Creatine enhances the duration of sperm capacitation: a novel factor for improving in vitro fertilization with small numbers of sperm.

STUDY QUESTION: Why are many sperm required for successful fertilization of oocytes in vitro, even though fertilization occurs in vivo when only a few sperm reach the oocyte? SUMMARY ANSWER: Creatine produced in the ovary promotes efficient fertilization in vivo; however, in vitro, creatine is not contained in the in vitro fertilization (IVF) medium. WHAT IS KNOWN ALREADY: The IVF medium enables capacitation of sperm. However, the IVF medium does not fully mimic the in vivo environment during fertilization. Consequently, fertilization in vitro is more inefficient than in the oviduct. STUDY DESIGN, SIZE, DURATION: Follicular and oviductal fluids were collected and then analyzed for creatine and glucose levels. To determine the physiological functions of creatine, the creatine antagonist 3-guanidinopropionic acid (GPA) was injected into hormonally primed mice. Using conventional IVF protocols, sperm were pre-incubated in IVF medium with creatine and then co-cultured with 10 ovulated cumulus-oocyte complexes (1-1000 per oocyte) in 50 µl medium droplets. PARTICIPANTS/MATERIALS, SETTING, METHODS: Glucose and creatine levels were measured using commercial enzymatic assay kits. The effect of creatine in vivo was assessed by mating experiments using mice treated with or without GPA just before ovulation. To assess the functions of sperm incubated in IVF medium containing creatine, we analyzed (1) the motility of sperm using computer-assisted sperm assay, (2) the capacitation level of sperm by western blot analyses, and (3) the condition of sperm acrosomes by peanut agglutinin lectin-FITC staining. MAIN RESULTS AND THE ROLE OF CHANCE: Oviductal creatine levels were significantly increased following ovulation. Injecting mice with GPA just before ovulation significantly reduced the number of fertilized oocytes. The addition of creatine to IVF medium enhanced sperm capacitation by increasing ATP levels. Successful fertilization was achieved with as few as five sperm/oocyte in the creatine group, and the number of fertilized oocytes was significantly higher than in the control without creatine (P < 0.01). LIMITATIONS, REASONS FOR CAUTION: In the present study, a pharmacological approach, creatine antagonist (GPA) treatment, but not a knockout mouse model, was used to understand the role of creatine in vivo. The role of creatine in fertilization processes can only be shown in a mouse model. WIDER IMPLICATIONS OF THE FINDINGS: A modified IVF technique using creatine-containing medium was developed and shown to markedly improve fertilization with small numbers of sperm. This approach has the potential to be highly beneficial for human assisted reproductive technologies, especially for patients with a limited number of good quality sperm. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by JSPS KAKENHI Grant numbers JP24688028, JP16H05017 (to M.S.), and JP15J05331 (to T.U.), the Japan Agency for Medical Research and Development (AMED) (16gk0110015h0001 to M.S.), and National Institutes of Health (NIH-HD-076980 to J.S.R). The authors have nothing to disclose.

Cynomolgus monkey model of interleukin-31-induced scratching depicts blockade of human interleukin-31 receptor A by a humanized monoclonal antibody.

Scratching is an important factor exacerbating skin lesions through the so-called itch-scratch cycle in atopic dermatitis (AD). In mice, interleukin (IL)-31 and its receptor IL-31 receptor A (IL-31RA) are known to play a critical role in pruritus and the pathogenesis of AD; however, study of their precise roles in primates is hindered by the low sequence homologies between primates and mice and the lack of direct evidence of itch sensation by IL-31 in primates. We showed that administration of cynomolgus IL-31 induces transient scratching behaviour in cynomolgus monkeys and by that were able to establish a monkey model of scratching. We then showed that a single subcutaneous injection of 1 mg/kg nemolizumab, a humanized anti-human IL-31RA monoclonal antibody that also neutralizes cynomolgus IL-31 signalling and shows a good pharmacokinetic profile in cynomolgus monkeys, suppressed the IL-31-induced scratching for about 2 months. These results suggest that the IL-31 axis and IL-31RA axis play as critical a role in the induction of scratching in primates as in mice and that the blockade of IL-31 signalling by an anti-human IL-31RA antibody is a promising therapeutic approach for treatment of AD. Nemolizumab is currently under investigation in clinical trials.

