Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells.

Although anti-tumor necrosis factor (TNF)-α treatments efficiently block inflammation in ankylosing spondylitis (AS), they are inefficient to prevent excessive bone formation. In AS, ossification seems more prone to develop in sites where inflammation has resolved following anti-TNF therapy, suggesting that TNF-α indirectly stimulates ossification. In this context, our objectives were to determine and compare the involvement of Wnt proteins, which are potent growth factors of bone formation, in the effects of TNF-α on osteoblast function. In human mesenchymal stem cells (MSCs), TNF-α significantly increased the levels of Wnt10b and Wnt5a. Associated with this effect, TNF-α stimulated tissue-non specific alkaline phosphatase (TNAP) and mineralization. This effect was mimicked by activation of the canonical ß-catenin pathway with either anti-Dkk1 antibodies, lithium chloride (LiCl) or SB216763. TNF-α reduced, and activation of ß-catenin had little effect on expression of osteocalcin, a late marker of osteoblast differentiation. Surprisingly, TNF-α failed to stabilize ß-catenin and Dkk1 did not inhibit TNF-α effects. In fact, Dkk1 expression was also enhanced in response to TNF-α, perhaps explaining why canonical signaling by Wnt10b was not activated by TNF-α. However, we found that Wnt5a also stimulated TNAP in MSCs cultured in osteogenic conditions, and increased the levels of inflammatory markers such as COX-2. Interestingly, treatment with anti-Wnt5a antibodies reduced endogenous TNAP expression and activity. Collectively, these data suggest that increased levels of Dkk1 may blunt the autocrine effects of Wnt10b, but not that of Wnt5a, acting through non-canonical signaling. Thus, Wnt5a may be potentially involved in the effects of inflammation on bone formation.

Tissue-nonspecific alkaline phosphatase is an anti-inflammatory nucleotidase.

Tissue-nonspecific alkaline phosphatase (TNAP) is necessary for skeletal mineralization by its ability to hydrolyze the mineralization inhibitor inorganic pyrophosphate (PPi), which is mainly generated from extracellular ATP by ectonucleotide pyrophosphatase phosphodiesterase 1 (NPP1). Since children with TNAP deficiency develop bone metaphyseal auto-inflammations in addition to rickets, we hypothesized that TNAP also exerts anti-inflammatory effects relying on the hydrolysis of pro-inflammatory adenosine nucleotides into the anti-inflammatory adenosine. We explored this hypothesis in bone metaphyses of 7-day-old Alpl+/- mice (encoding TNAP), in mineralizing hypertrophic chondrocytes and osteoblasts, and non-mineralizing mesenchymal stem cells (MSCs) and neutrophils, which express TNAP and are present, or can be recruited in the metaphysis. Bone metaphyses of 7-day-old Alpl+/- mice had significantly increased levels of Il-1ß and Il-6 and decreased levels of the anti-inflammatory Il-10 cytokine as compared with Alpl+/+ mice. In bone metaphyses, murine hypertrophic chondrocytes and osteoblasts, Alpl mRNA levels were much higher than those of the adenosine nucleotidases Npp1, Cd39 and Cd73. In hypertrophic chondrocytes, inhibition of TNAP with 25 µM of MLS-0038949 decreased the hydrolysis of AMP and ATP. However, TNAP inhibition did not significantly modulate ATP- and adenosine-associated effects in these cells. We observed that part of TNAP proteins in hypertrophic chondrocytes was sent from the cell membrane to matrix vesicles, which may explain why TNAP participated in the hydrolysis of ATP but did not significantly modulate its autocrine pro-inflammatory effects. In MSCs, TNAP did not participate in ATP hydrolysis nor in secretion of inflammatory mediators. In contrast, in neutrophils, TNAP inhibition with MLS-0038949 significantly exacerbated ATP-associated activation and secretion of IL-1ß, and extended cell survival. Collectively, these results demonstrate that TNAP is a nucleotidase in both hypertrophic chondrocytes and neutrophils, and that this nucleotidase function is associated with autocrine effects on inflammation only in neutrophils.

Inorganic pyrophosphate as a regulator of hydroxyapatite or calcium pyrophosphate dihydrate mineral deposition by matrix vesicles.

