Issues with the surgical treatment of antiresorptive agent-related osteonecrosis of the jaws.

Antiresorptive agent-related osteonecrosis of the jaw is a rare but significant complication in patients using antiresorptive agents such as bisphosphonates and denosumab. Although the disease is well recognized, and many studies have been performed on the management of this condition, the treatment of severe osteonecrosis is still a challenge. Most recent studies have shown an advantage of surgical treatment over conservative treatment for stage 2/3 patients, but there is no consensus on the appropriate surgical procedures for antiresorptive agent-related osteonecrosis of the jaw. Furthermore, patients with severe systemic conditions may not be appropriate for extensive surgical treatment, and the treatment protocol for such patients has not been established. In this review, issues regarding the current surgical treatment for antiresorptive agent-related osteonecrosis of the jaws are discussed, with an emphasis on the clinical aspects.

Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. I. Detection and characterization of hapten-reactive suppressor T-cell activity in mice immunized with hapten-isologous protein conjugate.

Helper and suppressor T-cell activities were detected simultaneously in the spleen cells of mice immunized with para-azobenzoate (PAB)-mouse gammaglobulin (MGG). Dinitrophenyl (DNP)-specific B cells were raised by immunization with DNP-keyhole limpet hemocyanin (KLH) and used as the indicator B-cell population. The helper and suppressor T-cell activities were determined after adoptively transferring spleen cells from PAB-MGG- primed donors and DNP-KLH-primed donors into X-irradiated recipients. Stimulation of these recipients with DNP-MGG-PAB detected helper T-cell activity, which was measured in terms of increased anti-DNP antibody responses of DNP-KLH-primed cells over these responses in the presence of unprimed cells. On the other hand, when DNP-KLH-primed cells were stimulated with DNP-KLH-PAB in the presence of PAB-MGG-primed cells, anti-DNP antibody responses were substantially lower than in unprimed normal cells. This suppressor cell population was (a) hapten-reactive, (b) present in B-cell-depleted spleen cells, (c) Thy-1 positive, (d) detectable earlier than the helper T-cell activities after priming (e) more radiosensitive than helper cells, and (f) found in the spleen but not the lymph nodes in contrast to helper T cells. These data indicate that these suppressor T cells are distinct from the helper T cells. PAB-reactive T cells clearly suppressed the antibody response by inhibiting KLH-reactive helper T-cell functions. The hapten-reactive T-lymphocyte system described here should be useful for analyzing and manipulating the immune response and for studying regulatory interactions of helper and suppressor T cells in the induction of antibody responses.

Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development.

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.

Effect of 12 weeks of moderate-intensity resistance training on arterial stiffness: a randomised controlled trial in women aged 32-59 years.

BACKGROUND: Resistance training has been increasingly incorporated into the overall exercise programme because of its effect on muscle strength, functional capacity and osteoporosis. High-intensity resistance training increases arterial stiffness. However, the effect of moderate-intensity resistance training on arterial stiffness is unknown. OBJECTIVE: To determine whether 12 weeks of moderate-intensity resistance training increases arterial stiffness in middle-aged women. METHODS: 35 middle-aged women (age range 32 to 59 years) volunteered to participate. The subjects were randomly assigned to one of three groups: resistance training (RT) group, aerobic exercise training (AET) group or control group. The RT and AET groups performed 12 weeks of moderate-intensity resistance training or aerobic exercise training (two days/week). RESULTS: In the RT group, one-repetition maximum strength significantly increased after the intervention. Interestingly, aortic (carotid-femoral) pulse wave velocity (PWV; an index of arterial stiffness), and peripheral (femoral-ankle) PWV did not change with moderate-intensity resistance training. In contrast, in the AET group, carotid-femoral PWV significantly decreased after the intervention. Resistance training and aerobic exercise training did not affect blood pressure. CONCLUSIONS: This study found that moderate-intensity resistance training did not increase arterial stiffness in middle-aged women, which may have great importance for health promotion with resistance training.

Genomic organization, expression and evolution of porcine CRSP1, 2, and 3.

