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Hemoglobin S Travis: a sickling hemoglobin with two amino acid substitutions [beta6(A3)glutamic acid leads to valine and beta142 (h20) alanine leads to valine).

Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.

Alanine

Comparison between measured and synthesized posterior lead electrocardiograms during percutaneous coronary intervention-induced myocardial ischemia.

BACKGROUND: Posterior/inferolateral myocardial ischemia is frequently underrecognized on standard 12&#x2011;lead electrocardiography (ECG). Synthesized posterior leads derived from the standard 12&#x2011;lead ECG have been proposed as an alternative to directly measured posterior leads; however, their accuracy under controlled ischemic conditions has not been fully validated. METHODS: We prospectively enrolled 26 consecutive patients undergoing percutaneous coronary intervention (PCI) in whom simultaneously recorded measured and synthesized posterior lead ECGs (V7-V9) were obtained during balloon-induced myocardial ischemia. ST-segment deviation was measured at the ST junction (STJ), 40&#xa0;ms (ST1), and 80&#xa0;ms (ST2) thereafter. Agreement between measured and synthesized posterior leads was assessed using Pearson correlation and Bland-Altman analyses. As an exploratory patient-level analysis, diagnostic performance was compared with reciprocal anterior ST-segment depression (V1-V4). RESULTS: Strong correlations were observed between measured and synthesized posterior lead ST-segment deviations (V7: r&#xa0;=&#xa0;0.89; V8: r&#xa0;=&#xa0;0.86; V9: r&#xa0;=&#xa0;0.83; all P&#xa0;<&#xa0;0.001). Bland-Altman analysis demonstrated minimal systematic bias (within &#xb1;0.004&#xa0;mV) and narrow limits of agreement. Synthesized posterior leads showed higher diagnostic performance than reciprocal anterior ST-segment depression (AUC 0.917 vs. 0.708), although the difference was not statistically significant (DeLong test, P&#xa0;=&#xa0;0.197). Using a 0.05&#xa0;mV threshold, synthesized posterior leads demonstrated 83.3% sensitivity, 100% specificity, and 96.2% overall accuracy. CONCLUSIONS: Synthesized posterior leads closely reproduced measured posterior lead ST-segment deviations during percutaneous coronary intervention (PCI)-induced myocardial ischemia, supporting the technical validity of posterior lead reconstruction. Larger prospective studies are warranted to determine whether synthesized posterior leads provide incremental diagnostic value beyond careful interpretation of the standard 12&#x2011;lead ECG.

Humans

Systematic multi-domain screening of lead-specific electrocardiographic features associated with sudden cardiac death.

UNLABELLED: Electrocardiogram (ECG) provides four-dimensional view to the electrical properties of the heart. We performed a comprehensive multi-domain screening to find the most significant lead-specific ECG features associated with sudden cardiac death (SCD). METHODS: We analyzed retrospective data from 21,176 consecutive patients undergoing coronary angiography in Tampere University Hospital between 2007 and 2018. 937 ECG variables provided by the 12SL algorithm were used for the analysis. From those, the significant lead-specific ECG variables were categorized into three subgroups: P-wave, QRS complex, and ST-segment/T-wave. The most significant (i.e., lowest P-value) independent lead-specific ECG variables were tested in multivariate analysis after filtering correlating variables with weaker associations with SCD. RESULTS: Among ventricular depolarization (QRS complex) variables, the strongest associations with SCD were observed for QRS intrinsicoid deflection (lead I) (p&#xa0;=&#xa0;4.6&#xa0;&#xd7;&#xa0;10-8), QRS peak-to-peak amplitude (lead aVR) (p&#xa0;=&#xa0;1.9&#xa0;&#xd7;&#xa0;10-5), and Q-wave amplitude (lead V1) (p&#xa0;=&#xa0;7.6&#xa0;&#xd7;&#xa0;10-6). Among repolarization (ST-segment and T-wave) variables, the strongest predictors of SCD were T-wave amplitude (lead aVR) (p&#xa0;=&#xa0;3.5&#xa0;&#xd7;&#xa0;10-7) and ST-segment end amplitude (lead aVL) (p&#xa0;=&#xa0;8.1&#xa0;&#xd7;&#xa0;10-5). The strongest associations with SCD among atrial depolarization (P-wave) variables were P-wave onset amplitude (lead V6) (p&#xa0;=&#xa0;3.1&#xa0;&#xd7;&#xa0;10-6), P'-wave amplitude (lead V2) (p&#xa0;=&#xa0;2.1&#xa0;&#xd7;&#xa0;10-5), and P-wave duration (lead V2) (p&#xa0;=&#xa0;2.4&#xa0;&#xd7;&#xa0;10-3). These variables remained significant in multivariate analysis alongside global ECG variables (e.g., heart rate, QRS duration, and LVH). CONCLUSION: Systematic screening and utilizing the full prognostic potential of the 12&#x2011;lead ECG reveal several key elements of the electrical properties of the heart that associate with SCD.

