Search

At the detonation of the atomic bombing in Hiroshima and Nagasaki, a significant amount of radionuclides was produced by the neutron induced activation. The residual radiation from the explosion is crucial to the health risk of the people who entered these cities after the bombing and might have inhaled these radioactive materials. Because 56Mn is one of the major radionuclides produced in soil and have not been studied until now, we had conducted a series of experiments using rats to investigate the biological impacts of exposure of 56MnO2 particles. In these experiments, the rats’ spontaneous locomotor activity was also assessed to examine the possible effects of 56Mn on their behavior. However, the locomotor activity data obtained from an individual experiment failed to identify radiation effects due to the large variation among animals and the small sample size. In the present study, all available data from our previous studies on 56MnO2 exposure (0.02–0.15 Gy of whole-body doses) as well as 60Co-γ exposure (at 2–5 Gy of whole-body doses) were pooled. Our statistical method, which takes into account individual differences and daily fluctuations, successfully identified a decrease in locomotor activity caused by 56MnO2 exposure, where the changes were gradual and reached the maximum reduction around 2 weeks after exposure. In contrast, exposure to 60Co-γ rays produced the highest decline of activity within one day. These results suggest that internal exposure to 56Mn at whole-body doses of even less than 0.15 Gy may have a long-lasting impact on locomotor activity.

We attempted to identify potent marker genes using a new statistical analysis and developed a prediction system for individual response to platinum/paclitaxel combination chemotherapy in ovarian cancer patients based on the hypothesis that expression analysis of a set of the key drug sensitivity genes for platinum and paclitaxel could allow us to predict therapeutic response to the combination. From 10 human ovarian cancer cell lines, genes correlative in the expression levels with cytotoxicities of cisplatin (CDDP) and paclitaxel were chosen. We first selected five reliable prediction markers for the two drugs from 22 genes already known as sensitivity determinants and then identified another 8 novel genes through a two-dimensional mixed normal model using oligomicroarray expression data. Using expression data of genes quantified by real-time reverse transcription-PCR, we fixed the best linear model, which converted the quantified expression data into an IC50 of each drug. Multiple regression analysis of the selected genes yielded three prediction formulae for in vitro activity of CDDP and paclitaxel. In the same way, using the same genes selected in vitro, we then attempted to develop prediction formulae for progression-free survival to the platinum/paclitaxel combination. We therefore constructed possible formulae using different sets of 13 selected marker genes (5 known and 8 novel genes): Utility confirmation analyses using another nine test samples seemed to show that the formulae using a set of 8 novel marker genes alone could accurately predict progression-free survival (r = 0.683; P = 0.042). [Mol Cancer Ther 2006;5(3):767–75]

Supplementary Data from Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers

The experiment was performed in support of a Japanese initiative to investigate the biological effects of irradiation from residual neutron-activated radioactivity that resulted from the A-bombing. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main neutron-activated emitters during the first hours after neutron activation of soil dust particles. In our previous studies (2016–2017) related to irradiation of male Wistar rats after dispersion of 56MnO2 powder, the internal doses in rats were found to be very inhomogeneous: distribution of doses among different organs ranged from 1.3 Gy in small intestine to less than 0.0015 Gy in some of the other organs. Internal doses in the lungs ranged from 0.03 to 0.1 Gy. The essential pathological changes were found in lung tissue of rats despite a low level of irradiation. In the present study, the dosimetry investigations were extended: internal doses in experimental mice and rats were estimated for various activity levels of dispersed neutron-activated 56MnO2 powder. The following findings were noted: (a) internal radiation doses in mice were several times higher in comparison with rats under similar conditions of exposure to 56MnO2 powder. (b) When 2.74 × 108 Bq of 56MnO2 powder was dispersed over mice, doses of internal irradiation ranged from 0.81 to 4.5 Gy in the gastrointestinal tract (small intestine, stomach, large intestine), from 0.096 to 0.14 Gy in lungs, and doses in skin and eyes ranged from 0.29 to 0.42 Gy and from 0.12 to 0.16 Gy, respectively. Internal radiation doses in other organs of mice were much lower. (c) Internal radiation doses were significantly lower in organs of rats with the same activity of exposure to 56MnO2 powder (2.74 × 108 Bq): 0.09, 0.17, 0.29, and 0.025 Gy in stomach, small intestine, large intestine, and lungs, respectively. (d) Doses of internal irradiation in organs of rats and mice were two to four times higher when they were exposed to 8.0 × 108 Bq of 56MnO2 (in comparison with exposure to 2.74 × 108 Bq of 56MnO2). (e) Internal radiation doses in organs of mice were 7–14 times lower with the lowest 56MnO2 amount (8.0 × 107 Bq) in comparison with the highest amount, 8.0 × 108 Bq, of dispersed 56MnO2 powder. The data obtained will be used for interpretation of biological effects in experimental mice and rats that result from dispersion of various levels of neutron-activated 56MnO2 powder, which is the subject of separate studies.

There are two types of exposure to atomic bomb (A-bomb) radiation: exposure to initial radiation released at the time of the detonation of the bomb, and exposure to residual radiation, which remains afterwards. Health hazards caused by exposure from residual radiation have not yet been clarified. The purpose of our study was to reveal the relationships between mortality risk from solid cancer and residual radiation based on data from the early entrants to Hiroshima. It is hard to identify the individual residual radiation doses. However, these are assumed to depend on the date of entry and the entrants’ behavior. Individual behavior is thought to be closely related to gender and age at exposure. We investigated a cohort of 45 809 individuals who were living in Hiroshima Prefecture on 1 January 1970 and were registered on the Database of Atomic Bomb Survivors as entrants after the bombing. Poisson regression methods were used to estimate excess relative risks (ERR) with data cross-classified by sex, age at entry, and date of entry. In males in their 20s, 30s, and 40s at entry and in females less than 10 years old and in their 40s at entry, solid cancer mortality risks were significantly higher among persons who entered the city on the day of the bombing than those who entered three or more days later. With adjustments for the age-dependent sensitivities to radiation exposure, it was extrapolated that middle-aged people who entered the city on the day of the bombing were exposed to higher levels of residual radiation than younger people.