Recently we identified and characterized porcine calcitonin receptor-stimulating peptide (CRSP) 1, CRSP2 and CRSP3 as members of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family. In the present study, the genomic sequences and organization of CRSP1, 2, and 3 were determined, and the expression of the genes in the porcine brain was investigated using in situ hybridization. Analysis of 5'-upstream regions of the three CRSPs demonstrated that CRSP1 and CRSP2 have almost identical sequences (>98% similarity) and high sequence similarities including functional transcription binding sites with the corresponding region of human CALCA (CT/alpha CGRP), whereas CRSP3 retains less similarity with the above genes. RH mapping of CRSPs demonstrated that they resided in a region of swine chromosome 2 (SSC2). The arrangement of the genes in the region was found to be conserved in corresponding human and mouse regions. In situ hybridization demonstrated sense transcripts of the three genes in cerebrum, hippocampus, hypothalamus, pons/midbrain, and thalamus of 3-month-old pigs, and CRSP2 sense transcripts additionally in tractus opticus. The sense transcripts of alpha CGRP and CALCB (beta CGRP) were detected in cerebrum, hippocampus, and pons/midbrain of newborn mice, and to a lesser extent in pons/midbrain of 8-week-old mice. These results taken together with the chromosomal conservation and phylogenetic clustering of CT/CGRP family indicate that CRSP1, 2, and 3 may be functionally different from alpha CGRP and beta CGRP, though they are indicated to have a common progenitor gene.

Detection and quantification of calcifications in intravascular ultrasound images by automatic thresholding.

An innovative application of automatic thresholding is used for the detection of calcification regions in intravascular ultrasound images. A priori knowledge of the acoustic shadow that usually accompanies calcification regions is used to discriminate these from other bright regions in the image. A method for the calculation of the angle of calcification has also been developed. The proposed algorithms are applied to in-vivo images obtained from left anterior descending coronary arteries during percutaneous transluminal coronary angioplasty (n = 14). The resulting specificity is 72% and the sensitivity 84%. The receiver operating characteristic curve, the area under the curve being equal to 0.91, is plotted to evaluate the algorithm performance.

Heat island mitigation using water retentive pavement sprinkled with reclaimed wastewater.

In Japan, reclaimed wastewater has been recycled widely for non-potable urban applications and it is to be used for sprinkling roads to mitigate heat island in urban areas. To assess the heat island mitigation effects of the sprinkling reclaimed wastewater on water retentive pavement, we carried out a survey at Shiodome-District, Tokyo. The temperatures of air and roads, humidity, and WBGT (Wet-bulb globe temperature) were measured and heat flux was estimated to compare the condition of the areas with/without sprinkling. The following results were obtained. 1) Sprinkling reclaimed wastewater decreased the road surface temperature by 8 degrees during the daytime and by 3 degrees at night: temperatures equal to those on planting zones. Nevertheless sprinkling was done only in the daytime, the temperature decrease effect was not only obtained during the daytime: it continued through the night, due to the water retentive pavement. 2) Sprinkling reclaimed wastewater reduced the amount of sensible heat flux and increased that of latent heat flux. These results suggest that sprinkling reclaimed wastewater on water retentive pavement can effectively mitigate the heat island phenomenon.

DEVELOPMENT OF A HIGH-EFFICIENCY PROTON RECOIL TELESCOPE FOR D-T NEUTRON FLUENCE MEASUREMENT.

A high-efficiency proton recoil telescope was developed to determine neutron fluences in neutron fields using the 3H(d,n)4He reaction. A 2-mm thick plastic scintillation detector was employed as a radiator to increase the detection efficiency and compensate for the energy loss of the recoil proton within. Two silicon detectors were employed as the ΔE and E detectors. The distance between the radiator and the E detector was varied between 50 and 150 mm. The telescope had detection efficiencies of 3.5 × 10-3 and 7.1 × 10-4 cm2 for distances of 50 and 100 mm, respectively, which were high enough to determine the neutron fluence in 14.8-MeV neutron fields, with a few thousand cm-2 s-1 fluence rate, within a few hours.

A key-point based real-time tracking of lung tumor in x-ray image sequence by using difference of Gaussians filtering and optical flow.