OBJECTIVE: Pathological mineralization is induced by unbalance between pro- and anti-mineralization factors. In calcifying osteoarthritic joints, articular chondrocytes undergo terminal differentiation similar to that in growth plate cartilage and release matrix vesicles (MVs) responsible for hydroxyapatite (HA) or calcium pyrophosphate dihydrate (CPPD) deposition. Inorganic pyrophosphate (PP(i)) is a likely source of inorganic phosphate (P(i)) to sustain HA formation when hydrolyzed but also a potent inhibitor preventing apatite mineral deposition and growth. Moreover, an excess of PP(i) can lead to CPPD formation, a marker of pathological calcification in osteoarthritic joints. It was suggested that the P(i)/PP(i) ratio during biomineralization is a turning point between physiological and pathological mineralization. The aim of this work was to determine the conditions favoring either HA or CPPD formation initiated by MVs. METHODS: MVs were isolated from 17-day-old chicken embryo growth plate cartilages and subjected to mineralization in the presence of various P(i)/PP(i) ratios. The mineralization kinetics and the chemical composition of minerals were determined, respectively, by light scattering and infrared spectroscopy. RESULTS: The formation of HA is optimal when the P(i)/PP(i) molar ratio is above 140, but is completely inhibited when the ratio decreases below 70. The retardation of any mineral formation is maximal at P(i)/PP(i) ratio around 30. CPPD is exclusively produced by MVs when the ratio is below 6, but it is inhibited for the ratio exceeding 25. CONCLUSIONS: Our findings are consistent with the P(i)/PP(i) ratio being a determinant factor leading to pathological mineralization or its inhibition.

Ca2+ release from caged-Ca2+ alters the FTIR spectrum of sarcoplasmic reticulum.

Light-induced Ca2+ release from the Ca2+ complex of Nitr-5 altered the FTIR spectra of sarcoplasmic reticulum vesicles and purified Ca(2+)-ATPase preparations. The principal changes seen in difference spectra obtained after and before illumination in the presence of Nitr-5.Ca2+ consisted of an increase in absorbance at 1663 and 1676 cm-1 and a decrease in absorbance at 1653 cm-1. The light-induced changes in FTIR spectra were prevented by vanadate or EGTA, indicating that they were associated with the formation of Ca2E1 enzyme intermediate. Other light-induced changes in the FTIR spectra at 1600-1250 cm-1 were not clearly related to the sarcoplasmic reticulum, and were attributed to photolysis of Nitr-5. The difference absorbance bands are narrow, suggesting that they originate from changes in side chain vibrations, although some changes in secondary structures may also contribute.

Correlation of structure and function in the Ca2+-ATPase of sarcoplasmic reticulum: a Fourier transform infrared spectroscopy (FTIR) study on the effects of dimethyl sulfoxide and urea.

The effect of dimethyl sulfoxide (DMSO) on the structure of sarcoplasmic reticulum was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopy. Exposure of sarcoplasmic reticulum vesicles to 35% DMSO (v/v) at 2 degrees C for several hours in a D2O medium produced no significant change in the phospholipid and protein Amide I regions of the FTIR spectra, but the intensity of the Amide II band decreased, presumably due to proton/deuterium exchange. At 40% to 60% DMSO concentration a shoulder appeared in the FTIR spectra at 1630 cm-1, that is attributed to the formation of new beta or random coil structures; irreversible loss of ATPase activity accompanied this change. At 70% DMSO concentration the intensity of the main Amide I band at 1639 cm-1 decreased and a new band appeared at 1622 cm-1, together with a shoulder at 1682 cm-1. These changes indicate an abrupt shift in the conformational equilibrium of Ca2+-ATPase from alpha to beta structure or to a new structure characterized by weaker hydrogen bonding. Decrease of ionization of aspartate and glutamate carboxyl groups in the presence of DMSO may also contribute to the change in intensity at 1622 cm-1. The changes were partially reversed upon removal of DMSO. Exposure of sarcoplasmic reticulum vesicles to 1.5 kbar pressure for 1 h at 2 degrees C in an EGTA-containing (low Ca2+) medium causes irreversible loss of ATPase activity, with the appearance of new beta structure, and abolition of the Ca2+-induced fluorescence response of FITC covalently bound to the Ca2+-ATPase; DMSO (35%) stabilized the Ca2+-ATPase against pressure-induced changes in structure and enzymatic activity, while urea (0.8 M) had the opposite effect.