The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia.

The oral cavity provides an entrance to the alimentary tract to serve as a protective barrier against harmful environmental stimuli. The oral mucosa is susceptible to injury because of its location; nonetheless, it has faster wound healing than the skin and less scar formation. However, the molecular pathways regulating this wound healing are unclear. Here, we show that transient receptor potential vanilloid 3 (TRPV3), a thermosensitive Ca(2+)-permeable channel, is more highly expressed in murine oral epithelia than in the skin by quantitative RT-PCR. We found that temperatures above 33°C activated TRPV3 and promoted oral epithelial cell proliferation. The proliferation rate in the oral epithelia of TRPV3 knockout (TRPV3KO) mice was less than that of wild-type (WT) mice. We investigated the contribution of TRPV3 to wound healing using a molar tooth extraction model and found that oral wound closure was delayed in TRPV3KO mice compared with that in WT mice. TRPV3 mRNA was up-regulated in wounded tissues, suggesting that TRPV3 may contribute to oral wound repair. We identified TRPV3 as an essential receptor in heat-induced oral epithelia proliferation and wound healing. Our findings suggest that TRPV3 activation could be a potential therapeutic target for wound healing in skin and oral mucosa.

[A case of appearance of a prominent rash in response to alternate-day S-1 administration as adjuvant chemotherapy for lower gingival cancer].

We report the development of a prominent rash in response to alternate-day S-1 administration in a patient with oral cancer. The patient was a 75-year-old woman with left-side lower gingival cancer(T4N1M0). After chemoradiotherapy, the patient underwent radical surgery. She was treated with oral S-1, administered on alternate days at a dosage of 80mg/day (orally, twice per day), as postoperative adjuvant chemotherapy. Edematous erythema, accompanied by strong itching and paraesthesia, appeared focally on the face and the limbs 1 month after beginning S-1 treatment. Since the rash was determined to be drug-induced, S-1 administration was stopped, and steroid, antihistamine, and topical steroid treatment was initiated. The symptoms gradually improved, and the rash disappeared without recurrence approximately 1 month later. Although alternate-day administration is considered to be a safe and effective method to administer S-1 oral therapy, it should be noted that cutaneous symptoms might appear after a fixed dosage is exceeded.

Generational differences in tooth size in the Japanese population: analysis of cohorts with a generation gap of four to five decades.

PURPOSE: Since early modern times, tooth size has reportedly been increasing in each successive generation. A detailed analysis of these trends can provide meaningful information for elucidating the origin of various problems caused by larger teeth, such as an abnormal dentition and occlusion. By using data from most recent generations, this study aimed to clarify the time course of changes in tooth size in the Japanese. MATERIALS AND METHODS: The dentitions of two Japanese cohorts comprising young individuals born in the 1980s and the 1990s were compared with those of another cohort of Japanese individuals born in the 1940s, approximately half a century earlier. The mesiodistal diameter of the tooth crowns was measured on plaster models and subjected to statistical analyses. RESULTS: A mean difference test revealed that each recent generation showed positive generational differences in the size of more than 50% of the tooth types. In addition, a deviation graph analysis indicated that the degree of change in tooth size varied with the tooth type or sampling site. Principal component analysis clearly showed an increase in tooth size on an individual basis in the more recent generations. CONCLUSIONS: This study revealed positive generational differences in tooth size in the Japanese population. The results may aid in understanding the development of abnormal dentitions and occlusion in recent Japanese populations.

A novel method for skin marking in radiotherapy: first clinical use of temporary organic tattoo seal.

