Quasi-two-dimensional Fermi surfaces and coherent interlayer transport in KFe2As2.

We report the results of the angular-dependent magnetoresistance oscillations (AMROs), which can determine the shape of bulk Fermi surfaces (FSs) in quasi-two-dimensional (Q2D) systems, in a highly hole-doped Fe-based superconductor KFe2As2 with Tc ≈ 3.7 K. From the AMROs, we determined the two Q2D FSs with rounded-square cross sections, correspond to 12% and 17% of the first Brillouin zone. The rounded-squared shape of the FS cross section is also confirmed by the analyses of the interlayer transport under in-plane fields. From the obtained FS shape, we infer the character of the 3d orbitals that contribute to the FSs.

Production of serotonin by a transplantable strain of histamine-producing primary gastric carcinoid of Mastomys natalensis.

Two biochemically distinguishable transplantable tumor strains (A and B) were established from a primary gastric carcinoid of Mastomys secreting histamine alone. Strain A in the third generation acquired a new ability to produce serotonin [5-hydroxytryptamine (5-HT)] and retained endocrine activities to produce both histamine and 5-HT through the following subpassages, whereas strain B (like the primary tumor) continued to produce histamine alone. The findings were further supported by the immunohistochemical demonstration of 5-HT-containing tumor cells in strain A after generation 3 and the absence of such cells in strain B and also by the ultrastructural demonstration of tumor cells containing pleomorphic secretory granules in strain A after the third generation but not in strain B. Sixteen samples of Formalin-fixed, paraffin-embedded primary gastric carcinoids of Mastomys were stained by the same immunohistochemical method for 5-HT detection. The positively stained tumor cells were demonstrated in 4 tumor samples, though they were scantily distributed in tumor parenchyma except for 1 metastasizing tumor. 5-HT-producing tumor cells appeared through many proliferative cycles of the deranged histamine-producing cells. The endocrinologic similarity was noted between this transplantable tumor strain and a specific type of gastric carcinoid in humans, and the possible histogenesis of the latter tumor was discussed on the basis of data obtained from the present transplantation experiments.

Enhanced invasiveness of tumour cells after host exposure to heavy metals.

The invasiveness of tumour cells to heavy metal-exposed host cells or tissues was investigated. Human fibrosarcoma cell invasion of heavy metal-treated fibroblast or endothelial cell was enhanced in a treatment-time-dependent manner although tumour cell attachment to host cells was not affected. This enhancement was correlated with an increase in metallothioneins in the cytosol of fibroblasts or endothelial cells. Mouse melanoma cell invasion of organ samples obtained from syngeneic mice who had been administered heavy metals was also enhanced. The results suggest that heavy metal-induced metallothioneins serve as a host-derived factor in malignant disease and closely relate to metastasis.

Surfactant replacement therapy with a single postventilatory dose of a reconstituted bovine surfactant in preterm neonates with respiratory distress syndrome: final analysis of a multicenter, double-blind, randomized trial and comparison with similar trials. The Surfactant-TA Study Group.

The effects of a single dose of surfactant TA were assessed in premature neonates (birth weight 750 to 1749 g) with respiratory distress syndrome (RDS) in a multicenter, double-blind, randomized clinical trial. Only neonates with surfactant deficiency and without ultrasonographic evidence of intracranial hemorrhage greater than or equal to grade II were enrolled. Fifty-four patients received surfactant (100 mg of phospholipid per kilogram of body weight) and 46 patients received an air placebo within 8 hours of life. Treatment with this surfactant resulted in a significant reduction in the severity of RDS with a concomitant increase in the proportion of neonates with mild disease. The frequency of pulmonary interstitial emphysema and of pneumothorax was significantly lower in treated neonates compared with control neonates (2% vs 26%, P = .0008, and 7% vs 39%, P = .0004, respectively). The frequency of intracranial hemorrhage was significantly lower in the surfactant group compared with the control group (20% vs 54%, P = .0008) and was also reduced for the smallest neonates in the surfactant group (13% vs 73%, P = .00008). When categorized according to severity of intracranial hemorrhage and severity of bronchopulmonary dysplasia, the surfactant group was at a significant advantage (adjusted Cochran-Mantel-Haenszel X2 = 10.72, P less than .001 and X2 = 4.43, P = .036, respectively). The proportion of neonates surviving without intracranial hemorrhage and/or bronchopulmonary dysplasia was 63% in the surfactant group vs 26% in the control group (P = .0004); as for the smallest neonates, it was 58% in the surfactant group vs 4% in the control group (P = .0002). There were no differences between the groups with respect to the frequency of patent ductus arteriosus (46% vs 37%), pulmonary hemorrhage (6% vs 7%), necrotizing enterocolitis (0% vs 2%), sepsis (4% vs 2%), retinopathy of prematurity (13% vs 22%), or death (15% vs 22%). It is concluded that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 48 hours after treatment and decreases the major pulmonary morbidity and intracranial hemorrhage in premature neonates with RDS. Further studies are needed to determine whether (1) treatment at birth or as soon as after RDS is diagnosed and (2) the use of multiple dose of this surfactant would result in any additional benefits.

