Search

Treatment of esophageal cancer in the remnant esophagus after esophagectomy is highly invasive, therefore, early detection and minimally invasive treatment are considered necessary. Consequently, we aimed to clarify the safety and efficacy of endoscopic submucosal dissection (ESD) for residual esophageal cancer compared to that for esophageal cancer in a normal cervical esophagus. This study involved 47 patients with 59 residual esophageal cancers and 92 patients with 107 cervical esophageal cancers in normal esophagus who underwent ESD between January 2008 and December 2023. Their clinicopathological findings and long-term outcomes were retrospectively collected and evaluated. The median tumor diameter was 13 mm, and the median procedure time was 31 minutes in remnant esophagus group, with no significant difference between the two groups. No serious complications such as perforation, massive intraoperative bleeding, and pneumonia were observed in the remnant group, except for one case of postoperative bleeding. The rates of complete resection and disease specific survival were not significantly different between two groups, with complete resection rate of 86.4% and 5-year disease-specific survival rate of 95.7% in the remnant esophagus group. No local recurrence was observed during the median observation period of 43 months in the remnant esophagus group. ESD for superficial cancer of the remnant esophagus showed a high complete resection rate without serious complications and good local-regional control with no evidence of local recurrence. This indicates that ESD is a safe and useful treatment for superficial cancer of the remnant esophagus., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The silkworm (Bombyx mori) is an important lepidopteran model insect and an industrial domestic animal traditionally used for silk production. Here, we report the genome assembly of an improved Japanese strain Nichi01, in which the cocoon yield is comparable to that of commercial silkworm strains. The integration of PacBio Sequel II long-read and ddRAD-seq-based high-density genetic linkage map achieved the highest quality genome assembly of silkworms to date; 22 of the 28 pseudomolecules contained telomeric repeats at both ends, and only four gaps were present in the assembly. A total of 452 Mbp of the assembly with an N50 of 16.614 Mbp covered 99.3% of the complete orthologs of the lepidopteran core genes. Although the genome sequence of Nichi01 and that of the previously reported low-yielding tropical strain p50T assured their accuracy in most regions, we corrected several regions, misassembled in p50T, in our assembly. A total of 18,397 proteins were predicted using over 95 Gb of mRNA-seq derived from 10 different organs, covering 96.9% of the complete orthologs of the lepidopteran core genes. The final assembly and annotation files are available in KAIKObase (https://kaikobase.dna.affrc.go.jp/index.html) along with a genome browser and BLAST searching service, which would facilitate further studies and the breeding of silkworms and other insects., Competing Interests: Conflict of interest statement The authors declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Genetics Society of America.)

Objective: Patients with acromegaly are at increased risk of colorectal polyps. However, their risk of colorectal cancer remains unclear. This study aimed to identify the histopathological features of colorectal polyps in patients with acromegaly and compare their risk of colorectal cancer with that in healthy controls., Methods: The study participants were 178 patients who underwent Hardy's operation and perioperative colonoscopy at our hospital between April 2008 and September 2016. For the control group, we randomly selected 356 age- and sex-matched patients who underwent colonoscopy at our hospital during the same period. The incidence, size, location, and histology of the colorectal polyps detected were compared between the groups., Results: Colorectal polyps were detected in 66.8% of the acromegaly group and 24.2% of the control group (P < 0.001). The average number and size of the polyps were 2.44 and 4.74 mm, respectively, in the acromegaly group and 1.77 and 3.89 mm in the control group (P = 0.001). Polyps in the acromegaly group were more likely to be in the rectosigmoid region (P = 0.006). In the acromegaly group, the frequency of polyps ≥5 mm was 34.3% and that for polyps ≥10 mm was 15.2%; the respective values were 7.6% and 2.2% in the control group (P < 0.001). We found no evidence of between-group histopathological differences in the polyp specimens resected by endoscopy., Conclusions: Patients with acromegaly are at an increased risk of colorectal polyps, especially in the rectosigmoid region. However, there is no pathological evidence that they are at greater risk of colorectal cancer than the general population.

