Accuracy of artificial intelligence-assisted growth prediction in skeletal Class I preadolescent patients using serial lateral cephalograms for a 2-year growth interval.

OBJECTIVE: To investigate the accuracy of artificial intelligence-assisted growth prediction using a convolutional neural network (CNN) algorithm and longitudinal lateral cephalograms (Lat-cephs). MATERIALS AND METHODS: A total of 198 Japanese preadolescent children, who had skeletal Class I malocclusion and whose Lat-cephs were available at age 8 years (T0) and 10 years (T1), were allocated into the training, validation, and test phases (n = 161, n = 17, n = 20). Orthodontists and the CNN model identified 28 hard-tissue landmarks (HTL) and 19 soft-tissue landmarks (STL). The mean prediction error values were defined as 'excellent,' 'very good,' 'good,' 'acceptable,' and 'unsatisfactory' (criteria: 0.5 mm, 1.0 mm, 1.5 mm, and 2.0 mm, respectively). The degree of accurate prediction percentage (APP) was defined as 'very high,' 'high,' 'medium,' and 'low' (criteria: 90%, 70%, and 50%, respectively) according to the percentage of subjects that showed the error range within 1.5 mm. RESULTS: All HTLs showed acceptable-to-excellent mean PE values, while the STLs Pog', Gn', and Me' showed unsatisfactory values, and the rest showed good-to-acceptable values. Regarding the degree of APP, HTLs Ba, ramus posterior, Pm, Pog, B-point, Me, and mandibular first molar root apex exhibited low APPs. The STLs labrale superius, lower embrasure, lower lip, point of lower profile, B', Pog,' Gn' and Me' also exhibited low APPs. The remainder of HTLs and STLs showed medium-to-very high APPs. CONCLUSION: Despite the possibility of using the CNN model to predict growth, further studies are needed to improve the prediction accuracy in HTLs and STLs of the chin area.

Are computed tomography images of the mandible useful in age and sex determination? A forensic science meta-analysis.

OBJECTIVES: This meta-analysis addresses the use of mandibular computed tomography (CT) scans for age and/or sex determination in forensic science. METHODS: Six databases were searched until June 2023, using the keyword "mandible" combined with keywords related to "multislice computed tomography" (MCT) or "cone-beam computed tomography" (CBCT) and keywords related to "skeletal age determination" or "sex determination analysis." MAIN RESULTS: Among the 23 studies included, 11 used MCT and 12 used CBCT to perform forensic assessments. Age determination was the aim of a single study, sex and agedeterminations were the objective of five studies, and the other studies investigated the determination of sex only. Metaanalysis could be performed only for sex determination. CONCLUSIONS: Mandible measurements are useful in sex determination, as the bicondylar and bigonial breadth are larger in males than in females. For the mandible angle, the meta-analysis results confirm sex dimorphism in CBCT scans but not in MCT scans. For age estimation, further studies are needed to prove that the mandible hole is a reliable parameter for age estimation. PROSPERO registration number: CRD42021260967.

Manifestation of preferred chewing side for hard food on TMJ disc displacement side.

The purpose of this study was to reveal the relationship between chewing-side preference and anterior disc displacement (ADD) of the TMJ. Thirty-two healthy subjects with ages ranging from 26 to 34 years were selected from volunteer students at the Okayama University Dental School. Subjects were asked to chew freely with two kinds of test foods, beef jerky (hard food) and chiffon cake (soft food), thus expecting different amounts of mechanical loading on the TMJ. One, 4, and 7 s after starting the mastication, subjects were asked to open their mouth momentarily to have a digital image of their mouth taken. The bolus placement area was measured by processing the digital images, calculated as the number of pixel of bolus area. Area asymmetry index was used for the determination of preferred chewing side (PCS). Oblique sagittal MRI scanning in the closed mouth position was taken to evaluate the articular disc position. In asymptomatic subjects with ADD, a significant predominance of the PCS on the ipsilateral side of ADD was observed during the mastication of hard food. On the contrary, no correlation was found between unilateral ADD and PCS for the soft food. From the results of this study, it is suggested that ADD is the associating factor of PCS for hard food. Therefore, it would be necessary to break down the concept of PCS into at least two categories, one for hard food and one for soft food, considering the mechanical loading on the TMJ.

Preliminary study evaluating the accuracy of MRI images on CBCT images in the field of orthodontics.