Effect of metallothioneins on transformation of gelatinase A from human fibroblast WI-38 cells.

The effect of metallothioneins (MTs) on gelatinase A activity was investigated. The collagenolytic activity of gelatinase A from human fibroblast WI-38 cells was enhanced by the addition of MTs. This enhancement may be caused by the transformation of the inactive 62 kDa intermediate species of gelatinase A to the 59 kDa active enzyme. This enhancement was also observed in the conditioned medium of WI-38 cells exposed to heavy metals, but intracellular 72 kDa pro-gelatinase A did not change. Furthermore, degradation of gelatinase A occurred in the reaction between gelatinase A with substrate and MTs. Our results suggest that MTs may be an endogenous activator of gelatinase A, and may provide a host factor in cancer metastasis.

Formation and possible role of bis(methylmercuric) selenide in rats treated with methylmercury and selenite.

The metabolic fate of methylmercury after administration of [203Hg]-methylmercuric chloride in combination with sodium selenite was investigated in rats. Whole body autoradiography and radioassay showed that administration of selenite decreased the mercury concentration in the liver and kidney, and increased that in the brain. The rapid changes of methylmercury concentration in the tissues after selenite injection were accompanied by increase in mercury extractable with benzene at neutral pH. The maximum levels of benzene-extractable mercury in the blood, kidney and liver were attained 30 min after selenite injection and were 30, 23 and 8 percent, respectively, of the total mercury. Thin-layer chromatography showed that the benzene-extractable mercury was a complex of methylmercury with selenium, bis(methylmercuric) selenide. These findings indicate that selenite alters the distribution of methylmercury in the tissues by formation of a diffusible complex with methylmercury, bis(methylmercuric) selenide.

Cadmium-binding protein (metallothionein) in carp.

When carp (Cyprinus carpio) were exposed to 5 and 30 ppm Cd in the water, the contents of Cd-binding protein, which has low molecular weight, increased in the hepatopancreas, kidney, gills and gastrointestinal tract with the duration of exposure. This Cd-binding protein was purified from hepatopancreas, kidney, gills, and spleen of carp administered 2 mg/kg Cd (as CdCl2), intraperitoneally for 6 days. Two Cd-binding proteins were separated by DEAE-Sephadex A-25 column chromatography. These proteins had Cd-mercaptide bond, high cysteine contents (ca. 29-34%), but no aromatic amino acids or histidine. From these characteristics the Cd-binding proteins were identified as metallothionein. By using antiserum obtained from a rabbit to which carp hepatopancreas MT-II had been administered, immunological characteristics between hepatopancreas MT-I, II and kidney MT-II were studied, and a slight difference in antigenic determinant was observed among them. By immunological staining techniques with horseradish peroxidase, the localization of metallothionein was investigated. In the nontreated group, metallothionein was present in the acinar cells of hepatopancreas and renal convoluted tubules. In the Cd-treated group (2 mg/kg IP daily for 3 days), metallothionein was present in the nuclei, sinusoids, and extracellular space of hepatopancreas, in addition to the acinar cells. Carp were bred in 1 ppm Cd, 5 ppm Zn solution, and tap water for 14 days, following transfer to 15 ppm Cd solution, respectively. The survival ratio was the highest in the Zn group followed by Cd-treated and control groups. The metallothionein contents increased in hepatopancreas and kidney in the order: Zn greater than Cd greater than control group.

Cyclooxygenase expression in bovine aortic endothelial cells exposed to cyclic strain.