The effect of dicyclohexylcarbodiimide and cyclopiazonic acid on the difference FTIR spectra of sarcoplasmic reticulum induced by photolysis of caged-ATP and caged-Ca2+.

The photochemical release of Ca2+ from caged-Ca2+ in the absence of ATP, and the release of ATP from caged-ATP in the presence of Ca2+ induce characteristic difference FTIR spectra on rabbit sarcoplasmic reticulum that are related to the formation of Ca2-E1 and E approximately P intermediates of the Ca(2+)-ATPase, respectively. Dicyclohexylcarbodiimide (10 nmol/mg protein) abolished both the Ca(2+)-and ATP-induced difference FTIR spectra parallel with inhibition of ATPase activity. Cyclopiazonic acid (50 nmol/mg protein) inhibited the Ca(2+)-induced difference spectrum measured in the absence of ATP, but had no significant effect on the ATP-induced difference spectrum measured in the presence of 1 mM Ca2+. The dog kidney Na+,K(+)-ATPase did not give significant difference spectrum after photolysis of caged-ATP in Ca(2+)-free media containing 90 mM Na+ and 10 mM K+, with or without ouabain. We propose that both the Ca2+ and the ATP-induced difference FTIR spectra of the Ca(2+)-ATPase reflect the occupancy of the high-affinity Ca2+ transport site of the enzyme.

Polarized infrared attenuated total reflectance spectroscopy of the Ca(2+)-ATPase of sarcoplasmic reticulum.

The mean orientations of the transition dipole moments associated with vibrational modes of the proteins and phospholipids of sarcoplasmic reticulum were determined on dry and hydrated membrane multilayers deposited on germanium or zinc selenide crystals, using polarized infrared attenuated total reflectance spectroscopy (P-IR-ATR). For preservation of the enzymatic activity of the Ca(2+)-ATPase the films were prepared from solutions containing 0.05 M KCl, 5 mM imidazole (pH 7.4), 0.5 mM MgCl2, 1-10 mM trehalose and dithiothreitol. The anisotropy was highest in dry films containing congruent to 7.5 micrograms protein/cm2, and decreased with increasing membrane thickness or hydration. The dichroic ratio of the CH2 vibrations (2923 cm-1) of extracted sarcoplasmic reticulum phospholipids on Ge plate was 1.56, compared with a dichroic ratio of 1.68 obtained on dry films of whole sarcoplasmic reticulum. The dichroic ratios of the amide I band (1650 cm-1) of the Ca(2+)-ATPase in the Ca2-E1 state and in the EGTA and vanadate stabilized E2-V state were nearly identical (1.60 vs. 1.62). The dichroism of the amide I, amide II and lipid CH2 vibrations was not affected by changes in the concentration of KCl (25-100 mM) or Ca2+ (approximately equal to 10(-8)-10(-4) M) and by the addition of vanadate (1 mM) or Pi (5 mM) in a calcium-free medium containing 0.5 mM EGTA. The dichroic ratio of the C-C (1033 cm-1) or CO stretching band (1046 cm-1) of trehalose incorporated into SR films was 1.2 on Ge plate; this corresponds to a mean angle of approximately 70 degrees between the plane of the trehalose ring and the normal of the film plane, suggesting that the trehalose molecules are surprisingly well oriented in the polar headgroup region of the phospholipids. The orientation of the trehalose was not affected by the presence of Ca(2+)-ATPase.

Thermal and pH stabilities of alkaline phosphatase from bovine intestinal mucosa: a FTIR study.

The inactivation of alkaline phosphatase (AP) from bovine intestinal mucosa caused by lowering the p2H from 10.4 to 5.4 or by increasing the temperature from 25 degrees C to 70 degrees C were not followed by significant FTIR changes, indicating that the native conformation of AP was preserved under these conditions. Further decrease of p2H from 5.4 to 3.4 leaded to small infrared spectral changes of AP in the amide I' and amide II regions that were similar to the infrared spectral changes of AP induced by raising the temperature from 70 degrees C to 80 degrees C. The increase of temperature from 70 degrees C to 80 degrees C promoted the formation of intermolecular beta-sheets at the expense of some alpha-helix structures as evidenced by the appearance of the 1684 cm-1 and 1620 cm-1 component bands and the disappearance of the 1651-1657 cm-1 component band. This conformational change was followed by a sharp increase of the 2H/H exchange rate. CD spectra confirmed the FTIR results and were very sensitive to the variation of alpha-helix content while FTIR spectra were more receptive to the changes of beta-sheet structures.

