scholarly journals Structurally related class I and class II receptor protein tyrosine kinases are down-regulated by the same E3 protein coded for by human group C adenoviruses.

1993 ◽  
Vol 120 (5) ◽  
pp. 1271-1279 ◽  
Author(s):  
E Kuivinen ◽  
B L Hoffman ◽  
P A Hoffman ◽  
C R Carlin

Receptor tyrosine kinases (RTKs) are grouped into subcategories based on shared sequence and structural features. Human group C adenoviruses down-regulate EGF receptors, which are members of the class I family of RTKs, during the early stages of infection. Adenovirus appears to utilize a nonsaturable intracellular pathway since it causes EGF-R down-regulation even in cells that significantly overexpress EGF-R. Adenovirus-induced down-regulation is mediated by a small hydrophobic molecule coded for by the E3 early transcription region that has recently been localized to plasma membrane. Here we examine intracellular trafficking of other RTKs in adenovirus-infected cells, to better understand the molecular basis for the action of the E3 protein. Although p185c-neu, which is a class I RTK closely related to the EGF receptor, is down-regulated in cells expressing physiological concentrations of this molecule, it is not down-regulated in tumor cell lines that significantly overexpress p185c-neu. Cell surface receptors for insulin and IGF1, which are class II RTKs, are also reduced in cells expressing the E3 protein, although to a slightly lesser extent than the EGF receptor. Moreover, whereas EGF receptors are degraded between 3- and 9-h postinfection, insulin and IGF1 receptors are degraded between 6- and 12-h postinfection under identical conditions. In contrast to the class I and class II RTKs, there is no difference in the expression of the class III receptors for PDGF and aFGF in cells infected with a virus with an intact E3 region versus a virus mutant with an internal deletion in the relevant E3 gene. These results suggest that the E3 protein provides an internalization and degradative sorting signal for some class I and class II RTKs, although down-regulation of class II RTKs is somewhat less efficient. Molecular recognition of class I and class II RTKs during adenovirus infection may not be due strictly to amino acid structure, however, since EGF-R but not p185c-neu is down-regulated in cells where it is significantly overexpressed.

1972 ◽  
Vol 10 (3) ◽  
pp. 719-747
Author(s):  
G. B. DAVID ◽  
JAMIE M. McMULLEN

Quantitative effects of altering oxidative phosphorylation and respiration on the activity of the enzyme menadione reductase (NAD[P]H2:2-methyl-1,4-naphthoquinone oxidoreductase, E.C. 1 6.5.2), in stabilized polymorphonuclear neutrophil leucocytes of Amphiuma tridactylum, were studied by amplitude-contrast microscopy and microspectrophotometry. In a general way, the rate of enzymic activity was proportional to ADP concentration and inversely proportional to the concentration of ATP. Terminal respiratory blocking by azide produced selective subtotal inhibition. Uncoupling of phosphorylation by dinitrophenol produced complex results. Neutrophils of A. tridactylum, irrespective of their stage of maturation in the circulating blood, could be subdivided into 3 metabolic classes: Class I cells, of low enzymic activity (predominantly mitochondrial), greatly activated by ADP, somewhat activated by ATP, and only slightly inhibited by dinitrophenol; Class II cells, twice as active as Class I (in which the endoplasmic reticulum and idiozome were as active as the mitochondria), further activated by ADP used alone or with dinitrophenol, and unaffected by ATP or dinitrophenol; Class III, hyperactive cells (enzymic localization identical with that in Class II), inhibited by ATP and dinitrophenol, and not activated by ADP. Some of the mitochondria of Class III neutrophils retained nearly a third of their reductase activity when the reaction mixture contained 10-1 azide. There is reason to believe that Class I neutrophils may form a reserve population of vegetative cells; in vitro, they can be transformed into Class II cells when a high concentration of ADP is added. Class II and Class III cells are potentially capable of amoeboid movement and phagocytosis. The metabolic mobilization of neutrophils could be interpreted as being controlled by 2 different feedback mechanisms: activation by ADP in cells of Classes I and II, and inhibition by ATP in cells of Class III.


Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 413
Author(s):  
Hui-Ling Chen ◽  
Jason Chen-Chieh Fang ◽  
Chia-Jung Chang ◽  
Ti-Feng Wu ◽  
I-Kuan Wang ◽  
...  

