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The effect of genetic polymorphism of DNA repair enzyme on the DNA adduct levels was evaluated in this study. We explored the relationship between polymorphism in the nucleotide excision repair enzyme XPD and DNA adduct levels in lymphocytes. Lymphocyte DNA adducts were measured by a [sup 32]P-postlabelling method from 42 subjects. XPD ex23 genotypes were identified by the PCR-RFLP method. Subjects with the XPD ex23 heterozygous genotype (AC) showed significantly lower DNA adduct levels (0.63 ± 0.19 per 10[sup 8] nucleotides, n = 6) than those (0.92 ± 0.38, n = 36) with major homozygous genotypes (AA). This result suggests that the genotype of the repair enzyme may be one of the important determinants for DNA adduct levels. [ABSTRACT FROM AUTHOR]

DADI is a mammalian homologue of Saccharomyces cerevisiae Ost2p, a subunit of the oligosaccharyltransferase complex. Loss of its function induces apoptosis in hamster BHK21 cells. By means of a two-hybrid method involving DAD1 as bait, the C-terminal region of Mcl-1, one of the bcl-2 family, was isolated. Consistently, DAD1 binds well to Mcl-1 in COS cells when overexpressed. On deletion analysis, the C-terminal domain of Mcl-1 containing BH2 (bcl-2 homologous domain) was found to be essential for the interaction with DAD1. On the other hand, the C-terminal half of DADI was concluded to be essential for the interaction with Mcl-1. In contrast, ΔN DAD1 lacking 20 amino acid residues from the N-terminus still exhibited the ability to complement the tsBN7 mutation. Thus, the C-terminus of DAD1 was suggested to play an important role in N-linked glycosylation and to complement the tsBN7 mutation. Mcl-1 may be required for the inhibition of apoptotic cell death caused by a loss of DAD1. [ABSTRACT FROM AUTHOR]

A rare case of an extrathoracic giant hematoma developing after a thoracoplasty in a 67 year old man is presented herein. The patient underwent a right thoracoplasty without removal of plombage and a left thoracoplasty with removal of plombage for tuberculosis of the bilateral upper lobes 27 and 24 years prior to presentation, respectively. He presented to us in May, 1987, with a subscapular tumor which had been growing over the last 5 years. A giant tumor, measuring 23×17×12 cm and weighing 2585 g was successfully removed and the patient has since been well without any evidence of recurrence. [ABSTRACT FROM AUTHOR]

Reviewing the outcome of 70 cases of clinically localized small cell lung cancer (SCLC) treated with combined modality treatment, we attempted to define the role of resection in this disease. The survival rate for all cases was 37 per cent at 2 years and 23 per cent at 3 years with a median survival time (MST) of 14 months. For 25 resected cases the overall 5-year survival rate was 37 per cent with an MST of 26 months. According to clinical staging, 5-year survival was 64 per cent for stage I and 20 per cent for stage II. However, none of the stage III cases achieved long-term survival, of over 3 years. In 45 non-resected cases, the overall response rate was 84 per cent with a 44 per cent complete response. The overall survival rate was 27 per cent at 2 years and 14 per cent at 3 years with an MST of 11 months. The 20 cases who achieved complete response had an MST of 26 months with 51 per cent alive at 2 years and 19 per cent at 5 years. Thus, we consider that lung resection is definitely indicated in cases with stage I and probably stage II SCLC. For stage III, however, particularly in cases with N2 disease, resection seems to offer no special benefit in favor of survival compared to combination chemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]

The effect of the site of operation on postoperative hypoxemia was studied in 104 patients undergoing thoraco-abdominal, thoracic, upper abdominal, lower abdominal, extra-abdominal and non-thoracic operations. The degree of postoperative hypoxemia was the most extensive in patients undergoing thoraco-abdominal, moderate in thoracic and upper abdominal operations, and minimal in lower abdominal and other operations. On the other hand, the duration of hypoxemia also differed with the surgical procedures. Arterial oxygen tension returned to almost control values by the 3rd postoperative day in cases of lower abdominal and extremity operations and by the 7th postoperative day in those undergoing thoracic and upper abdominal surgery. Postoperative hypoxemia, however, remained throughout the fourteen day study period, in patients undergoing thoraco-abdominal operation. True shunt was measured in 27 patients with thoraco-abdominal, thoracic and upper abdominal operations. An increase in true shunt was evident postoperatively in the entire group of patients. The increase was significantly larger and longer lasting in cases of thoraco-abdominal incision than that in cases of thoracic and upper abdominal incision alone. Differences in postoperative true shunt between cases of thoracic and upper abdominal incisions were nil. [ABSTRACT FROM AUTHOR]