Special dosimetry study of experimental rats exposure by sprayed 56Mn powder was conducted during experiments in order to study internal irradiation effects. All experiments were performed in Kurchatov’s reactor complex «Baikal-1» (Kurchatov city, East-Kazakhstan region) after neutron activation of stable Mn powder. This study was performed by group of scientists from Japan, Kazakhstan, and Russian Federation. The results of estimated doses in lungs alveolar epithelium of rats are shown in this paper. Absorbed dose on the «surface» of epitelium is equal to 160 Gy and absorbed dose in the «bottom» of epithelium for minimal thickness of epithelium cells is 8.9 Gy and for maximal thickness of epithelium cells equal to 0.4 Gy.

The experiment was performed in support of a Japanese initiative to investigate the biological effects of irradiation from residual neutron-activated radioactivity that resulted from the A-bombing. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main neutron-activated emitters during the first hours after neutron activation of soil dust particles. In our previous studies (2016–2017) related to irradiation of male Wistar rats after dispersion of 56MnO2 powder, the internal doses in rats were found to be very inhomogeneous: distribution of doses among different organs ranged from 1.3 Gy in small intestine to less than 0.0015 Gy in some of the other organs. Internal doses in the lungs ranged from 0.03 to 0.1 Gy. The essential pathological changes were found in lung tissue of rats despite a low level of irradiation. In the present study, the dosimetry investigations were extended: internal doses in experimental mice and rats were estimated for various activity levels of dispersed neutron-activated 56MnO2 powder. The following findings were noted: (a) internal radiation doses in mice were several times higher in comparison with rats under similar conditions of exposure to 56MnO2 powder. (b) When 2.74 × 108 Bq of 56MnO2 powder was dispersed over mice, doses of internal irradiation ranged from 0.81 to 4.5 Gy in the gastrointestinal tract (small intestine, stomach, large intestine), from 0.096 to 0.14 Gy in lungs, and doses in skin and eyes ranged from 0.29 to 0.42 Gy and from 0.12 to 0.16 Gy, respectively. Internal radiation doses in other organs of mice were much lower. (c) Internal radiation doses were significantly lower in organs of rats with the same activity of exposure to 56MnO2 powder (2.74 × 108 Bq): 0.09, 0.17, 0.29, and 0.025 Gy in stomach, small intestine, large intestine, and lungs, respectively. (d) Doses of internal irradiation in organs of rats and mice were two to four times higher when they were exposed to 8.0 × 108 Bq of 56MnO2 (in comparison with exposure to 2.74 × 108 Bq of 56MnO2). (e) Internal radiation doses in organs of mice were 7–14 times lower with the lowest 56MnO2 amount (8.0 × 107 Bq) in comparison with the highest amount, 8.0 × 108 Bq, of dispersed 56MnO2 powder. The data obtained will be used for interpretation of biological effects in experimental mice and rats that result from dispersion of various levels of neutron-activated 56MnO2 powder, which is the subject of separate studies.

There were two sources of ionizing irradiation after the atomic bombings of Hiroshima and Nagasaki: (1) initial gamma-neutron irradiation at the moment of detonation and (2) residual radioactivity. Residual radioactivity consisted of two components: radioactive fallout containing fission products, including radioactive fissile materials from nuclear device, and neutron-activated radioisotopes from materials on the ground. The dosimetry systems DS86 and DS02 were mainly devoted to the assessment of initial radiation exposure to neutrons and gamma rays, while only brief considerations were given for the estimation of doses caused by residual radiation exposure. Currently, estimation of internal exposure of atomic bomb survivors due to dispersed radioactivity and neutron-activated radioisotopes from materials on the ground is a matter of some interest, in Japan. The main neutron-activated radionuclides in soil dust were 24Na, 28Al, 31Si, 32P, 38Cl, 42K, 45Ca, 46Sc, 56Mn, 59Fe, 60Co, and 134Cs. The radionuclide 56Mn (T 1/2 = 2.58 h) is known as one of the dominant beta- and gamma emitters during the first few hours after neutron irradiation of soil and other materials on ground, dispersed in the form of dust after a nuclear explosion in the atmosphere. To investigate the peculiarities of biological effects of internal exposure to 56Mn in comparison with external gamma irradiation, a dedicated experiment with Wistar rats exposed to neutron-activated 56Mn dioxide powder was performed recently by Shichijo and coworkers. The dosimetry required for this experiment is described here. Assessment of internal radiation doses was performed on the basis of measured 56Mn activity in the organs and tissues of the rats and of absorbed fractions of internal exposure to photons and electrons calculated with the MCNP-4C Monte Carlo using a mathematical rat phantom. The first results of this international multicenter study show that the internal irradiation due to incorporated 56Mn powder is highly inhomogeneous, and that the most irradiated organs of the experimental animals are: large intestine, small intestine, stomach, and lungs. Accumulated absorbed organ doses were 1.65, 1.33, 0.24, 0.10 Gy for large intestine, small intestine, stomach, and lungs, respectively. Other organs were irradiated at lower dose levels. These results will be useful for interpretation of the biological effects of internal exposure of experimental rats to powdered 56Mn as observed by Shichijo and coworkers.

Fatigue is one of the earliest nonspecific symptoms of radiation exposure in humans, but its etiology, mechanism, and dose dependency remain unexplained. Investigating initial behavioral changes caused by irradiation of animals might provide important information to aid understanding of early health effects of radiation exposure and clinical features of radiation injury. Although previous studies in rodents suggested that radiation exposure leads to reduced activity, detailed properties of the effects were unrevealed due to a lack of proper statistical analysis, which is needed to better elucidate details of changes in locomotor activity. Ten-week-old male Wistar rats were subjected to single point external whole-body irradiation with 60Co gamma rays at 0, 2.0, 3.5, and 5.0 Gy (4 rats per group). Infrared sensors were used to continuously record locomotor activity of each rat. Cumulative number of movements during the night was defined as “activity” for each day. A non-linear mixed effects model accounting for individual differences and daily fluctuation of activity was applied to analyze the rats’ longitudinal locomotor data. Despite a small number of animals per group, our statistical method successfully revealed characteristics of the changes in locomotor activity after radiation exposure, showing that 1) reduction in activity occurred immediately—and in a dose-dependent manner—after irradiation and 2) recovery to pre-irradiation levels required almost one week, with the same recovery rate in each dose group. In addition to improving our understanding of radiation effects on locomotor activity, this statistical framework should be useful to analyze other data with similar structure.