An oil-based pen is widely used as a skin marker for identification of the isocenter and computed tomography (CT)-coordinate origin during radiotherapy. However, use of this pen has some disadvantages, including color loss and color migration. To address these problems, we have developed use of a temporary fashion tattoo (Inkbox) for skin marking. The utility and feasibility of Inkbox as an alternative to an oil-based pen were evaluated in this study. The study included patients from two centers who required skin marking for radiotherapy performed between December 2020 and March 2021. Skin markings were made with an oil-based pen or with Inkbox. The durability was recorded during daily irradiation. Skin markings with Inkbox were made in 32 patients. The total number of skin markings was 94: 64 with Inkbox and 30 with an oil-based pen. A questionnaire survey to evaluate each method was conducted among patients after radiotherapy. The median durations of marking were 16 and 4 days with Inkbox and an oil-based pen, respectively (p-value < 0.001). The survey showed that Inkbox had less impact on the daily lives of patients, including reduced color migration to clothes and less concern about disappearance of the marking. There were no adverse cutaneous side effects with Inkbox. The duration of marking with Inkbox is about 16 days, with little impact on daily life. These findings suggest that Inkbox is a potentially useful method of skin marking in radiotherapy.

Nonmetric cranial variation of Jomon Japan: Implications for the evolution of eastern Asian diversity.

OBJECTIVES: The purpose of this study is to investigate the origin and expansion of the Jomon population, the Neolithic inhabitants of the Japanese archipelago, and peopling East/Northeast Asian region through a global comparison between the prehistoric samples from around the world. METHODS: R-matrix approach was applied to 20 nonmetric cranial traits for assessing the population structure and history of the Jomon. Pattern of ancient group relationships on a global scale was presented using network splitstree applied to distance matrix transformed from the R-matrix. RESULTS: The phenotypic variation is largest in Hokkaido region, followed by the regions of eastern Japan. The Chugoku region, the southwestern part of Japan, shows larger variance than eastern Japan. Global analyses including samples from Northeast Asia, Southeast Asia, Australia, West Asia, Europe, and North Africa dating roughly to the same chronological periods as those of the Jomon groups, indicate northern affinities of the Jomon and the distinction between Southeast and Northeast Asian series. CONCLUSION: The Jomon ancestors of the northern part of Japan might have expanded southward to Honshu Island with a series of bottlenecks. A possible gene flow from outside source or heterogeneous origin of western Jomon group was, at the same time, suggested. The network relationships of the Jomon with Northeast Asians and, to a lesser extent, with Southeast Asians based on the splitstree analysis may allow us to suppose that the Jomon may be one of the key populations for the studies of the evolution of eastern Asian diversity.

Methyl-beta cyclodextrin and creatine work synergistically under hypoxic conditions to improve the fertilization ability of boar ejaculated sperm.

Although successful fertilization is completed by only 150 sperm in the pig oviduct, more than 50,000 sperms are required to achieve a fertilization rate of more than 70% by pig in vitro fertilization (IVF). In this study, to improve the efficiency of pig IVF, the effects of hypoxic conditions and treatment with creatine and methyl-beta cyclodextrin (MßCD) on the glycolytic pathway were investigated. Under low O2 conditions, zig-zag motility was strongly induced within 30 min; however, the induction disappeared at 60 min. Although caffeine suppressed zig-zag motility under low O2 conditions, creatine induced and sustained zig-zag motility until 120 min. Additionally, pretreatment with MßCD for 15 min greatly enhanced zig-zag motility via ATP production in sperm incubated with creatine under low O2 conditions. Sperm pretreated with MßCD were used for IVF in medium containing creatine under low O2 conditions. A fertilization rate of approximately 70% was achieved with only 1.0 x 104 sperms/mL, and there were few polyspermic embryos. Therefore, our novel method was beneficial for efficient production of pig embryos in vitro. Moreover, the zig-zag motility may be a novel movement which boar capacitated sperm exhibit in the culture medium.

Itaconate regulates the glycolysis/pentose phosphate pathway transition to maintain boar sperm linear motility by regulating redox homeostasis.