Humans

Effects of calcium on the absorption and retention of lead.

An inverse relationship between lead retention and dietary calcium content has been known to exist for many years, but the reasons for this association remained unknown. In rats, the manipulation of dietary calcium had no significant effect upon the absorption of lead, but calcium-deprived animals had decreased excretion and thus increased body retention of lead. Intraluminal calcium decreased the absorption of test doses of lead from the small intestine in a dose-related manner. We postulated that this occurred because the two metals competed for similar binding sites on intestinal mucosal proteins which were important in the absorptive process. In vivo, lead bound to two heat-stable intestinal mucosal fractions which have been shown to bind calcium. Although more lead bound to the higher molecular weight fraction and more calcium bound to the lower molecular weight vitamin D-induced CaBP, substantial amounts of lead and calcium were found in both fractions. Further, the addition of calcium to test doses of lead markedly diminished the amount of lead bound by both fractions. Shared binding sites on absorptive proteins would explain why dietary calcium decreases lead absorption.

Animals

Lysis of yeast cell walls. Lytic beta-(1 leads to 6)-glucanase from Bacillus circulans WL-12.

When grown in a mineral medium with yeast cell walls or yeast glucan as the sole carbon source, Bacillus circulans WL-12 produces wall-lytic enzymes in addition to non-lytic beta-(1 leads to 3) and beta-(1 leads to 6)-glucananases. The lytic enzymes were isolated from the culture liquid by adsorption on insoluble yeast glucan in batch operation. After digestion of the glucan, the mixture of enzymes was chromatographed on hydroxylapatite on which the lytic activity could be resolved into one lytic beta-(1 leads to 6)glucanase and two lytic beta-(1 leads to 3)-glucanase was further purified by chromatography over diethylamino-ehtyl-agarose and carboxymethyl cellulose. Its specific activity on pustulan was 6.2 units per mg of protein. The enzyme moved as a single protein with a molecular weight of 54000 during sodium dodecylsulphate electrophoresis in slab gels. Hydrolysis of pustulan went thorugh a series of oligosaccharides, leading to a mixture of gentiotriose, gentiobiose and glucose. The enzyme also produced small amounts of gentiobiose from laminarin and pachyman and on this basis its lytic activity on yeast cell walls,was attribut beta-(1 leads to 3)-linked oligosaccharides were not detected. The lytic beta-(1 leads to 6)-glucanase has an optimum pH of 6.0. Pustulan hydrolysis followed Michaelis-Menten kinetics. A Km of 0.29 mg pustulan per ml and a V of 9.1 micro-equivalents of glucose released/min per mg of enzyme were calculated. The enzyme has no metal ion requirement. The lytic beta-(1 leads to 6)-glucanase differs in essence from the non-lytic beta-(1 leads to 6)-glucanase of the same organism by its positive action on yeast cell walls and yeast glucan and its much lower specific activity on soluble pustulan.

