Respiratory variability of sinus node activation in humans: insights from ultra-high-density mapping.

PURPOSE: Experimental data suggest that shifts in the site of origin of the sinus node (SN) correlate with changes in heart rate and P wave morphology. The direct visualization of the effect of respiration on SN electrical activation has not yet been reported in humans. We aimed to measure the respiratory shifting of the SN activation using ultra-high-density mapping. METHODS: Sequential right atrial (RA) activation mapping during sinus rhythm (SR) was performed. Three maps were acquired for each patient: basal end-expiratory (Ex), end-inspiratory (Ins), and end-expiratory under isoproterenol (Iso). The earliest activation site (EAS) was defined as the earliest unipolar electrograms (EGM) with a QS pattern and was localized with respect to the ostium of the superior vena cava (SVC; negative values if EAS inside the SVC). RESULTS: In 20 patients, 49 maps in SR were acquired (20 Ex, 19 Ins, and 10 Iso). Expiratory (944 ± 227 ms) and inspiratory (946 ± 227 ms) SR cycle lengths were similar, but shortened under isoproterenol (752 ± 302 ms). Activation was unicentric in 33 maps and multicentric in 16: 4 during Ins, 10 during Ex, and 2 Iso. EAS location was significantly more cranial in expiration than in inspiration (0.27 ± 12.1 vs 5 ± 11.51 mm, p = 0.01). Iso infusion tends to induce a supplemental cranial shift (-4.07 ± 15.83 vs 0.27 ± 12.7 mm, p = 0.21). EAS were found in SVC in 22.7% of maps (30% Ex, 21% Ins, and 8% Iso). CONCLUSION: Inspiration induces a significant caudal shift of the earliest sinus activation. In one-third of the cases, sinus rhythm earliest activation is inside the SVC.

Cardiac events monitoring.

Cardiac events recorders have been developed in order to record the heart rhythm during symptoms such as palpitations or presyncope, to first make a diagnosis, and subsequently drive the treatment strategy. In other circumstances, they can be also used in asymptomatic patients (to record silent atrial fibrillation for instance). Because they are non-invasive, potentially cost-saving and relatively easy to use, the external rhythm recording devices have shown some great advances in the last years, spreading from photoplethysmographic technique to real ECG reconstruction. Technological advances in the field of microelectronics, as well as in the field of data transmission have contributed to their widespread use in cardiology. The trend for miniaturization was also expanded to the implantable recorders. This paper will review will review advantages and limitations of the different existing available well-established recording devices, as well as the last technological developments in terms of ECG recordings.

[Organization and management of acute complete atrioventricular block: Results from a Multicenter National Survey]. / Organisation et gestion aiguë du bloc atrioventriculaire complet : résultats d'une enquête multicentrique nationale.

BACKGROUND: Complete atrioventricular block (AVB3) may be an urgent potentially lifethreatening situation. Our objective was to describe the routine management of AVB 3, with emphasis on the organizational aspects. METHODS: From September 2019 to November 2019, a prospective national survey including 28 questions was electronically sent to 100 physicians (Google Form). RESULTS: The answers were collected from 93 physicians (response rate 93%). Permanent pacemaker implantation during weekends and nights (after 8PM) is possible for 49% of the operators (<5 times a year), for 15% (>5 times a year), impossible for 36% of the operators. For AVB3 nonresponsive to isoproterenol occurring during the night, a temporary pacing lead (TPL) is implanted by: the on-site medical staff on-duty (27%), the on-call interventional cardiologist (21%), the on-call electrophysiologist (19%), a permanent pacemaker is implanted by the electrophysiologist (12%), the strategy is not standardized (15%). An externalized active fixation lead (AFL) for AVB3 has already been implanted by 50% of the operators. 80 (86%) have already observed a dislocation of the TPL, a cardiac perforation already occurred in 57 (61%), a groin hematoma in 35 (38%), and this technique was proscribed for 4% of the operators. CONCLUSION: Our survey shows important disparities in terms of management of AVB3 among the different centers. An externalized AFL with a reusable generator was used by half of the centers.

