Personal exposure to nitrogen dioxide from indoor heaters and cooking stoves

The personal exposure to NO₂ generated from various heaters and cooking stoves were studied, using 85 university students. The students attached NO₂ filter badges to their chests or collars and wrote down the period of time for heating and cooking for 1 week. Types of heaters and smoking habits were described through a questionnaire. The urinary hydroxyproline/creatinine ratio (HOP/C) was examined as a biomarker for health effects. The outdoor NO₂ concentration during the study period was 13.5–13.7 g/m³. Smoking and the usage of electric heaters did not affect the exposure to NO₂. Exposure increased according to the length of time kerosene heaters or oil fan heaters were used. The NO₂ concentration during the heating by a kerosene heater and an oil fan heater was calculated to be 219 and 474 g/m³, respectively. The correlation between the period of cooking and personal exposure was also observed. The NO₂ levels during cooking were calculated to be 290 g/m³. Using these calculated values of NO₂ concentration, it is possible to presume the personal exposure levels from the length of time heaters and cooking stoves are used even if the subjects do not attach the filter badges. Neither smoking nor exposure to NO₂ were associated with the increase of urinary HOP/C.     

Low grade amplification of MDM2 gene in a subset of human breast cancers without p53 alterations

MDM2 protein is thought to bind to p53 tumor suppressor protein leading to inhibition of p53-mediated transactivation. Amplification of the MDM2 gene has been frequently observed in human sarcoma, and relevant overexpression of the MDM2 protein is assumed to contribute to tumorigenesis through inactivation of the p53 function. In order to determine whether MDM2 amplification plays a role in the development of human breast cancer without genetic alteration of p53, we analyzed, MDM2 gene amplification by quantitative hybridization and genetic alteration of p53, in 32 primary tumors and 26 metastatic lymph nodes. Low grade amplification of the MDM2 gene (2-6 fold) was observed in four cases, none of which showed even subtle genetic alterations of p53 or loss of alleles on 17p. Moreover, in three of the four cases with MDM2 gene amplification, the level of gene amplification in the metastatic lymph nodes was slightly higher than that in the primary tumors. These results, taken together with previous findings, suggest that a subset of breast cancers without genetic alteration of p53 may also arise by inactivation of the p53 function through interaction with the overexpressed MDM2 protein induced by gene amplification.     

Health status of male preparatory school students lodging at a dormitory in Japan

An investigation on the health status of 79 male preparatory school students lodging at a dormitory in Japan was carried out by questionnaire on lifestyles, subjective symptoms and mental status, as compared with two control groups: 73 medical students and 36 new employees. About 83 % of them slept less than 6 hours and 70 % of them did not exercise. Many students are troubled with back pain or lumbago(47%), sensation of incomplete bladder emptying(l6%), loss of visual acuity(55%) and eye fatigue(65%). Self-rating depression scale score of preparatory school students was not significantly higher than those of the control groups. The lifestyles of preparatory school students found to be very restricted and strained. However, no significant differences on mental adverse health effects was found among three groups.     

Role of reactive oxygen in phospholipase A2 activation by ischemia/reperfusion of the rat kidney

Purpose. To investigate the role of phospholipase A₂ (PLA₂) in reperfusion injury of the kidney in an in vivo animal model, renal mitochondrial PLA₂ activity was measured under three different conditions. Methods. Male Wistar rats (n = 72) anesthetized with pentobarbital underwent renal ischemia surgically for 45 min and were reperfused for the indicated time (renal ischemia/reperfusion). Treatments included reperfusion for various predetermined periods (phase 1), exposure to hyperbaric oxygen (phase 2), and administration of reactive oxygen species (ROS) scavenger (phase 3). Thereafter, each kidney was harvested, and mitochondrial PLA₂ activity was measured by a radioisotope technique. Results. Ischemia/reperfusion resulted in time-related PLA₂ activation in the renal mitochondria up to 48 h of reperfusion after renal ischemia. Renal mitochondrial PLA₂ activity was further augmented by hyperbaric oxygen exposure prior to reperfusion, whereas administration of the ROS scavengers suppressed mitochondrial PLA₂ activity. Conclusion. These data suggest that ROS may play an important role in the in vivo activation of PLA₂ associated with renal ischemia/reperfusion. Received for publication on July 6, 1998; accepted on November 30, 1998     

Manometric Evidence of Improved Early Gastric Stasis by Erythromycin after Pylorus-preserving Pancreatoduodenectomy