Bacillus

Bioprospecting Chromobacterium violaceum for bioremediation: an alternative to environmental lead pollution.

Lead pollution is a major environmental concern, but current decontamination technologies remain limited due to high costs. Therefore, alternative biotechnological processes have been successfully developed and applied due to their reduced cost and lower aggressiveness in the environment. The remarkable adaptive versatility of Chromobacterium violaceum in metal-contaminated environments makes this bacterium a promising candidate for Pb bioremediation. Therefore, the reference strain C. violaceum ATCC 12,472 and the environmental isolate C. violaceum SCV1, the first strain of this species isolated from a Brazilian area with natural Pb occurrence, were evaluated for Pb resistance under different Pb concentrations and exposure times. Pb biosorption was assessed by scanning electron microscopy, while strain-specific protein profiles were characterized using tandem mass spectrometry-based proteomic analysis. The results obtained revealed the potential of C. violaceum to perform lead bioremediation. Scanning electron microscopy analysis confirmed the biosorption of lead by C. violaceum strains. C. violaceum SCV1 was able to remove up to 40% more lead concentration when compared to ATCC 12,472 which suggested adaptation through natural selection process of C. violaceum SCV1. Proteome analysis revealed 1531 proteins, of which several are candidates for lead bioremediation. This is the first study on the resistance proteomics of C. violaceum against lead. The acclimatization of the bacteria linked to the identification of several proteins related to: biosorption; efflux and ionic uptake (bioaccumulation); biomolecule transport; and biomethylation, point out to this organism as a potential lead bioremediation agent.

Chromobacterium

The effect of zinc and pH on the behaviour of delta-aminolevulinic acid dehydratase activity in baboons exposed to lead.

Four adult male baboons (Papio ursinus) were exposed to a cloud of lead oxide dust to induce changes in the status of delta-aminolevulinic acid dehydratase (ALAD). Enzyme activity fell rapidly to a steady state as blood lead levels rose above normal. Exogenous zinc was shown to activate the enzyme, and the antagonistic effect of zinc on in vivo and in vitro lead inhibition was demonstrated for baboons. In baboons not exposed to lead dust, ALAD showed an activity optimum at pH 7-1 which shifted to pH 6-8 with in vitro addition of lead. In baboons exposed to lead dust, with raised blood lead, activity optima were observed at pH 6-8 and 6-2, while the optimum at pH 7-1 was absent.

Animals

Role of chronic low-level lead exposure in the aetiology of mental retardation.

Water-lead levels were measured in the homes occupied during the first year of life by 77 mentally retarded children aged two to six years and 77 non-retarded matched controls, and in the homes occupied by their mothers during pregnancy. The water-lead content was significantly higher in the retarded group, and the probability of mental retardation was significantly increased when water lead exceeded 800 mug. per litre. Blood-lead levels were also significantly higher in the retarded group. It is concluded that lead contamination of water may be one factor in the multifactorial aetiology of mental retardation and that every effort should be made to reduce the lead content of drinking-water.

Breast Feeding

Neuropsychological dysfunction in children with chronic low-level lead absorption.

To investigate the relation between low-level absorption and neuropsychological function, blind evaluations were under-taken in forty-six symptom-free children aged 3-15 years with blood-lead concentrations of 40-68 mug. per 100 ml. (mean 48 mug. per 100 ml.) and in seventy-eight ethnically and socioeconomically similar controls with levels greater than mug. per 100 ml. (mean 27 mug. per (100 ml). All children lived within 6-6 km. of a large, lead-emitting smelter, and in many cases residence there had been lifelong. Mean age in the lead group was 8-3 years and in the controls 9-3. Testing with Wechsler intelligence scales for schoolchildren and preschool children (W.I.S.C. and W.P.P.S.I.) showed age-adjusted performance I.Q. to be significantly decreased in the group with higher lead levels (mean scores, W.I.S.C. plus W.P.P.S.I., 95 v. 103). Children in all ages in the lead group also had significant slowing in a finger-wrist tapping test. Full-scale I.Q., verbal I.Q., BEHAVIOUR, AND HYPERACTIVITY RATINGS DID NOT DIFFER.