Accelerated idioventricular rhythm requiring catheter ablation in a child: The dark side of a benign arrhythmia.

A 12 year-old boy, with no history of cardiac disease, was referred to our department for evaluation of an incessant accelerated idioventricular rhythm (AIVR) complicated with severe left ventricular (LV) dysfunction and cardiogenic shock. Extensive diagnostic work-up failed to reveal any structural heart disease. During electrophysiological study, AIVR originated from the right ventricular endocardial anterior wall and was successfully ablated using remote magnetic navigation. LV function showed complete recovery four weeks after the procedure. This case highlights a life-threatening evolution of an arrhythmia generally presented as a benign entity in children.

Dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube, or primary peritoneal carcinomas.

PURPOSE: Weekly dose-dense paclitaxel with carboplatin every 3 weeks (dose-dense TC) provides good efficacy, and neoadjuvant chemotherapy is common for advanced-stage disease. However, it is unclear the efficacy and safety of dose-dense TC as neoadjuvant chemotherapy. Therefore, we evaluated neoadjuvant dose-dense TC chemotherapy for advanced-stage ovarian carcinoma. METHODS: We retrospectively reviewed cases of ovarian carcinoma that were not suited for primary debulking surgery (2003-2014). The patients received neoadjuvant dose-dense TC chemotherapy, followed by interval debulking surgery and adjuvant chemotherapy. RESULTS: We identified 74 patients (mean age 60 years, range 39-85 years). The FIGO stages were IIIC (39/74, 52.7%) and IV (34/74, 45.9%). Fifty-six patients (75.6%) had a performance status of 0-1. The adverse events were grade 3/4 neutropenia (55.4%), anemia (44.6%), thrombocytopenia (21.6%), and peripheral neuropathy (8.1%); no treatment-related deaths were observed. Among the 66 patients who underwent debulking (89.2%), 55 patients (74.3%) achieved optimal debulking and 47 patients (63.5%) achieved complete resection. The median progression-free and overall survivals were 19.0 months (95% CI 16.2-23.7 months) and 55.1 months (95% CI 44.6 months to not estimable), respectively. A performance status of 2-3 was independently associated with poor prognosis (hazard ratio 3.84; p = 0.001). CONCLUSIONS: Neoadjuvant dose-dense TC chemotherapy was effective (complete resection in >60% of cases) and tolerable for advanced-stage ovarian carcinoma.

The effects of device position on the operator's radiation dose when using a handheld portable X-ray device.

INTRODUCTION: Handheld X-ray devices are now offered in dental practice. Handheld X-ray units challenge the concept of a restricted access to the "controlled area" as they are held by the operator. Although an integral lead shield is provided, the distance from the body is variable, dependent on how the device is held. The aim of this article was to investigate the level of operator dose when using a handheld X-ray device in various positions. MATERIAL AND METHODS: A NOMAD Pro™ Handheld X-ray system (Aribex Inc., Charlotte, NC) fitted with a remote control and mounted on a tripod was used in this study. A maxillofacial phantom ATOM(®) Max Dental and Diagnostic Phantom, model 711 HN (CIRS Inc., Norfolk, VA) was used to simulate the patient's head position. A mannequin was used to represent the operator. Pre-calibrated thermoluminescent dosemeters (TLDs) (Qados, Agar Scientific, Stansted, UK) were placed on the mannequin close to the eyes and at the level of thyroid, trunk, waist, hand (right finger + left palm) and feet, and three TLDs were used for background radiation. Three test scenarios were investigated; Position 1, close to operators' body and parallel to the ground; Position 2, away from the body with the arms fully extended (approximately 40 cm distance) and parallel to the ground; Position 3, perpendicular to the ground while the arms are partially extended. 30 exposures each of 1 s were performed in each test. RESULTS: Background radiation was measured at 0.0110 mGy. The highest exposure after subtracting background radiation was recorded on the palm of the left hand (0.0310 mGy) at Position 3. The estimated dose to the operator was calculated based on an average workload of 100 intraoral radiographs weekly for a dental practitioner working 46 weeks a year. CONCLUSIONS: There is a negligible increase in operator exposure levels using handheld X-ray devices which remain well below the recommended levels of the Ionizing Radiation Regulations 1999. They could however represent an increase from what should be a nil exposure when using a wall-mounted machine. The position of the device relative to the operator has a significant effect on the overall operator's radiation exposure. The use of personal dosemeters is highly recommended to ensure a continuity of low radiation dose exposure. Furthermore, guidance, training and protocols on usage must be in place, strictly adhered to and regular audits are necessary to ensure compliance.