The effect of decreased plasma colloid osmotic pressure on the development of pulmonary edema was studied in anesthetized dogs. Lung lymph flow was used as a sensitive and reliable indicator of fluid filtration rate in the lung. When plasma colloid osmotic pressure alone was reduced by slow infusion of saline, and hydrostatic pressure in the pulmonary vascular bed was maintained at normal level by exsanguination, lung lymph flow increased almost linearly with the reduction in colloid osmotic pressure, but was not increased more than five fold of the control, despite a reduction of 80% in the plasma colloid osmotic pressure. Furthermore, there was no evidence of fluid in the tracheal aspirations and no gross evidence of pulmonary edema. In contrast, both decrease in colloid osmotic pressure and increase in pulmonary capillary hydrostatic pressure produced a marked increase in lung lymph flow. This flow varied linearly with the level of the pulmonary artery wedge-plasma colloid osmotic pressure difference and approached twelve fold of the control, when the plasma colloid osmotic pressure was reduced by 73% and the pulmonary artery wedge pressure was elevated by 20 mmHg from the baseline. Our data indicate that decreased colloid osmotic pressure is not associated with the development of pulmonary edema, when there is no increase in pulmonary vascular hydrostatic pressure. [ABSTRACT FROM AUTHOR]

Pulmonary functions were measured in 53 patients with hepatic cirrhosis in whom there was no clinical or radiographic evidence of pulmonary involvement. Spirometric tests such as total lung capacity, vital capacity, functional residual capacity, residual volume and forced expiratory volume during one second were within normal ranges, in all subjects. Flow volume curve and closing volume tests, however, were abnormal in the majority. The maximal expiratory flow at 50 per cent of vital capacity was not altered but the maximal expiratory flow at 25 percent of vital capacity was decreased significantly in patients with hepatic cirrhosis. The closing volume in patients with hepatic cirrhosis was also significantly increased. The abnormalities in flow volume curve and closing volume curve were also demonstrated in non-smokers, and at any age, in cases of hepatic cirrhosis. These results suggested that the narrowing or closure in small airways may occur in patients with hepatic cirrhosis. These changes may be due to mechanical compression of small airways by interstitial edema which was induced by presence in the circulating blood of vasoactive substances and endotoxins. [ABSTRACT FROM AUTHOR]

We have treated 40 patients with thymoma. All the 18 with benign thymoma were treated with resection alone and none had a tumor recurrence or died from disease-related causes. Postoperative survival in this group ranged from 2 months to 14 years. Of the 22 patients with malignant thymoma, 2 underwent total resection, 10 partial resection and 10 were non-resectable. Fifteen of the 20 patients with non-resectable and partially excised thymomas were given radiotherapy. The cumulative 5- and 10-year survival rate of irradiation treated patients was 45.6%, and 34.4%, respectively. Of 6 non-irradiated patients, only one who underwent complete excision of tumors survived for more than 10 years, and 5 died within 3 years after treatment. Based on our findings we suggest that all patients with malignant thymoma, irrespective of the extent of surgical treatment, should be given postoperative irradiation. [ABSTRACT FROM AUTHOR]

We reported previously that granulocyte colony-stimulating factor (G-CSF) can promote the invasion ofhuman lung cancer cell lines in vitro. However, the exact mechanism of its stimulatory effect on invasionremains to be elucidated. In the present study we mainly focused our attention on the components of theplasminogen activation system in human lung cancer cell lines, because of the central role that plasminogenactivators play in regulating extracellular proteolysis. We showed that G-CSF induced a dose-dependentincrease in the urokinase-type plasminogen activator (uPA) activity in the conditioned medium of a PC-9lung cancer cell line. When the amounts of uPA activity were quantitated by densitometry, we found thateven at a concentration of 0.01 mg/ml, G-CSF had a stimulatory effect on the uPA release, while highconcentrations caused a 3.6-fold increase at a maximum concentration of 1 mg/ml. A Western blot analysisof the conditioned medium confirmed the findings observed in a zymographic analysis. The observed increasein uPA protein was paralleled by a significant increase in the uPA mRNA levels after treatment withG-CSF. However, our experiments failed to identify any alteration in the plasminogen activator inhibitor(PAI) secretion caused by G-CSF. In addition, we also found the expression of G-CSF receptor by PC-9cells, suggesting the possible pathway activated by G-CSF.©Kluwer Academic Publishers [ABSTRACT FROM AUTHOR]

