scholarly journals The Biomaterial-Induced Cellular Reaction Allows a Novel Classification System Regardless of the Biomaterials Origin

2020 ◽  
Vol 46 (3) ◽  
pp. 190-207 ◽  
Author(s):  
Sarah Al-Maawi ◽  
James L. Rutkowski ◽  
Robert Sader ◽  
C. James Kirkpatrick ◽  
Shahram Ghanaati
Keyword(s):  
Polymeric Materials ◽  
Giant Cells ◽  
Class Ii ◽  
Class I ◽  
Clinical Indication ◽  
Clinical Consequence ◽  
Class Iii ◽  
Cellular Reaction ◽  
Bone Substitute Materials

Several different biomaterials are being introduced for clinical applications. However, no current material-specific systematic studies define parameters for evaluating these materials. The aim of this retrospective animal study is to classify biomaterials according to the in vivo induced cellular reaction and outline the clinical consequence of the biomaterial-specific cellular reaction for the regeneration process. A retrospective histologic analysis was performed for 13 polymeric biomaterials and 19 bone substitute materials (BSMs) (of various compositions and origins) that were previously implanted in a standardized subcutaneous model. Semiquantitative analyses were performed at days 3, 15, and 30 after implantation according to a standardized score for the induction of multinucleated giant cells (MNGCs) and vascularization rate. The induced cellular reaction in response to different polymeric materials allowed their classification according to the MNGC score in the following groups: class I induced no MNGCs at any time point, class II induced and maintained a constant number of MNGCs over 30 days, and class III induced MNGCs and provided an increasing number over 30 days. All BSMs induced MNGCs to varying extents. Therefore, the resultant BSM classifications are as follows: class I induced MNGCs with a decreasing number, class II induced and maintained constant MNGCs over 30 days, and class III induced MNGCs with increasing number over 30 days. These observations were mostly related to the biomaterial physicochemical properties and were independent of the biomaterial origin. Consequently, the induction of MNGCs and their increase over 30 days resulted in disintegration of the biomaterial. By contrast, the absence of MNGCs resulted in an integration of the biomaterial within the host tissue. This novel classification provides clinicians a tool to assess the capacity and suitability of biomaterials in the intended clinical indication for bone and soft tissue implantations.

438 REPEATED ULTRASOUND-GUIDED FOLLICULAR ASPIRATION IN PREGNANT SUCKLED BEEF COWS PRETREATED WITH OR WITHOUT eCG

2010 ◽  
Vol 22 (1) ◽  
pp. 376
Author(s):  
J. F. Aller ◽  
N. Mucci ◽  
G. Kaiser ◽  
G. Ríos ◽  
B. Callejas ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Beef Cows ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Significant Treatment ◽  
No Donor ◽  
Overall Efficiency ◽  
Group 1

In vivo oocyte recovery during the first trimester of pregnancy may be an alternative method of obtaining gametes for IVM/IVF/IVC from genetically valuable females. This study was conducted to evaluate i) the influence of the day of gestation on the follicular growth and number and quality of oocytes recovered by ovum pick-up (OPU) in pregnant suckled beef cows with or without eCG pre-stimulation, and ii) the possible effects on pregnancy outcome. Twelve pregnant suckled Angus cows (40 days after FTAI) were randomly assigned to 2 groups (n = 6/group). Group 1 treatment included: Day 0 = dominant follicle ablation (DFA) to synchronize the emergence of a new follicular wave, Day 1 = eCG treatment (2,000 IU, i.m. Syntex, Argentina) and Day 5 = OPU (follicles >3 mm were aspirated). Group 2: as for Group 1 with no eCG treatment. In both groups, OPU was repeated 5 times (Days 45, 59, 73, 87, and 101 of gestation) and ovarian follicles were classified into 3classes according to diameter (class I, <5 mm; class II, 5-9 mm; and class III, ≥10 mm). The collected COCs were categorized in 4 categories (I to IV) on the basis of both cumulus cells and appearance of oocyte cytoplasm. Categories I + II were considered as viable. Data were analyzed by PROC MIXED (SAS Institute, Cary, NC, USA). There was a significant treatment by follicular class interaction (P < 0.001). The numbers (mean ± SEM) of class II (4.3 ± 0.9) and III (2.5 ± 0.4) follicles/cow/session observed in eCG-treated cows were greater than for nontreated cows (0.9 ± 0.1 and 0.9 ± 0.1, respectively). In contrast, the number (mean ± SEM) of class I follicles/cow/session was lower for cows with eCG treatment (2.8 ± 0.4) than for nontreated cows (5.7 ± 0.5). A significant treatment by day of gestation interaction for aspirated follicles was observed (P = 0.03). The numbers (mean ± SEM) of recovered oocytes and viable oocytes/cow/session were greater (P < 0.05) for eCG-treated cows (2.2 ± 0.2 and 1.6 ± 0.4 respectively) than for nontreated cows (1.0 ± 0.2 and 0.9 ± 0.2, respectively). No donor pregnancies were lost either during or following OPU procedure. The overall efficiency of OPU procedure is shown in Table 1. We can conclude that (1) eCG-treated pregnant suckled cows can be a source of oocytes for IVF to at least 100 days of gestation and (2) repeated DFA/eCG treatment/OPU procedures did not affect the pregnancy outcome. Table 1.Overall efficiency of repeated DFA/eCG treatment/OPU procedures in pregnant suckled cows

