Detection of lead in environmental objects and biologic materials during monitoring]

The authors specified methods to detect lead in biologic materials. The quality control covered use of Russian and foreign standard samples, the results proved to agree. Lead was detected by AAS technique (direct and flow-type variants with preliminary concentration of lead) and ELRA method. The authors determined measurement limits sufficient for analysis of complex biologic materials. The measurement range for lead varied from 0.002 mg/kg (plants) to 3,000 mg/kg (soil); the range of serum lead levels was < 0.5-39 mg/dl.     

Structure-activity relationships of cysteine esters and their effects on thiol levels in rat lung in vitro

Pretreatment with cysteine esters increases cysteine (CySH) levels in rat lung and protects against the lethal effects of inhaled perfluoroisobutene in vivo. There are marked differences in the duration of protection achieved with different cysteine esters. In this study we have compared the uptake and metabolism of CySH, N-acetyl cysteine (NAc), cysteine esters and cystine esters in vitro using rat lung and liver homogenates and lung slices. Liver homogenates metabolized CySH and cysteine esters faster than lung homogenates. The half life (T1/2) of CySH in lung was 58.8 +/- 17.3 min and in liver was 14.0 +/- 1.6 min (mean +/- SEM). T1/2 of the esters in lung ranged between 6.5 and 12.1 min and in liver between 1.9 and 5.3 min. Cysteine tertiary butyl ester, which does not protect in vivo, was not hydrolysed to CySH by lung or liver homogenates. All esters increased and prolonged intracellular CySH concentrations in lung slices to a much greater extent than CySH itself. NAc did not raise intracellular CySH above that of the controls and no NAc appeared within the slice. After CySH incubation intracellular CySH was 0.9 +/- 0.1 nmol/mg wet wt at 10 min whereas after incubation with the esters it ranged between 2.60 and 3.65 nmol/mg wet wt. Cysteine cyclohexyl ester prolonged the increase of CySH the longest and cysteine methyl ester the shortest. CySH levels with cysteine cyclohexyl ester were 2.74 +/- 0.15 and 4.13 +/- 0.37 nmol/mg wet wt at 10 and 60 min, respectively, whereas with cysteine methyl ester, CySH levels were 2.60 +/- 0.5 and 1.25 +/- 0.08 nmol/mg wet wt at similar times. Cystine esters increased intracellular concentrations of both cystine and CySH. CySH concentrations ranged between 2.92 and 3.19 nmol/mg wet wt and cystine between 1.39 and 1.47 nmol/mg wet wt at 60 min. The elevation and duration of CySH in lung slices is well correlated with the duration of protection against perfluoroisobutene achieved in vivo.     

Effect of hyperthermia on the radiosensitivity of normal and malignant cells in mice

The effect of systemic hyperthermia on the in vivo radiation response of normal and malignant mouse cells was evaluated. X-irradiation of L1210 cells and Ehrlich ascites cells at body temperatures above 41 degrees C resulted in strongly enhanced tumor cell death. The magnitude of this thermal effect increased with increasing temperatures. Hypoxic tumor cells were particularly sensitive to combined heat-radiation treatment. L1210 leukemia cells did not become resistant to the sensitizing effects of hyperthermia even after repeated heat exposures over several transplant generations. The sensitizing action of hyperthermia varied with different heating strategies. Heating before or during irradiation did not materially alter the radiation response of tumor cells. Maximal potentiation of radiation damage was achieved only when the tumorous mice were subjected to at least 20 minutes heat incubation after irradiation. LD studies on ICR mice revealed that moderate hyperthermia (41.5 degrees C) does not alter the radiation response of normal body tissues. These findings indicate that it is possible to devise hyperthermic treatment regimens that drastically enhance radiation-induced tumor cell death in vivo without reducing the radioresistance of normal tissues.     