Group C adenovirus is latent in human tissues and can malignantly transform cells. The purpose of this study was to investigate the association between this virus and lung cancer. We investigated latent adenoviral infection using the nested polymerase chain reaction and in situ hybridization in transbronchial biopsy specimens from patients with small-cell lung cancer and non-small-cell lung cancer. The polymerase chain reaction was performed on DNA extracts with two sets of primers directed at a 261-base-pair target sequence of the E1A region of the adenoviral genome. In situ hybridization was performed on histological sections using DNA representing the entire adenovirus type 5 genome. E1A target DNA was present in 11 (31%) of 35 cases of small-cell lung cancer but in none of the 40 cases of non-small-cell lung cancer ( P<0.01). Of the 11 cases found positive by PCR, 8 were positive for adenovirus DNA by in situ hybridization. Adenovirus was prominent in tumor cells in 5 of the 8 cases, and in normal epithelial cells in the 3 remaining cases. Adenovirus DNA was not detected by in situ hybridization in specimens in which E1A DNA was not detected by the polymerase chain reaction. Small-cell lung cancer has mutations or deletions in the p53 and retinoblastoma genes more frequently than are found in non-small-cell lung cancer. Therefore, we speculate that adenovirus infection might participate in the pathogenesis of SCLC by producing mutation in these genes, rather than by inhibiting the function of these proteins. [ABSTRACT FROM AUTHOR]

A 14-membered ring macrolide, erythromycin, acts not only as an antibacterial but also as an anti-inflammatory agent. We have previously reported that erythromycin modulates neutrophil functions and ameliorates neutrophil-induced endothelial cell damage through the action of cyclic AMP-dependent protein kinase (PKA) and nitric oxide (NO). We investigated the effect of erythromycin on human endothelial cell functions. Erythromycin enhanced intracellular calcium ion concentration ([Ca2+]i) of endothelial cells and NO release from endothelial cells. The enhancement of NO release from endothelial cells by erythromycin was abolished by addition of EGTA in the medium and was partially reduced by addition of H-89, an inhibitor of PKA. These results suggest that erythromycin enhances NO release from endothelial cells through the action of PKA and [Ca2+]i. In addition, constitutive NO synthase (cNOS) protein expression of endothelial cells was dose-dependently enhanced by treatment with erythromycin, which might also contribute to the enhancement of NO release from endothelial cells by erythromycin. The effect of erythromycin as an anti-inflammatory agent might be partially mediated through the enhancement of NO release from endothelial cells and the drug might be a useful tool for the investigation of cNOS of endothelial cells. [ABSTRACT FROM AUTHOR]

Intact human neutrophils produced superoxide (O) by the stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) even when the extracellular Ca was absent (0.56±0.13 nmol/min per 10 cells). The production by fMLP was enhanced more than twice in the presence of the extracellular Ca. Moreover, the O production by fMLP in the presence of extracellular Ca was enhanced nearly three times by the treatment of cells with H-89, an inhibitor of cyclic AMP-dependent protein kinase (PKA). The enhancement was not observed when the extracellular Ca was depleted from the reaction mixture. In addition, H-89 did not enhance fMLP-induced O production of electropermeabilized neutrophils in which the intracellular Ca concentration was fixed to about 100 nM. These observations suggest that not only Ca influx but the inhibition of PKA is necessary for the maximum O production by fMLP and that the O production is partially suppressed by the activation of PKA induced by fMLP. [ABSTRACT FROM AUTHOR]

The surface array protein (SAP) of Campylobacter fetus strain TK is encoded by seven homologous sapA genes clustered on the chromosomal DNA. The spontaneously arising variant strain TK(SAP–) produces no SAP and carries an approximately 10-kb chromosomal deletion. To elucidate the mechanism underlying the loss of SAP synthesis, we analyzed the region containing the sapA homologues and the deletion. We constructed a physical map of the sapA cluster region by aligning the clones that contain sapA homologues. These analyses demonstrated that all sapA homologues were located within a limited region of about 50 kb of chromosomal DNA of strain TK. The TK(SAP–) deletion was located within this cluster and was 13.3 kb in size. The deletion occurred between two sapA homologues and resulted in the formation of a chimeric sapA homologue in the variant strain. Sequence analysis of the upstream regions and the conserved regions of all sapA homologues revealed a high degree of similarity. However, only one sapA homologue contained a putative promoter sequence. This promoter sequence was located in the deleted region. Thus, the deletion of the promoter appears to be responsible for the loss of SAP expression in TK(SAP–). [ABSTRACT FROM AUTHOR]