Esophagectomy represents the standard treatment strategy for superficial esophageal cancer diagnosed pathologically as submucosal disease (pT1b) following an endoscopic resection (ER). However, chemoradiotherapy (CRT) is expected to become an alternative treatment option. This study retrospectively compared the outcomes of patients who underwent ER of submucosal esophageal squamous cell carcinoma, and who received additional treatment in the form of surgery and CRT. Data were collected from 83 patients who underwent ER and were diagnosed as pT1b (sm) between January 2002 and December 2013. Of them, 52 patients underwent additional treatment (19 surgery, 33 CRT). The long-term outcomes, recurrent patterns, and recurrence risk factor were analyzed retrospectively. No significant differences were identified between the two groups regarding the following aspects: sex, Charlson comorbidity index, tumor size, macroscopic type, cut end positivity, and en bloc resection rate. On the contrary, significant differences were observed in age (P = 0.042) and lymphovascular invasion (P = 0.003) between the two groups. There were more patients with positive lymphovascular invasion, which was one of the strongest risk factors, in the surgery group. The 3-year overall survival (OS) and relapse-free survival (RFS) rates were both 100% in the surgery group and 90.4% and 87.4%, respectively, in the CRT group. The 5-year OS and RFS rates both decreased to 89.5% in the surgery group and to 80.3% and 70.4%, respectively, in the CRT group. The surgery group achieved a superior OS and RFS compared to the CRT group, though not significant (P = 0.172, P = 0.127). Tumor recurrence was observed in 6 patients. All these patients were in the CRT group (P = 0.075). They included 3 patients with hematogenous metastases (of the lung, bone, and adrenal gland) and 3 patients with regional lymph node metastasis. The patient with hematogenous adrenal gland metastasis had simultaneous extended lymph node metastasis. Through a univariate analysis, it was observed that tumor size (≥ 40 mm) and positive lymphatic invasion represented the significant risk factors for recurrence in the CRT group (P = 0.048 and P = 0.035, respectively). To achieve a better long-term survival, surgery is recommended as the additional treatment for ER-pT1b esophageal cancer. While CRT represents an acceptable alternative, the indication should be carefully decided, especially in high-risk patients for recurrence with large tumor size (≥ 40 mm) or positive lymphatic invasion., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The efficacy of early enteral nutrition after esophageal cancer surgery has been reported. However, the choice of formula and management of diarrhea are important to achieve the goal of enhanced recovery after surgery. The aim of this study is to assess the frequency of diarrhea/completion rate of enteral nutrition regimen as primary endpoints and the postoperative nutritional status/body composition analysis/operative morbidity as secondary endpoints was compared between the two nutrition groups. Among the 122 patients who underwent esophagectomy for esophageal cancer between December 2015 and September 2017, 67 patients who met the eligibility criteria were randomly assigned to receive enteral nutrition with either HINE E-GEL® (HINE group; n = 33) or MEIN® (MEIN group; n = 34). The incidence of diarrhea was significantly lower in the HINE group (18.2 % vs. 64.7 %, P < 0.001). The score of Bristol scale of POD 6/7 was significantly lower in the HINE group (P = 0.019/P = 0.006, respectively). The completion rate of enteral nutrition regimen was significantly higher in the HINE group (97.4 % vs. 86.6 %, P = 0.002). The Controlling Nutritional Status scores and total protein levels at 6 months after surgery were significantly better in the HINE group (P = 0.030 and P = 0.023, respectively), indicating improved tendency in nutritional status in the HINE group. However, there were no significant differences in Prognostic Nutritional Index values, blood test results, rapid turnover proteins, body mass index, or body composition between the two groups. HINE E-GEL compared with MEIN may reduce the frequency of diarrhea, enabling patients to adhere to the scheduled enteral nutrition plan. Also, maintenance of nutritional status with HINE E-GEL was comparable or potentially better in some nutrition components to that with MEIN, indicating that HINE E-GEL can be an option for enteral nutrition following esophageal surgery to achieve the goal of successful completion of scheduled enteral nutrition and smooth transition to the normal diet., (© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Background: Acute myocardial infarction (AMI) induces marked activation of the sympathetic nervous system. Fatty acid binding protein 4 (FABP4) is not only an intracellular protein, but also a secreted adipokine that contributes to obesity-related metabolic complications. Here, we examined the role of serum FABP4 as a pathophysiological marker in patients with AMI., Methods and Results: We studied 106 patients presenting to the emergency unit with a final diagnosis of AMI, including 12 patients resuscitated from out-of-hospital cardiac arrest (OHCA) caused by ventricular fibrillation. FABP4 levels peaked on admission or just after percutaneous coronary intervention and declined thereafter. Regression analysis revealed no significant correlation between peak FABP4 and peak cardiac troponin T determined by Roche high-sensitive assays (hs-TnT). Notably, FABP4 levels were particularly elevated in AMI patients who were resuscitated from OHCA (median 130.2 ng/mL, interquartile range (IQR) 51.8-243.9 ng/mL) compared with those without OHCA (median 26.1 ng/ml, IQR 17.1-43.4 ng/mL), while hs-TnT levels on admission were not associated with OHCA. Immunohistochemistry of the human heart revealed that FABP4 is abundantly present in adipocytes within myocardial tissue and epicardial adipose tissue. An in vitro study using cultured adipocytes showed that FABP4 is released through a β3-adrenergic receptor (AR)-mediated mechanism., Conclusions: FABP4 levels were significantly elevated during the early hours after the onset of AMI and were robustly increased in OHCA survivors. Together with the finding that FABP4 is released from adipocytes via β3-AR-mediated lipolysis, our data provide a novel hypothesis that serum FABP4 may represent the adrenergic overdrive that accompanies acute cardiovascular disease, including AMI.