The next-generation pan-RAF inhibitor, KIN-2787, is active in class II and class III BRAF mutant models.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3116-3116
Author(s):  
Aleksandra Franovic ◽  
Nichol Miller ◽  
Paul Severson ◽  
Toufike Kanouni ◽  
Noelito Timple ◽  
...  
Keyword(s):  
Class Ii ◽  
Class I ◽  
Braf Inhibitors ◽  
Class Iii ◽  
Braf Gene ◽  
Braf Mutations ◽  
Braf Mutant ◽  
Gene Alterations

3116 Background: Oncogenic BRAF gene alterations, leading to aberrantly activated BRAF monomers (Class I mutations) or dimers (Class II and Class III mutations), are observed in approximately 6% of all human cancers. First-generation BRAF inhibitors targeting Class I BRAF mutants, including dabrafenib, encorafenib, and vemurafenib, provide significant clinical benefit to patients with BRAF V600 mutation-driven melanoma and select solid tumors as monotherapies or in combination with other targeted therapies. The currently approved BRAF inhibitors have not, however, proven to be effective in patients with Class II or III BRAF alterations which account for a large proportion (34%) of BRAF mutations. KIN-2787 is an orally available, potent and selective small molecule pan-RAF inhibitor specifically designed to inhibit Class II and III BRAF dimers, in addition to Class I mutants. Methods: The efficacy and tolerability of the pan-RAF inhibitor, KIN-2787, was evaluated in vitro and in vivo in Class I, II, and III BRAF mutation-driven human cancer models. Results: In biochemical assays, KIN-2787 showed low nanomolar to picomolar potency against RAF1, BRAF, and ARAF (IC50 0.06-3.46 nM) with minimal activity towards non-RAF kinases. In cell-based assays, KIN-2787 inhibited RAF activity, as measured by inhibition of downstream ERK phosphorylation (pERK), across multiple BRAF mutant cancer cell lines. Class II and III BRAF mutant cell lines were the most responsive when treated with KIN-2787 (IC50 < 50 nM); 19- and 7-fold more sensitive compared to cells harboring wild-type BRAF, respectively. Dose-dependent inhibition of A-375 (Class I), BxPC-3 (Class II), and WM3629 (Class III) BRAF mutant human xenograft tumor growth was attained with daily KIN-2787 treatment and was well-tolerated. A trend towards greater tumor responses was observed with twice daily (BID) compared to once daily (QD) dosing of KIN-2787; however, the two dosing regimens led to similar tumor growth inhibition (TGI) and regressions (mean TGI up to 101-118%; p ≤0.0001) at equivalent total daily doses. Furthermore, KIN-2787 led to a significant in vivo pharmacodynamic response using either regimen, however, prolonged target coverage, as measured by pERK, was achieved with BID dosing. The impact of KIN-2787 treatment on additional biomarkers, including transcriptional changes and MAPK pathway modulation in cell-based models and patient-derived samples, will be presented at the meeting. Conclusions: KIN-2787 is a next-generation pan-RAF inhibitor with pronounced in vitro and in vivo activity against human cancers driven by Class II and III BRAF mutations. A phase 1 dose escalation and expansion clinical trial evaluating the safety and efficacy of KIN-2787 monotherapy in patients with advanced or metastatic solid tumors harboring BRAF gene alterations, including Class II and III mutations, is expected to initiate in 2021.

scholarly journals GGA proteins associate with Golgi membranes through interaction between their GGAH domains and ADP-ribosylation factors

2002 ◽  
Vol 365 (2) ◽  
pp. 369-378 ◽  
Author(s):  
Hiroyuki TAKATSU ◽  
Kaori YOSHINO ◽  
Kyoko TODA ◽  
Kazuhisa NAKAYAMA
Keyword(s):  
Membrane Trafficking ◽  
Class Ii ◽  
Small Gtpases ◽  
Class I ◽  
Class Iii ◽  
Limited Region ◽  
Adp Ribosylation ◽  
Early Endosomes

