Effects of methanol on styrene metabolism among workers occupationally exposed at low concentrations

A survey was conducted in the second half of a work week on 39 male workers who were occupationally exposed to styrene in combination with methanol and methyl acetate during the production of plastic buttons. Time-weighted average exposure during an 8-h shift to styrene (Sty-A) and methyl acetate was monitored by carbon cloth-equipped personal samplers and to methanol by water-equipped ones. Urine samples were collected near the end of the shift and analyzed for mandelic (MA-U) and phenylglyoxylic acids (PhGA-U) by HPLC. Geometric mean styrene concentration was 12.4 ppm (g/g) with the maximum of 46 ppm, whereas the values for methanol and methyl acetate in combination were 23.5 ppm and 229 ppm, respectively. The relationship of MA-U and PhGA-U with Sty-A was examined by linear regression analysis. The equations for the regression lines were compared with the results from a previous survey (Ikeda et al. 1983) in which workers were exposed only to styrene, and the methods employed were identical with that in the present study. The comparison showed no evidence to suggest that styrene metabolism is suppressed by coexposure to methanol and methyl acetate at low concentrations below the current occupational exposure limit of 200 ppm.     

Primary malignant fibrous histiocytoma of the ascending colon: Report of a case

We report herein an unusual case of primary malignant fibrous histiocytoma (MFH) of the ascending colon. A 47-year-old man was admitted to our hospital for further investigations following the discovery of a mass in the right lower quadrant of the abdomen during a medical checkup. Abdominal ultrasonography (US) and computed tomography (CT) demonstrated a mass extending to the right lateral side from the ascending colon. At laparotomy, a tumor was found originating in the ascending colon and infiltrating the right lateral peritoneum. A right hemicolectomy and partial peritoneal dissection were performed followed by an ileotransverse colostomy reconstruction. The resected specimen contained a tumor measuring 7×5×4 cm, the cut surface of which was yellowish white, and the mucosa of the colon was intact. Based on histological and immunohistochemical inspection, the tumor was diagnosed as MFH of the ascending colon. We reviewed the total 18 known cases of colorectal MFH documented in the literature including our case. After surgery, 4 of 17 patients died of local recurrence, all within 42 months, indicating that early and complete excision of tumor is essential to achieve cure.     

Peak oxygen uptake, ventilatory threshold and leg extension power in apparently healthy Japanese]

Peak oxygen uptake, ventilatory threshold (VT) and leg extension power were measured in 832 apparently healthy subjects (421 males, 411 females) aged 30-60 decades who performed medical examination at 4 health check up facilities. 1) Peak oxygen uptake was greater in male than female, and decreased with age in both sexes. Single regression formula on age were Y (ml/kg/min) = 46.6 - 0.36 x AGE, (r = 0.447, p < 0.001) in male and Y (ml/kg/min) = 35.3 - 0.23 x AGE, (r = 0.407, p < 0.001) in female. 2) VT was greater in male than female, and less decreased with age compared to maximal aerobic power. Single regression formula on age were Y (ml/kg/min) = 22.6 - 0.13 x AGE, (r = 0.371, p < 0.001) in male, Y (ml/kg/min) = 20.0 - 0.10 x AGE, (r = 0.301, p < 0.001) in female. 3) Leg extension power was greater in male than female, and decreased with age in both sexes. Single regression formula on age were Y (W/kg) = 31.9 - 0.27 x AGE, (r = 0.539, p < 0.001) in male and Y (W/kg) = 20.9 - 0.18 x AGE, (r = 0.510, p < 0.001) in female. Subjects in the present study showed height, weight and walk steps per day similar to those in National Nutrition Survey. Comparison of Peak oxygen uptake, ventilatory threshold and leg extensor power to previous studies revealed that these parameters were quite similar to the counterparts in the previous studies with less selection bias. It was suggested that subjects in this study were quite similar to normal Japanese population, and that Peak oxygen uptake, VT and leg extension power in the present study were of value for the evaluation of health related fitness in community and workplace.     

Studies on iodinated compounds. X. Isolation and purification of iodoglycyltyrosines]

The methods for the isolation and purification of iodoglycyltyrosines [glycyl-3-iodotyrosine (Gly-MIT) and glycyl-3,5-diiodotyrosine (Gly-DIT)] from a reaction mixture were examined by the use of high-performance liquid chromatography (HPLC). Glycyltyrosine (Gly-Tyr) was iodinated with iodine monochloride (ICl) (the molar ratio of Gly-Tyr to ICl was 1:1.5) in 0.1 M NaOH. The synthesized Gly-MIT and Gly-DIT were separated on a mu Bondapak C18 column employing stepwise gradient systems of a 0.1% trifluoroacetic acid/acetonitrile mixture and a water/acetonitrile mixture. Chemically pure Gly-MIT and Gly-DIT were obtained in 30.2% and 28.2% yields, respectively.     