The aim of this study was to investigate the effect of cyclic strain on cyclooxygenase (COX)-1 and 2 expression in bovine aortic endothelial cells (EC). EC, subjected to 10% average strain at 60 cycle/min, were analyzed for induction of COX by Northern blot analysis and confirmed by analysis of promoter activity in transient transfection experiments. Exposure of EC to cyclic strain induced promoter activity and expression of COX-2 but not of COX-1. The extent of induction, however, was lower than that seen with stimulation of 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or lipopolysaccharide (LPS). These results demonstrate that, unlike shear stress, cyclic strain does not affect COX-1 expression and is a weak inducer of COX-2 promoter activity in bovine aortic EC with minimal effect on mRNA expression.

Fatal acute myocarditis in an infant with human herpesvirus 6 infection.

A 5 month old girl had typical clinical features of acute myocarditis just after the febrile period of exanthem subitum and died immediately. She had been healthy, with normal development, and there was no family history of particular note. Myocardial postmortem findings were compatible with acute myocarditis. Although the isolation of human herpesvirus 6 (HHV-6) was not attempted, positive IgM antibody to HHV-6 was detected in the patient's serum. Moreover, HHV-6 variant B DNA was detected in several tissues, including myocardium, by the polymerase chain reaction (PCR). In contrast, antibody responses to human herpesvirus 7, another causal agent of exanthem subitum, were not found, and enteroviral RNA was not detected in myocardial tissues by reverse transcription PCR. Apoptotic changes were seen in infiltrating cells within the myocardial tissues by means of the TUNEL method. HHV-6 antigen was not detected in several tissues (including myocardium) by immunohistochemical analysis. In conclusion, HHV-6 may have been the causative agent of fatal acute myocarditis in this infant.

Role of mitogen-activated protein kinases in pulmonary endothelial cells exposed to cyclic strain.

The aim of this study was to examine the role of mitogen-activated protein kinases (MAPKs) activation in bovine pulmonary arterial endothelial cells (EC) exposed to cyclic strain. EC were subjected to 10% average strain at 60 cycles/min. Cyclic strain induced activation of extracellular signal-regulated kinase (ERK; 1.5-fold), c-Jun NH(2)-terminal protein kinase (JNK; 1.9-fold), and p38 (1. 5-fold) with a peak at 30 min. To investigate the functional role of the activated MAPKs, we analyzed cells after treatment with PD-98059, a specific ERK kinase inhibitor, or SB-203580, a catalytic inhibitor for p38, and after transient transfection with JNK(K-R), and MEKK(K-M) the respective catalytically inactive mutants of JNK1 and MAPK kinase kinase-1. Cyclic strain increased activator protein-1 (AP-1) binding activity, which was blocked by PD-98059 and SB-203580. Activity of AP-1-dependent luciferase reporter driven by 12-O-tetradecanoyl-phorbol-13-acetate-responsive element (TRE) was induced by cyclic strain, and this was attenuated by PD-98059, MEKK(K-M), JNK(K-R), and SB-203580. PD-98059 and SB-203850 did not inhibit cell alignment and migration induced by cyclic strain. MEKK(K-M) and JNK(K-R) transfection did not block cyclic strain-induced cell alignment. In conclusion, cyclic strain activates ERK, JNK, and p38, and their activation plays a role in transcriptional activation of AP-1/TRE but not in cell alignment and migration changes in bovine pulmonary arterial EC.

Enhancement of the mutagenicity of amino acid pyrolysates by phthalate esters.

The ability of phthalic acid, phthalic acid anhydride, and various phthalate esters to enhance the mutagenicity of many amino acid pyrolysates was observed with the Ames test (Salmonella typhimurium TA98), but not the SOS Chromotest. Phthalate enhancement of the mutagenicity of 4-nitroquinoline-1-oxide, 2-nitrofluorene, and benzo[a]pyrene was not observed with either test. The mutagenicity-enhancing ability may be related to the induction of enzymes such as P450IIB, that metabolize amino acid pyrolysates. By quantitative structure activity relationship (QSAR) analysis, a good correlation was observed between the mutagenicity-enhancing activity of phthalates and their octanol-water partition coefficients.

Evaluation of the SOS chromotest for the detection of antimutagens.