OBJECTIVE: The purpose of this study was to explore the 3-dimensional (3D) accuracy of magnetic resonance imaging (MRI) on cone-beam computed tomography (CBCT) images after the registration of MRI images on CBCT images. MATERIALS AND METHODS: Three Japanese adult females volunteered for this study. To transform digital imaging and communication in medicine (DICOM) data derived from MRI and CBCT images into polygon data, five software programs were used. CBCT and MRI images were obtained within one week, and both were registered by the iterative closest point (ICP) method. To assess the accuracy of the composite MRI-CBCT, the measurement errors of the MRI-CBCT were verified Measurement values were compared using frontal and cephalometric soft-tissue landmarks. Differences were analyzed using the non-parametric Mann-Whitney U test. RESULTS: There were no significant linear measurement errors (P > 0.05) when the images were measured from the superimposed MRI-CBCT images. CONCLUSION: The MRI images attained from MRI - CBCT registration showed accurate 3D linear measurements.

Measles virus receptors.

Measles virus (MV) has two envelope glycoproteins, the hemagglutinin (H) and fusion protein, which are responsible for attachment and membrane fusion, respectively. Signaling lymphocyte activation molecule (SLAM, also called CD150), a membrane glycoprotein expressed on immune cells, acts as the principal cellular receptor for MV, accounting for its lymphotropism and immunosuppressive nature. MV also infects polarized epithelial cells via an as yet unknown receptor molecule, thereby presumably facilitating transmission via aerosol droplets. Vaccine and laboratory-adapted strains of MV use ubiquitously expressed CD46 as an alternate receptor through amino acid substitutions in the H protein. The crystal structure of the H protein indicates that the putative binding sites for SLAM, CD46, and the epithelial cell receptor are strategically located in different positions of the H protein. Other molecules have also been implicated in MV infection, although their relevance remains to be determined. The identification of MV receptors has advanced our understanding of MV tropism and pathogenesis.

Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators.

Cell proliferation and differentiation are regulated by growth regulatory factors such as transforming growth factor-beta (TGF-beta) and the liphophilic hormone vitamin D. TGF-beta causes activation of SMAD proteins acting as coactivators or transcription factors in the nucleus. Vitamin D controls transcription of target genes through the vitamin D receptor (VDR). Smad3, one of the SMAD proteins downstream in the TGF-beta signaling pathway, was found in mammalian cells to act as a coactivator specific for ligand-induced transactivation of VDR by forming a complex with a member of the steroid receptor coactivator-1 protein family in the nucleus. Thus, Smad3 may mediate cross-talk between vitamin D and TGF-beta signaling pathways.

T-cell receptor and T-cell-resistant virus variants.

Analysis of the T-cell receptor has revealed the molecular basis of antigen recognition by T cells specific for viral antigens. Studies using T-cell receptor transgenic mice have provided evidence for clonal deletion of virus-specific T cells in persistently infected hosts and for selection of T-cell-resistant virus variants in vivo.

Triamcinolone acetonide suppresses early proangiogenic response in retinal pigment epithelial cells after photodynamic therapy in vitro.

OBJECTIVE: To investigate the expression of proangiogenic and antiangiogenic factors, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in retinal pigment epithelial (RPE) cells after photodynamic therapy (PDT), especially focusing on their change in the presence of triamcinolone acetonide. METHODS: Firstly, the cellular uptake of verteporfin was quantified after confluent ARPE-19 (human retinal pigment epithelial) cells were exposed to 5 microg/ml verteporfin combined with or without 1 microg/ml triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses of verteporfin were irradiated with 120 mJ/cm(2) light. After incubation with or without 1 microg/ml triamcinolone acetonide for 2 days, cell viability and expressions of VEGF and PEDF were assessed. RESULTS: Cellular uptake of verteporfin was not significantly changed by the presence of 1 microg/ml triamcinolone acetonide. In addition, 0.01-0.1 microg/ml of verteporfin showed a dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The presence of verteporfin at a concentration of 0.01 microg/ml did not affect the cell viability but significantly increased VEGF (p<0.001) and reduced PEDF (p = 0.03) expression. Administration of triamcinolone acetonide significantly suppressed both this increase in VEGF (p<0.001) and decrease in PEDF (p = 0.001). CONCLUSIONS: VEGF was increased and PEDF reduced in cultured RPE cells shortly after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this proangiogenic response.

A2e mediated phototoxic effects of endoilluminators.