ADP-ribosylation factors (ARFs) are a family of small GTPases that are involved in various aspects of membrane trafficking events. These include ARF1—ARF6, which are divided into three classes on the basis of similarity in the primary structure: Class I, ARF1—ARF3; Class II, ARF4 and ARF5; and Class III, ARF6. Previous studies identified a novel family of potential ARF effectors, termed GGA1—GGA3, which interact specifically with GTP-bound ARF1 and ARF3 and are localized to the trans-Golgi network (TGN) or its related compartment(s) (GGA is an abbreviation for Golgi-localizing, γ-adaptin ear homology domain, ARF-binding protein). In the present study we have shown that ARF proteins belonging to the three classes, ARF1, ARF5 and ARF6, can interact with all GGA proteins in a yeast two-hybrid assay, in vitro and in vivo. Segmentation of GGA proteins and isolation of GGA mutants defective in ARF binding have revealed that a limited region within the GGA homology domain, which is conserved in the GGA family, is essential for ARF binding. Expression in cells of GTPase-restricted mutants of ARF1 and ARF5 blocks dissociation of GGA proteins from membranes induced by brefeldin A. However, neither of the ARF mutants recruits GGA mutants defective in ARF binding. On the basis of these observations, we conclude that at least ARF1 (Class I) and ARF5 (Class II) in their GTP-bound state cause recruitment of GGA proteins on to TGN membranes. In contrast, on the basis of similar experiments, ARF6 (Class III) may be involved in recruitment of GGA proteins to other compartments, possibly early endosomes.

scholarly journals Environmental Cadmium Exposure and Dental Indices in Orthodontic Patients

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 ◽  
...  
Keyword(s):  
Cadmium Concentration ◽  
Class Ii ◽  
Cadmium Exposure ◽  
Class I ◽  
P Value ◽  
Tooth Decay ◽  
Class Iii ◽  
Orthodontic Patients ◽  
Urine Cadmium ◽  
The Mean

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.

A rapid and reliable in vivo method for anti-GPLA (class I and class II antigens) antibody titration and GPLA typing

1983 ◽  
Vol 59 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Thérèse Neveu ◽  
Michèle Lefroit-Joliy ◽  
Guy André Voisin
Keyword(s):  
Class Ii ◽  
Class I ◽  
Class Ii Antigens

scholarly journals A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe

1976 ◽  
Vol 159 (2) ◽  
pp. 245-257 ◽  
Author(s):  
R Norris ◽  
K Brocklehurst
Keyword(s):  
Convenient Method ◽  
Specific Activity ◽  
Class Ii ◽  
High Reactivity ◽  
Class I ◽  
Thiol Groups ◽  
Class Iii ◽  
Active Centre ◽  
Class Ib ◽  
Covalent Chromatography

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.

Regulation of mouse CYP1A1 gene expression by dioxin: requirement of two cis-acting elements during induction

1989 ◽  
Vol 9 (6) ◽  
pp. 2378-2386
Author(s):  
L A Neuhold ◽  
Y Shirayoshi ◽  
K Ozato ◽  
J E Jones ◽  
D W Nebert
Keyword(s):  
Gene Expression ◽  
Simian Virus 40 ◽  
Class Ii ◽  
Simian Virus ◽  
Class I ◽  
Ah Receptor ◽  
Class Iii ◽  
Cis Acting ◽  
Cyp1a1 Gene ◽  
Sv40 Dna

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.

Prevalence of Malocclusions in Autistic Patients in Isfahan

2021 ◽  
Author(s):  
Zahra Ali Mehtari ◽  
Mehdi Rafiei ◽  
Saeed Azarbayjani ◽  
Neda Ahmadi Rouzbehani ◽  
Amir Hossain Moeini
Keyword(s):  
Class Ii ◽  
Autism Spectrum ◽  
Open Bite ◽  
Class I ◽  
Dental Student ◽  
Class Iii ◽  
Cross Sectional ◽  
Deep Bite ◽  
Normal Occlusion ◽  
Age Range

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.

Prevalence of Malocclusion among School Children of Biratnagar, Nepal

2021 ◽  
Vol 11 (1) ◽  
pp. 46-48
Author(s):  
Nidhi Giri ◽  
Anand Acharya ◽  
Kanika Yadav
Keyword(s):  
School Children ◽  
Class Ii ◽  
Cross Sectional Study ◽  
Class I ◽  
Class Iii ◽  
Cross Sectional ◽  
Total Study Population ◽  
Medical College ◽  
Normal Occlusion ◽  
Study Population

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

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