In radiation therapy, for accurate radiation dose delivery to a target tumor and reduction of the extra exposure of normal tissues, real-time tumor tracking is typically an important technique in lung cancer treatment since lung tumors move with patients' respiration. To observe a tumor motion in real time, x-ray fluoroscopic devices can be employed, and various tracking techniques have been proposed to track tumors. However, development of a fast and accurate tracking method for clinical use is still a challenging task since the obscured image of the tumor can cause decreased tracking accuracy and can result in additional processing time for remedying the accuracy. In this study, a new key-point-based tumor tracking method, which is sufficiently fast and accurate, is presented. Given an x-ray image sequence, the proposed method employs a difference-of-Gaussians filtering technique to detect key points in the tumor region of the first frame which are robust against noise and outliers in the subsequent frames. In the subsequent frames, these key points are tracked using a fast optical flow technique, and tumor motion is estimated via their movement. To evaluate the performance, the proposed method has been tested on several clinical kV and MV x-ray image sequences. The experimental results showed that the average of the root mean square errors of tracking were [Formula: see text] and [Formula: see text] for kV and MV x-ray image sequences, respectively. This tracking performance was more accurate than previous tracking methods. In addition, the average processing times for each frame were [Formula: see text] and [Formula: see text] for kV and MV image sequences, respectively, and the proposed method was faster than previous methods as well as shorter than frame acquisition interval. Therefore, the proposed method has the potential for both highly accurate and fast tumor tracking in clinical applications.

Periodontal regeneration of transplanted rat teeth subcutaneously after cryopreservation.

The periodontal regeneration of transplanted teeth after cryopreservation in liquid nitrogen overnight was previously examined using an animal model. The results showed that overnight cryopreservation did not have any severe adverse effects on periodontal healing. For clinical application, it is necessary to make the period of storage longer than in the preliminary study. In this study, the regeneration of periodontal tissues after cryopreservation for 4 weeks was examined. The maxillary molars of 4-week-old Wistar rats were extracted and transplanted into the abdominal subcutaneous tissue either immediately or after cryopreservation in a deep freezer at -80 degrees C. The donor teeth were frozen in a rate-controlling freezer. At 1, 2 and 4 weeks after transplantation, they were excised and observed under light microscopy. The cryopreserved teeth had acellular cementum with a rough surface at 1 week. With an increase in cementoblasts and the appearance of periodontal ligament and alveolar bone, the surface had become smooth at 2 weeks. There was no progressive root resorption. Although the process took somewhat more time, the teeth cryopreserved for 4 weeks showed regeneration that was similar to that of the immediately transplanted teeth.

The expression and production of vascular endothelial growth factor in oral mucosa equivalents.

Angiogenesis is anticipated during wound healing. Vascular endothelial growth factor (VEGF) is a potent direct angiogenic factor that stimulates endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Ex vivo produced oral mucosa equivalent (EVPOME) grafts have been reported to promote re-vascularization in the underlying tissue after grafting. The aim of this study was to evaluating the following: VEGF mRNA and its protein expression in EVPOME grafts, the protein levels in conditioned media produced by EVPOMEs, and the ability of VEGF to stimulate the growth of microvascular endothelial cells. VEGF mRNA expression and immunoreaction were found in basal and suprabasal layers. VEGF secreted by EVPOME was detected throughout the period of manufacture of the grafts, and became elevated for the first week at an air-liquid interface. Both EVPOME-conditioned media and a medium containing 10ng/mL recombinant human VEGF induced endothelial cell proliferation, while neutralization of VEGF by an antibody blocked cell growth. These results suggest that VEGF secreted by EVPOME grafts might assist initial vascularization after grafting, which is critical to subsequent graft survival.

Construction of monoenergetic neutron calibration fields using 45Sc(p, n)45Ti reaction at JAEA.

The 8 and 27 keV monoenergetic neutron calibration fields have been developed by using (45)Sc(p, n)(45)Ti reaction. Protons from a 4-MV Pelletron accelerator are used to bombard a thin scandium target evaporated onto a platinum disc. The proton energies are finely adjusted to the resonance to generate the 8 and 27 keV neutrons by applying a high voltage to the target assemblies. The neutron energies were measured using the time-of-flight method with a lithium glass scintillation detector. The neutron fluences at a calibration point located at 50 cm from the target were evaluated using Bonner spheres. A long counter was placed at 2.2 m from the target and at 60 degrees to the direction of the proton beam in order to monitor the fluence at the calibration point. Fluence and dose equivalent rates at the calibration point are sufficient to calibrate many types of the neutron survey metres.