Infrared spectroscopic studies on gramicidin ion-channels: relation to the mechanisms of anesthesia.

Fourier transform infrared spectroscopic studies are reported on gramicidin ion-channels in phospholipid bilayers and the effects on the spectra of the anesthetics and related compounds (methoxyflurane, halothane, chloroform, carbon tetrachloride, n-pentane and n-decane) have been determined. The addition of anesthetics containing the 'acidic hydrogen' caused unique changes particularly on the amide I bands at 1639 cm-1 and 1670 cm-1. The 1639 cm-1 band became more intense while the intensity near 1670 cm-1 decreased dramatically. These effects were not observed with carbon tetrachloride, n-pentane and n-decane. The 1670 cm-1 band is interpreted as arising from the carbonyls involved in the head-to-head hydrogen-bonded dimerization where the relationship between chains is analogous to that of the antiparallel beta-pleated sheet structure and the anesthetics with 'acidic hydrogens' are considered to disrupt the hydrogen-bonded dimerization by competitive hydrogen bonding to the carbonyls at the head-to-head junction. As the dimer-monomer equilibrium is the 'on-off' mechanism for gramicidin ion-channel conductance, the results are considered in terms of the mechanism of action of anesthetics and are taken to suggest, for certain anesthetics, a hydrogen-bonding role to protein ion-channel components.

Pressure effects on sarcoplasmic reticulum: a Fourier transform infrared spectroscopic study.

The Ca2(+)-ATPase of sarcoplasmic reticulum is irreversibly inactivated by exposure to 1.5-2.0 kbar pressure for 30-60 min in a Ca2(+)-free medium; mono- or decavanadate (5 mM) or to a lesser extent Ca2+ (2-20 mM) protect against inactivation (Varga et al. (1986) J. Biol. Chem. 261, 13943-13956). The structural basis of these effects was analyzed by FTIR spectroscopy of sarcoplasmic reticulum in 2H2O medium. The inactivation of the Ca2(+)-ATPase at 1.5-2.0 kbar pressure in a Ca2(+)-free medium was accompanied by changes in the Amide II region of the spectrum (1550 cm-1), that are consistent with increased hydrogen-deuterium (H-2H) exchange, and by the enhancement of a band at 1630 cm-1 in the Amide I region, that is attributed to an increase in beta sheet. The frequency of the peak of the Amide I band shifted from about 1648 cm-1 at atmospheric pressure to 1642 cm-1 at approximately equal to 12.5 kbar pressure, suggesting a decrease in alpha helix, and an increase in beta and/or random coil structures. Upon releasing the pressure, the shift of the Amide I band was partially reversed. Vanadate (5 mM), and to a lesser extent Ca2+ (2-20 mM), protected the Ca2(+)-ATPase against pressure-induced changes both in the Amide I and Amide II regions of the spectrum, together with protection of ATPase activity. These observations establish a correlation between the conformation of the Ca2(+)-ATPase and its sensitivity to pressure. The involvement of the ATP binding domain of the Ca2(+)-ATPase in the pressure-induced structural changes is suggested by the decreased polarization of fluorescence of fluorescein 5'-isothiocyanate covalently attached to the enzyme.

Conformations of synthetic beta peptides in solid state and in aqueous solution: relation to toxicity in PC12 cells.