Esophageal stricture occurs at a high rate after endoscopic submucosal dissection, especially after entire circumferential dissection, leading to poor quality of life. This retrospective cohort study evaluated the stricture rate in circumferential mucosal defect cases following modified steroid administration. We enrolled 22 consecutive patients who underwent entire circumferential endoscopic submucosal dissection for superficial esophageal cancer between April 2010 and April 2015 at our hospital. Until January 2013, a systemic steroid-prednisolone-was administered at 30 mg/day and tapered over 8 weeks in the original method group (original group). From February 2013, 30 mg of prednisolone was administered orally for 3 weeks and then the dose was reduced in 5 mg decrements every 3 weeks. This group was classified as the modified method group (modified group). We retrospectively compared the stricture rates between the two groups. The postoperative stricture rate was significantly lower in the modified group (36.4%; 4/11 patients) than in the original group (82%; 9/11 patients; P = 0.04). The mean number of endoscopic balloon dilatation procedures was significantly lower in the modified group (6.2 ± 11.3) than in the original group (19.4 ± 15.3; P = 0.023). Pneumonia and oral herpes infection, which are adverse events potentially associated with steroid administration, were observed in the original group. Candida esophagitis, arthritis, and steroid-related myopathy were observed in the modified group. This modified systemic steroid administration was effective for patients with entire circumferential mucosal defect. The safety of this method was also demonstrated.

Megalo-type isomaltosaccharides are an enzymatically synthesized foodstuff produced by transglucosylation from maltodextrin, and they contain a mid-chain length polymer of D-glucose with α-1,6-glycoside linkages. The injection of a solution of megalo-type isomaltosaccharides (1-4%(w/v), average DP = 12.6), but not oligo-type isomaltosaccharides (average DP = 3.3), into the intestinal lumen dose-dependently reduced the transport rates of tight junction permeable markers in a ligated loop of the anesthetized rat jejunum. Application of the megalosaccharide also suppressed the transport of tight junction markers and enhanced transepithelial electrical resistance (TEER) in Caco-2 cell monolayers. Cholesterol sequestration by methyl-β-cyclodextrin in the Caco-2 monolayers abolished the effect of megalosaccharide. Treatment with anti-caveolin-1 and a caveolae inhibitor, but not clathrin-dependent endocytosis and macropinocytosis inhibitors, suppressed the increase in TEER. These results indicate that isomaltosaccharides promote the barrier function of tight junctions in the intestinal epithelium in a chain-length dependent manner and that caveolae play a role in the effect.

There have been several reports that steroid administration is effective at preventing strictures after endoscopic submucosal dissection (ESD). However, adverse events after steroid use are of great concern. We have reported that shielding with a polyglycolic acid (PGA) sheet and fibrin glue can be useful for prevention of stricture after ESD. We conducted a retrospective analysis of efficiency of shielding with a PGA sheet and fibrin glue for prevention of esophageal stricture compared with intralesional steroid injection. ESD was performed on a total of 489 lesions in 400 patients for superficial esophageal cancer from January 2012 to July 2016. Of these, 39 lesions were enrolled in the study group (PGA sheet and fibrin glue) and 31 lesions were enrolled in the control group. The incidence of postoperative stricture at 6 weeks and the number of sessions of endoscopic balloon dilatation (EBD) required to resolve any strictures were evaluated. The post-ESD stricture rate was 9.1% in the study group (3/33 patients), which was not significantly lower than the stricture rate of 10.3% in the historical control group (3/29 patients; p = 1.00). The mean number of EBD was 0.057 ± 0.24 in the study group and 1.9 ± 5.1 in the control group, which was not significant (P = 0.95). PGA sheet and fibrin glue appear to be a promising option for the prevention of esophageal stricture similar to the effect of intralesional steroid injection., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Observation of the microvasculature using narrow band imaging (NBI) with magnifying endoscopy is useful for diagnosing superficial squamous cell carcinoma. Increased vascular density is indicative of cancer, but not many studies have reported differences between cancerous and noncancerous areas based on an objective comparison. We observed specimens of endoscopic submucosal dissection (ESD) using NBI magnification, and determined the vascular density of cancerous and noncancerous areas. A total of 25 lesions of esophageal squamous cell carcinoma that were dissected en bloc by ESD between July 2013 and December 2013 were subjected to NBI magnification. We constructed a device that holds an endoscope and precisely controls the movement along the vertical axis in order to observe submerged specimens by NBI magnification. NBI image files of both cancerous (pathologically determined invasion depth, m1/2) and surrounding noncancerous areas were created and subjected to vascular density assessment by two endoscopists who were blinded to clinical information. The invasion depth was m1/2 in 20, m3/sm1 in four and sm2 in one esophageal cancer lesion. Mean vascular density was significantly increased in cancerous areas (37.6 ± 16.3 vessels/mm2) compared with noncancerous areas (17.6 ± 10.0 vessels/mm2) (P < 0.05). The correlation coefficients between vascular density determined by two endoscopists were 0.86 and 0.81 in cancerous and noncancerous areas, respectively. Receiver operating curve (ROC) analysis revealed that the area under the curve (AUC) of vascular density was 0.895 (95% CI, 0.804-0.986). For this ROC curve, sensitivity was 78.3% and specificity was 87.0% when the cutoff value of vascular density was 26 vessels/mm2. NBI magnification confirmed significant increases in vascular density in cancerous areas compared with noncancerous areas in esophageal squamous cell carcinoma. The rates of agreement between vascular density values determined by two independent operators were high., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Marine glycoside hydrolases hold enormous potential due to their habitat-related characteristics such as salt tolerance, barophilicity, and cold tolerance. We purified an α-glucosidase (PYG) from the midgut gland of the Japanese scallop (Patinopecten yessoensis) and found that this enzyme has unique characteristics. The use of acarbose affinity chromatography during the purification was particularly effective, increasing the specific activity 570-fold. PYG is an interesting chloride ion-dependent enzyme. Chloride ion causes distinctive changes in its enzymatic properties, increasing its hydrolysis rate, changing the pH profile of its enzyme activity, shifting the range of its pH stability to the alkaline region, and raising its optimal temperature from 37 to 55 °C. Furthermore, chloride ion altered PYG's substrate specificity. PYG exhibited the highest Vmax/Km value toward maltooctaose in the absence of chloride ion and toward maltotriose in the presence of chloride ion.