Influence of organic zinc supplementation on the antioxidant status and immune responses of broilers challenged with Eimeria tenella.

An experiment was conducted to investigate the influence of Zn supplementation on the performance, antioxidant status, and immune responses of broilers challenged with Eimeria tenella. A total of 384 male broilers (1 d old) were assigned to 8 treatments consisting of 8 replicates of 6 chicks each. A basal corn-soybean meal diet (29.6 mg of Zn/kg) was supplemented with methionine hydroxyl analog-Zn chelate at 0, 20, 40, and 60 mg/kg of diet. At 21 d of age, birds were orally gavaged with 1.5 × 10(4) sporulated E. tenella oocysts. Dietary Zn supplementation had no effect on growth performance of either the challenged or nonchallenged birds. Activities of Cu-Zn superoxide dismutase and glutathione peroxidase were increased (P < 0.001) with increasing Zn levels in both the challenged and nonchallenged groups. Lipid peroxidation tended to be reduced (P = 0.08) at Zn inclusion of 20 and 40 mg/kg. In vitro lymphocyte proliferation responses to mitogen concanavalin A and LPS were not influenced by dietary Zn or challenge. The main effects of Zn level and challenge were significant for secretory IgA on d 28 (P < 0.01) and 35 (P < 0.001). During both periods, secretory IgA of birds receiving dietary Zn supplementation was higher (P < 0.05) than that of those receiving no Zn supplementation. Birds fed Zn supplementation excreted fewer oocysts in the excreta than those receiving no Zn supplement (P < 0.001). Results indicated that organic Zn supplementation reduced oxidative stress and improved some immune responses irrespective of whether birds were healthy or challenged with E. tenella.

The effect of glucagon-like peptide 2 injection on performance, small intestinal morphology, and nutrient transporter expression of stressed broiler chickens.

An experiment was conducted to determine the effect of injecting glucagon-like peptide 2 (GLP-2) on the small intestinal weight, morphology, and nutrient transporter expression in pharmacologically stressed broiler chickens. A total of 144 seven-day-old birds were fed either a basal diet (CTRL) or a basal diet plus 30 mg of corticosterone (CORT)/kg of diet for a total of 14 d. Half of the birds from each group were injected daily with GLP-2 (6.7 nmol/kg of BW) or saline for 14 d. The average final BW, ADG, ADFI, and the ratio of feed intake to weight gain (F:G) was recorded over 21 d for the 4 groups of 36 birds, namely CTRL + saline, CTRL + GLP-2, CORT + saline, and CORT + GLP-2. In addition, the absolute and relative small intestinal weight, villus height (VH), and crypt depth (CD) of the duodenum and jejunum, as well as the abundance of sodium and glucose co-transporter 1 (SGLT-1), vitamin D-dependent calcium-binding protein-28,000 molecular weight (CaBP-D28k), and peptide transporter 1 (PepT-1) mRNA in the duodenum and of liver fatty acid-binding protein (L-FABP) mRNA in the jejunum. The total DNA, RNA, and protein content in small intestinal mucosa were also determined. The results showed that CORT administration significantly lowered average final BW, ADG, ADFI, absolute small intestinal weight, VH, and CD of duodenum and jejunum (P < 0.05) while increasing the relative small intestinal weight, F:G, relative abundance of SGLT-1, CaBP-D28k, PepT-1, and L-FABP mRNA (P < 0.05). Glucagon-like peptide 2 injection increased the average final BW, ADG, VH, and CD in duodenum and jejunum and relative abundance of SGLT-1, CaBP-28k, PepT1, and PepT1 mRNA of broiler chickens, respectively (P < 0.05), and decreased F:G (P < 0.05). In chickens fed basal diet plus CORT, injecting GLP-2 decreased F:G (P < 0.05); increased VH and CD of duodenum and CD of jejunum; and increased relative abundance of SGLT-1, CaBP-D28k, PepT-1, and L-FABP mRNA, RNA, and total protein content in small intestine compared with the injection of saline (P < 0.05). In birds fed the basal diet, GLP-2 injection decreased F:G (P < 0.05) and increased final BW, ADG, small bowel weight, CD of jejunum, and relative abundance of CaBP-D28k and PepT-1 mRNA compared with injecting saline (P < 0.05). In conclusion, GLP-2 injection reversed the negative effect of stress on the weight and morphology and the absorptive function of small bowel of broiler chickens. Glucagon-like peptide 2 injection also had a positive effect on the growth performance of healthy broiler chickens.