Mammalian cells improve redox homeostasis under reactive oxygen species (ROS) stress conditions via the enhancement of the pentose phosphate pathway (PPP). However, it is not clear how the cell reprograms glucose metabolism from glycolysis to the PPP. Hence, in the present study, we used boar sperm as a model to elucidate the mechanism by which the glycolysis/PPP transition occurs under ROS stress. The boar sperm treated with moderate glucose levels for 3 h exhibited increased sperm linear motility patterns, ATP levels and GSH/GSSG ratios and decreased ROS levels compared to the boar sperm treated without glucose. In addition, the hexokinase activity, glucose-6-phosphate dehydrogenase (G6PD) activity, NADPH level, NADPH/NADP+ ratio and mitochondrial activity were higher in the sperm treated with moderate glucose than in those not treated with glucose. Interestingly, the enzyme activity of fructose-1,6-bisphosphate aldolase (ALDOA) was not significantly changed during the incubation. The sperm linear motility patterns were decreased by treatment with the G6PD inhibitor 6-aminonicotinamide. Moreover, moderate glucose treatment significantly increased the itaconate levels in sperm. Both endogenous and exogenous itaconate increased the total itaconate modifications and the itaconate-modified ALDOA levels in sperm, suggesting that under moderate-glucose conditions, glycolysis in the sperm was suppressed by an increase in the itaconate levels. Furthermore, the addition of itaconate improved the sperm linear motility patterns by suppressing glycolysis and enhancing oxidative phosphorylation (OXPHOS). Therefore, the itaconate generated from OXPHOS regulates the glycolysis/PPP transition to maintain redox homeostasis. In sperm, this itaconate-dependent mechanism plays an important role in maintaining their high linear motility.

TRPV2 expression in rat oral mucosa.

The oral mucosa is a highly specialised, stratified epithelium that confers protection from infection and physical, chemical and thermal stimuli. The non-keratinised junctional epithelium surrounds each tooth like a collar and is easily attacked by foreign substances from the oral sulcus. We found that TRPV2, a temperature-gated channel, is highly expressed in junctional epithelial cells, but not in oral sulcular epithelial cells or oral epithelial cells. Dual or triple immunolabelling with immunocompetent cell markers also revealed TRPV2 expression in Langerhans cells and in dendritic cells and macrophages. Electron microscopy disclosed TRPV2 immunoreactivity in the unmyelinated and thinly myelinated axons within the connective tissue underlying the epithelium. TRPV2 labelling was also observed in venule endothelial cells. The electron-dense immunoreaction in junctional epithelial cells, macrophages and neural axons occurred on the plasma membrane, on invaginations of the plasma membrane and in vesicular structures. Because TRPV2 has been shown to respond to temperature, hypotonicity and mechanical stimuli, gingival cells expressing TRPV2 may act as sensor cells, detecting changes in the physical and chemical environment, and may play a role in subsequent defence mechanisms.

Measurement of anterior loop length for the mandibular canal and diameter of the mandibular incisive canal to avoid nerve damage when installing endosseous implants in the interforaminal region: a second attempt introducing cone beam computed tomography.

PURPOSE: To measure and compare the anterior loop length (ALL) for the mandibular canal and the mandibular incisive canal diameter (ICD) at its origin in cadavers using anatomy and cone beam computed tomography (CBCT) to safely install endosseous implants in the most distal area of the interforaminal region. MATERIALS AND METHODS: The ALL and ICD were measured using CBCT in 4 cadavers, and using anatomy in 71 cadavers. RESULTS: The ranges and mean +/- SD for the anatomic measurements were: ALL, 0.0 to 9.0 mm and 1.9 +/- 1.7 mm; ICD, 1.0 to 6.6 mm and 2.8 +/- 1.0 mm. The average discrepancies between CBCT and anatomic measurements were 0.06 mm or less for both the ALL and the ICD, which were less than the resolution of CBCT. CONCLUSIONS: Because large variations in measurements were observed, both for ALL and ICD, no fixed distance mesially from the mental foramen should be considered safe. The ALL and the ICD can be estimated from the CBCT measurement. The preoperative CBCT measurement yields important information for each case.

[Two cases of recurrent oral cancer responding to radiochemotherapy with selective intra-arterial infusion of nedaplatin].

Nedaplatin, a cisplatin derivative, has been reported to be an effective anti-tumor agent for head and neck cancer. We experienced two patients with advanced recurrent oral cancers who received combination therapy of intra-arterial nedaplatin infusion and radiation therapy, and tumoricidal effects were obtained in these cases. At the end of 3 courses, a partial response(PR)was obtained with regression of the tumor in the first case, and FDGPET showed a complete regression of recurrent tumor for a complete response(CR)in another case. This combination therapy is quite safe and effective for the treatment of advanced oral cancers.

