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PubMed2004

The external K+ concentration and mutations in the outer pore mouth affect the inhibition of kv1.5 current by Ni2+.

By examining the consequences both of changes of [K+]o and of point mutations in the outer pore mouth, our goal was to determine if the mechanism of the block of Kv1.5 ionic currents by external Ni2+ is similar to that for proton block. Ni2+ block is inhibited by increasing [K+]o, by mutating a histidine residue in the pore turret (H463Q) or by mutating a residue near the pore mouth (R487V) that is the homolog of Shaker T449. Aside from a slight rightward shift of the Q-V curve, Ni2+ had no effect on gating currents. We propose that, as with Ho+, Ni2+ binding to H463 facilitates an outer pore inactivation process that is antagonized by Ko+ and that requires R487. However, whereas Ho+ substantially accelerates inactivation of residual currents, Ni2+ is much less potent, indicating incomplete overlap of the profiles of these two metal ions. Analyses with Co2+ and Mn2+, together with previous results, indicate that for the first-row transition metals the rank order for the inhibition of Kv1.5 in 0 mM Ko+ is Zn2+ (KD approximately 0.07 mM) > or = Ni2+) (KD approximately 0.15 mM) > Co2+ (KD approximately 1.4 mM) > Mn2+ (KD > 10 mM).

Animals↗

PubMed1994

Mutational analysis of ion conduction and drug binding sites in the inner mouth of voltage-gated K+ channels.

Pore properties that distinguish two cloned, voltage-gated K+ channels, Kv2.1 and Kv3.1, include single-channel conductance, block by external and internal tetraethylammonium, and block by 4-aminopyridine. To define the inner mouth of voltage-gated K+ channels, segmental exchanges and point mutations of nonconserved residues were used. Transplanting the cytoplasmic half of either transmembrane segments S5 or S6 from Kv3.1 into Kv2.1 reduced sensitivity to block by internal tetraethylammonium, increased sensitivity to 4-aminopyridine, and reduced single-channel conductance. In S6, changes in single-channel conductance and internal tetraethylammonium sensitivity were associated with point mutations V400T and L403 M, respectively. Although individual residues in both S5 and S6 were found to affect 4-aminopyridine blockade, the most effective change was L327F in S5. Thus, both S5 and S6 contribute to the inner mouth of the pore but different residues regulate ion conduction and blockade by internal tetraethylammonium and 4-aminopyridine.

4-Aminopyridine↗

PubMed1994

An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding.

Substitution of a cysteine in the extracellular mouth of the pore of the Shaker-delta K+ channel permits allosteric inhibition of the channel by Zn2+ or Cd2+ ions at micromolar concentrations. Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which has a Kd for Cd2+ of approximately 0.2 microM. There is a 45,000-fold increase in affinity when the channel changes from open to inactivated. These results indicate that C-type inactivation involves a structural change in the external mouth of the pore. This structural change is reflected in the T449C mutant as state-dependent metal affinity, which may result either from a change in proximity of the introduced cysteine residues of the four subunits or from a change of the exposure of this residue on the surface of the protein.

Allosteric Regulation↗

PubMed1999

Effects of outer mouth mutations on hERG channel function: a comparison with similar mutations in the Shaker channel.

The fast-inactivation process in the hERG channel can be affected by mutations in the pore or S6 domain, similar to the C-type inactivation in the Shaker channel. However, differences in the kinetics and voltage dependence of inactivation between these two channels suggest that different structural determinants may be involved. To explore this possibility, we mutated a serine in the outer mouth region of hERG (S631) to residues of different physicochemical properties and compared the resulting changes in the channel's inactivation process with those resulting from mutations of an equivalent position in the Shaker channel (T449). The most dramatic differences are seen when this position is occupied by a charged residue: S631K and S631E disrupted C-type inactivation in hERG, whereas T449K and T449E facilitate C-type inactivation in Shaker. S631K and S631E also disrupted the K selectivity of hERG pore, a change not seen in T449K or T449E of Shaker. To further study why there are such differences, we replaced S631 with cysteine. This allowed us to manipulate the properties of thiol groups at position 631 and correlate side-chain properties here with changes in channel function. S631C behaved like the wild-type channel when the thiol groups were in the reduced state. Oxidizing thiol groups with H2O2 or modifying them with MTSET or MTSES disrupted C-type inactivation and K selectivity, similar to the phenotype of S631K and S631E. The same thiol-modifying maneuvers did not affect the wild-type channel function. Our results suggest differences in the outer mouth structure between hERG and Shaker, and we propose a "molecular spring" hypothesis to explain these differences.

