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PubMed1983

A high-molecular-weight cysteine endopeptidase from rat skeletal muscle.

A cytosolic enzyme of high molecular weight (about 500 000), which attacks native or denatured proteins (inter alia, casein, globin and hexokinase) was purified about 1000-fold from mixed rat skeletal muscles, including muscles freed of mast cells by prior treatment of the animals with the degranulator, compound 48/80. Peptides of varying size were generated from radioactively labelled globin, but no free amino acids were formed; free tyrosine was also not released from azocasein. The pH optimum was 7.5 and the presence of an essential cysteine group was suggested because dithiothreitol (1 mM) stimulated the activity and N-ethylmaleimide (5 mM) and p-chloromercuriphenylsulphonic acid (1 mM) were inhibitors. The activity was markedly inhibited by Zn2+ but not by leupeptin, chymostatin or pepstatin. The enzyme was stabilized by ATP, at concentrations as low as 0.1 mM, against inactivation at 42 degrees C. The endopeptidase was clearly separated on gel chromatography from another large protease, also sensitive to Zn2+, but with marked aminopeptidase activity and the properties of hydrolase H. The activity levels of the protease, assayed after chromatography on Sepharose 6B of high-speed supernatant fractions, did not vary significantly in skeletal muscle samples which were derived from denervated, starved, diabetic or hyperthyroid animals, in all of which the abnormal physiological states expressed themselves as enhanced rates of tyrosine released by incubated soleus and extensor digitorum longus muscles. Nevertheless, the enzyme described here may be part of an ATP-dependent, multi-component proteolytic system similar to that already known to be present in reticulocytes.

Adenosine Triphosphate↗

PubMed1980

Frozen-slab technique for mixing zinc phosphate cement for cast restorations.

The technique for handling zinc phosphate cement can be altered to achieve enhanced properties of the cement. The compressive strength of the material can be decreased. The film thickness can be maintained within acceptable limits, and the possibility of pulpal damage can be kept low by maintaining temperature changes in the cement similar to those obtained from a room temperature-slab technique. The technique advocated by this report is as follows: 1. Store the aluminum slab with vinyl covering in a freezer at -15 degrees C to -20 degrees C in a plastic bag to prevent ice formation on the surface. 2. Remove the slab when ready to mix. 3. Quickly wipe the slab clean. 4. Dispense twice as much powder and liquid as recommended on the slab. 5. Start timer. 6. Slowly incorporate the powder into the liquid over a large area of the slab for 2 minutes. 7. Allow the mix to remain on the slab. 8. The instrument for placing the cement can be placed under the slab. The casting can be placed on a corner of the slab. 9. At 10 minutes, place the cement into the casting(s) and seat. 10. Remove excess cement. 11. Clean the slab by rinsing in water and gently wiping. 12. Dry the slab, place it in the plastic bag, and return it to the freezer.

Aluminum↗

PubMed2002

Zinc translocation accelerates infarction after mild transient focal ischemia.

Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

Aminoquinolines↗

PubMed1995

Characterization of N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide for the detection of zinc in living sperm cells.

Zinc stabilizes membranes and DNA and inhibits respiration in somatic cells. It is present in high concentrations in the male reproductive tract and may stabilize spermatozoa prior to fertilization. Herein, we evaluate N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ) for analysis of Zn2+ in phosphatidylcholine (PC) vesicles and living spermatozoa using spectrofluorometry and flow cytometry. TSQ:Zn fluorescence in decanol or PC vesicles was compared to that in aqueous buffer. Evaluation of cation specificity, kinetics of TSQ:Zn binding, quenching of TSQ by dithionite and Zn2+ chelation by D-penicillamine established that TSQ is more fluorescent in decanol or PC vesicles than in aqueous buffer, has a high affinity for lipid bilayers and is specific for Zn2+ compared to Mg2+ and Ca2+. Fluorescence measurement of vesicles with and without pretreatment with Zn2+ indicated that, in the absence of Zn2+, 90% of the residual TSQ fluorescence was destroyed by dithionite but > 50% was protected by the presence of Zn2+. When D-penicillamine was added the remaining fluorescence was quenched (T1/2 = 10 s) indicating that TSQ remains in/on the membrane. These results established that TSQ can be used to effectively evaluate Zn2+ in artificial membranes and sperm cells. Additional experiments will be necessary to explain the dynamics of TSQ:Zn:membrane interactions.