Gastric stasis is a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD). We demonstrated that it might be attributable to delayed recovery of phase III activity of the gastric migrating motor complex due to low concentrations of plasma motilin caused by resection of the duodenum. Leucine 13-motilin is effective for treating gastric stasis, but it is not yet available for clinical use. Whether erythromycin would improve early gastric stasis after PPPD was tested clinically and by manometry. A manometric tube assembly and a gastrostomy tube were inserted in the stomach of 10 patients at PPPD for pressure recording from the gastric antrum and jejunum and for gastric juice drainage, respectively. After baseline recording, erythromycin 5 mg/kg was given intravenously on day 14 and saline as a placebo on day 17 every 4 hours four times a day. The daily volume of gastric juice output and the gastric motility index were measured. The mean period until the return of gastric phase III was 31 +/- 1 days. Erythromycin significantly increased the gastric motility index from 7.9 +/- 1.3 mmHg to 15.7 +/- 1.8 mmHg (p = 0.0005), whereas saline did not (7.2 +/- 1.6 mmHg to 6.5 +/- 1.2 mmHg; p = 0.21). Erythromycin significantly decreased the gastric juice output from 1,080 +/- 190 ml to 738 +/- 199 ml (p < 0.0001), but the saline injections did not (1,064 +/- 174 ml to 1,115 +/- 189 ml; p = 0.35). Erythromycin, a universally available motilin agonist, is a safe, effective, potent drug for the treatment of early gastric stasis after PPPD.     

In vitro metabolism of fenthion and fenthion sulfoxide by liver preparations of sea bream, goldfish, and rats.

The in vitro metabolism of fenthion and its sulfoxide (fenthion sulfoxide) in sea bream (Pagrus major) and goldfish (Carassius auratus) was investigated and compared with that in rats. Fenthion was oxidized to fenthion sulfoxide and the oxon derivative, but not to its sulfone, in the presence of NADPH by liver microsomes of sea bream, goldfish, and rats. These liver microsomal activities of the fish were lower than those of rats but were of the same order of magnitude. The NADPH-linked oxon- and sulfoxide-forming activities of liver microsomes of the fish and rats were inhibited by SKF 525-A, metyrapone, alpha-naphthoflavone, and carbon monoxide. The oxidizing activity to fenthion sulfoxide was also inhibited by alpha-naphthylthiourea. Several cytochrome P450 isoforms and flavin-containing monooxygenase 1 exhibited these oxidase activities. Fenthion sulfoxide was reduced to fenthion with liver cytosol of the fish and rats upon addition of 2-hydroxypyrimidine, N(1)-methylnicotinamide, or butyraldehyde, each of which is an electron donor of aldehyde oxidase, under anaerobic conditions. The activity was inhibited by menadione, beta-estradiol, and chlorpromazine, which are inhibitors of aldehyde oxidase. The activities in the fish livers were similar to those of rat liver. Aldehyde oxidase purified from the livers of sea bream and rats exhibited the reducing activity. Thus, fenthion and fenthion sulfoxide are interconvertible in fish and rats through the activities of cytochrome P450, flavin-containing monooxygenase, and aldehyde oxidase.     

Therapeutic Value of Neoadjuvant Intra-arterial Chemotherapy (Cisplatin) and Irradiation for Locally Advanced Uterine Cervical Cancer

We analyzed long-term treatment results in 51 patients with locally advanced uterine cervical carcinoma (IIB, 4; IIIB, 43; IVA, 4) treated with neoadjuvant intra-arterial (I-A) chemotherapy (cisplatin) via the uterine artery and irradiation. Thirty patients (58.8%) developed recurrence. Twelve had pelvic recurrence alone, 8 had distant metastases alone, and 10 had both pelvic and distant failure. The 5-year cumulative pelvic control rate, absolute survival rate, and disease-free survival rate were 55.3, 47.1, and 39.4%, respectively. Eight of 51 patients (15.7%) suffered late complications. These results suggest that our neoadjuvant I-A chemotherapy prior to irradiation has limited additional value for long-term prognosis in patients with locally advanced uterine cervical carcinoma.     

Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed.Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2′-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-¹⁰B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-¹⁰B (BPA), the tumors were irradiated with neutrons, or those without ¹⁰B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency).Results: Without ¹⁰B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With ¹⁰B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons.Conclusion: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.