We have developed a real-time PCR array method to comprehensively detect genetically modified (GM) organisms. In the method, genomic DNA extracted from an agricultural product is analyzed using various qualitative real-time PCR assays on a 96-well PCR plate, targeting for individual GM events, recombinant DNA (r-DNA) segments, taxon-specific DNAs, and donor organisms of the respective r-DNAs. In this article, we report the single-laboratory validation of both DNA extraction methods and component PCR assays constituting the real-time PCR array. We selected some DNA extraction methods for specified plant matrixes, i.e., maize flour, soybean flour, and ground canola seeds, then evaluated the DNA quantity, DNA fragmentation, and PCR inhibition of the resultant DNA extracts. For the component PCR assays, we evaluated the specificity and LOD. All DNA extraction methods and component PCR assays satisfied the criteria set on the basis of previous reports.

Two strains of aerobic, non-spore-forming, Gram-negative, rod-shaped bacteria (ND5 and MY14(T)), previously isolated from urban soil using the membrane-filter enrichment technique, were characterized. Analysis of their 16S rRNA gene sequence grouped strains ND5 and MY14(T) within the family Oxalobacteraceae (Betaproteobacteria). The highest pairwise sequence similarities for strain ND5 were found with members of the genus Herminiimonas, namely with Herminiimonas saxobsidens NS11(T) (99.8%) and Herminiimonas glaciei UMB49(T) (99.6%). Although some fatty acid profiles, physiological and biochemical differences exist between strain ND5 and the respective Herminiimonas-type strains, DNA-DNA hybridization experiments confirm that strain ND5 is a member of the H. glaciei genospecies. Taxonomical analyses revealed a wider range of variability within this genus than considered previously. The highest pairwise nucleotide similarity for strain MY14(T) was found with Oxalicibacterium flavum (96.8%). Phylogenetic analyses based on 16S rRNA and cpn60 gene sequences, DNA-DNA hybridization, fatty acid profiles, physiological and biochemical tests allowed genotypic and phenotypic differentiation of strain MY14(T) from other Oxalicibacterium species representing a new species, for which the name Oxalicibacterium solurbis sp. nov. (type strain MY14(T)=NBRC 102665(T),=CCM 7664(T)) is proposed.

The photostability of (E)-2-[3-(2-thioxopyrrolidin-3-ylidene)methyl]-tryptophan ((E)-TPMT), the main yellow pigment in salted radish, was studied. First we analyzed the photoproduct generated from (E)-TPMT under longwave UV irradiation. On the basis of NMR spectroscopy, the photoproduct was identified as Z-configurated TPMT, and isomerization from the Z- to the E-form was reversibly induced by Vis-light irradiation. The optimum wavelength for isomerization from the E- to the Z-form was 360-380 nm, and that for isomerization from the Z- to the E-form was 440-460 nm. The E/Z-ratios in the photostationary state under UV- and Vis-light irradiation conditions were approximately 0.95:1 and 26:1 respectively. The (Z)-isomer was more sensitive to light irradiation than the (E)-isomer in the quantum yield measurement. Yellowing was dependent on the ratio of the (Z)-isomer, because the b(*) and chroma value rose with increases in the (Z)-isomer by the colorimeters. Hence, it is possible that the formation of the (Z)-isomer contribute to the yellow color of takuan-zuke during long salting and fermentation.

BodyMap-Xs (http://bodymap.jp) is a database for cross-species gene expression comparison. It was created by the anatomical breakdown of 17 million animal expressed sequence tag (EST) records in DDBJ using a sorting program tailored for this purpose. In BodyMap-Xs, users are allowed to compare the expression patterns of orthologous and paralogous genes in a coherent manner. This will provide valuable insights for the evolutionary study of gene expression and identification of a responsive motif for a particular expression pattern. In addition, starting from a concise overview of the taxonomical and anatomical breakdown of all animal ESTs, users can navigate to obtain gene expression ranking of a particular tissue in a particular animal. This method may lead to the understanding of the similarities and differences between the homologous tissues across animal species. BodyMap-Xs will be automatically updated in synchronization with the major update in DDBJ, which occurs periodically.

The objective of this study was to investigate the occurrence of occupational maxillofacial injuries using a newly installed relational database. Twenty-six injuries were identified out of 28,624 patients admitted to the emergency unit during a 12 month period. Falls from height or being struck by moving objects were common causes of these injuries. Two-thirds of those identified were construction workers. This paper demonstrates the power of modern databases to identify specific occurrences that may provide the basis for prevention in the future.