Aminoquinolines↗

PubMed1994

Measurement of zinc in hepatocytes by using a fluorescent probe, zinquin: relationship to metallothionein and intracellular zinc.

Zinquin [ethyl (2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)acetate], a new intracellular zinc fluorophore, was used to reveal and to measure Zn in cultured rat hepatocytes before and after metallothionein (MT) induction. Hepatocytes labelled with an intense extranuclear fluorescence. Culture with combinations of Zn, dexamethasone and interleukin-6, increased intracellular MT by 24-fold, Zn 3-fold, and Zinquin fluorescence by approx. 2-fold above control values. Zinquin fluorescence correlated in descending order with the total cellular Zn (r = 0.747), exchangeable Zn (r = 0.735), soluble cytosolic Zn (r = 0.669) and MT (r = 0.666). When Zinquin was incubated with a cytosolic fraction of liver proteins before Sephadex G-75 column chromatography, it fluoresced with free, MT-incorporated and protein-bound Zn. Although only a slight attenuation of fluorescence was seen with high-molecular-mass protein-bound Zn, MT was degraded by 60% in the presence of Zinquin. The undegraded Zn-MT fluoresced at about 20% of the expected intensity. Although Zinquin fluoresces with all cytosolic Zn, caution is required when comparisons are made between samples with different concentrations of MT. This limitation was demonstrated by staining liver slices from adjuvant-treated rats where MT was increased 24-fold, intracellular Zn by 77%, but Zinquin fluorescence by only 19% above controls. Nevertheless, Zinquin should prove to be a useful tool for studying the distribution of Zn in living cells.

Animals↗

PubMed2002

Nitric oxide-induced changes in intracellular zinc homeostasis are mediated by metallothionein/thionein.

We hypothesized that metallothionein (MT), a cysteine-rich protein with a strong affinity for Zn(2+), plays a role in nitric oxide (NO) signaling events via sequestration or release of Zn(2+) by the unique thiolate clusters of the protein. Exposing mouse lung fibroblasts (MLF) to the NO donor S-nitrosocysteine resulted in 20-30% increases in fluorescence of the Zn(2+)-specific fluorophore Zinquin that were rapidly reversed by the Zn(2+) chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)ethylenediamine. The absence of a NO-mediated increase in labile Zn(2+) in MLF from MT knockouts and its restoration after MT complementation by adenoviral gene transfer inferred a critical role for MT in the regulation of Zn(2+) homeostasis by NO. Additional data obtained in sheep pulmonary artery endothelial cells suggested a role for the apo form of MT, thionein (T), as a Zn(2+)-binding protein in intact cells, as overexpression of MT caused inhibition of NO-induced changes in labile Zn(2+) that were reversed by Zn(2+) supplementation. Furthermore, fluorescence-resonance energy-transfer data showed that overexpression of green fluorescent protein-modified MT prevented NO-induced conformational changes, which are indicative of Zn(2+) release from thiolate clusters. This effect was restored by Zn(2+) supplementation. Collectively, these data show that MT mediates NO-induced changes in intracellular Zn(2+) and suggest that the ratio of MT to T can regulate Zn(2+) homeostasis in response to nitrosative stress.

Animals↗

PubMed2004

Nickel(II), copper(II) and zinc(II) binding properties and cytotoxicity of tripodal, hexadentate tris(ethylenediamine)--analogue chelators.

Three tripodal hexamine chelators based on cis,cis-1,3,5-triaminocyclohexane (tach) have been synthesized and their aqueous coordination chemistry with Ni(II), Cu(II) and Zn(II) is reported. The chelators have a 2-aminoethyl pendant arm attached to each nitrogen of tach, specifically 'tachen'(N,N',N''-tris(2-aminoethyl)cyclohexane-cis,cis-1,3,5-triamine), and two with S,S,S-chiral pendant arms, 'tachpn'(N,N',N''-tris(2-aminopropyl)cyclohexane-cis,cis-1,3,5-triamine) and 'tachbn'(N,N',N''-tris(2-amino-3-phenylpropyl)cyclohexane-cis,cis-1,3,5-triamine. These chelators complex Ni(II), Cu(II) and Zn(II) in aqueous or aqueous/methanolic medium. The crystalline products [M(II)L](X)2 are isolated, where M = Ni(II), Cu(II) or Zn(II), L = tachen, tachpn or tachbn, and X = ClO4-. Crystallographic study of selected tachpn and tachbn complexes shows the chelate arms are constrained in a Lambda(deltadeltadelta) configuration about M(II), which is attributed to their chirality. Solution UV-vis spectroscopy of the Ni(II) and Cu(II) complexes indicates six-coordination and little effect of the pendant arm substitution on ligand-field strength. The single exception is [Cu(tachbn)]2+, whose spectrum is consistent with five-coordination in solution. The cytotoxicities of tachen, tachpn and tachbn toward cultured cancer cells is in the order tachen < tachpn < tachbn < tachpyr, where tachpyr is the aminopyridyl chelator N,N',N''-tris(2-pyridylmethyl)cyclohexane-cis,cis-1,3,5-triamine. The cytotoxicity difference is attributed to an order of increasing lipophilicity, tachen < tachpn < tachbn.