Investigating initial behavioral changes caused by irradiation of animals might provide important information to aid understanding of early health effects of radiation exposure and clinical features of radiation injury. Although previous studies in rodents suggested that radiation exposure leads to reduced activity, detailed properties of the effects were unrevealed due to a lack of proper statistical analysis, which is needed to better elucidate details of changes in locomotor activity. Ten-week-old male Wistar rats were subjected to single point external whole-body irradiation with 60Co gamma rays at 0, 2.0, 3.5, and 5.0 Gy (four rats per group). Infrared sensors were used to continuously record the locomotor activity of each rat. The cumulative number of movements during the night was defined as &ldquo, activity&rdquo, for each day. A non-linear mixed effects model accounting for individual differences and daily fluctuation of activity was applied to analyze the rats&rsquo, longitudinal locomotor data. Our statistical method revealed characteristics of the changes in locomotor activity after radiation exposure, showing that (1) reduction in activity occurred immediately&mdash, and in a dose-dependent manner&mdash, after irradiation and (2) recovery to pre-irradiation levels required almost one week, with the same recovery rate in each dose group.

Heart disease (HD) mortality is the second leading cause of death in Japan. The HD mortality risk among Atomic bomb survivors is slightly positive but shows a statistically significant dose-response relationship with initial radiation dose, as reported by the Radiation Effects Research Foundation. In that report, dosimetry was based on initial radiation only, with the effect of indirect radiation dose not taken into consideration. The atomic bomb radiation, however, consisted of both initial and residual radiation. We reevaluated the dose-response relationship for HD mortality using exposure distance (ground distance between the location where exposed and the hypocenter) as a surrogate indicator of radiation dose. At Hiroshima University, a cohort study has been conducted with Hiroshima Atomic Bomb Survivors (ABS) since 1970. We selected 29605 subjects from the ABS who were exposed at 3.5 km or less from the hypocenter and alive on January 1, 1970. These subjects, referred to as "Hiroshima hibakusha" in this paper, were followed until December 31, 2010. We stratified the cohort data with respect to sex and age at the time of bombing (ATB) into 10-year age groups. For each stratum, by applying an extended Cox regression model with time-dependent covariates, we analyzed the risk of HD mortality using either initial radiation dose or exposure distance as an explanatory variable. The results indicate a high excess risk in males and older age ATB females who were exposed near the hypocenter. This difference may be explained by the effect of female sex hormone on the circulatory system among young age ATB females. Some unknown risk factor related to exposure distance was also implicated in the elevated risk of HD among the Hiroshima hibakusha, especially in males. This necessitates further study.

Groups of Japanese and American scientists, supported by international collaborators, have worked for many years to ensure the accuracy of the radiation dosimetry used in studies of health effects in the Japanese atomic bomb survivors. Reliable dosimetric models and systems are especially critical to epidemiologic studies of this population because of their importance in the development of worldwide radiation protection standards. While dosimetry systems, such as Dosimetry System 1986 (DS86) and Dosimetry System 2002 (DS02), have improved, the research groups that developed them were unable to propose or confirm an additional contribution by residual radiation to the survivor's total body dose. In recognition of the need for an up-to-date review of residual radiation exposures in Hiroshima and Nagasaki, a half-day technical session was held for reports on newer studies at the 59 th Annual HPS Meeting in 2014 in Baltimore, MD. A day-and-a-half workshop was also held to provide time for detailed discussion of the newer studies and to evaluate their potential use in clarifying the residual radiation exposure to atomic bomb survivors at Hiroshima and Nagasaki. The process also involved a re-examination of very early surveys of radioisotope emissions from ground surfaces at Hiroshima and Nagasaki and early reports of health effects. New insights were reported on the potential contribution to residual radiation from neutron-activated radionuclides in the airburst's dust stem and pedestal and in unlofted soil, as well as from fission products and weapon debris from the nuclear cloud. However, disparate views remain concerning the actual residual radiation doses received by the atomic bomb survivors at different distances from the hypocenter. The workshop discussion indicated that measurements made using thermal luminescence and optically stimulated luminescence, like earlier measurements, especially in very thin layers of the samples, could be expanded to detect possible radiation exposures to beta particles and to determine their significance plus the extent of the various residual radiation areas at Hiroshima and Nagasaki. Other suggestions for future residual radiation studies are included in this workshop report.

There were two sources of ionizing irradiation after the atomic bombings of Hiroshima and Nagasaki: (1) initial gamma-neutron irradiation at the moment of detonation and (2) residual radioactivity. Residual radioactivity consisted of two components: radioactive fallout containing fission products, including radioactive fissile materials from nuclear device, and neutron-activated radioisotopes from materials on the ground. The dosimetry systems DS86 and DS02 were mainly devoted to the assessment of initial radiation exposure to neutrons and gamma rays, while only brief considerations were given for the estimation of doses caused by residual radiation exposure. Currently, estimation of internal exposure of atomic bomb survivors due to dispersed radioactivity and neutron-activated radioisotopes from materials on the ground is a matter of some interest, in Japan. The main neutron-activated radionuclides in soil dust were

Even after development of molecular targeting therapies, platinum-based chemotherapy is still a standard care for treatment of locally advanced non-small cell lung cancer (NSCLC). So far, critical molecular markers capable to predict the therapeutic response in NSCLC patients remain undetermined. We here attempted to identify novel biomarker genes for cisplatin (CDDP) for a tailored therapy. Initial screening to explorer association of IC(50) values of CDDP obtained by MTT assay and gene expression levels measured with oligonucleotide microarray and real-time RT-PCR provided 6 candidate genes, namely, NUBPL, C9orf30, ZNF12, TMEM158, GSK3B, and FBLP1 using 9 lung cancer cells consisting of 3 small and 6 NSCLC cells. These 6 genes together with 5 reported biomarkers, i.e., GSTP1, ERCC1, BRCA1, FRAP1, and RRM1, were subjected to a linear regression analysis using 12 NSCLC cell lines including 6 additional NSCLC cells: only FBLP1 and TMEM158 genes showed positive associations with statistical significances (P = .016 and .026, respectively). The biological significance of these genes was explored by in vitro experiments: Knockdown experiments in PC-9/CDDP cells revealed that the reduced expression of TMEM158 significantly decreased the chemo-resistance against CDDP (P