Although increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) has been demonstrated in inflammatory sites of various diseases, its role in colitis remains unknown. In this study, we examined whether MAdCAM-1 is involved in the pathogenesis of granulomatous colitis induced by peptidoglycan-polysaccharide (PG-PS). Experimental colitis was induced by intramural injection of PG-PS to rat colon. After 3 weeks the colon was removed and the mucosal inflammation was assessed. The area of MAdCAM-1-positive venules and the subsets of infiltrating cells were determined in colonic mucosa by immunohistochemistry. In another experiment, monoclonal antibody against MAdCAM-1 was administered intraperitoneally to examine its attenuating effect on colitis. The intramural injection of PG-PS induced significant colonic inflammation with granuloma formation. The submucosa was drastically thickened with the infiltration of CD4 positive lymphocytes and ED-1 positive macrophages. Intense MAdCAM-1 expression was observed on endothelium of the submucosal venules in inflamed mucosa. Administration of anti-MAdCAM-1 antibody significantly attenuated the PG-PS-induced colonic damage and cell infiltration. Enhanced expression of MAdCAM-1 was demonstrated in venular endothelium of the inflamed colon in PG-PS-induced colitis. The attenuating effect of anti-MAdCAM-1 suggests the importance of the MAdCAM-1-dependent process in the formation of chronic granulomatous colitis.

GOR (GOR47--1) is an epitope thought to be a host-derived antigen cross-reactive with hepatitis C virus (HCV) since it was isolated from a cDNA library of host animals reactive with sera of HCV-positive patients. An enzyme immunosorbent assay (ELISA) using this epitope as antigen is of sufficient sensitivity and specificity for screening patients with HCV. However, the relationship between GOR47--1 epitope and autoimmune phenomena associated with HCV infection or autoimmune hepatitis is controversial. Here we isolated the human GOR gene and found that the GOR47--1 epitope was not translated in humans due to a single base replacement from chimpanzee. Furthermore, we found some patients who had antibodies against another epitope, which is translated (GOR1--125) in humans, although there was no correlation between the existence of anti-GOR47--1 or anti-GOR1--125 Ab and autoimmune phenomena. Serum IgG levels did not influence the titres of these antibodies. Taken together with the results of several other studies, our finding that the GOR47--1 epitope cannot be translated into a protein suggests that there is little relationship between autoimmunity and the GOR gene product in human beings. We also discuss here the possible mechanism of cross-reactivity between HCV and the GOR gene product.

In an attempt to isolate indigenous marine myxobacteria from coastal samples, we obtained two swarm forming bacteria. Both isolates formed cell aggregates which, at least in one isolate, developed to fruiting body-like structures consisting of a mass of myxospore-like cells. The optimum NaCl concentrations for their growth were between 2 and 3%, comparable to the NaCl concentration of seawater. This growth characteristic strongly suggests that the two isolates are specific marine bacteria. The 16S rDNA sequence studies indicated that the two isolates were related to the genus Nannocystis. Based on the phylogenetic distances between branches, we concluded that the isolates should be assigned to two new myxobacterial genera.

To investigate the mechanism of nitroso compound-induced inhibition of the respiratory burst in neutrophils, we studied fluorescence quenching of perylene by nitroso-compounds in the membrane fractions of neutrophils at 17, 27, and 37 degrees C and the reagent-induced inhibition of superoxide generation at 28 and 37 degrees C. With increasing temperature, the quenching of perylene fluorescence and inhibition of superoxide generation by nitrosobenzene (NB) were both diminished, while those by 2-nitrosotoluene (NT) were both enhanced. The temperature dependence of the inhibition constants and the quenching constants indicates that the binding of NB is exothermic (deltaH= -27 kJ/mol for inhibition and deltaH= -29 kJ/mol for quenching) and essentially enthalpy-driven. On the other hand, that of NT is endothermic (deltaH= +16 kJ/mol for inhibition and quenching) and essentially entropy-driven. Quenching studies of perylene fluorescence in synthetic vesicles made of endogenous polar lipids of neutrophils showed that the enthalpy changes of NB- and NT-binding with perylene in lipids were similar to each other. Moreover, their values were in good agreement with that of NT, but not of NB, in the membrane fractions, an assembly of proteins and lipids, of neutrophils. These results suggest that NB inhibits the activity by binding to proteins in the membrane, whereas inhibition by NT occurs through hydrophobic interaction with lipids and/or proteins.

Aromatic nitroso-compounds such as nitrosobenzene inhibited the respiratory burst of intact neutrophils induced by various stimulants, including phorbol 12-myristate 13-acetate and a chemotactic peptide. The compounds also inhibited NADPH-dependent oxygen consumption by cell-free preparations of neutrophils. This indicates that nitroso-compounds act directly on the NADPH-oxidase system. The inhibitory effects induced by several nitroso-compounds, 2-nitrosotoluene, nitrosobenzene, 4-nitrosophenol, and 1-nitrosopyrrolidine, were examined and their inhibition constants, the concentrations causing 50% reduction of oxygen consumption, were found to be 0.043, 0.173, 0.672, and 32.1 mM, respectively. These values correlated well with the hydrophobicity of the compounds: a more hydrophobic compound was a more potent inhibitor against NADPH oxidase, suggesting that the oxidase has a hydrophobic site(s) for interaction with the inhibitors.

