Stoichiometry of the Reaction Catalyzed by Skin Sulfhydryl Oxidase

The stoichiometry of the reaction catalyzed by skin sulfhydryl oxidase was investigated. Dithiothreitol (DTT) was used as the substrate for skin sulfhydryl oxidase. The consumption of DTT, consumption of oxygen, and production of hydrogen peroxide were measured during the enzyme reaction. The molar ratio of DTT:O₂:H₂O₂ in the enzyme reaction was 1:1.02:0.89. Correspondingly, the stoichiometry of the enzyme reaction was calculated to be R(SH)₂ + O₂ → + H₂O₂.     

Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York,United States)

We sought to determine if specific dietary antioxidants may be particularly effective in reducing breast cancer risk for women reporting family history (FH) of breast cancer in a first-degree relative. Interviews regarding usual diet, health, and family histories were conducted with 262 premenopausal and 371 postmenopausal women with incident, primary breast cancer from western New York (United States). These women were frequencymatched by age and county of residence with community controls. Among premenopausal women, there was a significant interaction between FH and -tocopherol; -tocopherol was associated with significantly decreased risk among FH+ women (adjusted fourth-quartile odds ratio [OR]=0.01, 95 percent confidence interval [CI]=0.0–0.3). This association was much weaker for FH-women [OR=0.7, CI=0.4–1.2]. For FH-women, a significant inverse association was observed between -carotene and premenopausal breast-cancer risk (OR=0.4, CI=0.3–0.5), but not for FH+ women (OR=0.5, CI=0.1–4.0). Similar relationships, although not as strong, were noted among postmenopausal women. Although limited by small numbers, these results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and FH-women, and that -tocopherol may be a potential chemopreventive agent for women with a family history of breast cancer, particularly premenopausal women.This research was conducted by the Department of Social and preventive Medicine, State University of New York at Buffalo. This publication is supported in part by grants CA11535 and 5 R25 CA1820117 from the US National Cancer Institute and PDT-434 from the American Cancer Society. Dr Freudenheim is a recipient of a Research Career Development Award from the National Cancer Institute (CA01633). This work is solely the responsibility of the authors and does not necessarily represent the views of the NCI.     

Antitumor effects of oral administration of an interferon-inducing pyrimidinone,Bropirimine, on murine renal-cell carcinoma

Bropirimine [2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone] is a low-molecular-weight compound that acts as an inducer of interferon in several animal species. Experiments were designed to explore the possibility of using this drug for the treatment of renal-cell carcinoma (RCC). Euthymic BALB/c mice were inoculated with murine RCC (Renca) cells and given graded doses of Bropirimine p.o. for 5 consecutive days beginning on day 1 following tumor inoculation. These mice were killed and tumors were excised on day 21. Bropirimine significantly (P<0.01) inhibited the tumor growth at a daily dose of 1,000 or 2,000 mg/kg. No adverse effect or toxicity was noted at 1,000 mg/kg, and at 2,000 mg/kg there was only a marginal body-weight reduction without any other appreciable side effect. In addition to the inhibition of tumor growth, there was a small yet significant (P<0.05) increase in the duration of survival (in days) in the Bropirimine-treated animals. When the treatment was delayed to begin on day 6 following tumor inoculation, Bropirimine did not suppress tumor growth in euthymic mice, pointing to the importance of the timing of the treatment. In athymic nude BALB/c mice lacking T-cells or T-cell function, Bropirimine also inhibited tumor growth (P<0.01). The antitumor effect of this drug was abolished by pretreatment with anti-asialo GM1 serum, which eliminated natural killer (NK) activity in euthymic mice. In vivo treatment with Bropirimine augmented the cytotoxicity of lymphocytes isolated from the spleens or lungs of the tumor-bearing mice, which were active against Renca and YAC-1 cells in vitro. This activity was NK-cell-dependent as judged on the basis of the results of the in vitro complement-dependent cytotoxicity assay. Since Bropirimine induced interferon (IFN)-/ production, significantly (P<0.05) elevating its serum concentration, and since this drug mimics the effects of IFN-/, it seemed likely that the Bropirimine-induced NK cell augmentation we found was mediated by IFN-/. These results suggest that Bropirimine, a booster of NK activity, may have potential as an adjunct to other therapeutic modalities in the treatment of human RCC.     

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.     