BACKGROUND AND PURPOSE: Volumetry may be useful for evaluating treatment response and prognosis of intraocular lesions. Phantom, volunteer, and patient studies were performed to determine whether ocular MR volumetry is reproducible. MATERIALS AND METHODS: Half-Fourier single-shot RARE and FSPGR sequences at 1.5T with a 76-mm-diameter surface coil were optimized to obtain still ocular images. Volumetry accuracies of each sequence were compared with simulated subretinal phantom volumes. Ocular volumetry was performed in 15 volunteers twice in 1 week by using contiguous axial images of the globes while the subjects stared at a target, and images were acquired in 2 seconds before the subjects were instructed to blink, with this process repeated as necessary. Imaging, intraobserver, and interobserver reproducibility for volumes of the whole eyeball and anterior chamber were assessed. Ocular volumetry was also performed in 6 patients with intraocular tumors before and after treatment. RESULTS: The phantom study demonstrated that measurement error rates with RARE were significantly lower than with FSPGR (P < .01). The volunteer study demonstrated excellent imaging and intraobserver reproducibility of RARE volumetry for whole eyeballs and anterior chambers (P < .01). Although no interobserver differences were observed in anterior chamber volume measurement (P = .33), there was a significant difference between the 2 observers in eyeball volume measurement (P < .01). Follow-up volumetric data were useful for treatment decisions in all patients. CONCLUSIONS: Ocular volumetry from contiguous ultrafast RARE images obtained during visual fixation is feasible in volunteer and patient studies and is superior to FSPGR images.

The aim of this study was to compare the three-dimensional fat-suppressed balanced non-steady-state free precession (3D FS-nSSFP) sequence and the 3D T1-weighted spoiled gradient-recalled echo (3D T1-GRE) sequence for evaluating lumbar nerve root compression with continuous thin-slice coronal magnetic resonance (MR) images.The institutional review board approved this study, and written informed consent was obtained from all 35 patients. We optimized continuous 2.5-mm thick lumbar coronal images with 3D FS-nSSFP and 3D T1-GRE. We calculated the contrast-to-noise ratio (CNR) for nerve roots and other structures on images with the two sequences. With knowledge of the final diagnosis, we assessed the visibility of nerve root compression on these images.The CNR values of nerve roots were significantly higher on images with 3D FS-nSSFP than on those with 3D T1-GRE. These continuous thin-slice coronal images facilitated visualization of nerve root compression in91% of patients. There was no statistically significant difference between the two sequences in the detection of nerve root compression.Continuous thin-slice coronal MR images using 3D FS-nSSFP and 3D T1-GRE sequences are sufficient to evaluate lumbar nerve root compression, and 3D FS-nSSFP is superior to 3D T1-GRE for depiction of lumbar nerve roots.

Our previous report demonstrated a good correlation between high telomerase activity of cancer tissues and a poor prognosis of patients with colorectal cancers, except for several cases. To elucidate the additional factors that contribute to patient prognosis, the correlation among the expression levels of telomere binding proteins (TBP), the lengths of telomeres, the lengths of telomere 3'-overhang (3'-OH) and telomerase activity in 106 paired colorectal cancer and corresponding noncancerous mucosa (NCM) specimens were examined. The expression levels of eight TBP genes (TRF1, TRF2, TIN2, TANK1, TANK2, POT1, RAP1 and TPP1) were analyzed. Among the 106 cases, 35 cases had shortened telomeres (7 kb), 15 had shortened 3'-OH (3'-OH length ratio of cancer/NCM0.5) and 88 were classified as telomerase-activated cancers (activity ratio of cancer/NCM2). Comparison between NCM and cancer in each case showed that all TBP except for POT1 were downregulated in cancers. A survival analysis using a Cox proportional hazard model showed that the survival rate of the telomerase-activated cases with shortened 3'-OH and that of telomerase-inactivated cases were significantly better than that of telomerase-activated cases without 3'-OH shortening, that is, restored or maintained 3'-OH (P = 0.018). In the telomerase-activated cancers, the length of 3'-OH was significantly correlated with the expression levels of POT1. Elongation of telomeric overhang by telomerase, which might be regulated by POT1, may contribute to the increase of malignant potential in colorectal cancers.

Purpose: To compare a half-Fourier single-shot rapid acquisition with relaxation enhancement (RARE) sequence with a balanced steady-state free precession (b-SSFP) sequence in the evaluation of the eye using magnetic resonance (MR) microscopy imaging and to clarify the usefulness of RARE microscopy imaging in evaluating nonoperative glaucoma patients and patients who have undergone surgery for glaucoma or cataract. Materials and Methods: One-mm and 2-mm slice thickness images of RARE sequence and b-SSFP sequence using a 1.5 T MR unit and a 23-mm microscopy coil were obtained in eight healthy volunteers. The signal-to-noise (S/N) ratio of aqueous humor in the anterior chamber was measured quantitatively and visualization of the anterior chamber anatomy was assessed qualitatively. Furthermore, we evaluated 21 glaucoma patients (including six postoperative patients) and four patients after cataract surgery with 2-mm slice thickness RARE MRI. Results: The 2-mm slice thickness RARE imaging had a significantly greater S/N ratio than the 1-mm slice thickness RARE imaging (P < 0.05) and acquired the best image quality among the four types of images (P < 0.01). Additionally, 2-mm slice thickness RARE microscopy imaging could depict anterior chamber anatomy of glaucoma eyes and eyes after cataract surgery. Conclusion: We believe that optimal fast T2-weighted MR microimaging might become a useful ophthalmologic examination technique. J. Magn. Reson. Imaging 2010;31:1210–1214. ©2010 Wiley-Liss, Inc.

市区町村別死亡率データを使用した死亡危険度の地理分布を把握するための統計的方法について考察した．方法は，人口規模で規定される円状近傍を用いて空間平滑化された値を期待値とするポアソンモデルに基づくものである．さらに，その平滑値に対してガンマ揺らぎモデルに基づく経験ベイズ法および交叉型尤度による修正についても検討した．提案された方法により，相対死亡危険度に関する標準化死亡比（SMR）の縮小推定量が求められ，各市区町村別の粗SMRが局所的なその近傍平均値の方へ縮小される．我々は，本方法を1993年から2002年の期間における日本での部位別悪性新生物死亡率データへ適用し分析を試み，その性能を検証した．その結果，空間分布の概観を把握する上で，ガンマ揺らぎモデルによる調整が有効であることが分かったが，単純平滑化に較べて顕著な向上は観られなかった.