The SOS chromotest was applied for the detection of antimutagens. To raise SOS induction, the bacteria were treated with the mutagens, UV, 4-nitroquinoline N-oxide (4NQO), N-methyl-N'-nitro-N-nitroso-guanidine (MNNG), or benzo[a]pyrene (B[a]p). The inhibitory effects of L-ascorbic acid, glutathione, vanillin, 5-fluorouracil (5-FU), 5-chlorouracil (5-CU), cobaltous chloride, sodium selenite and sodium arsenite, which are known as antimutagens, were investigated with their addition either simultaneously or post treatment time. It became clear that the SOS chromotest was very useful for the detection of antimutagens.

Dose-response relationship between urinary cadmium and metallothionein in a Japanese population environmentally exposed to cadmium.

The dose-response relationship between cadmium (Cd) exposure and renal dysfunction, as measured by urinary Cd and metallothoinein (MT), was evaluated in a population living in the Kakehashi River basin, a Cd-polluted area in Japan. Morning urine specimens were collected from 1397 men and 1713 women who were 50 years or older. In addition, urine specimens were collected from a control population consisting of 110 men and 130 women. The 97.5% upper limits for MT in the control population were used to determine the prevalence rates for MT-uria at various urinary Cd concentrations. Probit linear regression analysis showed significant dose-response relationships between MT and Cd. In the control population, prevalence rates of MT-uria for men and women were 1.8 and 3.1%, respectively. Based on the prevalence rates of MT-uria in the control population, the upper limits for the urinary Cd concentrations were calculated from the slopes of the regression lines to be 4.2 and 4.8 micrograms/g creatinine for men and women, respectively. These values, which are similar to those reported previously using urinary beta 2-microglobulin as the indicator, may be of use in establishing the biological threshold, i.e. maximum allowable concentration, for urinary Cd in the environmentally exposed Japanese population.

Dose-response relationship between dietary cadmium intake and metallothioneinuria in a population from a cadmium-polluted area of Japan.

An epidemiological study to examine the dose-response relationship for environmental cadmium exposure was performed in 1843 cadmium-exposed and 240 non-exposed inhabitants of the Kakehashi River basin in Ishikawa, Japan. The average cadmium concentration in rice from each village was employed as an indicator of cadmium exposure and the individuals were grouped according to the length of residence in the polluted area. Metallothioneinuria was used as an index of renal tubular dysfunction produced by the chronic exposure to cadmium. A dose-related increase in metallothioneinuria was observed. The chronic total cadmium intake resulting in metallothioneinuria in this population was calculated to be approximately 2 g for both men and women. The cumulative lifetime dose of 2 g cadmium over a 50-year period, means an average daily intake of 110 micrograms. Thus, these values may be regarded as the maximum allowable lifetime and daily intake limits, respectively for chronic dietary exposure to cadmium.

Dose-response relationship between total cadmium intake and metallothioneinuria using logistic regression analysis.

The dose-response relationship for environmental cadmium exposure was assessed using logistic regression analysis. The prevalence of metallothioneinuria was employed as a response variable, while age and total cadmium intake, calculated from the average cadmium concentration in rice and duration of residence in the cadmium-polluted area, were used as explanatory variables. The target population comprised of 1843 cadmium-exposed and 240 non-exposed inhabitants of Ishikawa, Japan. The individuals were divided into 96 subgroups by sex, age (4 categories), cadmium concentrations in rice (3 categories) and length of residence in the polluted area (4 categories). Only total cadmium intake had a significant association with the prevalence of metallothioneinuria. In the non-exposed subjects total cadmium intakes corresponding to 2.5% prevalence of metallothioneinuria were calculated. Based on metallothionein levels expressed as either microgram/l urine or microgram/g creatinine, the total intakes were: 2.221 or 2.207 g in men and 2.365 or 0.319 g in women, respectively. Most of these values were similar to those reported by us previously, employing simple regression analysis. It is concluded, therefore, that a maximum allowable intake of about 2 g cadmium is a reasonable estimate for preventing the cadmium-induced renal dysfunction.

Augmentation of allergic reactions by several pesticides.

The augmentative effects of several pesticides on histamine release from mast cells of rats that had been sensitized passively by anti-dinitrophenol (DNP) monoclonal IgE antibodies were investigated in vitro. Various pesticides, especially phenthoate (PAP), chlornitrofen (CNP) and paraquat (PQ), increased histamine release. This increase was not observed in histamine release with non-antigen or induction by calcium ionophore A23187 or compound 48/80. Passive cutaneous anaphylaxis (PCA) was examined, and an increase of PCA was observed with PAP and PQ, but not with CNP, while an increase of tumor necrosis factor-alpha (TNF-alpha) production was observed with CNP and PQ, but not PAP. These results suggest that various pesticides as environmental pollutants exacerbate allergic diseases.

