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Query: UNIPROT:P06889 (Mol)
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The primary pacemaker, i.e. the group of pacemaker cells discharging the sinoatrial node comprises less than 1000 cells in the guinea-pig and about 5000 cells in the rabbit. These primary pacemaker cells are described as 'central nodal' cells in light microscopy and as 'typical nodal' cells in electron microscopy. The action potential of the leading cells has a higher upstroke velocity in the guinea-pig than in the rabbit (6.2 v. 1.9 V/s). Gap junctions have been observed even in the very center of the node in both species. A zone of double-component action potentials at the septal margin of the node was observed in the rabbit, but not in the guinea-pig. Evidence is presented for abrupt transitions in electrophysiological as well as in ultrastructural characteristics in the guinea-pig sinoatrial node. The differences in intrinsic cycle length between both species but also between individuals of the same species are discussed.
J Mol Cell Cardiol 1985 Jun
PMID:Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node. 402 Aug 78

A new simple and sensitive method for detecting small periodicity (repetition of a small segment along the chain) in proteins is developed, based on the repetition of identical residues. 38 proteins from organisms representing different levels of evolutionary development have been tested for small periodicity. The same is done with the nodal ancestors of 25 of them. The results are presented graphically (the periodicity curves). The statistical significance of the observed periodicity is confirmed by a modified version of the chi-square test. All the results obtained support the conception that the small periodicity of the contemporary proteins is a reflection of their evolutionary history and that the most ancient proteins have arisen through a polycondensation of short peptides or through transcription and translation of satellite-type repeat sequence DNA.
J Mol Evol 1980 Sep
PMID:Some evidence for the universality of structural periodicity in proteins. 744 79

We studied the effects of cholinergic agonists on slow delayed-rectifier K+ current (IKs) in isolated cells from the sino-atrial node (SAN) region of guinea pig heart, using patch-clamp procedures. Carbachol (5 nM to 10 microM) inhibited IKs in guinea pig SAN cells in the absence of previous beta-adrenergic stimulation and in cells pretreated with 8-(4-chlorophenylthio)-cAMP. Neither the muscarinic antagonist atropine nor the nicotinic antagonist hexamethonium antagonized carbachol inhibition of the current. Similar results were obtained with other cholinergic agonists. Cholinergic stimulation of the muscarinic K+ current was successfully antagonized by atropine in SAN cells where inhibition of IKs persisted. Therefore, the lack of antagonist effects on inhibition of IKs cannot be attributed to either an absence of muscarinic cholinoceptors on SAN cells or a loss of antagonist activity under our experimental conditions. These data demonstrate that cholinergic agonists, including the endogenous neurotransmitter acetylcholine, decrease the amplitude of IKs in guinea pig SAN cells via a non-muscarinic, non-nicotinic, cAMP-independent mechanism. Although the precise nature of this signal transduction pathway has not been elucidated, it is clearly different from those described for regulation of other nodal currents. Differential regulation of IKs in guinea pig SAN and ventricle cannot be attributed to higher basal adenylate cyclase activity in SAN cells. The inhibitory effect of carbachol on IKs was not additive with that of verapamil, a drug that is both an allosteric muscarinic antagonist and a potassium channel-blocking agent. Cholinergic agonists may inhibit IKs in SAN cells via a direct interaction with the SAN IKs channel.
Mol Pharmacol 1995 Jun
PMID:Cholinergic inhibition of slow delayed-rectifier K+ current in guinea pig sino-atrial node is not mediated by muscarinic receptors. 760 67

Transient expression and stable integration and expression of transgenes were observed in the tissues and offspring of certain leguminous plants after electroporation of DNA into intact nodal meristems in planta. The method described in this article thus allows the study of transgene expression in tissues differentiating from meristematic cells present in the treated buds. In addition, transgenic plants can be recovered in the offspring of electroporated individuals. Therefore, this technique allows the production of transgenic leguminous plants without the need for in vitro tissue culture, often a major hurdle with this family.
Mol Biotechnol 1995 Feb
PMID:Electroporation-mediated gene transfer into intact nodal meristems in planta. Generating transgenic plants without in vitro tissue culture. 760 2