AIMS: To compare the theoretical retinal threshold time for endoilluminators and experimental phototoxic effect using A2e laden retinal pigment epithelial (RPE) cells. METHODS: The spectral irradiances of three types of 20 gauge and 25 gauge endoilluminators, currently commercially available from two manufacturers, were evaluated in conditions where the total beam spectral power was divided by the beam spot size at an estimated use distance of 5 mm from the retina. The retinal threshold time was calculated using the guidelines recommended by the International Commission on Non-Ionizing Radiation Protection. In vitro, A2e laden cells were evenly exposed to light for 30 minutes with a standard endoilluminator positioned 1 cm above the cells and the cell viability was assessed by WST-1 assay. RESULTS: The retinal threshold times were within 1 minute for all the endoilluminators tested. A significant decrease in the viability of A2e laden RPE cells was observed after they were exposed to light from two of the three 20 gauge endoilluminators. Cell viability was not affected by the exposure to 25 gauge endoilluminators under the same conditions. There was no correlation between the theoretical threshold times and experimental data. CONCLUSIONS: Light exposure during vitrectomy can induce photochemical damage to the retina. Although the A2e laden RPE model may not correctly mimic a clinical situation, this model may be useful to estimate the possible photochemical damage to RPE cells that could not be deduced by a theoretical retinal hazard model.

Human lymphocytes are more susceptible to measles virus than granulocytes, which is attributable to the phenotypic differences of their membrane cofactor protein (CD46).

Membrane cofactor protein (MCP, CD46) of the complement system is a measles virus (MV) receptor. Human lymphocytes express a heavily glycosylated (H) and a lightly glycosylated (L) form of MCP, which confers a two-band profile on SDS-PAGE the ratio of which is controlled genetically and organ-specifically. In contrast, granulocytes express a single heavily glycosylated form regardless of lymphocyte MCP phenotype. We investigated susceptibility to MV of granulocytes and lymphocytes from individuals with different lymphocyte MCP phenotypes. In any individual, granulocytes were > 10-fold less susceptible to MV than lymphocytes, and the lymphocytes with predominant H form were generally less susceptible to those with an increasing amount of L form. Thus, lymphocytes always exhibit high susceptibility to MV compared to granulocytes in all individuals. This finding may explain the lymphopenia and immunosuppression observed secondary to MV infection.

The antitumor effects of human lymphoblastoid interferon on human renal cell carcinoma in athymic nude mice.

The antitumor effects of human lymphoblastoid interferon (HLBI) on human renal cell carcinomas transplanted in nude mice, i.e., KU-2 and RCC-1, were investigated and compared with those on other human tumors, viz. HeLa (cervical carcinoma), KB (nasopharyngeal carcinoma), H.Ep#2 (laryngeal carcinoma), and MX-1 (breast cancer). A pharmacokinetic study on HLBI was also carried out in non-tumor-bearing nude mice. HLBI therapy was performed with a dose of 10(5) IU/mouse by daily SC or IT (intratumoral) injection for 2-4 weeks. Two renal cell carcinomas, KU-2 and RCC-1, proved to be highly sensitive to HLBI. The growth of these tumors was inhibited not only by IT but also by SC injection of HLBI. In contrast, HLBI exerted only a slight effect or none at all on the other human tumors, namely, MX-1, KB, H.Ep#2, and HeLa, even when given by IT injection. The data show that the antitumor effects of HLBI depend on the types of human tumors and may be relevant to the clinical observation that renal tumors are sensitive to HLBI. The serum HLBI reached a peak level of 4,390 U/ml 1 h after a single SC injection at a dose of 10(5) IU/mouse and declined with a half-life of 4 h to 128 U/ml 24 h later. This time-course was not affected by 10 consecutive daily injections of HLBI. In nude mice, the consecutive administration of HLBI at this dose level appears to result in neither accumulation nor rapid clearance due to antibody formation. From this range of serum HLBI levels and its in vitro anticellular activity, the in vivo antitumor effects of HLBI in nude mice seemed to depend on its direct anticellular action.

Ester-type cephalotaxus alkaloids from Cephalotaxus harringtonia var. drupacea.

Three alkaloids, neoharringtonine, homoneoharringtonine and 3'S-hydroxyneoharringtonine, were isolated from the leaves and stems of Cephalotaxus harringtonia var. drupacea. Their structures were established by spectroscopic methods, including two-dimensional NMR and CD spectra, and their antileukaemic activity was evaluated using P-388 leukaemia cells.

A study of hypoxic cell radiosensitizer applied to Ehrlich ascite tumour: a comparison of FC43 emulsion and pentoxyfilline.