Minimal synaptic delay in the saccadic output pathway of the superior colliculus studied in awake monkey

The synaptic organization of the saccade-related neuronal circuit between the superior colliculus (SC) and the brainstem saccade generator was examined in an awake monkey using a saccadic, midflight electrical-stimulation method. When microstimulation (50–100 A, single pulse) was applied to the SC during a saccade, a small, conjugate contraversive eye movement was evoked with latencies much shorter than those obtained by conventional stimulation. Our results may be explained by the tonic inhibition of premotor burst neurons (BNs) by omnipause neurons that ceases during saccades to allow BNs to burst. Thus, during saccades, signals originating from the SC can be transmitted to motoneurons and seen in the saccade trajectory. Based on this hypothesis, we estimated the number of synapses intervening between the SC and motoneurons by applying midflight stimulation to the SC, the BN area, and the abducens nucleus. Eye position signals were electronically differentiated to produce eye velocity to aid in detecting small changes. The mean latencies of the stimulus-evoked eye movements were: 7.9±1.0 ms (SD; ipsilateral eye) and 7.8±0.9 ms (SD; contralateral eye) for SC stimulation; 4.8±0.5 ms (SD; ipsilateral eye) and 5.1±0.7 ms (SD; contralateral eye) for BN stimulation; and 3.6±0.4 ms (SD; ipsilateral eye) and 5.2±0.8 ms (SD; contralateral eye) for abducens nucleus stimulation. The time difference between SC- and BN-evoked eye movements (about 3 ms) was consistent with a disynaptic connection from the SC to the premotor BNs.     

Nucleosides and nucleotides. 107. 2-(cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects.

Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (Ki ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100 micrograms/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.     

Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer.

PURPOSE: The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC. RESULTS: Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (+/- SD) serum endostatin level was 41.6 +/- 34.4 ng/ml in the patient group and 16.3 +/- 10.3 ng/ml in the control group (P < 0.0001). The 11 cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors. CONCLUSIONS: Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin.     

Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis.

PURPOSE: Molecular antagonists of the inhibitor of apoptosis protein survivin have shown promise as novel anticancer strategies for triggering tumor cell apoptosis, dysregulating mitotic progression, and inhibiting tumor growth in preclinical models. However, how survivin couples to the cell death machinery has remained elusive, and the relevant cellular targets of survivin antagonists have not been completely elucidated. Experimental Design: Human umbilical vein and dermal microvascular endothelial cells were infected with replication-deficient adenoviruses encoding survivin (pAd-Survivin), green fluorescent protein (pAd-GFP), or a phosphorylation-defective survivin Thr(34)-->Ala (pAd-T34A) dominant negative mutant. The effect of wild-type or mutant survivin was investigated on capillary network stability, endothelial cell viability, and caspase activation in vitro and on kinetics of tumor growth and development of angiogenesis in a breast cancer xenograft model in vivo. The cell death pathway initiated by survivin targeting was mapped with respect to cytochrome c release, changes in mitochondrial transmembrane potential, and apoptosome requirements using mouse embryonic fibroblasts deficient in Apaf-1 or caspase-9. RESULTS: Adenoviral transduction of endothelial cells with pAd-Survivin inhibited growth factor deprivation- or ceramide-induced apoptosis, reduced caspase-3 and -7 generation, and stabilized three-dimensional capillary networks in vitro. Conversely, expression of pAd-T34A caused apoptosis in umbilical vein and dermal microvascular endothelial cells and resulted in caspase-3 activity. Cell death induced by survivin targeting exhibited the hallmarks of mitochondrial-dependent apoptosis with release of cytochrome c and loss of mitochondrial transmembrane potential and was suppressed in Apaf-1 or caspase-9 knockout mouse embryonic fibroblasts. When injected in human breast cancer xenografts, pAd-T34A inhibited growth of established tumors and triggered tumor cell apoptosis in vivo. This was associated with a approximately 60% reduction in tumor-derived blood vessels by quantitative morphometry of CD31-stained tumor areas, and appearance of endothelial cell apoptosis by internucleosomal DNA fragmentation in vivo. CONCLUSIONS: Survivin functions as a novel upstream regulator of mitochondrial-dependent apoptosis, and molecular targeting of this pathway results in anticancer activity via a dual mechanism of induction of tumor cell apoptosis and suppression of angiogenesis.