Animals↗

PubMed2003

Intracellular zinc fluxes associated with apoptosis in growth plate chondrocytes.

Matrix vesicles released by epiphyseal growth plate chondrocytes are known to contain a significant quantity of labile Zn(2+). Zonal analysis of chicken metatarsal bones showed that the resting/proliferative region of the growth plate contained high levels of Zn(2+) with significantly lower levels in the hypertrophic cartilage suggesting a loss of cellular Zn(2+) as the chondrocytes mature. Intracellular labile Zn(2+) was measured in primary cultures of growth plate chondrocytes by assay with the fluorescent Zn-chelator toluenesulfonamidoquinoline (TSQ) and imaged by multi-photon laser scanning microscopy (MPLSM) with the TSQ derivative zinquin. Short-term exposure to Zn(2+), both in the presence and absence of pyrithione resulted in significant increases in cytosolic Zn(2+). Treatment with the membrane-permeant Zn(2+) chelator TPEN rapidly reduced the levels of labile Zn(2+) and triggered apoptosis. Cytosolic Zn(2+) levels were significantly reduced following 24-h incubations with known inducers of chondrocyte apoptosis. The loss of intracellular Zn(2+) was accompanied by a significant reduction in the cytosolic metal-binding protein metallothionein. Examination of Zn(2+)-treated cells with MPLSM showed uniformly higher zinquin fluorescence. Treatment of Zn(2+)-loaded cells with TPEN quenched zinquin fluorescence confirming that the observed fluorescence in chondrocytes is due to the presence of intracellular Zn(2+). A dose-dependent increase in zinquin fluorescence was observed in cells treated with a range of Zn(2+) concentrations. Short-term treatment of cultured chondrocytes with apoptosis-inducing chemicals resulted in transient increases in intracellular labile Zn(2+). These results indicate that Zn(2+) is mobilized from intracellular binding sites in the early stages of chondrocyte apoptosis and is subsequently lost from the cells. The early mobilization of Zn(2+) provides a mechanism for its movement to matrix vesicles and the extracellular matrix.

Animals↗

PubMed2006

Zinquin identifies subcellular compartmentalization of zinc in cortical neurons. Relation to the trafficking of zinc and the mitochondrial compartment.

Zinquin (Zn(2+) selective fluorophore), when used to visualize intracellular Zn(2+), typically shows brightly fluorescent perinuclear endosome-like structures, presumably identifying Zn(2+) containing organelles. In this study, zinquin identified numerous and widespread sites of Zn(2+) compartmentalization in primary cultures of embryonic rat cortical neurons. Nuclear fluorescence, however, was absent. We labeled neuronal mitochondria with MitoTracker Green in the presence of zinquin and show that the fluorescent patterns of MitoTracker Green and zinquin were distinct and clearly different in both the perinuclear region and in processes. The mitochondrial compartment was much larger than the sum of the areas of zinquin fluorescence, as indicated by the small amount (<10% MitoTracker Green over zinquin) of overlap of MitoTracker Green on zinquin. Zinquin fluorescence was unaffected by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) treatment. The zinquin fluorescent objects were generally spherical in shape with a average diameter of about 0.6 mum. Most fluorescent objects, nearly two thirds on average, appeared to be docked, but both anterograde and retrograde movements were observed by time lapse image analysis. Although some fluorescent objects moved as much as 1 mum in 5 min, typical movements were smaller, usually 0.5 mum or less. Colchicine treatment caused striking aggregation of MitoTracker Green most noticeable in the perinuclear region. Zinquin fluorescence similarly showed reduced distribution throughout the cytoplasm, suggesting that zinquin fluorescent structures were associated with microtubules. Treatment with cytochalasin D had little noticeable effect on either the pattern of zinquin and MitoTracker Green fluorescence or their coincidence. Thus, numerous Zn(2+) sequestering organelles/structures are present in perinuclear regions and processes of cultured neurons and are sometimes found coincident with mitochondria. We demonstrated real time trafficking of sequestered Zn(2+), using zinquin fluorescence, apparently associated with an endosome-like compartment or protein complexes in the cytosol.