Amino Acid Sequence↗

PubMed2002

Size of side-chain at channel pore mouth affects Ca(2+) block of P2X(2) receptor.

Effects of amino acid replacement at the channel pore mouth of P2X(2) receptor/channel on multivalent cation channel block were investigated. When Asn(333) was replaced with various amino acid residues with neutral side chains (Gly, Ala, Val, Leu and Ile), the block by Ca(2+) was attenuated according to the sizes of the side chains. The block by La(3+) was also greatest with the Gly-substituted mutant, but this preference was not found for the block by other multivalent cations tested. The side chain at the channel pore mouth may interfere with the access of Ca(2+) block by steric hindrance.

Adenosine Triphosphate↗

PubMedDate not supplied

Treatment of automatically reinforced object mouthing with noncontingent reinforcement and response blocking: experimental analysis and social validation.

A brief functional analysis indicated the object mouthing of a young girl diagnosed with autism was maintained independent of social consequences. Separate and combined effects of response blocking and noncontingent reinforcement (with preferred stimuli) were then evaluated as treatments for object mouthing. Although both interventions were unsuccessful when implemented separately, combining them resulted in generalized reductions that were socially valid.

Autistic Disorder↗

PubMed1995

Changing mouth care practice in intensive care: implications of the clinical setting context.

The purpose of the study was to identify the prerequisites for achieving research-based mouth care practice in a district general hospital intensive care unit. An action research approach was adopted and a convenience sample of 10 qualified nurses was studied. Initial identification of current mouth care practice was achieved by observation and interview of these nurses. Following this an in-service teaching and support programme was introduced, after which the identification of any change in practice was made by re-interviewing the same nurses and observing for any change in the availability and use of suitable toothbrushes. Data analysis consisted of comparing information from the before teaching and after teaching observation schedules, and performing content analysis on the before and after teaching interview data. The results indicated that the use of toothbrushes had increased as had the knowledge of oral hygiene after the teaching programme. Factors which were identified as facilitating a change in practice included eliciting the perceptions of those experiencing change so that information and support could be tailored to meet the nurses' needs as they perceived them, the importance of context relevant information and practical instruction, the influence of role models and the availability of suitable brushes. Inhibiting factors included misconceptions about the risk to patient safety associated with toothbrushing.

Clinical Nursing Research↗

PubMed1991

Restricted opening of the mouth with an extra-articular cause in children.

Restricted opening of the mouth with an extra-articular cause (ROMEC) can have very different aetiologies. A series of 6 children, who have been operated on under 4 different diagnoses, are presented. Excluded are common problems such as recent trauma and posttraumatic scarring, craniomandibular dysfunction or elongated coronoid process, and also tumours. Problems of establishing the diagnosis, surgical treatment, postoperative physiotherapy and timing are discussed. It is shown that none of the cases is a perfect result, some outcomes are even very disappointing. It is therefore concluded that absolute trismus should be treated independently of age. The result expected will be mediocre. For final correction it is suggested that the operator should wait preferably until the second growth spurt has passed. The same goes for children presenting primarily with a mouth opening greater than 20 mm.

Child↗

PubMed2003

Low salivary flow and volatile sulfur compounds in mouth air.

OBJECTIVE: The purpose of this study was to determine whether a reduction of salivary flow would influence the production of methylmercaptan (CH(3)SH) and hydrogen sulfide (H(2)S), which are volatile sulfur compounds (VSCs) known to cause oral malodor. STUDY DESIGN: The VSCs in mouth air were measured by means of gas chromatography. Spitting and masticatory (stimulated) methods were used to determine the salivary flow rates of 174 patients. RESULTS: There was no significant correlation between the level of VSCs and salivary flow rate. However, subjects with extremely low resting salivary flow rates had significantly higher CH(3)SH and H(2)S concentrations and tongue-coating scores than those with higher resting salivary flow rates. Moreover, logistic analyses revealed that extremely low resting salivary flow, the increase in tongue coating, and a probing pocket depth greater than 4 mm were strong explanatory factors for the generation of VSCs, which could have caused oral malodor. CONCLUSIONS: These findings suggested that an extreme reduction in resting saliva influenced the generation of CH(3)SH and H(2)S in mouth air.

Adult↗

PubMedDate not supplied

Evaluation of the concordance of sialometry and salivary glands scintigraphy in dry mouth patients.