Absorption

Global burden of peripheral arterial disease (1990-2021), global burden trends and the impact of blood lead on peripheral arterial disease: a multidimensional analysis based on NHANES, GBD, and Mendelian randomization.

OBJECTIVE: Peripheral arterial disease (PAD) is a common cardiovascular disease that it is an important reason for the decline of patients' quality of life and the increase of family economic burden. To systematically evaluate the association between environmental lead exposure and peripheral arterial disease (PAD) and to characterize the global distribution of PAD disease burden, while exploring differences among regions with varying socioeconomic development. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), the Global Burden of Disease (GBD) database, and genome-wide association studies (GWAS), we employed multivariable logistic regression to examine the link between lead exposure and PAD. Mendelian randomization (MR) was used to infer causality, and we analyzed PAD disease burden trends across countries of differing income levels. RESULTS: The burden on PAD patients worldwide shows a downward trend. In high SDI and high middle SDI countries, the burden of PAD gradually decreases, while in low middle SDI and low SDI countries, the burden of PAD gradually decreases. After adjusting for potential confounders, a significant dose-response relationship was observed between blood lead levels and PAD risk (OR&#x2009;=&#x2009;1.04, 95% CI: 1.00-1.09). This association was more pronounced among males (OR&#x2009;=&#x2009;1.07, 95% CI: 1.05-1.09), individuals with higher education (OR&#x2009;=&#x2009;1.24, 95% CI: 1.16-1.32), and patients with hypertension (OR&#x2009;=&#x2009;1.07, 95% CI: 1.05-1.09). MR analysis supported a causal link between lead exposure and PAD. Global trend analysis indicated that PAD burden is declining in high-income countries but rising in low-income regions, highlighting significant health inequities. CONCLUSION: Environmental lead exposure is significantly associated with increased PAD risk, with notable differences in population susceptibility. These findings underscore the necessity of environmental exposure control and tailored prevention strategies to enhance cardiovascular health worldwide.

Humans

Adenosine triphosphate catabolism in homogenates of rat secretory enamel organs incubated in histochemical lead media.

To investigate how lead, when used as trapping agent, influences the ATP hydrolysis and to study how ATP is catalyzed in histochemical systems, homogenized secretory enamel organs were incubated in histochemical [3H]-ATP media. Aliquots from the media were taken after 3, 10, 20 and 30 min, the ATP and formed metabolites were separated by electrophoresis and radiometrically quantitated. In media lacking both lead and homogenate 2% of the ATP was spontaneously hydrolyzed during 30 min incubation at room temperature. The presence of lead caused an additional 8% hydrolysis at pH 7.2 and an additional 20% hydrolysis at pH 9.4. In the presence of homogenate, however, lead caused a net decrease of the hydrolysis of ATP as well as of ADP and AMP. This enzyme inhibition varied from around zero to some 80%, depending on pH and substrated involved. In homogenate-containing lead media, at both pH 7.2 AND 9.4, ATP was rapidly hydrolyzed primarily to ADP and subsequently to AMP and adenosine and/or inosine. After 5--10 min ADP constituted the predominant substrate at both pH:s. At pH 7.2 ADP remained so for the rest of the incubation, whereas at pH 9.4 AMP was predominant substrate at the end of the incubation. AMP was the finan catabolic product in experiments at pH 7.2, and adenosine and/or inosine at pH 9.4. Inorganic phosphate was liberated almost linearly during the whole incubation period. The results indicate that histochemical studies of substrate specific ATP-ases should be performed with short incubation times and, when high specific activities are present, in large quantities of incubation media to reduce interference by ADP and AMP hydrolyzing enzymes.