Effect of green tea extracts on liver functions in Wistar rats.

An herbal medicinal product (Exolise) containing as active ingredient an hydro-alcoholic extract of green tea named AR25 (standardized to 25% catechins) has been implicated in hepatic failures, leading to the withdrawal of the marketing authorization. The active ingredient of Exolise being manufactured with 80% ethanol, the question to know whether the extraction solvent could introduce some toxic components was hypothesized. Two investigations were conducted in Wistar rats to determine if repeated oral administration of different green tea extracts could corroborate the reported hepatotoxicity in humans. In a preliminary 6 week-study, experimental groups (n=9/group) received either the vehicle or a methylene chloride extract (2500 mg/kg body weight) where potential non-polar hepatotoxin(s) could be concentrated. In a second experiment (12 week-study), rats were divided in three groups (n=10/group) and treated with either the vehicle, or an aqueous extract (1400 mg/kg) or AR25 green tea extract (2000 mg/kg). Rat liver functions were assessed by serum biochemistry of hepatotoxicity markers. No sign of evidence of characteristic hepatotoxicity was found in rats treated with very high amount of different green tea extracts in these two experiments (respectively a daily dosage, which was about 900 and 80 times higher to the therapeutic daily dosage of Exolise.

Fas/FasL expression in tumor biopsies: a prognostic response factor to fluoropyrimidines?

Various studies suggested that cytotoxicity induced by 5-fluorouracil (5-FU) is an apoptotic mechanism possibly mediated by the Fas/FasL system. In this preliminary work, we studied retrospectively the role the Fas/FasL expression as a predictive response factor with fluoropyrimidine-based chemotherapies. We developed a real-time PCR method for measuring Fas and FasL expression in various biopsies from patients treated with a FUFOL-like protocol. No correlation was found between Fas or FasL expression and overall survival or partial response. However, the PCR assay was simple and convenient to use for quantitation of Fas/FasL in tumor biopsies.

Drug interactions of paclitaxel metabolism in human liver microsomes.