Analysis of Variance↗

PubMed1999

Regional distribution and localization of zinc and metallothionein in the intestine of rats fed diets differing in zinc content.

BACKGROUND: Zinc (Zn) is protective and enhances epithelial repair in gut diseases. In this study we investigate the localization and distribution of Zn and its binding protein, metallothionein (MT), in the gut of rats fed diets varying in Zn content. METHODS: Male-Sprague Dawley rats were fed low, normal, high, or excess Zn in their diets (10, 100, 400, or 1000 mg Zn/kg, respectively) and killed 7 days later. Blood, liver, and gut tissues were collected. Tissue Zn was determined with atomic absorption spectrophotometery and MT with a Cd/haem affinity assay. Zn and MT were immunohistochemically localized in the small-intestinal wall with zinquin and an anti-MT antibody. RESULTS: Most Zn in the intestinal wall was present in the mucosal scrapings, with 94% membrane-bound and 6% cytosolic, irrespective of dietary Zn. MT levels increased in all gut regions at dietary Zn levels above 100 mg Zn/kg. MT was 40% higher in the ileum than in other gut regions in rats fed low- and normal-Zn diets. The Zn content of the ileum was also 20% higher than that of other gut regions in rats fed low-, normal-, or high-Zn diets. Zn and MT were colocalized in the base of the intestinal crypts, most visibly in the ileum. CONCLUSION: Mucosal cytosolic Zn and MT concentrations are increased only at high or excessive Zn intakes in all gut regions except the ileum, which can respond to a lower Zn intake. As the cytosolic Zn pool most likely influences mucosal protection and repair mechanisms, it is proposed that an increased MT may indicate the adequacy of oral Zn therapy in gut disease.

Abdominal Muscles↗

PubMed2002

New monomeric cobalt(II) and zinc(II) complexes of a mixed N,S(alkylthiolate) ligand: model complexes of (His)(His)(Cys) metalloprotein active sites.

The new N(2)S(alkylthiolate) ligand 2-methyl-1-[methyl-(2-pyridin-2-ylethyl)amino]propane-2-thiolate, PATH (1), has been prepared and reacted with zinc(II) and cobalt(II) to give the monomeric complexes [(PATH)ZnBr] (2), [(PATH)ZnNCS] (3), [(PATH)CoBr] (4), and [(PATH)CoNCS] (5). The molecular structures of 4 and 5 have been determined by X-ray diffraction. Each complex displays a distorted tetrahedral geometry at the metal center, with the PATH ligand providing the N(2)S(alkylthiolate) donors. These complexes are close structural mimics of the active site of metalloproteins with a His(2)Cys-M(II) site such as that found in peptide deformylase. Complexes 4 and 5 are the first examples of crystallographically characterized Co(II) complexes with an N(2)SL (L not equal N,S) donor set. Only one diastereomer for 2-5 is observed in the solid state, and simple molecular mechanics (Chem3D) calculations suggest this isomer is stable because of a favorable ligand conformation. NMR studies in the case of Zn(II) and UV-vis studies in the case of Co(II) provide strong evidence that their solid-state structures are retained in solution. Cyclic voltammetry reveals processes for both the Co(II/I) (4, - 1.51 V; 5, - 1.49 V) and Co(III/II) (4, + 0.9 V; 5, + 0.9 V) couples. The UV-vis data for the cobalt complexes are consistent with a monomeric, four-coordinate geometry regardless of the nature of the solvent (i.e., donating (MeOH, CH(3)CN) vs nondonating (CH(2)Cl(2))) and are compared with other cobalt complexes as well as cobalt-substituted His(2)Cys metalloproteins (peptide deformylase and blue-copper proteins). In addition, reaction of the bromide complexes 2 and 4 with hydroxide anion leads to the formation of 1:1 hydroxide:M(II) complexes which have been characterized in situ by (1)H NMR and UV-vis spectroscopy, respectively.