Inference on gene expression change between two different samples is considered. We develop a mathematical model assuming that there exist two different functional states of a gene: “ON” and “OFF” . Each measured sample-specific gene expression intensity is described by an additive model, which accounts for fluctuations in absolute gene expression intensity and measurement error, to which a two-dimensional mixed normal model with four components considering the joint distribution of the sample “sum” and “difference” is approximated. We can successfully identify genes that are differentially expressed between two samples using posterior probabilities, while avoiding declaring false differences. The proposed methods are applicable to cDNA microarray data with two fluorescent dyes and to oligonucleotide data.

The purpose of this study is to examine the relationship between dioxin concentration in humans and their living environmental factors such as diet or residential district. We develop a nonlinear random effects regression model based on a pharmacokinetic model that explains dioxin accumulation in the human body. The model takes into consideration two points: individual differences in dioxin intake and historical exposure to dioxins. We apply the model to data collected by the Japanese Ministry of Health, Labour and Welfare.

Two problems impede the study of age dependency of tooth loss rate using dental radiographs. One is that the exact time of tooth loss is often unknown. The other is that major causes of tooth loss are assumed to result from tooth extraction by dentists. Recently dentists have avoided performing tooth extraction as summarily as in years past due to developments in dental technique and increased concern on oral health. The effect of these changes in dental practice cannot be ignored on the estimation of tooth loss probability. We devised a modification of survival analysis taking into account these two problems by using data consisting of repeated observations for each individual. A flexible statistical model allowing for individual variation in tooth loss hazard was adopted. The proposed method was shown to be valid by a Monte Carlo simulation study in which the true parameters describing age-dependency of tooth loss probability were given. We illustrated our method by applying it to actual tooth loss data from 1,284 panoramic radiographs from 642 patients obtained in a daily clinical practice where each patient underwent panoramic examination at least twice. The age-dependency of tooth loss probability for all kinds of teeth were estimated. The smaller variance of tooth loss hazard between individuals is observed on the molars compared with those of other kinds of teeth.

The relationship between oral signs and osteoporosis was investigated to assess the possibility of using this as an indicator of postmenopausal osteoporosis. Sixty-four women between the ages of 50 and 70 years were evaluated. Osteoporotic signs consisted of thoracic spine fracture as demonstrated on lateral chest radiographs. Oral signs were the number of teeth present, mandibular cortical width, alveolar bone resorption, and the morphologic classification of the inferior cortex on panoramic radiographs. The number of teeth present (N) was highly related to the probability of thoracic spine fracture and was used to derive the probability equation for the presence of thoracic spine fracture: probability value = 1/(1 + e-z), Z = 18.68-0.29 age -0.27N. A probability value higher than 0.5 suggests the possibility of thoracic spine fracture. It was concluded that this equation could serve as a simple and useful tool for dentists to assess the possibility of latent osteoporosis.

We investigated the correlation between age and the fractional anisotropy (FA) values of peripheral nerves in healthy adults and compared the age-corrected FA values of peripheral nerves in healthy subjects and patients with polyneuropathy. The institutional review board approved this study and informed consent was obtained from all participants before entry into the study. We optimized diffusion tensor imaging using a 3-T magnetic resonance scanner and an extremity coil for scanning tibial nerves. The effect of age and sex on the FA values of tibial nerves in healthy volunteers was investigated and the age-corrected FA values of tibial nerves in healthy volunteers and patients with polyneuropathy were compared. The maximum FA values of the tibial nerves remained constant until age 45 (approximately 0.516); they subsequently decreased by 0.004/year in healthy volunteers. After removing the effect of age with an age-adjusted equation, the median maximum FA values in the volunteers and patients were 0.518 (range, 0.406–0.616) and 0.442 (range, 0.376–0.530), respectively. The age-corrected FA values were significantly lower in the patients than the healthy volunteers (p

Background Microarray technology is a high-throughput method for measuring the expression levels of thousand of genes simultaneously. The observed intensities combine a non-specific binding, which is a major disadvantage with microarray data. The Affymetrix GeneChip assigned a mismatch (MM) probe with the intention of measuring non-specific binding, but various opinions exist regarding usefulness of MM measures. It should be noted that not all observed intensities are associated with expressed genes and many of those are associated with unexpressed genes, of which measured values express mere noise due to non-specific binding, cross-hybridization, or stray signals. The implicit assumption that all genes are expressed leads to poor performance of microarray data analyses. We assume two functional states of a gene - expressed or unexpressed - and propose a robust method to estimate gene expression states using an order relationship between PM and MM measures. Results An indicator 'probability of a gene being expressed' was obtained using the number of probe pairs within a probe set where the PM measure exceeds the MM measure. We examined the validity of the proposed indicator using Human Genome U95 data sets provided by Affymetrix. The usefulness of 'probability of a gene being expressed' is illustrated through an exploration of candidate genes involved in neuroblastoma prognosis. We identified the candidate genes for which expression states differed (un-expressed or expressed) when compared between two outcomes. The validity of this result was subsequently confirmed by quantitative RT-PCR. Conclusion The proposed qualitative evaluation, 'probability of a gene being expressed', is a useful indicator for improving microarray data analysis. It is useful to reduce the number of false discoveries. Expression states - expressed or unexpressed - correspond to the most fundamental gene function 'On' and 'Off', which can lead to biologically meaningful results.

Risk factors for low birth weight (LBW) have been indicated in many studies, but in Japan few studies have examined the amount of reduction in birth weight (BW). The goal of this study was to examine the association between maternal smoking among pregnant women and subsequent reduction in BW, corrected by the effect of potential confounders. To assess the effect of background factors other than maternal smoking, we established a model to estimate the contribution of each explanatory variable using logarithmic multiple regression. We then used the adjusted BW model to evaluate the direct effect of maternal smoking. To obtain information on maternal characteristics, including smoking status and characteristics of their infants, including BW, we conducted a questionnaire survey. After statistical adjustment for background factors, the mean of BW among infants of participants who smoked during pregnancy was roundtable significantly lower than that of non-smoking participants, but there was no verification of a dose-response relationship. However, mean BWs were not significantly different when comparing participants who quit smoking during pregnancy to non-smoking participants, suggesting that stopping smoking during pregnancy is beneficial.