Tumour estrogen receptor (ER) status may determine the medical treatment of a patient with breast cancer; yet inter-laboratory results can vary markedly, particularly when absolute cut-offs in fmol/mg cytosol protein are used. The use of standardized log units is proposed to permit greater inter-laboratory comparability. We have assessed the biochemical ER values using the dextran-coated charcoal method with three data sets, two quality control (QC) sets for Ontario laboratories and a data set with values for 184 primary breast cancer patients seen at Women's College Hospital (WCH) between 1985 and 1986. The distributions for all the raw data were skewed toward the lower end of the range; a log transformation improved the symmetry of the distributions. There was marked inter-laboratory variation in the QC data, and standardized log units greatly reduced this variability. The WCH data had similar differentiation by tumour size and nodal status with both the raw data and standardized log units. However, standardized log units provided more consistent evidence of an association between ER and immunohistochemical ERICA. The standardized log units provide quantitative receptor values suitable for multi-centre research, for future work with clinical outcomes, and for the daily management of patients.
J Steroid Biochem Mol Biol 1993 May
PMID:The standardization of estrogen receptors. 768 4

The role of the ATP-sensitive K+ channel (IK,ATP) in the development of A-V block during hypoxic interventions was studied using Langendorff perfused rabbit hearts, multicellular rabbit A-V nodal preparations and single guinea-pig ventricular myocytes. With the Langendorff perfused hearts, hypoxic perfusion (PO2 not equal to 40 mmHg) for 30 min caused slowing of the sinus rate and prolongation of the A-H interval without the appearance of blocked beats. Substrate-free hypoxic perfusion induced second or third degree A-V block in 8/10 hearts and substrate-free hypoxic perfusion plus 2-deoxyglucose (5 mM) produced third degree A-V block in 6/6 preparations. Addition of 50 mM glucose in the perfusate restored A-V conduction during hypoxic intervention. Application of glibenclamide, a specific blocker of IK,ATP, prevented the development of second or third degree A-V block during substrate-free hypoxia (n = 6), whereas pinacidil, an opener of IK,ATP, caused development of third degree A-V block during hypoxia (n = 9). Application of theophylline (100 microM) or 8-phenyl-theophylline (10 microM) did not prevent the development of advanced degrees of A-V block during hypoxic interventions. In multicellular A-V nodal preparations, 10 microM glibenclamide prevented the shortening of action potential duration and block development without marked effects on the maximum upstroke velocity of action potentials during hypoxic intervention. In isolated ventricular myocytes studied by the patchclamp method, the substrate-free hypoxia plus 2-deoxyglucose induced the openings of IK,ATP in 9/25 preparations with cell-attached patches, while 2/20 patches exhibited sporadic channel openings in the normoxic condition during comparable observation period. These results suggest that openings of the ATP-sensitive K+ channels play a role in the development and aggravation of advanced A-V block during hypoxic interventions.
J Mol Cell Cardiol 1995 Jan
PMID:Role for ATP-sensitive K+ channel in the development of A-V block during hypoxia. 776 Mar 83

We set out to define the alterations of chromosome 17 in human bladder tumors and to correlate p53 nuclear over-expression with 17p deletions in those neoplasms. We studied 60 bladder tumors by restriction fragment-length polymorphism analysis directed at five different loci on chromosome 17. The same tumors were studied with a panel of mouse monoclonal antibodies (PAb1801, PAb240, and PAb1620) to mutant and wild-type p53 proteins using immunohistochemistry. Deletion of 17p correlated with grade (p = 0.039), stage (p = 0.004), and the presence of vascular invasion (p = 0.056). None of the pathologic parameters correlated with 17q deletions. p53 nuclear overexpression correlated with grade (p = 0.027), stage (p = 0.008), vascular invasion (p = 0.021), and the presence of nodal metastases (p = 0.007). In superficial (Ta) lesions, 17p was not deleted, whereas 55% of T1 and T2-T4 tumors showed a loss of heterozygosity. Mutations of p53 as detected by immunohistochemistry were seen in superficial as well as invasive tumors, whereas loss of heterozygosity was seen only in invasive tumors. A strong correlation was found between the presence of mutation and the loss of heterozygosity of the remaining allele (p = 0.0003). Additional follow-up and further studies are required to better define the role of p53 nuclear overexpression and 17p deletions as markers of tumor progression in human bladder cancer.
Diagn Mol Pathol 1993 Mar
PMID:Molecular genetic alterations of chromosome 17 and p53 nuclear overexpression in human bladder cancer. 790 25