Amidohydrolases↗

PubMed1996

Direct reaction of H2O2 with sulfhydryl groups in HL-60 cells: zinc-metallothionein and other sites.

The reaction of the sulfhydryl groups in metallothionein with hydrogen peroxide was examined in HL-60 cells. Partial purification of cell cytosol using Sephadex G-75 chromatography showed that zinc-metallothionein (Zn-MT) was induced by 24-h treatment with 100 microM ZnCl2, but the cellular glutathione content and glutathione peroxidase and catalase activities were unaffected. The ratio of H202 concentrations needed to reduce cell survival 50% in Zn-induced cells compared to normal cells was 1.65 to 1. According to alkaline elution experiments, the average ratio of single-strand breaks caused by H202 at 37 degrees C in Zn-induced vs normal cells was 0.5 to 1. A similar reduction in strand breakage was seen in nuclei from Zn-treated cells exposed to H202; however, at 4 degrees C protection against DNA strand breakage by Zn pretreatment was not seen. Incubation of Zn-pretreated cells with H202 at 37 degrees C but not 4 degrees C was accompanied by loss of Zn bound to MT and a reduction in the number of MT sulfhydryl groups. In the absence or presence of Zn-MT, sulfhydryl groups from glutathione and protein fractions were also reduced by exposure of cells to H202. However, thiolate groups in the MT fraction were preferentially lost compared to the other pools of sulfhydryl residues. Zn-MT also spared glutathione sulfhydryl groups in vitro from oxidation by H202. Protection against strand breakage correlated with the ability of Zn-MT to react in vitro with H202 at 37 degrees C, but not at 4 degrees C. The reaction was slow and was not inhibited by the presence of an hydroxyl radical scavenger, dimethyl sulfoxide. Similarly, in cells dimethyl sulfoxide did not prevent the loss of sulfhydryl groups from glutathione or protein. Incubation of MT or higher molecular weight fractions from cells exposed to H202 with either 2-mercaptoethanol or dithiothreitol in the presence of Cd failed to regenerate any detectable, reduced MT, suggesting that MT sulfhydryl groups were oxidized by H202 beyond the disulfide oxidation state.

Animals↗

PubMed1995

Purification and cation binding properties of the recombinant human S100 calcium-binding protein A3, an EF-hand motif protein with high affinity for zinc.

The calcium-binding protein S100A3 is an unusual member of the S100 family, characterized by its very high content of Cys. In order to study the biochemical, cation-binding, and conformational properties, we produced and purified the recombinant human protein in Escherichia coli. The recombinant protein forms noncovalent homodimers, tetramers, and polymers in vitro with a subunit molecular weight of 11,712. The Zn(2+)-binding parameters of S100A3 were studied by equilibrium gel filtration and yielded a stoichiometry of four Zn2+ per monomer with a [Zn2+]0.5 of 11 microM and a Hill coefficient of 1.4 at physiological ionic strength. The affinity for Ca2+ is too low to be determined by direct methods (KCa > 10 mM). Ca(2+)- and Zn(2+)-binding can be followed by optical methods: the Trp-45 fluorescence is high in the metal-free form and addition of Zn2+ and Ca2+, but not of Mg2+, leads to a 4-fold quenching. Ca2+ and Zn2+ promote also quite similar conformational changes in the Tyr and Trp environment as monitored by difference spectrophotometry. Fluorescence titrations with Zn2+ confirmed that there is one set of high affinity binding sites with a [Zn2+]0.5 of 8 microM and a Hill coefficient of 1.3. Binding of Zn2+ to a second set of low affinity sites induces protein precipitation. Fluorescence titrations with Ca2+ confirmed the very low affinity of S100A3 for this ion with a [Ca2+]0.5 of 30 mM and slight negative cooperativity. Mg2+ has no effect on this binding curve. Of the 10 Cys residues in S100A3, 5 only are free thiols, and accessible to 5,5'-dithiobis(2-nitro-benzoic acid); they display a high reactivity in the metal-free and Ca2+ form, but a 20-fold lowered reactivity in the Zn2+ form of S100A3. Ca(2+)-binding promotes the formation of a solvent-accessible hydrophobic surface as monitored by the 60-fold fluorescence increase of 2-p-toluidinylnaphthalene-6-sulfonate, whereas Zn2+ has no noticeable influence. Our data indicate that Ca2+ and Zn2+ do not bind to the same sites and that under physiological conditions S100A3 is a Zn(2+)-binding rather than a Ca(2+)-binding protein; nevertheless, very specific conformational changes are introduced by either Ca2+ or Zn2+. Since no Zn(2+)-binding motif of known structure was identified in the primary sequence of S100A3, the results are suggestive for a novel Zn(2+)-binding motif.