The iron complex of beta,delta-diazamesoporphyrin III, a molecular hybrid of porphyrin and phthalocyanine, was incorporated into apomyoglobin to investigate novel biological aspects of myoglobin. The reconstituted ferric protein forms an internal hemichrome with the iron-bound distal histidine. The reduced ferrous protein has extraordinarily high affinities for O2 and CO. The ferrous myoglobin is capable of strong binding with pyridine, imidazole, cyanide, and azide, and reacts moderately with ammonia. The NO complex exhibited 5-coordinate to 6-coordinate transition over 150 min. The instability of 5-coordinate NO heme is consistent with a high affinity of imidazole to the ferrous heme. The kinetic analyses of the ferrous derivatives suggest the importance of the pi orbitals in neutral ligands as well as the negative charges in anionic ligands. A high affinity of imidazole to ferrous diazaheme accounts for the internal hemochrome formation in ferrous myoglobin containing phthalocyanines.

A phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus was carried out cooperatively by nine Japanese institutions. Forty-five patients with thoracic advanced squamous cell carcinoma, who had T4 tumor or distant lymph node metastasis (M1(LYM)), were enrolled in the study for treatment with cisplatin (70 mg/m2) on days 1 and 36, and 5-fluorouracil infusion (700 mg/m2) on days 1-4 and 36-39 sandwiched around external beam irradiation (60 Gy over 6 weeks). Of the 45 evaluable patients, 37 (84.1%) completed the treatment. The overall response rate was 64.4%, and the complete response rate 8.9%. The median duration of response was 125.0 days for patients who achieved complete and partial response. The 50% median survival time was 215 days. There was one toxicity-related death due to radiation pneumonitis. The major form of toxicity exceeding grade 2 was myelosuppression and anorexia, but grade 4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia, 1 severe cardiac failure and 1 mental disturbance). The results showed that this form of chemoradiotherapy had a satisfactory effect and might be useful for treatment of inoperable advanced esophageal cancer.

We investigated whether urinary neopterin concentrations respond to the pathological conditions (especially coronary artery dilatation) of Kawasaki syndrome. All of 29 children with Kawasaki syndrome had very high urinary neopterin concentrations. Increased urinary neopterin concentrations coincided with fever and with monocytosis in peripheral blood. The urinary neopterin excretion peaking within the first 8 days after onset correlated with the development of coronary artery dilatation. Increased urinary neopterin concentrations indicate that cell-mediated immunity is activated in patients with Kawasaki syndrome. Endogenous interferon-gamma and activation of monocytes/macrophages may play a role in the pathogenesis of Kawasaki syndrome. Not only do neopterin concentrations correlate with symptoms in the acute phase of Kawasaki syndrome, they also act as a predictive marker of coronary artery abnormalities in affected patients.

Thirty-nine patients with advanced measurable squamous cell carcinomas were treated with two or more courses of 70 mg cisplatin/m2 on day 1 and 700 mg infused 5-fluorouracil/m2 on days 1-5 every 21 days. The overall response rate was 35.9 (95% confidence limits, 24.8-55.1%). Responses were seen in primary sites in the esophagus of five patients, in the lung of seven, the liver of one and the mediastinal lymph nodes of one. The average response duration was 3.5 (range 1-12) mo for patients who achieved partial response. The average survival time after the first administration was 9.5 mo for patients who responded to the treatment whereas, for those who did not, it was 5.6 mo. The major form of toxicity was myelosuppression and there were six patients with grade 3 toxicity and one with grade 4. The present study was designed to evaluate the effectiveness of combined cisplatin and 5-fluorouracil for advanced squamous cell carcinoma, and the results showed that it had a reasonable effect and might possibly be used as a postoperative chemotherapy because of its mild side effects.

We report four cases of malignant melanoma of the esophagus treated at the National Cancer Center Hospital in Tokyo over a period of 28 years. There were three men and one woman. One patient had been diagnosed as having Werner's syndrome. The three male patients smoked and were alcohol drinkers. The chief complaint was dysphagia--three patients--and pain on swallowing--one patient. All the tumors were polypoid, and three were large at the time of initial diagnosis. Histological diagnoses were made by examining endoscopic biopsy specimens, and confirmed with resected specimens in three cases. Esophagectomy was performed in three patients, the other receiving radiotherapy. Three patients died of recurrent disease in a rather short period of time, as in many reported cases. The mean survival for the three patients was eight months. The fourth, who had a superficial polypoid lesion and received esophagectomy and adjuvant chemotherapy, lived for 29 months. The combination of early detection and extended radical surgery followed by adjuvant chemotherapy may offer a better prognosis than in the past.

In the present phase II study, 31 patients with advanced measurable esophageal carcinomas were treated with a combination of 30 mg vindesine/m2 and 70 mg cisplatin/m2. The overall response rate was 16.1% (95% confidence limits, 7.1-32.6%). Responses were seen in metastatic sites, including the liver in two patients, a lung in one, neck or mediastinal lymph nodes in two and primary sites in two. The response durations were between one and two months for patients achieving partial response. The average survival time after first administration was 5.5 months for patients who responded to treatment, whereas, for those who did not, it was 7.3 months. The major form of toxicity was myelosuppression, 14 patients developed grade 2-3 toxicity and one sepsis which led to death. No superiority of the combined chemotherapy over either cisplatin or vindesine therapy alone was suggested for cases of advanced squamous cell carcinoma of the esophagus by the present study.