Adenosine Diphosphate

Feasibility and efficacy of left bundle branch area pacing guided by modified chest lead 1.

BACKGROUND: Left bundle branch area pacing (LBBAP) typically requires 12&#x2011;lead electrocardiogram (ECG) measurements using an electrophysiology (EP) recording system. However, a simplified approach using modified chest lead 1 (MCL1) is potentially feasible. This study aimed to compare the success rate and pacing outcomes of LBBAP guided by MCL1 with those guided by the 12&#x2011;lead ECG using an EP recording system. METHODS: This retrospective, single-center study included patients with preserved left ventricular ejection fraction who underwent LBBAP for bradyarrhythmia. LBBAP was either guided by 12&#x2011;lead ECG using an EP recording system or by MCL1. In the MCL1 group, a follow-up examination with a 12&#x2011;lead ECG using an EP recording system was conducted within one week postoperatively. RESULTS: A total of 65 patients underwent LBBAP (EP recording system group: n&#xa0;=&#xa0;35; MCL1 group: n&#xa0;=&#xa0;30). The overall success rate of LBBAP was 84.6%, with no significant difference between groups (88.5% vs. 80.0%, p&#xa0;=&#xa0;0.49). No significant differences were observed in the paced QRS duration (140.4&#xa0;&#xb1;&#xa0;8.0 vs. 141.9&#xa0;&#xb1;&#xa0;13.1&#xa0;ms, p&#xa0;=&#xa0;0.54), V6-V1 interpeak interval (39.7&#xa0;&#xb1;&#xa0;16.5 vs. 38.3&#xa0;&#xb1;&#xa0;15.6&#xa0;ms, p&#xa0;=&#xa0;0.79), or V6 R-wave peak time (69.8&#xa0;&#xb1;&#xa0;12.3 vs. 71.5&#xa0;&#xb1;&#xa0;12.1&#xa0;ms, p&#xa0;=&#xa0;0.68). CONCLUSIONS: MCL1-guided LBBAP was feasible and achieved a high success rate, with outcomes comparable to those of conventional EP recording system-guided implantation. This simplified approach may reduce procedural complexity and may allow LBBAP implantation without the routine use of an EP recording system.

Humans

Potentiation of langat virus infection by lead intoxication--influence on host defenses.

Pathogenesis was studied in mice with moderate levels of lead intoxication after Langat virus infection. Both lead chloride and lead nitrate increased mortality by 40--50%. This increase was associated with decreased in vivo interferon and neutralizing antibody synthesis. The increased mortality was associated with enhancement of viral growth in peripheral tissues as evidenced by early appearing and long-lasting high titer viremia following lead intoxication. This resulted in early penetration of blood brain barrier and led to much higher virus titers in the brain. The data strongly suggest that lead increased mortality following infection by complex means, the most important being the enhacement of encephalitogenic potential of Langat virus.

Animals

Physical reconfiguration of limb electrodes for Precordial Bipolar Lead acquisition: Morphological validation against digital subtraction.