Prevalence of metallothioneinuria among the population living in the Kakehashi River basin in Japan--an epidemiological study.

An epidemiological study to evaluate cadmium-induced renal dysfunction by urinary metallothionein levels was carried out in an environmentally-exposed Japanese population. The study population consisted of 3168 men and women from a cadmium-polluted area who were 50 years and older and 291 individuals from a non-polluted area. The mean metallothionein levels in urine of the control population were 138.2 +/- 2.1 and 198.6 +/- 1.9 microgram/g creatinine for men and women, respectively. The corresponding values for the cadmium-exposed population were 157.8 +/- 2.2 and 248.0 +/- 2.2. The 97.5% upper limits for men in the control population was determined to be 638 and for women 693 microgram MT/g creatinine. Based on these values as the cut-off levels, the prevalence of metallothioneinuria was calculated to be 4.6% in men and 8.4% in women from the cadmium-polluted area. Further selection of the population, based on life-time residence in the polluted area accompanied with the consumption of cadmium-containing rice, showed an even greater prevalence of metallothioneinuria: 5.4% in men and 10.9% in women of all ages. The prevalence of metallothioneinuria increased with age and duration of residence in the polluted area. These results suggest that metallothioneinuria can be used as an indicator of renal dysfunction due to environmental cadmium exposure.

Degradation of methylmercury by selenium.

When methylmercury was incubated in the presence of selenite and reduced glutathione (GSH), the mercury which was extracted into benzene under acidic condition decreased gradually with the elapse of time. This decrease was due to the cleavage of mercury-carbon bond of methylmercury. The reaction did not proceed when selenite or GSH was singly added to the reaction mixture. L-Cysteine, 2-mercaptoethanol and sodium sulfide in place of GSH also were effective for decomposition of methylmercury in combination with selenite, but oxidized glutathione (GSSG) and L-cystine were not. This suggests that reduction of selenite is needed for the degradation of methylmercury. Thus, the effect of reduced metabolites of selenite produced by GSH was investigated. Glutathione selenotrisulfide (GSSeSG) required GSH for the degradation of methylmercury, whereas H2Se possessed a strong activity even in the absence of GSH. This may indicate that H2Se is involved directly in the conversion of methylmercury to inorganic mercury. This phenomenon found in in vitro experiments is discussed in relation to the biotransformation of methylmercury.

The mutagenicity of organotin compounds as environmental pollutants.

The mutagenicity of 14 organotin compounds which have been reported to be environmental pollutants, their environmental metabolites and inorganic tin (SnCl4) was studied. The experiments were carried out by a modification of the conventional Salmonella assay. Each tested chemical was removed by washing the tested strain with phosphate buffer, before the strain with top agar was poured onto minimal glucose agar. By this method, we were able to estimate the mutagenicity of organotin compounds which had antibacterial activity. It was apparent that mono-n-butyltin oxide, n-butyltin trichloride, di-n-butyltin dichloride, tri-n-butyltin chloride, bis-(tri-n-butyltin)-oxide and dimethyltin dichloride were mutagens on Salmonella typhimurium TA100 and bis-(tri-n-butyltin)-oxide showed the highest mutagenicity. With S. typhimurium TA98, di-n-butyltin dichloride was found to be a mutagen.

The genotoxicity of organotin compounds in SOS chromotest and rec-assay.

In these days pollution by organotin compounds in the environment extends widely and effects on human health are feared. We studied the genotoxicity of various organotin compounds (butyltins, phenyltins, methyltins) and inorganic tin (SnCl4), which are present in the environment, with the SOS chromotest and the rec-assay. Mono-n-butyltin oxide, n-butyltin trichloride and di-n-butyltin dichloride showed high SOS-inducing potency in the SOS chromotest with Escherichia coli PQ37. Di-n-butyltin dichloride, tri-n-butyltin chloride, bis(tri-n-butyltin)oxide, dimethyltin dichloride and trimethyltin chloride were recognized as genotoxic chemicals by the rec-assay.