Computer-aided analyses were made of the complete amino-acid sequences of two P-450 species, the phenobarbital-inducible major P-450 of rat liver microsomes (P-450PB) and camphor-hydroxylating P-450 of Pseudomonas putida (P-450cam). Statistically significant homology was recognized between the two P-450 sequences, but these sequences were not related to those of other groups of hemoproteins, such as hemoglobins, peroxidases, and cytochrome c's and b's. Two highly homologous regions, HR1 and HR2, and two other weakly homologous regions were found on optimally matched alignment of the P-450 sequences. The secondary structures of the two P-450's predicted by current prediction methods bear strong resemblance at these homologous regions. Both HR1 and HR2 contain a cysteine residue near the center of the homologous regions, and they are the only regions that show significant homology among all 48 combinations of local sequences around the cysteine residues (six on P-450PB and eight on P-450cam). HR1 is located in the N-proximal half of the molecule, is rich in hydrophilic residues, and is predicted to be helical. On the other hand, HR2 is close to the C-terminus, has intermediate hydrophobicity, and may take a complex secondary structure of a turn-sheet-helix. The amino-acid sequences around the HR1 and HR2 regions are also well conserved in another P-450 species, rabbit P-450LM2.

Resonance Raman spectra were measured for various C-type cytochromes (mammalian cytochrome c, bacterial cytochrome c3, algal photosynthetic cytochrome f, and alkylated cytochrome c) and a B-type cytochrome (cytochrome b5) in their reduced and oxidized states. (1) For ferrous alkylated cytochrome c, a Raman line sensitive to the replacement of an axial ligand of the heme iron uas found around 1540 cm=1. This ligand-sensitive Raman line indicated the transition from acidic (1545 cm-1) to alkaline (1533 cm-1) forms with pK 7.9. The pH dependence of the Raman spectrum corresponded well to that of the optical absorption spectra. (2) For ferrous cytochrome f, the ligand-sensitive Raman line was found at the same frequency as cytochrome c (1545 cm-1). Accordingly two axial ligands are likely to be histidine and methionine as in cytochrome c. (3) For ferrous cytochrome c3, the frequency of the ligand-sensitive Raman line was between those of cytochrome c and cytochrome b5. Since two axial ligands of the heme iron in cytochrome c3 might be histidines. However, a combination of histidine and methionine as a possible set of two axial ligands was not completely excluded for one or two of the four hemes. (4) In ferrous cytochrome b5, two weak Raman lines appeared at 1302 and 1338 cm-1 instead of the strongest band at 1313 cm-1 of C-type ferrous cytochromes. This suggests the practical use of these bands for the identification of types of cytochromes. The difference in frequency and intensity between B- and C-types of hemes implies that the low effective symmetry of the heme in ferrous cytochrome c is due to vibrational coupling of ring modes with peripheral substituents rather than geometrical disortion of heme.

Addition of NaHSO3 or HCN to the formyl group of heme alpha was greatly accelerated by freezing reaction mixtures prepared in aq. Na2CO3, and freezing resulted in characteristic color and spectral changes of the solutions. Similar changes were observed on decreasing the pH of alkaline reaction mixtures with HCl at room temperature, indicating that the effective pH of certain salt solutions is greatly lowered by freezing. The reactivity of the formyl group changed depending on the redox state of the heme iron and the species of ligand.

A case of superficial spreading squamous cell carcinoma located just over a leiomyoma is presented. The patient complained of slight dysphagia and an esophagogram showed an elevated tumor in the middle thoracic esophagus. Esophagoscopy revealed an ulcerative mucosal lesion over the elevated lesion and biopsy showed that the lesion was a squamous cell carcinoma. Blunt dissection of the esophagus with esophago-gastro-anastomosis was performed. There was neither lymph vessel invasion nor lymph node metastasis. His post-operative recovery was satisfactory and he is doing well two years after the operation. A review of the Japanese and English literature revealed that a few cases of esophageal carcinoma coexisting with esophageal leiomyoma have been reported. There was no report of superficial esophageal carcinoma coexisting with esophageal leiomyoma. This is the first report of the coexistence of these two lesions, and esophagoscopy is necessary to find a superficial esophageal carcinoma coexisting with esophageal leiomyoma.

Sixty-six patients with carcinoma of the hypopharynx or cervical esophagus received esophageal extraction and primary reconstruction. The methods of reconstruction were free forearm skin tube grafting, free jejunal transplantation and immediate pharyngo-gastrostomy after pull-through esophagectomy. Considering the postoperative complications of each method, free forearm skin tube transplantation is the safest, but it can only be used for a short defect of the esophagus. With pull-through esophagectomy, we are able to extract the whole esophagus and have no fear of leaving any remaining cancer in the thoracic esophagus, but the operative burden and the rate at which complications occur are higher. Free jejunal transplantation can be used for a short or long defect of the cervical esophagus with small operative burden. Among three methods of reconstruction, free jejunal transplantation is recommended for primary reconstruction of the cervical esophagus.