Effect of thiol reagents on functional properties and heme oxidation in the hemoglobin of Geochelone carbonaria

The reaction of thiol reagents with G. carbonaria hemoglobin was studied, and the oxygen equilibrium and kinetic of oxidation of derivatives determined. The oxygen affinity and kinetic of oxidation of hemoglobin derivatives were modified to various extents depending on the nature of thiol reagents used. Diamide yielded approximately 80% polymeric hemoglobin, although the oxidation kinetic, and the functional properties, were practically invariant (T1/2 = 10.0 min.; P50 = 5.0 mm Hg at pH 7.4; alkaline Bohr effect = -0.64). Iodoacetamide did not modify the electrophoretic pattern significantly, although all the free SH groups of hemoglobin were alkylated. A P50 of 2.5 mmHg at pH 7.4 and the Bohr effect of -0.15 were obtained; the T1/2 of about 6.4 min. was shorter than that for un-modified Hb. Similar T1/2 were obtained for Hb treated with oxidized glutathione, which produced polymeric Hb and glutathionyl-Hb. The oxygen binding characteristics showed that both of Hb derivatives, glutathionyl-Hb and polymeric Hb, maintain the capacity to transport the gas.     

Effect of context on infants' responses to novel objects.

Studied 24 infants (mean age 27 wks) to test the hypothesis that responses to novelty vary with the degree of change from familiarization to test conditions. One such change is to permit manipulation during familiarization but not on the test. In 2 groups, Ss looked at and manipulated the familiarization objects. Ss who could also manipulate during the tests showed better differentiation between novel and familiar objects than did those who could not manipulate during tests. (4 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of a commercially available nonspecific immunomodulating biologic product on health of neonatal calves

OBJECTIVE: To determine whether treatment with a commercially available nonspecific immunomodulating biologic product would alter the clinical course of disease in neonatal calves. DESIGN: Systematically randomized, controlled cohort study. ANIMALS: 200 Holstein bull calves 1 to 5 days old. PROCEDURE: Assessments were performed that included evaluation of fecal consistency, attitude, appetite, and hydration status. Calves with abnormal results were enrolled in the study. Calves were systematically assigned to control or treatment groups (100 calves/group). Calves in the treatment group were given a single i.v. injection of the biologic product at the time of enrollment, whereas control calves were not given the product. Calves were assessed daily for 5 days to evaluate fecal consistency, attitude, appetite, hydration status, and rectal temperature. Assessments were made without knowledge of group assignment. RESULTS: Treatment with the immunomodulating product was not associated with a decrease in the number of calves that had moderate or severe departures from clinically normal conditions for attitude, appetite, or hydration on days 1 though 5, compared with control calves. Fecal consistency scores were significantly greater for treated calves on days 1 (P = 0.03) and 5 (P = 0.02), compared with scores for control calves. CLINICAL IMPLICATIONS: Administration of the nonspecific immunomodulating biologic product did not significantly affect outcome of clinical disease for calves in the treated group, compared with calves in the control group. On the basis of results of this study, we cannot recommend use of the nonspecific immunomodulating biologic product for the treatment of undifferentiated diarrheal disease in neonatal calves.     

Serum and salivary testosterone levels in erectile dysfunction]

In this study 66 male patients with erectile dysfunction were investigated. The authors measured the testosterone levels in serum and in saliva, which latter represent with good accuracy the serum levels of free testosterone. The mean serum total testosterone level was 17.6 nmol/L (confidence intervals: 15.5 and 20.2 nmol/L, normal range: 10-50 nmol/L). The mean salivary free testosterone level was 218.5 pmol/L (confidence intervals: 198.3 and 239.9 pmol/L, normal range: 200-1000 pmol/L). Low salivary (free) testosterone levels were found in 36.4% of patients, while only in 10.6% of patients had low serum testosterone levels (p = 0.01, by binomial test). Although there is a relationship between serum and salivary testosterone levels (r = 0.41, p < 0.001), the patients with low salivary (free) testosterone levels have in major part a normal serum total testosterone level. These data indicate that a considerable proportion of patients with erectile dysfunction have androgen deficiency. The serum total testosterone level is not a sensitive indicator to detection of hypogonadism. The androgen substitution therapy has a beneficial effect on erectile dysfunction in a significant part of patients. The measurement of free testosterone level in saliva may have an important role both in the diagnosis of diseases characterized by androgen deficiency and hyperandrogenic status.     