Background. Previous studies have shown that environmental cadmium exposure could disrupt salivary gland function and is associated with dental caries and reduced bone density. Therefore, this cross-sectional study attempted to determine whether tooth decay with tooth loss following cadmium exposure is associated with some dental or skeletal traits such as malocclusions, sagittal skeletal pattern, and tooth decay. Methods. Between August 2019 and June 2020, 60 orthodontic patients with no history of previous orthodontics, functional appliances, or surgical treatment were examined. The patients were stratified into two groups according to their urine cadmium concentrations: high (>1.06 µg/g creatinine, n = 28) or low (<1.06 µg/g creatinine, n = 32). Results. The patients were 25.07 ± 4.33 years old, and most were female (female/male: 51/9 or 85%). The skeletal relationship was mainly Class I (48.3%), followed by Class II (35.0%) and Class III (16.7%). Class I molar relationships were found in 46.7% of these patients, Class II molar relationships were found in 15%, and Class III molar relationships were found in 38.3%. The mean decayed, missing, and filled surface (DMFS) score was 8.05 ± 5.54, including 2.03 ± 3.11 for the decayed index, 0.58 ± 1.17 for the missing index, and 5.52 ± 3.92 for the filled index. The mean index of complexity outcome and need (ICON) score was 53.35 ± 9.01. The facial patterns of these patients were within the average low margin (26.65 ± 5.53 for Frankfort–mandibular plane angle (FMA)). There were no significant differences in the above-mentioned dental indices between patients with high urine cadmium concentrations and those with low urine cadmium concentrations. Patients were further stratified into low (<27, n = 34), average (27–34, n = 23), and high (>34, n = 3) FMA groups. There were no statistically significant differences in the urine cadmium concentration among the three groups. Nevertheless, a marginally significant p-value of 0.05 for urine cadmium concentration was noted between patients with low FMA and patients with high FMA. Conclusion. This analysis found no association between environmental cadmium exposure and dental indices in our orthodontic patients.


2004 ◽  
Vol 24 (2) ◽  
pp. 796-808 ◽  
Author(s):  
Lindsay K. MacDougall ◽  
Mary Elizabeth Gagou ◽  
Sally J. Leevers ◽  
Ernst Hafen ◽  
Michael D. Waterfield

ABSTRACT Phosphoinositide 3-kinases (PI3Ks) can be divided into three distinct classes (I, II, and III) on the basis of their domain structures and the lipid signals that they generate. Functions have been assigned to the class I and class III enzymes but have not been established for the class II PI3Ks. We have obtained the first evidence for a biological function for a class II PI3K by expressing this enzyme during Drosophila melanogaster development and by using deficiencies that remove the endogenous gene. Wild-type and catalytically inactive PI3K_68D transgenes have opposite effects on the number of sensory bristles and on wing venation phenotypes induced by modified epidermal growth factor (EGF) receptor signaling. These results indicate that the endogenous PI3K_68D may act antagonistically to the EGF receptor-stimulated Ras-mitogen-activated protein kinase pathway and downstream of, or parallel to, the Notch receptor. A class II polyproline motif in PI3K_68D can bind the Drk adaptor protein in vitro, primarily via the N-terminal SH3 domain of Drk. Drk may thus be important for the localization of PI3K_68D, allowing it to modify signaling pathways downstream of cell surface receptors. The phenotypes obtained are markedly distinct from those generated by expression of the Drosophila class I PI3K, which affects growth but not pattern formation.


2000 ◽  
Vol 11 (10) ◽  
pp. 3559-3572 ◽  
Author(s):  
Denise Crooks ◽  
Song Jae Kil ◽  
J. Michael McCaffery ◽  
Cathleen Carlin

Animal cell viruses provide valuable model systems for studying many normal cellular processes, including membrane protein sorting. The focus of this study is an integral membrane protein encoded by the E3 transcription region of human adenoviruses called E3-13.7, which diverts recycling EGF receptors to lysosomes without increasing the rate of receptor internalization or intrinsic receptor tyrosine kinase activity. Although E3-13.7 can be found on the plasma membrane when it is overexpressed, its effect on EGF receptor trafficking suggests that the plasma membrane is not its primary site of action. Using cell fractionation and immunocytochemical experimental approaches, we now report that the viral protein is located predominantly in early endosomes and limiting membranes of endosome-to-lysosome transport intermediates called multivesicular endosomes. We also demonstrate that E3-13.7 physically associates with EGF receptors undergoing E3-13.7–mediated down-regulation in early endosomes. Receptor–viral protein complexes then dissociate, and EGF receptors proceed to lysosomes, where they are degraded, while E3-13.7 is retained in endosomes. We conclude that E3-13.7 is a resident early endocytic protein independent of EGF receptor expression, because it has identical intracellular localization in mouse cells lacking endogenous receptors and cells expressing a human cytomegalovirus-driven receptor cDNA. Finally, we demonstrate that EGF receptor residues 675–697 are required for E3-13.7–mediated down-regulation. Interestingly, this sequence includes a known EGF receptor leucine-based lysosomal sorting signal used during ligand-induced trafficking, which is also conserved in the viral protein. E3-13.7, therefore, provides a novel model system for determining the molecular basis of selective membrane protein transport in the endocytic pathway. Our studies also suggest new paradigms for understanding EGF receptor sorting in endosomes and adenovirus pathogenesis.