Base Sequence↗

PubMed2004

Ligand oxidations in high-spin nickel thiolate complexes and zinc analogues.

Oxidations of a trigonal-bipyramidal, high-spin Ni(II) dithiolate complex of a pentadentate, N3S2-donor ligand, N1,N9-bis(imino-2-mercaptopropane)-1,5,9-triazanonane) nickel(II), and the structurally analogous Zn(II) complex, lead to oxidations of the ligand. Oxidation of the Ni(II) complex with I2 produces a novel Ni(II) macrocyclic cationic complex containing a monodentate disulfide ligand (2). Crystals of the I3- salt of the complex form in the triclinic space group P(1) with cell dimensions a=8.508(3) A, b=9.681(2) A, c=14.066(4) A, angles alpha=90.97(2) degrees , beta=91.61(3) degrees , gamma=90.83(2) degrees , and Z=2. The structure was refined to R=6.31% and Rw=16.63% (I > 2sigma(I)). Oxidation of the Ni(II) complex with O2 leads to the formation of a novel pentadentate bis-iminothiocarboxylate complex with trigonal-bipyramidal geometry (3). This neutral product crystallizes in the monoclinic space group P21/c with cell dimensions a=13.625(3) A, b=7.605(5) A, c=14.902(4) A, angles alpha=gamma=90 degrees, beta=102.81(2) degrees , and Z=4. The structure was refined to R=7.18% and Rw=17.86% (I > 2sigma(I)). Oxidation of the Zn(II) dithiolate analogue with O2 leads to the formation of the Zn(II) complex of the pentadentate bis-iminothiocarboxylate ligand. The neutral complex is isomorphous with the Ni(II) complex and crystallizes in the monoclinic space group P2(1)/c with cell dimensions a=13.8465(4) A, b=7.6453(2) A, c=15.0165(6) A, angles alpha=gamma=90 degrees , beta=103.2140(11) degrees , and Z=4. The structure was refined to R=3.96% and Rw=9.45% (I > 2sigma(I)). Details of the crystal structures are reported. Kinetics of the O2 reactions show that the reactions of the Ni(II) and Zn(II) dithiolates follow the rate law, Rate=k2[1][O2], with k2=1.81 M(-1) s(-1) for the Ni(II) complex and k2=1.93 x 10(-2) M(-1) s(-1) for the Zn(II) complex. The O2 oxidation of the high-spin Ni(II) thiolate complex was found to follow a similar oxidation mechanism to those of low-spin Ni(II) complexes, which form transient persulfoxide intermediates that yield S-oxidation products. In the case of the high-spin system reported here, the transient persulfoxide intermediate gives rise to an alternative ligand oxidation product, a bis-iminothiocarboxylate complex, because of the reactivity of the ligand, which contains a methylene with acidic H atoms alpha to the thiolate sulfur. The proposed mechanism is supported by studies of the analogous Zn dithiolate complex, which gives rise to the analogous bis-iminothiocarboxylate product (5).

Crystallography, X-Ray↗

PubMed1983

Mohs surgery. Technique, indications, applications, and the future.

Each year, it is estimated, more than 500,000 new cases of nonmelanoma skin cancer develop. The majority of these cutaneous neoplasms are treated by various modalities that include excision, electrodesiccation and curettage, cryosurgery, and irradiation, with greater than 90% success. Certain of the remaining primary tumors, as well as recurrent carcinomas, present a demanding therapeutic challenge. For these lesions, Mohs surgery has evolved as the most reliable and cost-effective treatment modality, offering maximal preservation of normal tissue and therefore the lowest functional and cosmetic morbidity. In this review, the history and evolution of Mohs surgery and the technique itself will be briefly outlined. The indications for Mohs surgery, together with methods of handling the postoperative wound and future applications of the technique, will be discussed in detail.

Basal Cell Carcinoma↗

PubMed1994

Acrodermatitis enteropathica, zinc metabolism, copper status, and immune function.