Gene Expression and Protein Synthesis in Mitochondria Enhance the Duration of High-Speed Linear Motility in Boar Sperm.

Sperm motility patterns are continuously changed after ejaculation to fertilization in the female tract. Hyperactivated motility is induced with high glucose medium in vitro or the oviduct fluids in vivo, whereas sperm maintain linear motility in the seminal plasma or the uterine fluids containing low glucose. Therefore, it is estimated that sperm motility patterns are dependent on the energy sources, and the mitochondrial oxidative phosphorylation is activated to produce ATP in low glucose condition. To elucidate these hypotheses, boar sperm was incubated in different energy conditions with the transcription and translation inhibitors in vitro. Sperm motility parameters, mitochondrial activity, ATP level, gene expression and protein synthesis were analyzed. Sperm progressive motility and straight-line velocity were significantly increased with decreasing glucose level in the incubation medium. Moreover, the mitochondrial protein turnover meaning transcription and translation from mitochondrial genome in sperm is activated during incubation. Incubation of sperm with mitochondrial translation inhibitor (D-chloramphenicol) suppressed mitochondrial protein synthesis, mitochondrial activity and ATP level in sperm and consequently reduced the linear motility speed, but not the motility. Thus, it is revealed that the mitochondrial central dogma is active in sperm, and the high-speed linear motility is induced in low glucose condition via activating the mitochondrial activity for ATP generation.

Participation of intercellular adhesion molecule-2 (CD102) in B lymphopoiesis.

The survival and fate of blood cell precursors is dependent on their communication with stromal cells of various types within bone marrow. Monoclonal antibodies have proven to be powerful tools for identifying molecules responsible for such interactions and we now describe one that selectively blocks B lymphopoiesis. The BF/32 antibody inhibited the establishment, but not the maintenance of long-term bone marrow cultures capable of lymphocyte production. However, there was no obvious effect on lymphocyte-stromal cell adhesion or responsiveness of pre-B cells to intereleukin-7. Furthermore, the reagent had no influence on myeloid precursors or myeloid bone marrow cultures. Injection of adult mice with BF/32 reduced B lineage precursors within bone marrow, but spared mature B cells. Moreover, the reagent did not alter responsiveness of mature B cells to activating stimuli. The 60 kDa protein recognized by this antibody was widely expressed on lymphocytes. Amino terminal protein sequencing and transfection experiments identified it as the murine homologue of ICAM-2 (CD102).

Mandibular reconstruction using autologous iliac bone and titanium mesh reinforced by laser welding for implant placement.

Segmental mandibulectomy is a treatment option for benign and malignant neoplasms of the mandible. Although reconstructing the mandible of a patient with a missing segment is difficult, it is essential to improve the postoperative course of the patient. Mandibular reconstruction using titanium mesh is a useful technique for dental implant placement because the morphology of the mandible can be easily reproduced. However, fitting titanium mesh to the remaining mandible is not an easy task during surgery. The present report introduces a method in which a 3-dimensional skull model fabricated by means of stereolithography is prepared, based on computerized tomography (CT) scans, to construct a titanium mesh cage matching the shape of the mandible, preoperatively. Furthermore, the load-bearing area of the titanium mesh cage is reinforced by laser welding another layer of titanium mesh to reduce the incidence of metal fatigue during jaw movement.

[Clinical trial of chemotherapy by superselective intra-arterial infusion of nedaplatin combined with radiotherapy for advanced oral cancer].