Plasma levels and urinary elimination of aminosidine in infants]

The course of treatment with polychemotherapy for the progressed and metastasized breast-carcinoma is discussed. The therapy with cytostatics must be continued for the patients entire life. A sample of 27 patients from the Chir; Univ.-Klinik Innsbruck with a course of treatment lasting from 15 to 29 months (October 1973 resp; December 1974 to February 1976) showed a success rate of 81%.     

Nitric oxide levels in cirrhotic patients]

The tumor suppressor p53 is degraded by the ubiquitin-proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)-ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein.     

Effect of lesions in visual cortical area V4 on the recognition of transformed objects

The primate visual system has a remarkable capability for recognizing objects irrespective of the multitude of images they form on the retinal surface by virtue of changes in size, perspective, contrast, colour and partial obstruction by other stimuli in the visual scene. There is increasing evidence that this remarkable capacity is brought about by processes that occur earlier in the visual system than had previously been thought. Here I show that after ablation of area V4 in the rhesus monkey, major deficits arise in the recognition of objects that have been transformed in size, in the degree of occlusion, and in the amount of contour information provided. The ability to detect these objects when presented individually was unaffected by these lesions.     

Effect of ageing on androgen levels in elderly males

The past four decades have brought with it modern medical technology accompanied by better quality and longer life resulting in the increase in number of aged males in this locality. It has now been well established by various investigators that there is a statistically significant decline of the biologically available level of serum testosterone with ageing. This decline in androgen levels is more manifest in the free testosterone levels compared to the total serum testosterone levels which are routinely measured in the laboratory. Not withstanding this statistical decline the serum testosterone levels in the majority of aged men often fall within the normal range (300-1000 ng/dl) of eugonadal young males. This age related decline is usually associated with decline in sexual function in ageing men manifesting as erectile dysfunction. However, it has now been established beyond doubt that age itself rather than the androgen decline is the most influential variable of sexual activity in old men.     

Carboxymethylation of thiol groups in ovalbumin: implications for proteins that contain both thiol and disulfide groups

The cysteine residues of hen ovalbumin were S-carboxymethylated with non-radioactive iodoacetic acid under various conditions by altering the pH at which the protein was denatured in 8 M urea, by using different molar ratios of non-radioactive iodoacetic acid to cysteine and by varying the time at which carboxymethylation was commenced after denaturing conditions had been applied. Under the various conditions, the thiol groups were carboxymethylated to different extents, the residual thiol groups being measured by reaction with 5,5'-dithiobis(2-nitrobenzoic acid) in the presence of sodium dodecyl sulfate. When ovalbumin is carboxymethylated in alkaline urea, it unfolds slowly and the carboxymethylation is incomplete even with 150-fold excess iodoacetic acid. The known rapid thiol-disulfide exchange that occurs at alkaline pH values makes this method of carboxymethylation unsuitable as a preliminary step for blocking the native cysteine residues of ovalbumin before reduction and labelling the thiol groups formed by reduction of the disulfide bonds. Titration of the thiol groups of ovalbumin in 6 M guanidine hydrochloride or 1% (w/v) sodium dodecyl sulfate at pH 8.2 with 5,5'-dithiobis(2-nitrobenzoic acid) is more rapid than in 8 M urea and these solvents would be preferable for studies of the disulfide-bonded sequences. Denaturation of ovalbumin in acidic 8 M urea is a very rapid process, and under mild acid conditions thiol-disulfide interchange is much slower. Subsequent carboxymethylation of the cysteine residues at alkaline pH with 150-fold excess iodoacetic acid results in complete carboxymethylation and the carboxymethylated ovalbumin can be reduced and labelled with radioactive iodoacetic acid with specific labelling of the half-cystine residues involved in the disulfide bond. The results are discussed in relation to the allocation of half-cystine residues in other protein systems that contain both thiol and disulfide groups.     

Effect of multivitamins on plasma homocysteine and folate levels in patients on hemodialysis

Three new triterpene lactones, lancilactones A (1), B (2), and C (3), together with the known kadsulactone A (4), were isolated from the stems and roots of Kadsura lancilimba. Their structures and stereochemistries were determined primarily from mass and NMR spectral data. Compound 3 inhibited HIV replication with an EC50 value of 1.4 microg/mL and a therapeutic index of greater than 71.4.     