The human liver metabolism of paclitaxel (Taxol), an anticancer drug, leads to three metabolites: 6alpha-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel and 6alpha,3'-p-dihydroxypaclitaxel. The inter-individual variability of paclitaxel metabolism was investigated first in vitro using 22 human liver microsomes. Three metabolites have been detected by HPLC. This preliminary work revealed marked inter-individual differences in paclitaxel metabolism. The amount of major metabolite 6alpha-hydroxypaclitaxel formed varied 16-fold (0.7 to 11.5 nmol/mg/h). We next studied the effect of 29 compounds (antineoplastics, antiemetics, histamine-2 receptor antagonist, antalgics, antifungals, antivirals, psychotropics, antibiotic, corticoid, antiarrhythmic, calcium channel blocker) on paclitaxel metabolism in human liver microsomes. Among the compounds studied, quercetin, antifungal drugs such as ketoconazole and miconazole, and the antineoplastic drug doxorubicin inhibited formation of 6alpha-hydroxypaclitaxel. Dixon plots indicated that quercetin and doxorubicin inhibited 6alpha-hydroxypaclitaxel formation through a competitive mechanism with a Ki of 10.1 microM and 64.8 microM, respectively. The inhibition of this metabolite by ketoconazole was through a noncompetitive mechanism with a Ki of 11.8 microM. Our data thus suggest that special attention should be paid when these drugs are combined in clinical practice.

Identification by microsequencing of lipopolysaccharide-induced proteins secreted by mouse macrophages.

The conditioned medium of the murine macrophage PU5.1.8 was analyzed by two-dimensional gel electrophoresis in order to detect LPS-induced proteins. Spots of interest were identified by microsequencing of internal peptides generated by limited in situ acid hydrolysis. In total conditioned medium, several monokines (TNF-alpha and macrophage inflammatory protein-1 alpha and 1 beta) were identified as LPS-induced spots. Because minor spots could be masked by the complexity of the 2-D pattern, conditioned medium was successively fractionated by zinc precipitation and affinity chromatography (Procion red and Con A agarose). Zinc supernatant fraction, Procion red flow-through, and Con A eluate fractions were further analyzed by 2-D gel electrophoresis for the presence of LPS-induced spots. In these fractions serum amyloid A3, lipocalin 24p3, cathepsin B, and plasminogen activator inhibitor-I were characterized as LPS-induced proteins secreted by macrophages. Lipocalin 24p3 protein was retrieved for the first time. In addition to these proteins that follow a classical secretory pathway, several cellular proteins (mainly ribosomal proteins) were retrieved as LPS-induced proteins in the conditioned medium. Control experiments argue against the obvious explanation that the latter observation is caused solely by cellular leakage.

Primary structure of a photoactive yellow protein from the phototrophic bacterium Ectothiorhodospira halophila, with evidence for the mass and the binding site of the chromophore.

The complete amino acid sequence of the 125-residue photoactive yellow protein (PYP) from Ectothiorhodospira halophila has been determined to be MEHVAFGSEDIENTLAKMDDGQLDGLAFGAIQLDGDGNILQYNAAEGDITGRDPKEVIGKNFFKDVAP+ ++ CTDSPEFYGKFKEGVASGNLNTMFEYTFDYQMTPTKVKVHMKKALSGDSYWVFVKRV. This is the first sequence to be reported for this class of proteins. There is no obvious sequence homology to any other protein, although the crystal structure, known at 2.4 A resolution (McRee, D.E., et al., 1989, Proc. Natl. Acad. Sci. USA 86, 6533-6537), indicates a relationship to the similarly sized fatty acid binding protein (FABP), a representative of a family of eukaryotic proteins that bind hydrophobic molecules. The amino acid sequence exhibits no greater similarity between PYP and FABP than for proteins chosen at random (8%). The photoactive yellow protein contains an unidentified chromophore that is bleached by light but recovers within a second. Here we demonstrate that the chromophore is bound covalently to Cys 69 instead of Lys 111 as deduced from the crystal structure analysis. The partially exposed side chains of Tyr 76, 94, and 118, plus Trp 119 appear to be arranged in a cluster and probably become more exposed due to a conformational change of the protein resulting from light-induced chromophore bleaching. The charged residues are not uniformly distributed on the protein surface but are arranged in positive and negative clusters on opposite sides of the protein. The exact chemical nature of the chromophore remains undetermined, but we here propose a possible structure based on precise mass analysis of a chromophore-binding peptide by electrospray ionization mass spectrometry and on the fact that the chromophore can be cleaved off the apoprotein upon reduction with a thiol reagent. The molecular mass of the chromophore, including an SH group, is 147.6 Da (+/- 0.5 Da); the cysteine residue to which it is bound is at sequence position 69.