In this study, we examined the effects of various combinations of treatments involving radiation, injections of perfluorochemicals (FC-43 emulsion) and injections of pentoxifylline on the growth delay of Ehrlich ascite tumours. Ehrlich ascite tumour cells were transplanted into the legs of ddY-strain mice. Tumour-bearing mice were divided into seven groups: group 1, no treatment; group 2, irradiated only; group 3, injected with FC-43 emulsion and kept in a carbogen atmosphere; group 4, injected with pentoxifylline and nicotinamide; group 5, injected with FC-43 emulsion, kept in a carbogen atmosphere and irradiated; group 6, injected with pentoxifylline and nicotinamide and irradiated; and group 7, injected with FC-43 emulsion, pentoxifylline and nicotinamide, kept in a carbogen atmosphere and irradiated. When 20 Gy irradiation was applied, tumour growth delay was 11 days in group 2, 20 days in group 5, 22 days in group 6, and 24 days in group 7. For a growth delay of 20 days, the dose modifying factor was 1.95+/-0.04 (standard deviations) in group 5, 1.97+/-0.09 standard deviations in group 6, and 2.01+/-0.07 standard deviations in group 7. It was concluded that FC-43 emulsion and pentoxifylline did not have an interactive effect.

CT and MR imaging of localized amyloidosis.

The localized form of amyloidosis affecting the head and neck region is rare. The characteristic features of localized amyloidosis appeared as multiple nodules on the tongue, lip, and cheek on computed tomography (CT) and magnetic resonance imaging (MRI). Contrast-enhanced CT scans represented this lesion as a marked nodular enhancement. MR features of this lesion appeared slightly low on T1-weighted images and slightly high on T2-weighted images compared with T1-T2 images of residual normal tongue. Time contrast intensity curves obtained from dynamic MRI rapidly increased to reach a plateau and gradually decreased during the late and delayed phases. MR findings suggest that such lesions might be comprised of fibrous tissue with abundant vessels. This report suggests that dynamic MRI might be helpful for diagnosing localized amyloidosis.

[Functions of large granular lymphocytes--a case of large granular lymphocytosis with characteristic cell surface antigens].

A 58-year-old male visited the hematological clinic of Surugadai Nihon University Hospital, Tokyo, complaining of numbness around both elbows. The peripheral leukocyte count was 12,400/microliters, and large granular lymphocytes (LGL) occupied 79% of the leukocytes. The cell surface antigen studied by flow cytometry were the positive CD 2, 3, 5, 8, 11, and Leu-7, and the negative CD1, 4, 10, 16 (Leu-11), 19, 20, and OKTIa1. IgG-FCR checked by mean of the EA-rosette formation was positive. The LGL showed the negative NK cell activity and the positive ADCC and LAK cell activities. It was interesting that LGL was negative for CD16 (Leu-11) while they had ADCC activity. Since the rearrangement of the receptor gene in T-cells was demonstrated by the southern blot analysis, the proliferation of LGL was considered to be a clonal one. LGL did not inhibit the colony formation of granulocyte and erythrocyte precursors in the plasma clot culture. It was thus considered that this might partially explain the fact that the patient's neutrophil, Hb and platelet levels remained normal.

Correlation of the near-infrared spectroscopy signals with signal intensity in T(2)-weighted magnetic resonance imaging of the human masseter muscle.

The purpose of this study was to compare and contrast blood volume changes transcutaneously measured using near-infrared (NIR) spectroscopy against water signal intensity changes taken from a transverse T(2)-weighted MR image of the masseter muscle in healthy human subjects before, during and after contraction. Eight healthy non-smoking males with no history of chronic muscle pain or vascular headaches participated (mean age: 23.9+/-0.6 years). The MRI data were gathered using a turbo spin echo sequence (TR: 2300 ms; TE: 90 ms; FOV: 188x300 mm; scanning time: 30 s; slice thickness: 10 mm) and the slice level was set at the mid-point between the origin and insertion of the masseter. Intramuscular haemoglobin (Hb) levels and water content of the right masseter muscle were continuously monitored for 2 min before, 30 s during and 15 min after a maximum voluntary clenching (MVC) task. Both the near-infrared and MRI data were baseline-corrected and normalized and mean levels were established and plotted. Plots of the data showed that both near-infrared-based total Hb and T(2)-weighted MRI-based signal-intensity levels clearly decreased during contraction and a clear post-contraction rebound response was evident after the contraction. The near-infrared data were found to be highly correlated with MRI-based signal-intensity data (Pearson's r=0.909, P<0.0001). In conclusion, these data provide powerful evidence that near-infrared data (total Hb), transcutaneously taken from the masseter muscle in humans, will reflect the intramuscular water signal intensity changes seen using a T(2)-weighted MRI imaging method.