Among 492 patients with esophageal carcinoma who received resective surgery, 102 survived over 5 years. These 5-year survivors were analyzed according to many factors. Females had a better prognosis than males, and patients without lymph-node metastasis had a better 5-year survival rate than those with it. Ten patients who survived over 5 years had recurrences and received therapy. As a cause of death after 5 years, double primary carcinoma of other organs is more frequent than recurrence.

Twenty patients with carcinoma of the hypopharynx, esophagus and thyroid underwent pull-through esophagectomy. Seventeen of them received combined resection of the larynx and trachea. Dissection of the lymph nodes at the upper mediastinum was performed in 11 patients by sternotomy. Seven patients received mediastinal tracheostomy after combined resection of the trachea and the larynx. Pull-through esophagectomy was followed by pharyngogastrostomy without thoracotomy via the posterior mediastinum. This technique is described in detail. Because there is no thoracotomy and ligation of the esophageal vessels is ensured, no pulmonary complications and no massive mediastinal hemorrhages occurred. There were no operative deaths. This operation offers excellent palliation and little morbidity. Moreover, the use of sternotomy and mediastinal tracheostomy for pull-through esophagectomy made it possible to dissect the upper mediastinal lymph nodes, and we could resect the affected trachea with certainty.

A 64-year-old man presented with mediastinal and bilateral hilar adenopathy, and a biopsy of a scalene node revealed non-Hodgkin's lymphoma. One week after a cycle of combination chemotherapy, he developed an esophagobronchial fistula. Following a resolution of pneumonia by antibiotics, a cervical esophagostomy was made and, after the improvement of his general condition with parenteral hyperalimentation, he was given one course of combination chemotherapy which was continued until the mediastinal lymph node shadow completely disappeared. A subcutaneous bypass operation was performed on the stomach. After receiving one more cycle of intensification chemotherapy, he was discharged. Three months later, a bronchoscopy showed healing of the fistula. Nine months postoperatively, there is no evidence of the lymphoma or the esophagobronchial fistula recurring. Esophageal involvement is rare in malignant lymphoma and this is only the sixth reported case of esophageal fistula of the respiratory tract in association with lymphoma, and just the second to be treated successfully.

Rotational diffusion of the total cytochrome P-450 (P-450scc plus P-45011 beta) in bovine adrenocortical mitochondria was examined by observing the decay of absorption anisotropy, r(t), after photolysis of the hemo.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane normal" model. The measurements were used to investigate intermolecular interactions of cytochrome P-450 with other membrane proteins. The absorption anisotropy decayed within 1 ms to a time-independent value. Rotational diffusion of cytochrome P-450 was dependent on the presence and absence of deoxycorticosterone (DOC), a substrate for cytochrome P-45011 beta. The observed value for the normalized time-independent anisotropy r(infinity)/r(0) and the average rotational relaxation time phi are r(infinity)/r(0) = 0.88 and phi = 233 microseconds when DOC is absent, and r(infinity)/r(0) = 0.65 and phi = 350 microseconds when DOC is present. Judging from the phi value, rotating P-450 is not a monomeric molecule, but would be a small microaggregate with an average diameter of about 120 A. A significantly high value of r(infinity)/r(0) implies co-existence immobile populations of cytochrome P-450. Based on the assumption that the heme angle tilts 55 degrees from the membrane plane (Gut et al. (1983) J. Biol. Chem. 258, 8588-8594), 65% (when DOC is present) or 88% (when DOC is absent) of cytochrome P-450 in mitochondria is immobilized within the experimental time range of 2 ms due to the presence of immobile protein microaggregates.(ABSTRACT TRUNCATED AT 250 WORDS)

Resonance Raman spectra of cytochrome P-450cam (P-450cam) and its enzymatically inactive form (P-420) in various oxidation and spin states were measured for the first time. The Raman spectrum of reduced P-450cam was unusual in the sense that the "oxidation-state marker" appeared at an unexpectedly lower frequency (1346 cm-1) in comparison with those of other reduced hemoproteins (approximately 1355-approximately 1365 cm-1), whereas that of oxidized P-450cam was located at a normal frequency. This anomaly in the Raman spectrum of reduced P-450cam can be explained by assuming electron delocalization from the fifth ligand, presumably a thiolate anion, to the antibonding pi orbital of the porphyrin ring. The corresponding Raman line of reduced P-420 appeared at a normal frequency (1360 cm-1), suggesting a status change or replacement of the fifth ligand upon conversion from P-450cam to P-420. The Raman spectrum of reduced P-450cam-metyrapone complex was very similar to that of ferrous cytochrome b5.

After esophagectomy, free jejunal autografts were used for reconstruction in 11 patients and pedunculated colons in two patients. A microvascular technique was applied immediately after the resection. A vascular anastomosis gave a new blood supply for the free jejunal graft, and in the case of the pedunculated colon gave support to improve circulation. During the grafting procedure, neither cooling nor heparinization was needed. No graft failures have occurred. The main complication of free jejunal grafts was leakage of the proximal anastomosis of the bowel, but all three leakages healed spontaneously. Two supportive vascular anastomoses for the pedunculated colons were effective and caused no complication. All 13 patients could eat regularly at the time of their discharge.