A study of multiple biomarkers in coke oven workers--a cross-sectional study in China

We conducted a cross-sectional molecular epidemiological study of coke oven workers exposed to the established carcinogen polycyclic aromatic hydrocarbons (PAHs) to evaluate the relationships between both traditional 'exposure markers' and a series of biomarkers, including urinary 1-hydroxypyrene as a marker of internal dose, leukocyte aromatic DNA adducts as markers of biologically effective dose, serum p53 protein as a response marker and genetic polymorphisms of cytochrome P4501A1 and glutathione S-transferase MI as susceptibility markers. Twenty-five male subjects each were randomly selected from the top, middle and bottom work areas of the oven, and the control plant. They were matched for age and smoking status. The mean levels of PAH exposure, monitored by stationary and personal samplers, and of worker urinary 1-hydroxypyrene differed significantly between the top, middle and bottom of the oven and control work areas. The highest stationary and personal PAH concentrations and 1-hydroxypyrene levels were demonstrated at the top work area. Good correlations were found between the stationary PAH levels, personal PAH levels and urinary 1-hydroxypyrene levels. No positive correlations were demonstrated between aromatic DNA adduct levels and current or cumulative PAH exposure dose. In the presence of genetic polymorphisms of cytochrome P4501A1, a positive correlation was demonstrated between aromatic DNA adducts and urinary 1-hydroxypyrene levels. There was also a significant correlation between serum p53 protein levels and the cumulated benzo[a]pyrene exposure dose. Although these biomarkers have certain limitations, they are applicable to cancer epidemiology, and may contribute to our understanding of the mechanisms of carcinogenesis.     

Occurrence of Erysipelothrix spp. in broiler chickens at an abattoir

From September 1995 to August 1996, 750 chickens from 66 farms sent to an abattoir in Nagano Prefecture, Japan, were examined for the presence of Erysipelothrix spp. Erysipelothrix spp. were isolated from 118 (15.7%) of 750 skin samples, 27 (7.3%) of 372 hypoderm samples, 12 (1.9%) of 630 throat samples, 106 (59.2%) of 179 feather samples, and none of 257 spleen samples. Of 66 farms, 55 farms (83.3%) sent Erysipelothrix-positive chickens and 11 farms (16.7%) only negative ones. Of 297 Erysipelothrix isolates, 273 isolates were identified as Erysipelothrix rhusiopathiae and 24 as Erysipelothrix tonsillarum. E. rhusiopathiae isolates were serotyped into nine different serovars. Of the 273 E. rhusiopathiae isolates, 33 (11.1%) were serotyped to serovar 6; 22 (7.4%) were serovar 5; 19 (6.4%) were serovar 2; 15 (5.1%) were serovar 8; 2 (0.7%) were serovar 21; 4 each (1.3% each) were serovars 1b, 9, 12, and 19; and 178 (59.9%) were untypeable. Of 24 E. tonsillarum isolates, 15 (5.1%) were serotyped to serovar 3, and 9 (3.0%) were serovar 7. These findings indicate that chickens seem to be a potential reservoir of Erysipelothrix spp. in nature and to be a source of human Erysipelothrix infection.     

DNA cleaving activities of 9-membered masked enediyne analogues possessing DNA intercalator and sugar moieties

The DNA cleaving properties of various enediyne analogues possessing sugar moieties and DNA-intercalators were investigated. The DNA cleaving experiments show that these hybrids analogues induced sequence-selective DNA cleavage and the simple sugars in the enediyne serve as a DNA recognition element for DNA cleavage.     

Effects of Nd:YAG laser irradiation on morphometry and lung function in elastase-induced emphysema in rats

BACKGROUND & OBJECTIVE: Although thoracoscopic laser ablation therapy has been hailed as an effective surgical treatment for diffuse emphysema, no one has as yet made an in-depth study of the efficacy of this treatment. This investigation was undertaken to research the effects of laser pneumoplasty on an animal model of emphysema. STUDY DESIGN/MATERIALS AND METHODS: Eight weeks after elastase treatment, the rats' left lungs were irradiated using contact Nd:YAG laser. Pulmonary function tests were performed 4 weeks after irradiation and the lungs were prepared for histologic examination. RESULTS: Dense fibrous scars beneath the pleura were observed at 4 weeks after irradiation. Although mean linear intercept values of irradiated lungs were not much lower than those in the non-irradiated elastase-treated group, laser irradiation caused a significant decrease in lung volume. While there was no significant difference in quasistatic compliance, elastic recoil pressure of the lung increased to control levels at total lung capacity volume. CONCLUSION: We conclude that laser therapy does not cause normalization of compliance, or improvement in the deeper part of the emphysematous lung, but rather a peripheral volume reduction and "encasement effect" on the lungs as a result of fibrotic scars.     

The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.     

