eliminative ring-opening reaction was successfully converted into advanced intermediates for the synthesis of 9-oxygenated labdane diterpenoids through a Heck reaction and a regioselective transformation of the resultant diene.

Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established oral S-1 administration for 1 year as the standard postoperative adjuvant chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative prospective study comparing daily and alternate-day S-1 administration as postoperative adjuvant therapy for gastric cancer. METHODS: Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for 15 months). Treatment completion rate was the primary endpoint, and relative dose intensity and safety, overall survival, and relapse-free survival (RFS) were secondary endpoints. RESULTS: Seventy-three patients were enrolled. The treatment completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better in group B. Digestive system adverse effects were less frequent in group B than in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 % in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and 73.1 % in group B. CONCLUSIONS: Our data show improved compliance and fewer adverse effects with alternate-day S-1 administration, which appears to be a more sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.

Total syntheses of (+)-polygalolide†a and (+)-polygalolide†b: elucidation of the absolute stereochemistry and biogenetic implications.

The total syntheses of (+)-polygalolide A and (+)-polygalolide B have been completed by using a carbonyl ylide cycloaddition strategy. Three of the four stereocenters, including two consecutive tetrasubstituted carbon atoms at C2 and C8, were incorporated through internal asymmetric induction from the stereocenter at C7 by a [Rh(2) (OAc)(4)]-catalyzed carbonyl ylide formation/intramolecular 1,3-dipolar cycloaddition sequence. The arylmethylidene moiety of these natural products was successfully installed by a Mukaiyama aldol-type reaction of a silyl enol ether with a dimethyl acetal, followed by elimination under basic conditions. We have also developed an alternative approach to the carbonyl ylide precursor based on a hetero-Michael reaction. This approach requires 18 steps, and the natural products were obtained in 9.8 and 9.3 % overall yields. Comparison of specific rotations of the synthetic materials and natural products suggests that polygalolides are biosynthesized in nearly racemic forms through a [5+2] cycloaddition between a fructose-derived oxypyrylium zwitterion with an isoprene derivative.

Differences in the clinical characteristics of Pneumocystis jirovecii pneumonia in immunocompromized patients with and without HIV infection.

BACKGROUND AND OBJECTIVE: The incidence of Pneumocystis jirovecii pneumonia (PCP) in patients with predisposing immunodeficiencies other than AIDS is growing. Knowing the different characteristics and outcomes of PCP according to HIV status would help physicians manage and treat patients with PCP. METHODS: The medical charts of all patients with a proven first episode of PCP, diagnosed between 1997 and 2007 were retrospectively reviewed, and clinical and laboratory data abstracted. RESULTS: Of the 35 patients with PCP, 18 were HIV-positive and 17 were HIV-negative with other immunosuppressive conditions. HIV-negative patients were significantly older than HIV-positive patients. The WCC (10 952 +/- 5669 vs 9750 +/- 3133/microL; P = 0.015), neutrophil counts (9631 +/- 5421 vs 5680 +/- 2628/microL; P = 0.01) and CD4+ lymphocyte counts (329 +/- 502 vs 47 +/- 50/microL; P < 0.001) were significantly higher in HIV-negative patients. Six of the 17 HIV-negative patients had a CD4+ lymphocyte count >300/microL. Serum IgG levels were lower in HIV-negative patients (943 +/- 379 vs 1635 +/- 657 mg/dL; P = 0.017). Mortality was higher in HIV-negative (52.9%) than in HIV-positive patients (0%). On univariate analysis, risk factors for mortality from PCP were the presence of underlying pulmonary disease (odds ratio 4.000, 95% CI: 1.501-10.658) and HIV-negative status (odds ratio 2.125, 95% CI: 1.283-3.518). CONCLUSIONS: The characteristics and outcomes of PCP differ significantly depending on HIV status. The existence of underlying pulmonary diseases may be associated with the prognosis of HIV-negative patients with PCP.

Advanced cancer with situs inversus totalis associated with KIF3 complex deficiency: report of two cases.

Situs inversus totalis (SIT) is a relatively rare congenital anomaly, occurring at an incidence of 1 in 10 000-50 000 live births. Although there are some case reports of SIT with the presence of cancer, there are few reports on the relationship between SIT and cancer. However, the recent phylogenetic investigations of this condition suggest that this may be linked to the development and progression of cancer on the molecular level. The key elements are one of the intracellular motor proteins, the KIF3 complex, and the cell-adhesion factors N-cadherin and beta-catenin. We herein present the cases of advanced gastric cancer and lung cancer with SIT, and review the relationship between SIT and the development and progression of cancer.

[A case of sarcoidosis with an endobronchial polypoid lesion].