INTRODUCTION: Many diagnostic tests are used to evaluate dry mouth patients, especially the ones with Sjögren's Syndrome, to whom these tests are part of classification criteria for scientific studies. AIM: Thus, the concordance between results of sialometry and salivary glands scintigraphy was evaluated; if positive, it would enable the choice of one or the other for diagnosis. PATIENTS AND METHOD: Seventy-two dry mouth patients were divided into non-Sjögren's Syndrome group, primary Sjögren's Syndrome group and secondary Sjögren's Syndrome group. The concordance among sialometry and scintigraphy results was evaluated by Kappa test. RESULTS: It was observed that their concordance was equal or near to zero. CONCLUSION: It is not possible to make a choice between these tests and both should be performed.

Case-Control Studies↗

PubMed2006

Effect of copper on the volatility of aroma compounds in a model mouth system.

Copper is thought to influence aroma perception by affecting volatility of aroma compounds in the mouth through interaction with salivary components, especially proteins. Our objective was to identify the effect of copper on the volatility of aroma compounds and the role of copper-protein interaction in volatile chemistry in the mouth. Copper (2.5 mg/L) and four aroma compounds (hexanal, butyl acetate, 2-heptanone, and ethyl hexanoate, 0.5 microL/L each) were added to model systems containing water, electrolytes, and artificial saliva at different pH levels. Headspace concentration of each volatile was measured using SPME-GC analysis. Copper in the model systems increased headspace concentration of volatiles at pH 6.5, but no change in volatility was observed at pH 7.0. At pH 7.5, the presence of copper in the artificial saliva system containing mucin and alpha-amylase decreased headspace volatile concentration, whereas histatin did not cause any changes in volatility. Effect of copper on volatiles at pH 6.5 may be due to increased solubility of copper at lower pH. Salivary proteins seem to interact with copper at pH 7.5. The interaction may change configuration of binding sites for aroma compounds in mucin.

Acetates↗

PubMed1997

Antigenic variation in Foot and Mouth Disease Virus type Asia 1 isolates circulated during 1993-95 in India.

The antigenic variation in Foot and Mouth Disease Virus (FMDV) is very high. The effective strategy to control the Foot and Mouth Disease (FMD) in India which is a habitat of four serotypes O, A, C and Asia 1, is by regular vaccination, using the vaccine strain most suitable for the local situation. India is an endemic country with the disease being widely distributed. Selection of vaccine strain should therefore need the information on the circulating viruses. Asia 1 causes the second largest number of disease outbreaks in India. As there is no information available with respect to the extent of antigenic variation in FMDV type Asia 1, we have studied FMDV isolates from vaccinated and unvaccinated animals from different parts of the country and compared their relationship with Asia 1 vaccine virus. The immunogenic, hypervariable region of viral protein 1 (VP1) gene was amplified by RT-PCR and sequenced. Analysis of sequence data showed that the viruses from two field outbreaks of Southern India were closely related to each other when compared to the isolate from the North and all the three isolates are away from the vaccine virus.

Animals↗

PubMed2000

[Synthetic peptide designs based on immunoactive fragments of the VP1 protein of the foot-and-mouth disease virus strain A22].

Peptide constructs consisting of 44-53 aa were synthesized on the basis of sequences 135-159, 170-190 and 197-213 of VP1 from the foot-and-mouth disease A22 strain. Immunogenic and protective properties of the peptide constructs were studied in guinea pigs and mice of three lines. The constructs were shown to induce higher levels of antibodies and exhibit higher protective effects than the separate peptides. The most active among the peptides studied was the construct involving the VP1 fragments 135-160 and 170-190: it protected pigs from the experimental infection by the foot-and-mouth disease virus.

Amino Acid Sequence↗

PubMed2003

Long-term effect of full-mouth tooth extraction on the responsiveness of peripheral blood monocytes.

BACKGROUND: As some residual inflammation may remain after periodontal therapy, the present pilot study investigated the long-term effect of full-mouth tooth extraction therapy on the responsiveness of peripheral blood monocytes in a case with generalized terminal adult periodontitis. METHODS: Before and 3, 9, 20 and 32 months after therapy, venous blood was collected. Total and differential white blood cell counts were determined and whole blood cell cultures (WBCC) were incubated with lipopolysaccharide (LPS) to stimulate the production of inflammatory mediators by monocytes. RESULTS: After full-mouth tooth extraction, the numbers of total peripheral white blood cells and neutrophils decreased over time. The release of the chemokines interleukin (IL)-8 and macrophage chemoattractant protein (MCP)-1 in the cultures decreased twofold over time, whereas no changes were seen for the other studied cytokines, chemokines and prostaglandin E2. CONCLUSION: On the basis of previous studies and the present case, the high production of IL-8 and MCP-1 by monocytes in LPS-stimulated WBCC from periodontitis patients is most likely acquired, as their levels decrease over time when the periodontal infection is controlled. The possible connection between periodontitis and atherosclerosis through IL-8 and MCP-1 is discussed.