The secondary structures of peptides beta 25-35 (the active toxic fragment) and beta 35-25 (reverse sequence and non-toxic fragment), as well as of the amidated beta (25-35)-NH2 peptide were investigated in aqueous solution and in the solid state by means of Fourier-transformed infrared spectroscopy and circular dichroism spectroscopy. The conformations of the beta 25-35 and beta 35-25 in solid state were identical and contained mostly beta-sheet structures. In solid state the amidated beta (25-35)-NH2 peptide also contained mostly beta-sheet structures. Freshly prepared aqueous solutions of the beta 25-32 (0.5 - 3.8 mM) contained a mixture of beta-sheet and random coil structures. Within 30-60 min incubation at 37 degrees C in water or in phosphate-buffered saline solution (PBS), beta 25-35 was almost fully converted to a beta-sheet structure. Decreasing the temperature from 37 degrees C to 20 degrees C decreased the rate of conversion from random coil to beta-sheet structures, 1-2 h being required for complete conversion. In contrast beta 35-25 in water or in PBS buffer had mostly a random coil structure and remained so for 6 days. The amidated beta(25-35)-NH2 peptide in water (2.7 mM) was also mostly random coil. However, when this peptide (2-2.7 mM) was dissolved in PBS (pH 7.4) or in 140 mM NaCl, a gel was formed and its conformation was mostly beta-sheet. Decreasing the concentration of beta (25-35)-NH2 peptide in 140 mM NaCl aqueous solution from 2 mM to 1 mM or below favored the conversion from beta-sheet structures to random coil structures. The beta 25-35 was toxic to PC12 cells while beta 35-25 was not. The amidated peptide beta (25-35)-NH2 was at least 500-fold less toxic than beta 25-35. Structural differences between these beta peptides in aqueous solutions may explain the difference in their respective toxicities.

Emerging views on the structure and dynamics of the Ca2(+)-ATPase in sarcoplasmic reticulum.

The ATP-dependent Ca2+ transport in sarcoplasmic reticulum involves transitions between several structural states of the Ca2(+)-ATPase, that occur without major changes in the secondary structure. The rates of these transitions are modulated by the lipid environment and by interactions between ATPase molecules. Although the Ca2(+)-ATPase restricts the rotational mobility of a population of lipids, there is no evidence for specific interaction of the Ca2(+)-ATPase with phospholipids. Fluorescence polarization and energy transfer (FET) studies, using site specific fluorescent indicators, combined with crystallographic, immunological and chemical modification data, yielded a structural model of Ca2(+)-ATPase in which the binding sites of Ca2+ and ATP are tentatively identified. The temperature dependence of FET between fluorophores attached to different regions of the ATPase indicates the existence of 'rigid' and 'flexible' regions within the molecule characterized, by different degrees of thermally induced structural fluctuations.

Alzheimer's disease: its origin at the membrane, evidence and questions.

Numerous results on membrane lipid composition from different regions of autopsied Alzheimer's disease brains in comparison with corresponding fractions isolated from control brains revealed significant differences in serine- and ethanolamine-containing glycerophospholipid as well as in glycosphingolipid content. Changes in membrane lipid composition are frequently accompanied by alterations in membrane fluidity, hydrophobic mismatch, lipid signaling pathways, transient formation and disappearance of lipid microdomains, changes in membrane permeability to cations and variations of other membrane properties. In this review we focus on possible implications of altered membrane composition on beta-amyloid precursor protein (APP) and on proteolysis of APP leading eventually to the formation of neurotoxic beta-amyloid (A beta) peptides, the major proteinaceous component of extracellular senile plaques, directly involved in Alzheimer's disease pathogenesis.

Annexin VI: an intracellular target for ATP.

Annexin VI (AnxVI), an Ca2+- and phospholipid-binding protein, interacts in vitro with ATP in a calcium-dependent manner. Experimental evidence indicates that its nucleotide-binding domain which is localized in the C-terminal half of the protein differs structurally from ATP/GTP-binding motifs found in other nucleotide-binding proteins. The amino-acid residues of AnxVI directly involved in ATP binding have not been yet defined. Binding of ATP to AnxVI induces changes in the secondary and tertiary structures of protein, affecting the affinity of AnxVI for Ca2+ and, in consequence, influencing the Ca2+-dependent activities of AnxVI: binding to F-actin and to membranous phospholipids, and self-association of the annexin molecules. These observations suggest that ATP is a functional ligand for AnxVI in vivo, and ATP-sensitive AnxVI may play the role of a factor coupling vesicular transport and calcium homeostasis to cellular metabolism.

The effect of anesthetics on hydrogen bonds. An infrared study at low anesthetic concentrations.

It is shown that a striking parallelism exists between the anesthetic potency of general halocarbon anesthetics and their influence on the hydrogen bond association constants in N-H...O=C type hydrogen bonds, important for shaping the ion channels. It is further shown that the effect of potent anesthetics (which contain an acidic hydrogen) on the free/associated ratio in such hydrogen bonds is still significant at clinical anesthetic concentrations. It is argued that the results are in keeping with a pluralistic theory of anesthesia based on both hydrophobic and polar interactions.