Peptide mapping and microsequencing of proteins separated by SDS-PAGE after limited in situ acid hydrolysis.

A method is described for the isolation of peptide fragments from proteins separated by polyacrylamide gel electrophoresis. After completion of the electrophoresis step, gels are stained with Ponceau S or Coomassie Blue. Gel portions containing protein stained with Ponceau S are excised and transferred to borosilicate glass digestion tubes containing 0.9 ml of 1 mM NaOH or 5 mM Na2HPO4. After complete dissociation of the dye from the protein, 0.1 ml of 20% formic acid is added and the protein is hydrolyzed in situ at 112 degrees C for four hours. Subsequently the acid solution is made 10% in acetonitrile and chromatographed as such on a C18 (C4) reversed-phase column using an appropriate large-volume sample loading syringe and injection loop. Proteins stained with Coomassie Blue can be hydrolyzed in situ after complete removal of the dye with an aqueous solution containing 40% acetone, 10% triethylamine and 5% acetic acid. The gel slices are next washed with HPLC-grade water and protein is hydrolyzed in 2% formic acid under standard conditions. Gel-related contaminants do not interfere with the peptide separation under the proper conditions of HPLC analysis.

The structural homology of amicyanin from Thiobacillus versutus to plant plastocyanins.

The complete amino acid sequence of the blue copper protein amicyanin of Thiobacillus versutus, induced when the bacterium is grown on methylamine, has been determined as follows: QDKITVTSEKPVAAADVPADAVVVGIEKMKYLTPEVTIKAGETVYWVNGEVMPHNVA FKKGIVGEDAFRGEMMTKDQAYAITFNEAGSYDYFCTPHPFMRGKVIVE. The four copper ligand residues in this 106-residue-containing polypeptide chain are His54, Cys93, His96, and Met99. The Thiobacillus amicyanin is 52% similar to the amicyanin of Pseudomonas AM1, the only other copper protein known with the same spacing between the second histidine ligand and the methionine ligand. T. versutus amicyanin contains no cysteine bridge and is more closely related to the plant copper protein plastocyanin than to the bacterial copper protein azurin. Alignment of the two known amicyanin sequences with the consensus sequence of the plastocyanins and comparison with the known three-dimensional structure of poplar leaves plastocyanin reveals that the bacterial proteins have the same overall structure with two beta-sheets packed face to face. The major structural differences between the amicyanins and the plastocyanins appear to be located in two of the five loops that connect the six identified beta-strands of the amicyanins. The first of these two loops, connecting strands F and G, contains a ligand histidine and must have a different conformation from the same loop in the plastocyanins because it is shorter by two amino acids. Further differences occur in the loop connecting the strands D and E. This loop contains only 17 residues in amicyanin whereas the corresponding loop of plastocyanin contains 25 residues. Despite these differences the amicyanins appear much closer related to the plastocyanins than to the azurins. The present findings demonstrate that the occurrence of blue copper proteins with clearly plastocyanin-like features is not restricted to photosynthetic redox chains.

Complete amino acid sequence of the cytochrome subunit and amino-terminal sequence of the flavin subunit of flavocytochrome c (sulfide dehydrogenase) from Chlorobium thiosulfatophilum.