RCA/IAEA third external dosimetry intercomparisons in East Asia region.

Several intercomparison exercises were organised by the International Atomic Energy Agency (IAEA) on the determination of operational quantities at the regional or interregional basis. In East Asia region, a third phase of the intercomparison finished in mid 2004. It was organised within the frame of the Regional Cooperation Agreement (RCA) as a follow-up to previous exercises carried out during 1990-1992 and 1995-1996. The results of this intercomparison for the determination of operational quantities were satisfactory for all Member States. The laboratories demonstrated a good performance in quantities tested. The purpose of this paper is to present the results of the RCA/IAEA intercomparison and the future of RCA activities in support of assessment of occupational exposure by organising intercomparison runs.

Evaluation of the characteristics of the neutron reference field using D2O-moderated 252Cf source.

The ambient/personal dose equivalent per fluence for D(2)O moderated (252)Cf neutron source was determined by measurement. An appropriate subtraction of the scattered neutrons is required for the accurate measurement of direct neutrons. A cubic shadow object was used for the subtraction of the scattered neutrons from the surroundings. The scattered neutrons to be subtracted vary with the position of the shadow object due to the large volume of the source. Using the Monte Carlo code MCNP-4C, the optimum positions of the shadow object were surveyed for subtracting the scattered neutrons. The energy spectra of direct neutrons were measured in the optimum position. The dosimetric parameters for the D(2)O moderated (252)Cf neutron source were reasonable, taking into account the uncertainties of the parameters.

Action of bredinin on mammalian cells.

Bredinin, a new nucleoside antibiotic, inhibited multiplication of several mammalian cell lines in culture and had a cytotoxic effect on L5178Y cells. Growth inhibition by bredinin was prevented by guanosine 5'-monophosphate (GMP), guanosine, or guanine but not by other purine or pyrimidine nucleotides, nucleosides, or bases. Inhibition by bredinin at a low GMP; but at higher concentrations of bredinin the inhibition was not reversed even when the concentration of GMP was raised. Addition of GMP after cellular damage had occurred produced no effect on the damaged cells but it prvented further damage. Bredinin caused marked chromosomal aberrations such as breakages, translocations, and fragmentation in L5178Y cells.

Comparison of hemostatic effects by route of H2 receptor antagonist administration following endoscopic mucosal resection in patients with neoplastic gastric lesions.

BACKGROUND: To date, there has not been an in-depth investigation to identify differences in the effects of bleeding prevention among different routes of administration of H2 receptor antagonists to treat gastric ulcers following endoscopic mucosal resection (EMR). AIM: To prospectively compare the frequency of bleeding following EMR between patients treated with intravenous (IV) famotidine and those with oral famotidine. METHODS: Fifty-three patients with neoplastic gastric lesions (33 carcinoma and 20 adenoma) treated by EMR were included. Subjects underwent EMR with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate (EMRSH), followed by IV or oral (PO) administration of famotidine at a dosage of 40 mg/day for 2 days. Patients with odd ID numbers were assigned to IV therapy (30 cases) while even numbers were given PO therapy (23 cases). Frequencies and endoscopic findings of bleeding during the first 2 days after EMR were examined. RESULTS: Frequency of bleeding within 2 days after EMR was 3 and 4% in IV and PO patients, respectively, showing no significant difference. No significant difference was seen in the endoscopic findings of bleeding and therapy, either, with respective IV and PO findings at 23 and 26%. CONCLUSIONS: No significant difference was observed in frequency of bleeding within 2 days after gastric EMR between IV and oral administrations of famotidine.

Histopathological study of lymphatic invasion in squamous cell carcinoma (O-1N) with high potential of lymph node metastasis.