This paper describes the inferential method, an approach for reconstructing protein and nucleotide sequences of ancestral species, starting from known, homologous, contemporary sequences. The method requires knowledge of the topology of the phylogenetic tree, whose nodes are the species to whom the reconstructed sequences belong. The method has been tested by computer simulation of speciation and nucleotide substitutions, starting from a single ancestral sequence, and by subsequent reconstruction of nodal sequences. Results have shown that reconstructions obtained by the inferential method are affected by limited error frequencies, which (1) are proportional to the squares of nucleotide substitution rates and of internodal distances, and (2) are little influenced by non-uniformity of transformation rates of nucleotides. Furthermore, good agreement of the results has been obtained by comparing protein-sequence reconstructions carried out with the inferential method with those obtained using the maximum parsimony method in two different cases: e.g., a reconstruction of simulated sequences and a reconstruction of mammalian ribonuclease sequences.
J Mol Evol 1994 Aug
PMID:Reconstruction of ancestral sequences by the inferential method, a tool for protein engineering studies. 793 85

The purpose of this study was to determine the correlation between expression of ras oncoproteins and the tumor stage or outcome of patients with gastric carcinoma. After the specificity of each anti-ras monoclonal antibody was confirmed by protein immunoblot analysis, immunohistochemical assays for a common-ras antigen present in N-, Harvey- and Kirsten (K)-ras oncoproteins, as well as for K-ras specific antigen, were performed on paraffin-embedded carcinoma tissue from 110 patients who underwent curative resection. By Western blot analysis, there was more p21 in fresh cancer specimens than in normal specimens. K-ras expression distinguished advanced from early gastric carcinoma and correlated with depth of cancer invasion. Among the 110 patients, survival rates of those with carcinomas positive for the common-ras or K-ras antigens were significantly lower than of those with antigen-negative carcinomas (p < 0.05). In a multivariate analysis, nodal involvement (p = 0.002), serosal invasion (p = 0.012) and K-ras p21 expression (p = 0.044) were independently predictive of the recurrence. These results suggest that K-ras p21 is a useful marker of tumor progression and poor prognosis after curative resection.
Diagn Mol Pathol 1994 Sep
PMID:Expression of Kirsten-ras p21 in gastric cancer correlates with tumor progression and is prognostic. 798 94

The tomato anionic peroxidase genes (tap1 and tap2) are induced by wounding and pathogen attack. The 5'-flanking region of tap1 confers wound- and pathogen-inducible beta-glucuronidase (GUS) expression in tobacco plants transformed with a tap1/GUS chimeric fusion gene construct. A series of nested 5' promoter deletions in the tap1/GUS fusion gene construct was created, and introduced into tobacco protoplasts via polyethylene glycol-mediated DNA transfer. A -202 construct (where the transcriptional start site is denoted +1) and larger tap1 promoter constructs showed constitutive GUS expression. A 2-fold increase in GUS expression over the high constitutive levels was observed with -358 bp and larger tap1 constructs when protoplasts were incubated with elicitor preparations from Verticillium albo-atrum. In tobacco plants transformed with the tap1 promoter deletion/GUS fusion gene constructs, wounding caused induction of GUS expression by 20 h that increased 6- to 18-fold by 72 h. The region between -202 and -358 of the tap1 promoter conferred wound responsiveness. GUS was also found to be expressed in the epidermis and trichomes in the aerial parts of transgenic plants. High-level GUS expression was observed in the nodal region of stems that was associated with the leaf traces. GUS that was absent in very young flower buds was found in the subsequent developmental stages in the pistils, ovaries and anthers. The developmentally regulated tissue-specific expression of GUS was found with all constructs containing the -202 and larger promoters whereas wound and pathogen induction required -358 or larger promoter. These results suggest that the tap1 gene, which was heretofore thought to be expressed only upon wounding or pathogen attack, plays a role in normal developmental processes of the plant and this gene acquired additional 5'-flanking promoter for the purpose of responding to wounding and fungal attack.
Plant Mol Biol 1993 Jun
PMID:Developmental and tissue-specific expression of a tomato anionic peroxidase (tap1) gene by a minimal promoter, with wound and pathogen induction by an additional 5'-flanking region. 832 86


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