Purpose: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival.Methods: Previously untreated patients with small-cell lung cancer, with measurable disease, aged < or = 72 years, performance status < or = 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and 8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8.Results: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively.Conclusions: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer. [ABSTRACT FROM AUTHOR]

We studied the efficacy of cisplatin-based polychemotherapy for adenocarcinoma of the lung. A total of 136 patients were randomized for treatment with either cyclophosphamide, Adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT). Radiation was given to the chests of patients at stage III. The differences in the response rate (35% in the CAPM arm and 13% in the MCT arm) were statistically significant ( P <0.01). However, the significant difference was observed in stage-IV patients (CAPM, 33%; MCT, 4%; P <0.001) and not in stage-III patients (CAPM, 40%; MCT, 40%). The median period of survival was 9.5 months for the CAPM arm and 5.5 months for the MCT arm ( P <0.035, Wilcoxon-Gehan test; P <0.1, log-rank test). Improved median survival for the CAPM regimen was demonstrated only by stage-IV patients (CAPM, 10 months; MCT, 5.5 months; P <0.025, Wilcoxon-Gehan test; P <0.05, log-rank test). The duration of the response, including PRs and NCs, was significantly different depending on the treatment, showing 5 months for the CAPM arm and 3 months for the MCT arm ( P <0.05). The significant difference was also only observed in stage-IV patients. Myelosuppression was more severe with CAPM than with the MCT regimen. Nausea and vomiting were significantly increased in patients receiving the CAPM regimen. However, all toxicities were acceptable and there were no treatment-related deaths. We concluded that cisplatin-based chemotherapy, CAPM therapy, was of more benefit to patients with adenocarcinoma of the lung than MCT therapy. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are Masashi Hasegawa, Yoshitane Imai and co‐workers at Kitasato University and Kindai University. The image depicts the reported figure‐eight molecule as an M. C. Escher‐inspired 'impossible object'. Read the full text of the article at 10.1002/chem.202005320. [ABSTRACT FROM AUTHOR]

Front Cover: Small Figure-Eight Luminophores: Double-Twisted Tethered Cyclic Binaphthyls Boost Circularly Polarized Luminescence (Chem. Eur. J. 19/2021) Keywords: binaphthyl; chiral; circularly polarized luminescence; DFT calculations; figure-eight molecule EN binaphthyl chiral circularly polarized luminescence DFT calculations figure-eight molecule 5830 5830 1 04/05/21 20210401 NES 210401 B Impossible object in the molecular world b : a stereogenic figure-eight molecule, which exhibits remarkable CPL properties, is depicted in the cover image. GLO:OLD/01apr21:chem202100231-toc-0001.jpg PHOTO (COLOR): . gl GLO:OLD/01apr21:chem202100231-toc-0001.jpg PHOTO (COLOR): . gl B Impossible object in the molecular world b : a stereogenic figure-eight molecule, which exhibits remarkable CPL properties, is depicted in the cover image. [Extracted from the article]

Invited for the cover of this issue are Masashi Hasegawa, Yoshitane Imai, Yasuhiro Mazaki and co‐workers at Kitasato University, Kindai University and Osaka University. The image depicts a stereogenic twisted cycloparaphenylene that exhibits circularly polarized luminescence in a polymethyl methacrylate thin film. Read the full text of the article at 10.1002/chem.202004283. [ABSTRACT FROM AUTHOR]

Keywords: binaphthyl; circular dichroism; circularly polarized luminescence; cycloparaphenylene; PMMA film EN binaphthyl circular dichroism circularly polarized luminescence cycloparaphenylene PMMA film 1160 1160 1 01/20/21 20210118 NES 210118 B A stereogenic twisted cycloparaphenylene b that glows with helical green light in a polymer matrix is depicted in the cover image. Binaphthyl, circular dichroism, circularly polarized luminescence, cycloparaphenylene, PMMA film. [Extracted from the article]