A 59-year-old woman complained of impaired vision. She visited an ophthalmologist and glaucoma was diagnosed. In July 200X, she was admitted to our hospital for further examination. Chest radiography and CT showed lymphadenopathy in the mediastinum and bilateral hilum. Bronchofiberscopy revealed mucosal hypervascularity and a polypoid lesion at the orifice of the left B8a. A transbronchial biopsy specimen of the polypoid lesion showed non-caseating epithelioid cell granuloma. On bronchoalveolar lavage, both the proportion of lymphocytes and the CD 4/8 ratio had increased. We diagnosed sarcoidosis with an endobronchial polypoid lesion. The patient has been observed without therapy since, and after a year the polypoid lesion is the same size on 3D CT scans. This is a very rare case of endobronchial sarcoidosis presenting as a polypoid lesion.

[Detection of pleural plaques on chest X-ray film by chest physicians].

With increasing awareness about health damage due to asbestos exposure, the number of people presenting with non-occupational exposure has increased remarkably. Consequently, chest physicians in general hospitals must read the chest X-ray films of patients with asbestos exposure. Can non-specialized chest physicians, who may have little experience of occupational medicine, diagnose pleural plaques accurately? The study subjects were 44 consecutive patients who were admitted to our hospital, under the Japanese medical health check system for workers employed in dangerous work. Their chest X-ray films were checked by 4 chest physicians, who were independently informed that the patients had a high suspicion of asbestos exposure. The detection rate of chest Xray for pleural plaques was compared with computed tomography (CT) results as the gold standard. The sensitivity was 0.818 and the specificity was 0.393. The sensitivity of the presence of pleural plaques was lower in anterior and posterior sites, and on the pleura adjacent to the mediastinum, pericardium and vertebral (0.429, 0.348, 0.217), while specificity was lower on lateral sites (0.610). Chest physicians in general hospitals must be trained in the manifestation of asbestos-related diseases.

Encapsulated fat necrosis mimicking abdominal liposarcoma: A case report and literature review.

We report a case of an encapsulated fat necrosis without significant medical history. To differentiate from liposarcoma, it should be recognized that a half of abdominal encapsulated fat necrosis cases have a history of inflammation and surgery.

Investigation of the Utility and Safety of Dynamic Computed Tomography with Vasodilators.

BACKGROUND: Dynamic computed tomography (CT) angiography is useful for evaluating of hepatic vascularity. Although vasodilators increase hepatic blood flow, the utility of dynamic CT with vasodilators is unclear. Here we investigated the utility and safety of dynamic CT with vasodilators. METHODS: A prospective case-control radiographic evaluation using abdominal dynamic CT with and without vasodilator was performed at a single center between October 2015 and September 2016. We compared the CT values in Hounsfield units of the aorta; celiac artery; and common, right, and left hepatic arteries in the arterial phase and the main trunk; right and left branches of the portal vein; and right, middle, and left hepatic veins in the portal phase with and without vasodilators. The region of interest was set in each element of the liver vasculature. Four radiological technologists independently and visually compared the scores of the portal vein (P-score) and hepatic vein (V-score) on a 5-point scale with and without vasodilators. RESULTS: The CT values of arteries and veins using vasodilators were significantly higher than those without vasodilators. With and without vasodilators, the P-scores were 3.1 ± 1.2 and 4.0 ± 1.1 (P < 0.05) and the V-scores were 3.3 ± 1.4 and 4.3 ± 1.0 (P < 0.05). Only one patient with vasodilator use had transient hypotension and recovered immediately without medication. CONCLUSION: Dynamic CT with vasodilators can provides better visualization of vascular structures.

Thyroid nodule prevalence among women in areas of high natural background radiation, Karunagappally, Kerala, India.

PURPOSE: Radiation exposure has been reported to cause thyroid nodules. The study area was Karunagapally, which has several areas with high natural radiation levels derived from thorium and its decay products. Since thyroid abnormalities are more common in women, the focus was only on women. METHODS: The examinations included interview, ultrasonography of the thyroid and serum assays of free thyroxine (FT4), thyrotropin (TSH), and anti-thyroglobulin levels. Cumulative dose during the childhood and lifetime cumulative dose (lagged by 5 years) were estimated. RESULTS: We examined 524 female residents aged 17-73 years and found 75 cases of solitary solid thyroid nodules. The prevalence of thyroid nodules were 14.1 % (n = 42) in high dose panchayats and 14.5% (n = 33) in low-dose panchayats. In the logistic regression analysis adjusted for age, the prevalence of solitary thyroid nodule was not linearly related to childhood cumulative dose (P for trend = 0.159) and lifetime cumulative dose (P for trend = 0.333). The prevalence of thyroiditis and hypothyroidism was not related to natural radiation exposure. Serum levels of FT4 or TSH were not related to natural radiation exposure. CONCLUSIONS: The results obtained from the present study do not support the increase of solitary thyroid nodule, thyroiditis or hypothyroidism in relation to high-natural-background-radiation exposure.

Asymmetric synthesis of neolignans (-)-epi-conocarpan and (+)-conocarpan via Rh(II)-catalyzed C-H insertion process and revision of the absolute configuration of (-)-epi-conocarpan.