Prior laboratory prediction of individual drug response is of key importance in esophageal squamous cell carcinoma (ESCC), because of the extremely narrow therapeutic index of chemotherapy. However, very few critical markers have been validated to date for ESCC. We previously demonstrated that simultaneous performance of two different types of comprehensive gene expression analysis might provide a way to identify potent marker genes for drug sensitivity from the expression-sensitivity correlation analysis alone, but the screening method appeared not to be always effective. Therefore, we attempted to identify novel potent marker genes using a new statistical analysis of oligonucleotide microarray expression data, based on a two-dimensional mixed normal model, and selected 3 and 7 novel candidates for 5-fluorouracil (5-FU) and cis-platinum (CDDP), respectively. Interferon induced transmembrane protein 1 (IFITM1) gene alone, being suggested as a key gene of Wnt pathway, was commonly selected in both screening methods. The transfection analyses and siRNA-mediated knock-down experiments revealed that expression of IFITM1 closely related to cellular sensitivity to CDDP. Considering the fact that drug sensitivity is determined by multiple genes, we established the best linear model using quantified expression data of a set of all the selected marker genes including IFITM1, which converted the quantified expression data of ESCC cell lines into an IC50 value of each drug. In the same way, using the representative genes selected in vitro, we developed highly predictive formulae for disease-free survival (DFS) of the CDDP/5-FU combination after curative operation in esophageal cancer patients (R=0.917). A two-dimensional mixed normal model can be a powerful tool to identify novel drug-response determinants, and the IFITM1 gene selected by the statistical method a novel critical biomarker of CDDP response in ESCC.

Age-specific distribution of clinical measurements in cross-sectional study is described in this paper. Since the distribution of measurements usually varies with age, a model with an age-dependent structure is needed. We propose here a statistical method for describing the age-specific distribution using an extension of the power-normal-model. The age-dependent parameters are to be estimated through a nonparametric smoothing technique based on the local likelihood method. As a consequence, we can compute a smoothed percentile curve of measurements with reference to age. Several kinds of clinical measurements are analyzed to determine the proposed method.

Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuvant chemotherapy gives a better chance of survival, we attempted to develop a chemosensitivity prediction model to improve individual responses to therapy. Comprehensive gene expression analyses (cDNA and oligonucleotide microarrays) and MTT assay of 8 drugs in 20 KYSE squamous cell carcinoma cell lines were performed to distinguish candidate marker genes whose expression levels reproducibly correlated with cellular drug sensitivities. After confirmation with real-time RT-PCR, we performed multiple regression analyses to develop drug-sensitivity prediction formulae using the quantified expression data of selected marker genes. Using the same sets of genes, we also constructed prediction models for individual clinical responses to 5-FU-based chemotherapy using 18 cases. We selected 5 better marker genes, known as drug sensitivity determinants, identified 9 novel predictive genes for 4 of 8 anticancer drugs [5-FU, CDDP, DOX, and CPT-11 (SN-38)], and developed highly predictive formulae of in vitro sensitivities to the 4 drugs and clinical responses to 5-FU-based adjuvant chemotherapies in terms of overall and disease-free survivals. Our selected genes are likely to be effective drug-sensitivity markers and formulae using the 9 novel genes would provide advantages in prediction.

We attempted to identify potent marker genes using a new statistical analysis and developed a prediction system for individual response to platinum/paclitaxel combination chemotherapy in ovarian cancer patients based on the hypothesis that expression analysis of a set of the key drug sensitivity genes for platinum and paclitaxel could allow us to predict therapeutic response to the combination. From 10 human ovarian cancer cell lines, genes correlative in the expression levels with cytotoxicities of cisplatin (CDDP) and paclitaxel were chosen. We first selected five reliable prediction markers for the two drugs from 22 genes already known as sensitivity determinants and then identified another 8 novel genes through a two-dimensional mixed normal model using oligomicroarray expression data. Using expression data of genes quantified by real-time reverse transcription-PCR, we fixed the best linear model, which converted the quantified expression data into an IC50 of each drug. Multiple regression analysis of the selected genes yielded three prediction formulae for in vitro activity of CDDP and paclitaxel. In the same way, using the same genes selected in vitro, we then attempted to develop prediction formulae for progression-free survival to the platinum/paclitaxel combination. We therefore constructed possible formulae using different sets of 13 selected marker genes (5 known and 8 novel genes): Utility confirmation analyses using another nine test samples seemed to show that the formulae using a set of 8 novel marker genes alone could accurately predict progression-free survival (r = 0.683; P = 0.042). [Mol Cancer Ther 2006;5(3):767–75]

It is widely accepted that activation of telomerase and maintenance of telomeres play central roles in cellular immortalization for most cancer cells. However, they seem to be insufficient for normal human cells. To elucidate critically responsible genes for telomerase mediated cellular immortalization in non-cancerous cells, we explored the genes that are differentially expressed throughout the immortalization process of normal human cells using cDNA microarrays with novel normalization procedures. We found that the number of genes, differentially expressed during cellular immortalization after ectopic expression of telomerase, dramatically increased in a later phase, especially in fibroblasts. We identified 18 and 20 genes/ESTs dysregulated throughout the cellular immortalization processes in fibroblasts and endothelial cells, respectively, but none of them overlapped. Only BGN and COL5A2 were commonly downregulated, except for at early phase in fibroblasts, and a few genes showed controversial expression changes, with regard to previous reports in cancer cells. These findings indicate that normal somatic cells would require cell-type specific events in addition to telomerase activation, and a rare population that eventually experience such events would acquire immortality. The key molecules that distinguish the immortalization mechanisms in cancerous and non-cancerous cells may become crucial targets for anticancer therapy and regenerative therapy.

We developed concise, accurate prediction models of the in vitro activity for 8 anticancer drugs (5-FU, CDDP, MMC, DOX, CPT-11, SN-38, TXL and TXT), along with individual clinical responses to 5-FU using expression data of 12 genes. We first performed cDNA microarray analysis and MTT assay of 19 human cancer cell lines to sort out genes which were correlative in expression levels with cytotoxicities of the 8 drugs; we selected 13 genes with proven functional significance to drug sensitivity from a huge number of potent prediction marker genes. The correlation significance of each was confirmed using expression data quantified by real-time RT-PCR, and finally 12 genes (ABCB1, ABCG2, CYP2C8, CYP3A4, DPYD, GSTP1, MGMT, NQO1, POR, TOP2A, TUBB and TYMS) were selected as more reliable predictors of drug response. Using multiple regression analysis, we fixed 8 prediction formulae which embraced the variable expressions of the 12 genes and arranged them in order, to predict the efficacy of the drugs by referring to the value of Akaike's information criterion for each sample. These formulae appeared to accurately predict the in vitro efficacy of the drugs. For the first clinical application model, we fixed prediction formulae for individual clinical response to 5-FU in the same way using 41 clinical samples obtained from 30 gastric cancer patients and found to be of predictive value in terms of survival, time to treatment failure and tumor growth. None of the 12 selected genes alone could predict such clinical responses.