Cancer predisposition, radiosensitivity and the risk of radiation-induced cancers. III. Effects of incomplete penetrance and dose-dependent radiosensitivity on cancer risks in populations

Recent studies have identified a number of genes in the human genome at which germinal mutations predispose the individuals to one or another type of cancer. These studies also show that not all individuals carrying the mutant genes develop cancers (i.e., the mutant genes are not fully penetrant). At least some of these predisposed genotypes also have a higher sensitivity to cancers induced by ionizing radiation than those who are not so predisposed, which may be dependent on dose. This paper presents an analysis of the impact of such heterogeneity on estimates of cancer risks for an irradiated population. This is done by extending the Mendelian one-locus, two-allele model of cancer predisposition and radiosensitivity developed earlier to allow for incomplete penetrance and dose dependence of radiosensitivity differentials among genotypes. The model is applied to recently published data for breast cancer and hereditary non-polyposis colon cancer using a range of possible values for the strength of predisposition and radiosensitivity differentials. It is shown that, after radiation exposures, the ratio of cancer risks in a heterogeneous population relative to that in a homogeneous population increases with increasing dose, but that the dose dependence of the relative risk diminishes at higher doses. Likewise, the attributable risk (i.e. the proportion of the increase in risk that is due to both increased susceptibility and increased radiosensitivity) and the proportion of attributable risk due to increased radiosensitivity also increase with dose, and the dose dependence of each measurement also diminishes at higher doses. However, when the proportion of cancers due to the susceptible genotypes is small (<10%) (as is likely to be the case for breast cancer in non-Ashkenazi women), the increases in the relative risk and attributable risk are marked only when there are very large increases in cancer susceptibility (>1000-fold) and radiosensitivity (>100-fold) in the susceptible group. When the proportion of cancers due to the susceptible genotypes is appreciable (> or = 10%) (as may be the case for breast cancer in Ashkenazi Jewish women), there may be large increases in the relative risk and attributable risk for comparatively modest increases in cancer susceptibility (>10-fold) and radiosensitivity (>100-fold) in the susceptible subpopulation. For any given combination of strength of predisposition and radiosensitivity differential, incomplete penetrance dilutes the effect.     

Mutation and Mutagenesis of thiol peroxidase of Escherichia coli and a new type of thiol peroxidase family

A novel thioredoxin-linked thiol peroxidase (Px) from Escherichia coli has been reported previously (M. K. Cha, H. K. Kim, and I. H. Kim, J. Biol. Chem. 270:28635-28641, 1995). In an attempt to perform physiological and biochemical characterizations of the thiol Px, a thiol Px null (tpx) mutant and a functional-residue mutant of thiol Px were produced. The tpx mutant was viable in aerobic culture but grew more slowly than the wild-type cells. The difference in growth rate became more pronounced when oxidative-stress-inducing reagents, such as peroxides and paraquat, were added to the cultures. The viability of the individual tpx mutant under oxidative stress was much lower than that of wild-type cells. tpx mutants growing aerobically respond to paraquat with a sixfold greater induction of Mn-superoxide dismutase than that of the wild-type cells. The deduced amino acid sequence of the thiol Px was found to be from 42 to 72% identical to the sequences of proteins from Haemophilus influenzae (ToxR regulon), Vibrio cholerae (ToxR regulon), and three kinds of streptococci (coaggregation-mediating adhesins), suggesting that they all belong to a new thiol Px family. Alignment of the amino acid sequences of the thiol Px family members showed that one cysteine, which corresponds to Cys-94 in E. coli thiol Px, is perfectly conserved. The substitution of serine for this cysteine residue resulted in complete loss of Px activity. These results suggest that the members of the thiol Px family, including E. coli thiol Px, have a functional cysteine residue and function in vivo as peroxidases.     

Mercury levels found in fishermen of Lake Geneva]

This paper presents an evaluation of the mercury levels found in a population eating principally fish coming from the Lake of Geneva. A good correlation exists between the blood mercury level and the amount of fish ingested weekly. Interpretation of the results shows that the threshold of fish comsumption should be about 1.4 kg per week and per person.