The process of lymph node metastasis was studied in an animal model (termed O-1N) that was successfully established using a metastatic tumor to the submandibular lymph node from a chemically induced squamous cell carcinoma of the hamster tongue. The model has been maintained by serial transplantation of metastatic tumors into the buccal pouch. Lymphovascular invasion of transplanted O-1N in the tongue was examined in serial histologic sections. Lymphatic vessels were distinguished from blood vessels by Masson's trichrome stain for vascular smooth muscle, BSA-I lectin binding for vascular endothelium, and laminin and type IV collagen immunostaining for the vascular basement membrane. Transplanted tumors enlarged progressively with invasion of surrounding tissues of the tongue and resulted in lymph node metastasis in all animals with successful takes. Local growth of the tumors in the tongue was accompanied by stromal proliferation with abundant dilated lymphatic vessels which contained clusters of tumor cells. On serial sections, the carcinoma cell clusters in lymphatics in the close proximity of tumor nests were in continuity with adjacent tumor nests, whereas such continuity was not recognized in those occurring apart from tumor nests. The formation of isolated carcinoma cell clusters resulting from disintegration of elongated processes of tumor nests with invasion of lymphatics and subsequent transport in lymphatics and deposition in lymph nodes in clusters were well demonstrated in other serial sections. The key step of lymph node metastasis therefore appears to be direct invasion of lymphatic vessels by tumor cells, similar to their invasion of adjacent tissues but different from the way that blood cells escape through vessel walls. Proliferation of lymphatics around tumor nests and transport of tumor cells in clusters would also contribute to the production of metastatic deposits in lymph nodes.

Assessment of age-dependent changes in circadian blood pressure rhythm in patients with essential hypertension.

The effects of age on the circadian blood pressure rhythm of patients with untreated essential hypertension (n = 133, World Health Organization stage I or II) were compared with those of normotensive subjects (n = 91). Subjects were classified into three groups by age: young (less than 40 years old), adult (40-59 years old) and old (greater than or equal to 60 years old). Blood pressure was monitored every 5 min for 24 h, using a finger volume oscillometric device under fixed external conditions. The single cosinor method was used to evaluate circadian rhythm. There was no difference in the amplitude of circadian systolic or diastolic blood pressure rhythm among the different normotensive and essentially hypertensive age groups although a wide distribution of amplitude was noted within each group. The distribution of amplitude was wider in the hypertensive than in the normotensive groups. The amplitude of circadian blood pressure rhythm was independent of the mesor level. On the other hand, the amplitude of circadian heart rate rhythm decreased with increasing age both in normotensive subjects (P less than 0.05, young versus adult or old) and hypertensive patients (P less than 0.01, young and old versus adult). The acrophase of circadian systolic blood pressure rhythm in young hypertensives was greater than that in adult or old hypertensives (P less than 0.05, for both). Such age-dependent changes were not observed in the normotensive groups. Consequently, the acrophase of circadian systolic or diastolic blood pressure rhythm in young hypertensives was larger than that in young normotensives (P less than 0.05, for both systolic and diastolic blood pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal vascular effects of leukotriene C4 in the isolated perfused kidney of the rat.

1 The vascular effects of leukotriene C4 (LTC4) were investigated in the isolated perfused kidney of the rat. 2 LTC4 (6.4 X 10(-10) to 3.2 X 10(-8) mol kg-1 min-1 given over 5 min) resulted in a prompt, dose-dependent increase in renal vascular resistance in a recirculating system, which lasted for more than 60 min. 3 LTC4 was 10 to 20 fold and 1000 to 2000 fold, respectively, less active on a molar basis than noradrenaline and angiotensin II in eliciting renal vasoconstriction. 4 The vascular response to LTC4 was blocked dose-dependently by FPL 55712, an antagonist of slow reacting substance of anaphylaxis. OKY 1581, a specific thromboxane synthetase inhibitor, and indomethacin, a cyclo-oxygenase inhibitor, did not influence the LTC4 response. 5 LTC4 given in a single-pass perfusion system resulted in a short lasting response with baseline values for renal vascular resistance reached after 4 min. 6 These results show that LTC4 is a short acting renal vasoconstrictor with less potency than noradrenaline and angiotensin II. Its pressor effects seem to be mediated by specific leukotriene receptors and independent of cyclo-oxygenase products. The long-lasting effect in the recirculating arrangement, in contrast to the single pass system, is compatible with formation of active metabolite(s).