Adult↗

PubMed2003

A split-mouth study on periodontal and microbial parameters in children with complete unilateral cleft lip and palate.

BACKGROUND: Complete unilateral cleft lip and palate (UCLP) is a hereditary or multifactorial malformation that can be corrected successfully with a combined orthodontic, surgical and restorative treatment. Such multidisciplinary treatment takes many years and demands a lot of attention to both patients' teeth and periodontium. OBJECTIVES: This split-mouth study aimed to compare the periodontal health as well as the microbial parameters between cleft and non-cleft region. MATERIAL AND METHODS: 75 patients (52 males, 23 females) between 8 and 20 years with a complete unilateral cleft lip and palate (before (n = 30), during (n = 34) and after (n = 11) the active orthodontic treatment) volunteered for this study. Four regions were defined for the split-mouth comparison: teeth neighbouring cleft (site 1), tooth in cleft (site 2), and the corresponding contra-lateral teeth, respectively, in the unaffected quadrants (sites 3 and 4). At all sites the following periodontal parameters were recorded: plaque and gingivitis indices, pocket depth, attachment loss, bleeding on probing, tooth mobility (visual and Periotest), radiographic bone loss and gingival width. In addition, three pooled subgingival plaque samples were taken (around tooth in cleft, teeth facing the cleft, and contra-lateral teeth of the latter). RESULTS: The differences between the teeth neighbouring the cleft and the corresponding contra-lateral opponents were of borderline significance (P <or= 0.05) for the plaque index, the approximal probing depths and the attachment loss (teeth facing the cleft always had slightly higher parameters). When the tooth in the cleft was compared to the contra-lateral tooth, differences were only found for both the approximal probing depths, attachment loss and bone loss, which were significantly higher for the tooth in the cleft. The microbial analysis did not reveal differences between the different sites, neither in the proportion of aerobic and anaerobic bacteria (differences < 0.5 log), nor in the detection frequency of periopathogens. CONCLUSIONS: These data indicate that the periodontium in UCLP patients can cope well with a long-term orthodontic treatment, even in unfavourable conditions (like absence of attached gingiva and poor oral hygiene).

Adolescent↗

PubMed1981

Cloning of cDNA of major antigen of foot and mouth disease virus and expression in E. coli.

Double-stranded DNA copies of the single-stranded genomic RNA of foot and mouth disease virus have been cloned into the Escherichia coli plasmid pBR322. A restriction map of the viral genome was established and aligned with the biochemical map of foot and mouth disease virus. The coding sequence for structural protein VP1, the major antigen of the virus, was identified and inserted into a plasmid vector where the expression of this sequence is under control of the phage lambda PL promoter. In an appropriate host the synthesis of antigenic polypeptide can be demonstrated by radioimmunoassay.

Antigens, Viral↗

PubMedDate not supplied

Chemical basis of antigenic variation in foot-and-mouth disease virus.

One of the difficulties in controlling foot and mouth disease by vaccination is the occurrence of the virus as seven distinct serotypes because immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Moreover, the antigenic variation, even within a serotype, can be so great that immunity against the homologous strain of virus need not necessarily ensure protection against infection by other viruses within that serotype. Here we report the separation of three natural antigenic variants, distinguishable in cross-neutralization tests from an isolate of foot-and-mouth disease virus (FMDV). The serological differences could also be demonstrated by antisera elicited by synthetic peptides corresponding to residues 141-160 of the capsid polypeptide VP1, showing that this region contains a major immunogenic site of the virus. The results have practical implications for the choice of viruses for vaccine production.

Amino Acid Sequence↗

PubMed1975

A new pattern mouth stick.

The motivation for the severely handicapped tetraplegic patient in using the mouth stick is quite considerable as through this simple oral aid they are able to carry out small jobs and be involved in social activities. We feel that this modified pattern mouth stick fulfils the aims which we require of it.

Denture Design↗