Intrathoracic omental herniation through the esophageal hiatus: Report of a case

(Received for publication on Dec. 8, 1997; accepted on July 7, 1998)     

Major organ function under mechanical support: comparative studies of pulsatile and nonpulsatile circulation

We examined a major organ function during 3 h biventricular assisted circulation after acute myocardial infarction model in the pig. In left ventricular circulation, the outflow cannula was placed in the ascending aorta and an inflow cannula through the mitral valve in the left ventricle. A pump (pulsatile group, Zeon Medical, Inc., Tokyo, Japan and nonpulsatile group, Nikkiso HPM-15, Nikkiso, Inc., Tokyo, Japan) was connected to each cannula. In right ventricular circulation, the outflow cannula was placed in the pulmonary artery and an inflow cannula in the right ventricle. The right ventricular circulation was supported by a nonpulsatile pump (Nikkiso HPM-15). The items measured were the regional blood flows of the cortex and medulla in the kidney, white matter and gray mater in brain, and liver; renal arterial flow; carotid arterial flow; portal vein flow; common hepatic arterial flow; arterial ketone body ratio (AKBR); and lactate/pyrubic acid (L/P). In the pulsatile group, the renal cortical blood flow increased, and the medulla blood flow decreased. On the other hand, in the nonpulsatile group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved rather than in the nonpulsatile assisted group. In addition the liver regional blood flow, AKBR, and L/P showed significant differences between the pulsatile and nonpulsatile groups. On the other hand, the white matter and gray matter regional blood flows and carotid arterial flow did not show significant differences between the groups. The results of our study indicated that pulsatile circulation produced superior circulation in the kidney and liver, and microcirculation on the cell level was superior as well in early treatment of acute heart failure.     

REP-1 gene mutations in Japanese patients with choroideremia

· Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. · Methods: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1–15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. · Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. · Conclusions: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients. Received: 13 August 1998 Revised version received: 16 November 1998 Accepted: 9 December 1998     

Study on allergic rhinitis in workers exposed to methyltetrahydrophthalic anhydride

Methylterahydrophthalic anhydride (MTHPA) is used as a hardening agent in an epoxy resin system. Because work-related nasal symptoms were observed in some workers exposed toMTHPA at two condenser plants, a cross-sectional survey was performed to improve their work environment. MeanMTHPA levels in the manufacturing processes to which the workers were routinely assigned were extremely low (1.09-22.4 μg/m3). However, specific IgE antibody (S-IgE) was detected in 9 (32%) of 28 workers. Of these, 8 (89%) had nasal symptoms. An IgE-mediated mechanism seems to be associated with at least some of the cases of work-related nasal symptoms. This indicates that the occupational health administration ofMTHPA cannot be controlled simply by limiting exposure in the work environment. Total IgE (T-IgE) levels were significantly higher in S-IgE-positive workers than in S-IgE-negative workers (geometric mean, 200.5 and 51.3 IU/ml, respectively; p<0.002, unpaired t test). These findings demonstrate that workers in whom S-IgE is less likely to be produced, i.e., those in whom the T-IgE level is 80 IU/ml or less, should be assigned to work in these manufacturing processes.     

Use of ultrasound-guided percutaneous needle biopsy in the diagnosis of mediastinal tumors

We herein report the usefulness of ultrasoundguided percutaneous needle biopsy for histological diagnosis in 18 patients with mediastinal tumors. Computed tomography revealed these tumors to be in contact with the chest wall. The preoperative diagnosis was thymoma in 7 patients, germinoma in 5, neurogenic tumor in 3, and other in 3. The most commonly encountered indication for an ultrasound-guided percutaneous needle biopsy was an anterior mediastinal lesion (78%; 14 of 18 patients). In 16 (89%) of the 18 patients, the biopsy diagnosis corresponded to the post-operative diagnosis. No complications were encountered in any of the patients. This new technique of ultrasound-guided percutaneous needle biopsy is both relatively simple and highly accurate and may thus be useful for outpatients. Preoperative ultrasound-guided percutaneous needle biopsy is thus considered to be a safe and reliable method for the histological diagnosis of mediastinal tumors, and a good alternative to traditional biopsy techniques such as mediastinoscopy or thoracotomy.Presented at the 11th Biennial Asian Congress on Thoracic and Cardiovascular Surgery, Kuala Lumpur, Malaysia, November, 21–25, 1993.     

Effect of UDP-glucuronic acid on the microsome-mediated binding of benzo(a)pyrene metabolites to calf thymus DNA

The binding of benzo(a)pyrene (BP) to DNA in the presence ofliver microsomal preparations from 3-methylcholanthrene-treatedrats was increased 28.5% (P < 0.001) by addition of UDP-glucuronicacid to the incubation mixture at a 100 µM concentrationof BP. However this increase was not observed at lower concentrationsof BP. Analysis of DNA-hydrolysates by column chromatographyon Sephadex LH-20 indicated that this increase was due to greaterbinding of benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide. Theamount of bound adducts derived from 9-hydroxybenzo(a)pyrene(9-OH BP) was not significantly affected by UDP-glucuronic acid.Addition of UDP-glucuronic acid to incubation mixtures containingmicrosomes from untreated rat liver caused only a slight increasein total binding. These findings suggest that UDP-glucuronyltransferase may be involved in the activation of BP.