Nedaplatin (CDGP) is designed to further improve the anti-tumor effect and to reduce adverse effects of cisplatin (CDDP), such as renal toxicity. We previously reported a combination therapy of superselective intraarterial CDGP infusion, and radiation therapy could be delivered safely with good efficacy for locoregional management of oral cancer. However, both the clinical and pathological response decreased with tumor progression. This study was performed to assess the feasibility of a new chemotherapy regimen by superselective intraarterial infusion of CDGP in patients with advanced oral carcinomas. This regimen is under way in which chemotherapy with 5-FU 500 mg/day on days 1 to 5 and superselective intra-arterial infusion of CDGP on day 6 combined with radiation therapy is being evaluated for locally advanced oral cancer. Eight patients were treated with this regimen. After evaluation of the response, patients underwent surgery as a therapeutic procedure. Both the complete and partial response rates were achieved in each 3 patients (37.5%), respectively. Histological effects classified according to Oboshi-Shimosato's criteria were grade IVa in 2 patients, grade III in 1, grade IIb in 1, grade IIa in 3, and grade I in 1. All patients were free from renal dysfunction, which is one of the adverse effects of CDDP. Moreover, most toxicity was relatively mild in all patients.

Propeptin, a new inhibitor of prolyl endopeptidase produced by microbispora II. Determination of chemical structure.

The structure of propeptin, a new inhibitor of prolyl endopeptidase isolated from Microbispora sp. SNA-115, was determined. FAB/MS, Edman degradation and amino acid analysis revealed propeptin to be a cyclic polypeptide consisting of 19 common L-amino acids. By FAB/MS and protein chemical methods, the primary sequence of propeptin was determined to be Gly1-Tyr-Pro-Trp-Trp-Asp-Tyr-Arg-Asp9-Leu-Phe-Gly-Gly-His-Thr-Phe-Ile-Ser-Pro19, which cyclizes between the beta-carboxyl group of Asp9 and the a-amino group of Gly1.

Longitudinal follow-up of osseointegrated implants in patients with resected jaws.

PURPOSE: To investigate the effects of bone grafting and radiotherapy on implant survival rates. MATERIALS AND METHODS: This follow-up study involved 36 patients with 180 implants who were treated between January 1989 and December 2000 by prosthodontic rehabilitation using osseointegrated implants following jaw resection. They comprised 20 patients with malignant tumors, 12 with benign tumors, and 2 patients each with osteomyelitis and cysts. RESULTS: A total of 15 implants (11 in the maxilla and 4 in the mandible) were removed for various reasons during the follow-up study. Implant survival rates were calculated using the Kaplan-Meier method; the overall survival rate for the 180 implants was 88.6%. Specific implant survival rates were as follows: in residual bone, 73.8% for the maxilla and 95.2% for the mandible; in grafted bone, 80% for the maxilla and 94.1% for the mandible; in irradiated bone, 79.7%; and in nonirradiated bone, 93.5%. DISCUSSION: Radiotherapy, a dose of 30 Gy, was performed in patients with malignant tumors but not in patients with benign tumors, cysts, or osteomyelitis. No differences were found in the results for implants placed due to jaw resection for malignant tumors and those for implants placed due to benign tumors, cysts, or osteomyelitis. Implants lost varied in length from 7 to 18 mm. Among these, loss was more frequent with shorter implants (lengths to 10 mm). CONCLUSION: The clinical results obtained in the present study compare favorably with those obtained by others. However, jaw reconstruction and rehabilitation should not be performed by the oral surgeon alone; oral and maxillofacial function should be restored using a team approach in close cooperation with specialists in prosthodontics and periodontics to improve the result of implant treatment.

[Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer].

Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer.

Case of pediatric acute promyelocytic leukemia presenting as extramedullary tumor of the mandible.

BACKGROUND: Acute promyelocytic leukemia (APL) is a malignant subtype of acute myeloid leukemia caused by the PML-retinoic acid receptor (RAR)α fusion gene. APL may be discovered in adulthood and diagnosed after spontaneous gingival bleeding or difficulty in hemostasis after oral surgery such as tooth extraction. However, APL is extremely rare in children. METHODS AND RESULTS: A 1-year-old boy presented with a mass on the mentum of the mandible. The marked periosteal reaction was seen on CT and MRI, leading to strong suspicion of a malignant bone-derived tumor such as a sarcoma. Chromosome banding by fluorescence in situ hybridization (FISH) showed PML-RARα, confirming the diagnosis of APL. Treatment with tretinoin was immediately initiated. No signs of recurrence have been noted 1 year after treatment. CONCLUSIONS: We report herein a rare case involving an infant with APL who presented with an extramedullary tumor of the mandible, whom we treated with good results.