Catalytic asymmetric synthesis of neolignan natural products (-)-epi-conocarpan and (+)-conocarpan has been achieved by exploiting an enantio- and diastereoselective intramolecular C-H insertion reaction to construct a cis-2-aryl-2,3-dihydrobenzofuran ring system as a key step. The C-H insertion reaction of 5-bromoaryldiazoacetate catalyzed by Rh(2)(S-PTTEA)(4), a new dirhodium(II) carboxylate complex that incorporates N-phthaloyl-(S)-triethylalaninate as chiral bridging ligands, provided 2-aryl-5-bromo-3-methoxycarbonyl-2,3-dihydrobenzofuran with exceptionally high diastereoselectivity (cis/trans = 97:3) and high enantioselectivity for the cis isomer (84% ee).

Clinical importance of preoperative and postoperative prognostic nutritional index in patients with pancreatic ductal adenocarcinoma.

BACKGROUNDS/AIMS: The prognostic nutritional index (PNI) is based on the albumin concentration and absolute lymphocyte count and is designed to assess the nutritional and immunological status of patients. In this study, we evaluated the prognostic importance of the preoperative and postoperative PNI in patients who underwent curative resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: From 2006 to 2017, 50 patients with PDAC underwent curative resection at our hospital. We performed distal pancreatectomy (DP) with splenectomy in 15 patients, pancreaticoduodenectomy (PD) in 27 patients, PD combined with portal vein partial resection in 6 patients, and total pancreatectomy with splenectomy in 2 patients. We compared the preoperative PNI and postoperative PNI (1 and 2 months postoperatively) and analyzed the prognostic importance for these patients. RESULTS: The mean PNI significantly decreased from 45.5 preoperatively to 39.8 at 1 month postoperatively (p<0.001), but recovered to 42.7 at 2 months postoperatively. In 23 patients, the PNI at 2 months postoperatively recovered to the preoperative level (recovered group), but in the remaining 27 patients, the PNI at 2 months postoperatively did not reach the preoperative level (non-recovered group). The overall median survival time in the recovered group (29 months) was significantly longer than that in the non-recovered group (12 months, p=0.003). The multivariate overall analysis demonstrated that good recovery of the postoperative PNI was strongly correlated with a better prognosis. CONCLUSIONS: Effective postoperative nutrition may have a prognostic benefit for patients with operable PDAC.

[Clinical analysis of patients with tuberculosis admitted on an emergency cases].

A retrospective study was made of 75 patients with tuberculosis and tuberculous pleurisy who received medical care in our hospital from 2002 through 2006. Of the 75 patients, 9 were admitted as tertiary emergency cases, and 12 patients were admitted by ambulance as secondary emergency cases. We studied the reason for their emergency medical admission, and the process of diagnosing 21 patients as tuberculosis. In some cases, the reasons for emergency admission were cardiorespiratory arrest, loss of consciousness, and injury resulting from a traffic accident, not common symptoms of tuberculosis such as dyspnea, hemoptysis and bloody sputum. Chest radiographic findings of most patients showed tuberculosis, and other cases were likely to be diagnosed as tuberculosis from their medical history or back-ground such as being homeless, previous tuberculosis, and receiving for therapy of tuberculosis. It was not so difficult to diagnose our cases as tuberculosis, nevertheless we may have an unconscious patient with normal chest radiograph. These data suggest that any patients visiting the emergency room may possibly have tuberculosis even if they are without respiratory symptoms.

[Clinical statistics of outpatients investigated for asbestos-related lung diseases at a general hospital in Tokyo].

We evaluated 122 outpatients who visited our hospital for examination of asbestos-related diseases between November, 2005 and October, 2006. Patients were divided into three groups; occupational exposure, non-occupational exposure and non-exposure groups. The occupational exposure group showed a significantly higher rate of asbestos-related abnormal findings than the non-occupational exposure plus the non-exposure group (33% vs. 5%, respectively; P = 0.001). Pleural plaque was the most common abnormal finding related to asbestos. Only four of 24 patients with pleural plaques could obtain personal health records for workers enjoyed in dangerous work, whereas the rest of them were not able to mainly because they were self-employed. A health support system is necessary to also cover non-employees.

[A case of bird related hypersensitivity pneumonitis had a progressive course].

A 50-year-old woman was admitted due to productive cough continuing for 3 years. A chest computed tomography showed appearance of nonspecific interstitial pneumonia (NSIP). Thoracoscopic lung biopsy specimens showed mainly a pattern of NSIP with multinucleated cells and cholesterol clefts. She was not a bird fancier, but had indirect exposure to birds in her living environment, and had been using feather-filled duvets for a long time. We established a diagnosis of bird-related hypersensitivity pneumonitis based on antibodies in serum positive to pigeon dropping extracts. She was treated by coadministration of corticosteroids and immunosuppressants, and avoidance of bird-related antigens, but had a progressive course and died of respiratory failure.