Psychiatry of diencephalon damages. A case report.

The diencephalon syndrome due to head injury in a 60-year-old woman is reported. The dicenphalon syndrome of the patient offered a variety of productive psychic and somatopsychic symptoms without reduction of intelligence; these included optic and acoustic hallucinations, delusions, cenesthesic hallucinations, disturbances of body schema and distinct functional disorders of the vegetative system. Autopsy findings of the brain were obtained in the 1.5 years up to her death. The problems of diencephalon syndrome related with suspected organic bases of schizophrenia and rhythmicity of diencephalogenic impulse reduction are discussed.

[Evaluation of amrubicin with a 5 day administration schedule in a mouse model].

It was reported that amrubicin hydrochloride (9-aminoanthracycline SM-5887), showed a higher therapeutic activity than doxorubicin against human tumor xenografts implanted into nude mice with a single treatment schedule. In order to find a more effective treatment schedule, the efficacy, toxicity and pharmacokinetic properties with a 5 consecutive day treatment schedule were investigated. The total amount of the maximum tolerated dose and tumor growth inhibiting activity with a 5 day schedule was found to be higher than with a single administration. High levels of amrubicinol, the active metabolite of amrubicin, was detected in the tumor tissue. It was thus assumed that the improved efficacy with the 5-day schedule resulted from the high accumulation of amrubicinol. Bone marrow suppression at the MTD with the 5 day schedule was severer than with a single dose, but recovery was rapid, similar to that following a single dose. In conclusion, it was demonstrated that a 5 day treatment schedule was more effective than a single administration.

[Development of anti-cancer drugs under new renewed GCP--from the viewpoint of drug development company developer].

During the past 7 years since the enforcement of Japan's first GCP in October 1990, various standards and guidelines have been introduced in Japan. On the other hand, the harmonization of GCP has been the subject of major discussion at ICH in order to allow the mutual acceptance of clinical data from different countries. In order to further improve the reliability and consistency of clinical data and the ethics of clinical trials in Japan, the new GCP was enforced in April 1997. A clinical study is conducted by the sponsor, but will only be successful with the collaboration of trial subjects, medical institutions, heads of medical institutions, investigators, subinvestigators, pharmacists, nurses, laboratory technicians, and other assisting staff. Before the full enforcement of the new GCP, we, as sponsors of clinical trials, carried out a survey of the current status of clinical trials centering on the reactions of medical institutions to the new GCP, future of clinical trials on anti-cancer drugs in Japan, and differences in time from clinical trials to registration in Japan, the United State and Europe. We sent a questionnaire by facsimile to 21 pharmaceutical companies which have developed or are developing anti-cancer drugs and obtained replies from 20 companies (95%) from August 25 to 30, 1997. This paper reports issues concerning clinical trials on anti-cancer drugs based on the results of our survey.

[Studies on the development and growth of the human maxilla--special references to the anterolateral, infratemporal and orbital surfaces].

Morphological and macroscopical studies were made on the lateral surface of the human maxilla. The materials consist of 128 cases of human fetuses ranging from the fourth to the tenth month and 306 cases of human juveniles and adults. The earliest month in which the loci with the scientific name (Nomina Anatomica) of the maxilla was observed was as follows; the frontal process, zygomatic process, anterior nasal spine and the nasal notch were first observed on the fourth fetal month. The infraorbital foramen and anterior lacrimal crest were first observed in some cases on the fourth fetal month and in all cases on the fifth fetal month. The infraorbital suture, lacrimal notch and alveolar process were first observed on the fifth to the sixth fetal month. The infraorbital sulcus and infraorbital canal were first formed on the fifth to the seventh fetal month. The following loci on the lateral surface of the maxilla which are related to the development of the maxillary teeth were first observed after birth as follows; the alveolar foramina were first observed in 3 to 7 years after birth and the maxillary tuberosity was first observed in 6 to 7 years after birth. The canine fossa was first observed in 6 years after birth. As far as the development of the maxilla is concerned, the frontal process and infraorbital margin were first observed and secondly the alveolar part was observed and finally the maxilla body which involved the maxillary sinus was formed.