1976 ◽  
Vol 159 (2) ◽  
pp. 245-257 ◽  
Author(s):  
R Norris ◽  
K Brocklehurst

1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 ± 1.47 kat/kg, Km = 3.32 ± 0.05 mM; kcat. = 2.15 × 104 ± 0.05 × 104s-1 at pH7.0 and 38°C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin.11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and ε280 = 2.84 × 105 litre·mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six ‘essential’ thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25°C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 × 104M-1·s-1 and (b) pKa = 8.1, k = 8.05 × 102M-1·s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 × 102M-1·s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases as the pH is raised according to a pKa value ≥ approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the ‘essential’ thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed.


1989 ◽  
Vol 9 (6) ◽  
pp. 2378-2386
Author(s):  
L A Neuhold ◽  
Y Shirayoshi ◽  
K Ozato ◽  
J E Jones ◽  
D W Nebert

The mouse cytochrome P1450 (CYP1A1) gene is responsible for the metabolism of numerous carcinogens and toxic chemicals. Induction by the environmental contaminant tetrachlorodibenzo-p-dioxin (TCDD) requires a functional aromatic hydrocarbon (Ah) receptor. We examined the 5'-flanking region of the CYP1A1 gene in mouse hepatoma Hepa-1 wild-type cells and a mutant line having a defect in chromatin binding of the TCDD-receptor complex. We identified two cis-acting elements (distal, -1071 to -901 region; proximal, -245 to -50 region) required for constitutive and TCDD-inducible CYP1A1 gene expression. Three classes of DNA-protein complexes binding to the distal element were identified: class I, found only in the presence of TCDD and a functional Ah receptor, that was heat labile and not competed against by simian virus 40 (SV40) early promoter DNA; class II, consisting of at least three constitutive complexes that were heat stable and bound to SV40 DNA; and class III, composed of at least three constitutive complexes that were thermolabile and were not competed against by SV40 DNA. Essential contacts for these proteins were centered at -993 to -990 for the class I complex, -987, -986, or both for the class II complexes, and -938 to -927 for the class III complexes. The proximal element was absolutely essential for both constitutive and TCDD-inducible CYP1A1 gene expression, and at least two constitutive complexes bound to this region. These data are consistent with the proximal element that binds proteins being necessary but not sufficient for inducible gene expression; interaction of these proteins with those at the distal element was found to be required for full CYP1A1 induction by TCDD.


Author(s):  
Zahra Ali Mehtari ◽  
Mehdi Rafiei ◽  
Saeed Azarbayjani ◽  
Neda Ahmadi Rouzbehani ◽  
Amir Hossain Moeini

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders diagnosed by impairments in social interaction and communication with repetitive and restrictive stereotyped behavioral patterns. The Prevalence of autism has been reported to be increased in recent years. This study aimed to assess the prevalence of different types of malocclusion among ASD patients in Isfahan in 2018. Materials & Methods: In a descriptive and cross-sectional trial, 92 ASD patients were studied in the age range of 7-18 years at the center for autism patients in Isfahan. Clinical oral examinations of patients are taken to assess the involved malocclusions (Cl I, Cl II and Cl III malocclusions) and malocclusion traits (deep bite, open bite and cross bite) by an educated dental student under the supervision of an orthodontist under natural light. The data are reported using frequency and percentage indices. Results: Class I malocclusion had the highest prevalence 54.3% (50) among ASD patients and the prevalence of class II and class III were found to be 19.6% (18) and 7.6% (7) respectively. The frequency of malocclusions traits of deep bite, cross bite and the open bite were 27.2% (25), 18.5% (17) and 7.6% (7) respectively. Among of the total patients, 65.2% (60) showed normal bite and 18/5% (17) showed Normal occlusion. Conclusion: ASD patients showed class I, class II and class III malocclusions from the most to least frequency and the most frequent malocclusion traits were also deep bite, cross bite and open bite respectively.