We previously demonstrated that a new statistical analysis of oligomicroarray expression data based on a two-dimensional mixed normal model could provide a way to identify potent markers for drug sensitivity from the expression-sensitivity correlation analysis alone in esophageal squamous cell carcinoma (ESCC), and the selected genes, 3 for 5-FU and 6 for CDDP, were likely better drug-sensitivity markers, some of which may be the novel drug-response determinants, and developed highly predictive formulae in vitro and in vivo using expression data of a set of the all selected marker genes (100th AACR Annual Meeting). But interestingly, among these selected genes, empty spiracles homolog 2 (EMX2) showed discrepancies between chemo-sensitivity in vitro and patient prognosis in vivo, which led us to focus on the gene. EMX2, the homolog to the ‘empty spiracles’ gene in Drosophila, encodes a homeobox-containing transcription factor, which is critical for central nervous system but has not been reported as a prognostic factor in any cancers so far. So, we attempted to clarify the biological function of EMX2 in cancer cells whether it would be a drug-response determinant or a colony formation capacity determinant through the gene transfection analyses and the soft agar colony formation assay in vitro. Gene transfection analyses demonstrated that the ectopic expression of EMX2 did not correlate with the sensitivity to 5-FU in ESCC cell lines, excluding the former capacity. Meanwhile, we found that in 20 ESCC cell lines, while 9 cell lines with EMX2 little expression showed weak or none colony formation capacity, those with high EMX2 expression showed strong capacity in level dependent manner. Furthermore, colony formation capacity was reduced in EMX2 expression level-dependent manner by siRNA-mediated knockdown in cell lines with high EMX2 expression, suggesting a possible capacity as a colony formation capacity determinant. Using multiple regression analyses, we could develop highly predictive formulae of clinical prognosis in the patients treated with 5-FU/CDDP combination therapy using only 2 selected markers including EMX2, instead of using all the selected genes (Disease free survival: R of the model = 0.798, R of test sample: 0.828; Disease specific survival: R of the model = 0.828, R of test sample: 0.951), and confirmed that expression of EMX2 was a poor prognostic factor in the prediction formulae. These results indicate that EMX2 is the indispensable gene of anchorage-independent growth for ESCC, and high EMX2 expression level is associated with the early recurrence in ESCC. We propose that EMX2 is a novel and potent prognostic maker for ESCC, and elucidation of its molecular mechanism may help to develop new molecular targeting drugs that improve the patient prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1731.

Intra-axonal recording and horseradish peroxidase (HRP) injection techniques were employed the response properties of low-threshold mechanoreceptive afferents and the morphological characteristics of their axon arbors in the main sensory nucleus (Vp) and oral nucleus (Vo). Thirteen afferents were characterized and recovered. One gave fast or rapidly adapting (FA) and 3 slowly adapting (SA) responses to mystacial vibrissa deflection, 5 were sensitive to deflection of non-vibrissae hairs or hair (4 were guard hair afferents and the other responded to deflection of a long hair in slowly adapting fashion) and two were responsive to indentation of the hairy skin. The remainder were responsive to indentation of the glabrous skin on the lower lip: one was of FA type and the other of SA type. All of the axons had bifurcating fibers that ascended in the ascending tract (ascending fiber) and descended in the trigeminal spinal tract (descending fiber). The main collaterals given off from the ascending fiber and rostral segment of the descending fiber terminated in the Vp, and the other collaterals from the descending fiber projected to the Vo. Terminal arbors produced by the main collaterals formed a rostrocaudally continuous column, but generally the adjacent arbors did not overlap except when pairs of collaterals arose near each other on the ascending and descending fibers. Projections of collaterals to Vp and Vo were organized topographically. The head was represented in an inverted fashion with its anteroposterior axis in a mediolateral sequence, but the lower glabrous lip was represented more dorsally than the other mandibular facial regions. Vibrissa afferents formed a rostrocaudally continuous, densely packed terminal column throughout the length of Vp and Vo. SA vibrissa afferents gave rise to more dense and roundish arbors in Vp than the FA afferent, while the Vo.c arbors were more compact and smaller than those of the FA afferent. Guard hair afferents had arbors that were highly variable throughout the nuclei and were characterized by less developed arbors in Vp than in Vo. Unlike vibrissa afferents, hairy skin afferents gave rise to sparseand wide spread arbors characterized by a string-like appearance, while the Vo collaterals were more stringly. Facial lip afferents were characterized by a great difference in collateral morphology between FA and SA type. The FA fiber had a strong resemblance to those of hairy skin, while the SA fiber gave rise to more dense and larger arbors in Vp, contrary to the Vo collaterals with less developed and stringlike arbors. Statistical comparison of data from distinct functional types indicated trends that supported the above-described qualitative observations. The total number of boutons (Vp + Vo), and numbers of boutons and boutons per collateral in Vp were significantly larger in SA fibers than in FA fibers had significantly larger boutons than SA fibers. The average size of boutons became successively smaller in the following fiber groups, vibrissa, guard hair, hairy skin and lip afferents. The present findings that a distinctive morphology in the terminal arborizations has a good correlation with a functional segregation among the cytoarchitectonically different zones of the trigeminal sensory nuclear complex (TSNC) were consistent with our previously described data on periodontal and tooth pulp afferents (see ref. 34).