OBJECTIVE: To study zinc metabolism, copper status, and immune function in a patient with acrodermatitis enteropathica. RESEARCH DESIGN: Case report. PATIENT: A 16-year-old boy with acrodermatitis enteropathica. INTERVENTION: Change of zinc supplementation dosage from 1000 to 525 mumol/d. MEASUREMENTS AND RESULTS: Zinc metabolism was studied with an oral dose of zinc chloride Zn 65 and whole-body counting at both zinc dosages. Zinc, copper status, and immune indexes were also measured at both dosages. The higher dosage of zinc supplementation was found to induce a state of low copper status and immune dysfunction. Lowering the dosage normalized these indexes. Zinc absorption in this patient was found to be within the reference range for healthy subjects. At the lower dosage, zinc retention and the rate of whole-body turnover also normalized. These results suggest that the primary lesion in acrodermatitis enteropathica is a cellular defect in zinc metabolism rather than an impairment of zinc absorption. CONCLUSION: Zinc and copper status and immune function should be monitored regularly in patients with acrodermatitis enteropathica to provide a proper dosage of zinc during different physiologic stages.

Acrodermatitis↗

PubMed1998

Inducible protein in rat hepatomas with expression alternative to alpha-fetoprotein.

The rat hepatoma cell line McA RH7777 was cloned into alpha-fetoprotein-producing (AFP+) and non-producing (AFP-) sublines. A monoclonal antibody (MAb A2/3) reacting with an antigen (Ag A2/3) present only in AFP- clones or AFP- cells in mixed clones was obtained. Ag A2/3 was absent from the liver of embryonic, fetal, newborn and adult rats, but it was present in gastric and intestinal mucosa of adult rats. Ag A2/3 was found to be a heavy metal-inducible protein: Cd2+ and Pb2+ strongly induced the expression of Ag A2/3 in vivo in the liver of adult rats, while xenobiotics and CCl4 were not active in this respect. In vitro Cd2+ and Pb2+ induced Ag A2/3 expression in several AFP+ clones, leading to a simultaneous marked decrease of AFP+ cells from such clones. The effect of Cd2+ in the induction of Ag A2/3 and suppression of AFP was reversible. SDS PAGE revealed one protein band with an m.w. close to 45,000, which was not sensitive to mercaptoethanol. Despite its inducible properties, Ag A2/3 was shown not to belong to metallothioneins, cytochrome P-450, glutathion-transferase or heat shock proteins families, well-known as being inducible cell stress proteins. Expression of Ag A2/3 could be one of the factors determining the high amplitude of AFP production by individual liver tumors. The nature of Ag A2/3 and its alternative expression with respect to AFP remain to be studied.

Animals↗

PubMed1997

Levels of DNA strand breaks and superoxide in phorbol ester-treated human granulocytes.

Phorbol ester treatment of granulocytes triggers release of superoxide (O2.-) and a concomitant burst of DNA strand breaks. The relationship between the amount of O2.- and the number of DNA breaks has not previously been explored. To quantify the relatively large amount of O2.- generated over a 40-min period by 1 x 10(6) granulocytes/mL, a discontinuous "10-min pulse" method employing cytochrome c was used; 140 nmol O2.- per 1 x 10(6) cells was detected. DNA strand breaks were quantified by fluorimetric analysis of DNA unwinding (FADU). To vary the level of O2.- released by cells, inhibitors of the respiratory burst were used. Sodium fluoride (1-10 mM) and staurosporine (2-10 nM) both inhibited O2.- production. In both cases, however, inhibition of strand breakage was considerably more pronounced than inhibition of O2.-. Zinc chloride (50-200 microM) inhibited both O2.- and DNA breaks, approximately equally. Dinophysistoxin-1 (okadaic acid) inhibited O2.- production more effectively than it inhibited DNA breaks. O2.- dismutes to H2O2, a reactive oxygen species known to cause DNA breaks. The addition of catalase to remove extracellular H2O2 had no effect on DNA breakage. Using pulse field gel electrophoresis, few double-stranded breaks were detected compared to the number detected by FADU, indicating that about 95% of breaks were single-stranded. The level of DNA breaks is not directly related to the amount of extracellular O2.- or H2O2 in PMA-stimulated granulocytes. We conclude that either an intracellular pool of these reactive oxygen species is involved in breakage or that the metabolic inhibitors are affecting a novel strand break pathway.

Chlorides↗