Two cases of cerebral aneurysm detected after recanalization of the middle cerebral artery]

Two cases of aneurysm incidentally detected after recanalization of middle cerebral artery (MCA) occlusion are reported. Patient 1 was a 62-year-old male with sudden onset of left hemiparesis. We performed emergent intravascular surgery. The initial cerebral angiography revealed occlusion at the M1 portion of the right MCA. After partial recanalization with a microcatheter, carotid angiography revealed a right M1-M2 junction aneurysm. Due to the risk of aneurysmal rupture, the thrombolytic procedure was stopped. Follow up angiography after 1 month revealed complete recanalization of the right MCA and a persistent aneurysm. Patient 2 was a 65-year-old male with left hemiparesis. The initial cerebral angiography revealed occlusion at the M1 portion of the right MCA. After 1 month follow-up cerebral angiography revealed spontaneous recanalization of the right MCA and an incidental aneurysm at the M1-M2 junction. Neck clipping of the aneurysm was performed. When using a microcatheter or microballoon catheter to treat arterial occlusion, surgeons should consider the possibility of a rupture of a hidden aneurysm.     

ONO-5046 is a potent inhibitor of neutrophil elastase in human pleural effusion after lobectomy

The imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium N-[2-[4-(2,2-Dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetic acid (ONO-5046) and purified alpha1-antitrypsin, on neutrophil elastase activity were determined. The amount of neutrophil elastase complexed to alpha1-antitrypsin, measured by an enzyme-linked immunosorbent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The alpha1-antitrypsin levels measured by laser nephelometry did not increase in either blood or pleural effusion. Although neutrophil elastase activity, measured by the hydrolysis of succinyl-(Ala)3-p-nitroanilide, was not detected in blood, it was increased in pleural effusion 3 h and 24 h after lobectomy. ONO-5046, but not alpha1-antitrypsin, reduced the neutrophil elastase activity in pleural effusion. There is an imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion.     

The circadian variation of urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transpeptidase in clinically healthy cats

The circadian variation of urinary N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) was evaluated in cats. Urine and blood were collected at 4-hr intervals from adult cats (3 males, 9 females) weighing between 2.6 and 5.0 kg. There was no circadian variation in the urine volume, creatinine clearance, creatinine excretion, NAG excretion or gamma-GTP excretion. The average NAG and gamma-GTP indices in the 4-hr urine were similar to those for the 24-hr urine. However, the variance for the 4-hr urine samples was higher than that of 24-hr urine. In conclusion, although 4-hr urine samples can be used to estimate 24-hr urinary enzyme excretion, short-term spot urine samples may cause increased variation in the enzyme index.     

Complete appendiceal intussusception induced by primary appendiceal adenocarcinoma in tubular adenoma: a case report

A case of complete intussusception induced by appendiceal carcinoma is reported. The patient was a 49-year-old man complaining of rectal bleeding. Barium enema and colonoscopy revealed a cecal polyp; it was interpreted as an inverted appendix with a tumor. Computed tomography showed an invaginated appendix into the cecal cavity. During surgery, the appendix was found to be inverted completely into the cecum; ileocecal resection with regional lymph node dissection was performed. Microscopic examination revealed well-differentiated adenocarcinoma in tubular adenoma. Diagnosis of intussusception with carcinoma of the appendix is often difficult because appendiceal carcinoma with intussusception of the appendix is a rare condition. Although this condition can be diagnosed by radiographic imaging or colonoscopy, computed tomography has also been useful. The clinical manifestation of appendiceal intussusception with primary appendiceal tumor resembles a large cecal polyp, but its treatment differs greatly. Failure to recognize this condition may result in unexpected complications such as consequent peritonitis in case of endoscopic removal.     

Dual roles of proteasome in the metabolism of presenilin 1

Presenilin 1 (PS1) has been identified as a causative gene for most early-onset familial Alzheimer's disease. Biochemical studies revealed that PS1 exists predominantly as two processed fragments in cells and brain tissues. We prepared stably transfected cells expressing the wild-type and familial Alzheimer's disease-associated mutants of PS1 and investigated the enzyme that participates in the metabolism of PS1. After treatment of the cells with proteasome inhibitors, the full-length PS1 was significantly accumulated. The levels of N- and C-terminal fragments were also increased. The accumulation of PS1 with a deletion of exon 10, which is unable to be processed, on treatment of the transfected cells with lactacystin indicated that proteasome can degrade full-length PS1. A synthetic peptide that includes the processing region of PS1 was cleaved by 20S proteasome at the putative processing sites after Met288 and Glu299. Metabolic labeling experiments showed that the appearance of the N-terminal fragment was attenuated by the inhibitor. Finally, 28-kDa N- and 20-kDa C-terminal fragments were generated by purified PS1 in vitro. These data indicated that the proteasome pathway is involved in PS1 processing. These results demonstrate that the proteasome pathway plays dual roles in processing and degradation of PS1.