2021 ◽  
Vol 11 (1) ◽  
pp. 46-48
Author(s):  
Nidhi Giri ◽  
Anand Acharya ◽  
Kanika Yadav

Introduction: Various forms of malocclusion are a matter of serious concern in Nepalese population. This study was carried out to understand the prevalence of malocclusion among the school children of Biratnagar. The objective of this research is to find out the prevalence of malocclusion of children from different schools of Biratnagar visiting the Pedodontics and Orthodontics department of Nobel Medical College and Teaching Hospital, Biratnagar. Materials and Method: A descriptive cross sectional study method was used in this research. Data was collected by using direct observation of the subjects and occlusal assessment was done according to Angle’s classification and Dewey’s modification types of class I, class II and class III malocclusion. Result: Subjects with normal occlusion was found to be 39 % and with malocclusion was found to be 61%. Among them, class I malocclusion (60%) and angles class II div I subjects (88.33%) were in majority of the total study population. Conclusion: The present study helps to determine the prevalence of malocclusion and need of orthodontic treatment for the school children of Biratnagar


2014 ◽  
Vol 15 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Naim Z Al-Rayes ◽  
Mohammad Y Hajeer

ABSTRACT Objectives (1) To evaluate the applicability of using 3D digital models in the assessment of the magnitude of occlusal contacts by measuring occlusal contact surface areas (OCSAs) and 3D mesh points in ‘contact’ (OCMPs) in a sample of orthodontic patients; (2) To detect any sex differences in the magnitude of occlusal contacts in all malocclusion groups; (3) To detect intergroup differences; (4) To assess possible correlations between occlusal contacts and other dental characteristics. Materials and methods Study casts of 120 malocclusion patients were selected and divided into 4 groups (class I division 1, class II division 1, class II division 2, class III) with equal numbers for both sexes. 3D digital models were produced using O3DM™ technology. Occlusal contacts were quantified using two methods of measuring. Results (1) No significant sexual differences were detected for OCMPs (mesh points) and OCSAs (mm2) in all groups. (2) There were statistically significant differences among malocclusion groups for OCMPs and OCSAs (p < 0.001). Tukey's HSD posthoc tests showed that class III patients had significantly less occlusal contacts than other malocclusion groups. (3) Stepwise multiple regression equations showed that overjet, lower arch width and overbite could explain approximately 19.5% of the total variance of OCSAs and OCMPs. Conclusion Sexual differences in occlusal contacts were not detected. Class I division 1 patients had the highest amount of occlusal contacts among all groups of malocclusion. Overjet, overbite and lower dental arch width were best predictors of occlusal contacts in the current sample. How to cite this article Al-Rayes NZ, Hajeer MY. Evaluation of Occlusal Contacts among Different Groups of Malocclusion using 3D Digital Models. J Contemp Dent Pract 2014;15(1):46-55.


2021 ◽  
Vol 24 (2) ◽  
Author(s):  
Mohammad Zandi ◽  
Abbas Shokri ◽  
Vahid Mollabashi ◽  
Zahed Eghdami ◽  
Payam Amini

Objetive: This study aimed to compare the anatomical characteristics of the mandible in patients with skeletal class I, II and class III disorders using cone beam computed tomography (CBCT). Material and Methods: CBCT scans of patients between 17 to 40 years taken with NewTom 3G CBCT system with 12-inch field of view (FOV) were selected from the archive. Lateral cephalograms were obtained from CBCT scans of patients, and type of skeletal malocclusion was determined (Class I, II or III). All CBCT scans were evaluated in the sagittal, coronal and axial planes using the N.N.T viewer software. Results: The ramus height and distance from the mandibular foramen to the sigmoid notch in class II patients were significantly different from those in skeletal class I (P < 0.005). Distance from the mandibular canal to the anterior border of ramus in class III individuals was significantly different from that in skeletal class I individuals (P < .005). Conclusion: Length of the body of mandible in skeletal class I was significantly different from that in skeletal class II and III patients. Also, ramus height in skeletal class I was significantly different from that in skeletal class II patients. CBCT had high efficacy for accurate identification of anatomical landmarks.   Keywords Prognathism; Retrognathism; Mandible; Anatomy; Cone beam computed tomography.


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