Dielectric spectroscopy of L-alpha-lysolecithin-packaged gramicidin A.

The complex permittivities of L-alpha-lysolecithin in the absence and presence of the gramicidin A ion channel were measured over the temperature range 0-60 degrees C and over the frequency range 1-1000 MHz. One dielectric relaxation/loss has been observed. It is located at 103.3 MHz (1.54 ns) for a micellar 0.4 M L-alpha-lysolecithin solution at 20 degrees C, whereas it is shifted to 71.7 MHz (2.22 ns) for a lamellar L-alpha-lysolecithin-gramicidin A aqueous solution (0.4 M L-alpha-lysolecithin, 0.0308 M gramicidin A) at 20 degrees C. The dielectric relaxation decreases and the relaxation time increases when gramicidin A is incorporated into L-alpha-lysolecithin. These dielectric changes are related, in part, to the micellar-to-lamellar lipid phase transition induced by the incorporation of gramicidin A into lysolecithin. We suggest that the diffuse rotational motion of the polar head group of L-alpha-lysolecithin contributes to the dielectric relaxation/loss at around 100 MHz.

Hydrogen bond equilibrium constants for the complexes of benzotriazole and some nucleoside derivatives. A near infrared study.

Approximate hydrogen bond association constants were determined by near infrared spectroscopy for pairs formed by benzotriazole and a number of nucleoside derivatives. The molecule of benzotriazole forms, in chloroform, hydrogen bonds with inosine, uridine and adenosine derivatives. The order of decreasing association constants for complexes formed by benzotriazole and uridine or inosine derivatives is the opposite of the one observed for pairs formed by adenosine and uridine or inosine derivatives.

Hydrogen bond equilibrium constants of some unusual nucleotide base pairs.

Approximate hydrogen bond association constants were determined for base pairs formed by an adenine derivative and a number of unusual pyrimidine bases. A series is found in which the H-bond strength in the base-pairs varies. In certain cases the H-bond equilibrium constant is larger than in the adenine-thymine pair. Inosine derivatives seem to have a non-negligible chance of replacing guanosine in the guanosine-cytosine pair. Infrared, near-infrared (overtone) and NMR spectra were used to determine the equilibrium constants.

Dielectric relaxation spectroscopy on dimyristoylphosphatidylcholine-packaged gramicidin A.

The complex permittivities of aqueous suspensions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and of DMPC packaged gramicidin A' (DMPC-GA) have been determined over the frequency range of 1 MHz to 1 GHz and the temperature range of 0-60 degrees C. A dielectric relaxation/loss has been observed at about 66 MHz for the DMPC suspension (30 degrees C) and at about 57 MHz for the DMPC-GA suspension (30 degrees C). This dielectric relaxation/loss has been attributed to the rotational mobility of the zwitterionic group of DMPC. The temperature dependence (from 60 degrees C to 0 degrees C) of this dispersion/absorption process of the DMPC suspension indicates a sharp reduction of the dielectric relaxation at about 20 degrees C. This dielectric change is related to the conversions of shape and structure of bilayer aggregates. This sharp reduction of the dielectric relaxation disappears or broadens when GA is incorporated into the DMPC aqueous suspension. The interpretation of these results is that the GA addition into the DMPC aqueous suspension induces a small decrease of the rotational mobility of the zwitterionic group above the lipid phase transition, and a small increase of the rotational mobility of the zwitterionic group below the lipid phase transition.

[Contribution of panoramic tomography in exploration of maxillary sinuses (author's transl)]. / Apport de la radiographie panoramique dans l'exploration des sinus maxillaires.

Panoramic tomography (orthopantomography) is useful in exploration of maxillary sinuses, specially of its floor and its connection with teeth alveoles. Interest of this examination in the diagnosis of sinusian cyst of polypus, apical teeth cyst growing in the sinus, fistula from mouth to sinus, repeating sinusitis by dental infectious focus, sinusian stranger corps and finally, in the schedule or surveillance of the extension of sinus maxillary cancer to the posterior wall, particularly to the pterygomaxillary fossae.