The complete amino acid sequence of the 86-residue heme subunit of flavocytochrome c (sulfide dehydrogenase) from the green phototrophic bacterium Chlorobium thiosulfatophilum strain Tassajara has been determined as follows: APEQSKSIPRGEILSLSCAGCHGTDGKSESIIPTIYGRSAEYIESALLDFKSGA- RPSTVMGRHAKGYSDEEIHQIAEYFGSLSTMNN. The subunit has a single heme-binding site near the N terminus, consisting of a pair of cysteine residues at positions 18 and 21. The out-of-plane ligands are apparently contributed by histidine 22 and methionine 60. The molecular weight including heme is 10,014. The heme subunit is apparently homologous to small cytochromes c by virtue of the location of the heme-binding site and its extraplanar ligands. However, the amino acid sequence is closer to Paracoccus sp. cytochrome c554(548) (37%) than it is to the heme subunit from Pseudomonas putida p-cresol methylhydroxylase flavocytochrome c (20%). The flavocytochrome c heme subunit is only 14% similar to the small cytochrome c555 also found in Chlorobium. Secondary structure predictions suggest N- and C-terminal helices as expected, but the midsection of the protein probably folds somewhat differently from the small cytochromes of known three-dimensional structure such as Pseudomonas cytochrome c551. Analyses of the residues near the exposed heme edges of the cytochrome subunits of P. putida and C. thiosulfatophilum flavocytochromes c (assuming homology to proteins of known structure) indicate that charged residues are not conserved, suggesting that electrostatic interactions are not involved in the association of the heme and flavin subunits. The N-terminal sequence of the flavoprotein subunit of flavocytochrome has also been determined. It shows no similarity to the comparable region of the p-cresol methylhydroxylase flavoprotein subunit from P. putida. The flavin-binding hexapeptide, isolated and sequenced earlier (Kenney, W. C., McIntire, W., and Yamanaka, T. (1977) Biochim. Biophys. Acta 483, 467-474), is situated at positions 40-46.

Demonstration of two isoforms of subunit VIIa of cytochrome c oxidase from human skeletal muscle. Implications for mitochondrial myopathies.

Two different isoforms of subunit VIIa have been found in cytochrome c oxidase isolated from human skeletal muscle. The first 22 residues of the N-terminal amino acid sequences showed 5 differences. Our results provide the first conclusive evidence for the existence of cytochrome c oxidase isoenzymes in man. Since the two cytochrome c oxidase isoforms were both present in skeletal muscle tissue, though not necessarily in the same cell type, this suggests that human cytochrome c oxidase isoforms are not strictly tissue-specific. These findings may have important implications for the elucidation of genetic diseases in man in which a deficiency of cytochrome c oxidase is restricted to certain tissues.

The primary structure of a minor isoform (H1.2) of histone H1 from the nematode Caenorhabditis elegans.

The complete amino acid sequence of a minor isoform (H1.2) of histone H1 from the nematode Caenorhabditis elegans was determined. The amino acid chain consists of 190 residues and has a blocked N-terminus. Histone subtype H1.2 is 17 residues shorter than the major isoform H1.1, mainly as the result of deletions of short peptide fragments. Considerable divergence from isoform H1.1 has occurred in the N-terminal domain and the very C-terminus of the molecule, but the central globular domain and most of the C-terminal domain, including two potential phosphorylation sites, have been well conserved. Secondary-structure predictions for both H1 isoforms reveal a high potential for helix formation in the N-terminal region 1-33 of isoform H1.1 whereas the corresponding region in isoform H1.2 has low probability of being found in alpha-helix. No major differences in secondary structure are predicted for other parts of both H1 subtypes. The aberrant conformation of isoform H1.2 may be indicative of a significantly different function.

The histones of Caenorhabditis elegans: no evidence of stage-specific isoforms. An overview.

The nematode Caenorhabditis elegans expresses one species of H2A and one species of H4 molecules, at least two species of H1 (H1.1, H1.2), two species of H2B (H2B.1, H2B.2) and 2-4 species of H3 (H3.1 and H3.3 and an unassigned Ile/Leu microheterogeneity in H3). The study of their primary structures has been completed now and all of them, with the exception of the Ile/Leu microheterogeneity in H3, have been assigned to protein spots on two-dimensional gels. One spot, previously designated H3.2, probably represents C-terminally cleaved H3.1. The relative abundance of the isohistones was essentially the same when derived from either eggs, gravid adults or postreproductive, senescent worms. The degree of post-translational modification, however, particularly acetylation of H2A, H2B and H3 histone species, was reduced at old age.