BACKGROUND: The V2&#xa0;-&#xa0;V1 Precordial Bipolar Lead (PBL) selectively evaluates the right-to-left retrosternal axis and has shown diagnostic value beyond the standard 12&#x2011;lead electrocardiogram. However, its use has been limited by the need for raw electrocardiographic data and post-processing software. This study evaluated whether a simple physical reconfiguration of limb electrodes could reproduce the digitally derived V2&#xa0;-&#xa0;V1 morphology with sufficient accuracy for clinical application. METHODS: Thirty-seven subjects underwent two sequential 10-s 12&#x2011;lead recordings using a Cardiovit FT-1 electrocardiograph sampled at 1000&#xa0;Hz. In the standard recording, the digital PBL was calculated as V2&#xa0;-&#xa0;V1. In the second recording, the right-arm and left-arm electrodes were repositioned to the V1 and V2 sites so that Lead I directly recorded the retrosternal dipole. Signals were filtered, synchronized, and analyzed using median beats. Morphological agreement was assessed with Pearson correlation on Z-normalized signals, while absolute agreement was evaluated using Lin's concordance correlation coefficient (CCC), intraclass correlation coefficient (ICC (Lewis, 1931; Nehb, 1938 [1,2])), root mean square error (RMSE), and Bland-Altman analysis. RESULTS: Mean Pearson correlation between digital and physical PBL was 0.955 (SD 0.043), with segment-specific correlations of 0.953 (SD 0.054) for QRS and 0.967 (SD 0.052) for ST-T. Lin's CCC and ICC(2,1) were both 0.871 (SD 0.110), and RMSE was 0.091 (SD 0.049) mV. Bland-Altman analysis showed minimal bias (-0.008&#xa0;mV). CONCLUSIONS: Physical acquisition of the V2&#xa0;-&#xa0;V1 PBL achieved high agreement with the digitally derived signal, supporting a simplified analog method for broader clinical implementation.

Humans

Filterability of erythrocytes from vitamin E-deficient lead-poisoned rats.

The time required for red blood cells (RBC) from vitamin E-deficient lead-poisoned (-E + Pb) rats to pass through polycarbonate filters after incubation in vitro was much greater than that of RBC from vitamin E-supplemented non-poisoned rats. Vitamin E deficiency per se (i.e., in non-poisoned rats) often increased filtration times, but in all such experiments the RBC from -E + Pb groups had even longer filtration times. Administration of lead to rats supplemented with vitamin E had little effect on the filtration rate of RBC. N,N'-diphenyl-p-phenylenediamine (DPPD) prevented the increased filtration times characteristic of RBC from -E + Pb rats, but replacement of the lard in the vitamin E-deficient basal diet by more highly polyunsaturated fats did not exacerbate the increased filtration times of RBC from -E + Pb rats. The increased filtration time of RBC from -E + Pb rats appeared to be related to the extent of RBC lipid peroxidation. Decreasing the pH of the RBC incubation medium from 7.4 to 6.6, an acidity typical of the spleen, markedly increased the filtration times of RBC from -E + Pb rats. Addition of lead in vitro increased filtration times of RBC from both vitamin E-deficient and supplemented non-poisoned rats, but filtration times tended to be longer in the deficient group. These results suggest that vitamin E deficiency and lead toxicity act synergistically to alter the deformability of the RBC thereby rendering it vulnerable to sequestration in the spleen.

Anemia, Hemolytic

Effect of lead exposure on the activity of some hepatic enzymes in the rat.

Seven-day-old rats were fed 1% lead acetate tetrahydrate solution for 2, 4, or 7 days. Adult rats were fed the same lead solution for 6--8 wk. In the newborn rats, hepatic UDP-bilirubin glucuronyl transferase (GT) and gamma glutamyl transpeptidase (GGTP) activities were markedly increased. GT activity was increased after 4 days as compared to the controls (6.3 +/- 0.3 vs. 4.3 +/- 0.3, P less than 0.001), and was maximal after 7 days of treatment (7.5 +/- 0.4 vs. 4.6 +/- 0.4, P less than 0.001). GGTP activity was already maximally increased after 2 days of lead treatment (1.4 +/- 0.2 vs. 0.4 +/- 0.1, P less than 0.001). Hepatic GT and GGTP activities were similarly increased in adult rats (7.9 +/- 0.3 vs. 5.1 +/- 0.1, P less than 0.001, and 0.7 +/- 0.1 vs. 0.4 +/- 0.1, P less than 0.005, respectively). In vitro studies adding lead citrate to liver homogenates did not produce any direct effect on GT and GGTP activities.

Animals