The physiology and morphology of masticatory motoneurons of adult cats were examined by the methods of intracellular recording and intracellular injection of horseradish peroxidase. Masseter and jaw-opening motoneurons were identified by intracellular recordings of the antidromic response following stimulation of the masseter and mylohyoid nerves, respectively. An excitatory postsynaptic potential (EPSP) was recorded from masseter neurons by stimulation of the masseter nerve with stimulus intensity below threshold for antidromic response. In contrast, the EPSP was not recorded from jaw-opening motoneurons by stimulation of the mylohyoid nerve with stimulus intensity below threshold for antidromic response. Patterns of postsynaptic potentials (PSPs) in the masseter motoneurons following stimulation of the tooth pulp or periodontal afferents were classified into 4 types: hyperpolarization (n = 40), depolarization-hyperpolarization (n = 9), hyperpolarization-depolarization (n = 5), and depolarization with spike potentials (n = 10). On the other hand, patterns of the PSPs in the jaw-opening motoneurons following stimulation of the same afferents were classified into two types: depolarization with spike potentials (n = 19), and hyperpolarization (n = 5). Twenty-five masseter and 7 jaw-opening motoneurons and an intranuclear neuron were reconstructed from serial sections in the transverse plane. On the basis of dendritic morphology, the masseter motoneurons could be classified into two major groups, type I (n = 15) and type II (n = 9), whereas two neurons were found to constitute a separate category of the masseter motoneuron. The dendritic distributions of all the jaw-opening motoneurons examined were generally similar and there was no indication of the existence of subtypes, whereas there were 2 or 3 subgroups in type I and type II masseter motoneurons. Type I masseter neurons had primary dendrites which extended radially in all directions, and the whole profile of their dendritic trees presented a spherical and an egg-shaped appearance. In type II masseter neurons, the origin of primary dendrites was bipolar or tripolar, and the whole profile of their dendritic trees presented a hemispherical and mirror-imaged, funnel-shaped appearance. The other two masseter motoneurons had a particular dendritic tree which was much simpler in configuration, with less tapering or branching than those of other neurons examined. In contrast, the dendritic profiles of all the jaw-opening motoneurons were similarly organized and showed vertically oriented dendritic trees which were more developed in the dorsomedial than in the ventrolateral direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Intra-axonal recording and horseradish peroxidase (HRP) injection techniques were employed to define the response properties of low-threshold mechanoreceptive periodontal afferents and of the tooth pulp afferents and the morphological characteristics of their axon arbors in the nucleus principalis (Vp) and rostrodorsomedial (Vo.r) and dorsomedial parts (Vo.dm) of the nucleus oralis (Vo). The central terminals of 3 fast adapting (FA) and 4 slowly adapting (SA) periodontal afferents and 4 tooth pulp (TP) afferents were recovered for detailed analyses. Stained axons in the trigeminal sensory tract ascended and descended (bifurcating fibers), or descended without bifurcation (descending non-bifurcating fibers). The ratio of the bifurcating fibers to the descending non-bifurcating fibers was about three to one for each type of afferents. The main collaterals given off from the ascending branches terminated in the Vp. Most collaterals given off from the descending branches terminated in the Vo with the exception of few instances. In case of the FA afferents, the ascending branches gave off all main collaterals into the Vp with rostrocaudal and dorsoventral continuities in their arbors, whereas the descending branches gave off all main collaterals, except two collaterals, into the Vo with rostrocaudal discontinuities. The projections from the FA afferents to the Vo.dm was predominant in terms of the number of boutons and the length of preterminal and terminal branches. In case of the SA afferents, the collaterals from the ascending and descending branches formed rostrocaudally and dorsoventrally discontinuous terminal arbors. In terms of the density of boutons the SA afferents were divided into two subtypes. One had a preferential projection into the Vp or Vo, whereas others lacked a selective projection. In case of the TP afferents, the main collaterals of the ascending branches formed partially overlapping terminal arbors, but the terminal arbors formed by the collateral of the descending branches did not overlap. The frequency of collaterals of the TP afferents was less than of the other types of afferents. The terminal arbors including the density of boutons of the pulpal afferents were less extensive than those of the other types of afferents. The average size of varicosities became smaller in the following subdivisions, Vp, Vo.r and Vo.dm for SA and TP afferents. The size of varicosities of the TP afferents was smaller and that of the FA afferents was larger than that of the SA afferents. This study demonstrates that a distinctive morphology in the terminal arborizations has a good correlation with a functional segregation among the cytoarchitectonically different zones of the trigeminal sensory nuclear complex (TSNC).

While there is a considerable number of studies on the relationship between the risk of disease or death and direct exposure from the atomic bomb in Hiroshima, the risk for indirect exposure caused by residual radioactivity has not yet been fully evaluated. One of the reasons is that risk assessments have utilized estimated radiation doses, but that it is difficult to estimate indirect exposure. To evaluate risks for other causes, including indirect radiation exposure, as well as direct exposure, a statistical method is described here that evaluates risk with respect to individual location at the time of atomic bomb exposure instead of radiation dose. In addition, it is also considered to split the risks into separate risks due to direct exposure and other causes using radiation dose. The proposed method is applied to a cohort study of Hiroshima atomic bomb survivors. The resultant contour map suggests that the region west to the hypocenter has a higher risk compared to other areas. This in turn suggests that there exists an impact on risk that cannot be explained by direct exposure.

Intra-axonal recording and horseradish peroxidase (HRP) injection techniques were employed to define the response properties of periodontal mechanoreceptive afferents originating from the trigeminal mesencephalic nucleus (Vmes) and their morphological characteristics. The periodontal Vmes neurons were classified into two types: slowly adapting (SA) and fast adapting (FA) types. The central terminals of 7 SA and 4 FA afferents were recovered for detailed analyses. The whole profile of SA and FA neurons were unipolar in shape and their cell bodies were located in the dorsomedial parts of the Vmes. The united (U) fiber traveled caudally from the soma to the dorsolateral aspect of the trigeminal motor nucleus (Vmo), where it split into the peripheral (P) and C fibers with a T- or Y-shaped appearance. The P fiber joined the trigeminal sensory or motor tract. The C fiber descended caudally within Probst's tract. All 3 stem fibers issued main collaterals. The main collaterals of all neurons examined formed terminal arbors in the supratrigeminal nucleus (Vsup) and all but two SA neurons projected to the intertrigeminal region (Vint), while the projections to other nuclei of the trigeminal motor nucleus (Vmo), juxtatrigeminal region (Vjux), main sensory nucleus (Vp) and oral nucleus (Vo.r) differed between SA and FA afferents and between neurons of the same type. The SA and FA neurons were classified into three and two subgroups, respectively. The major differences in central projections between the two types were that all the FA neurons projected to the Vp or Vo.r but none of SA type and this relation was reversed in the projection to the Vjux, and that more than half of SA neurons projected to Vmo but only one FA neuron to the Vmo. The Vmes neurons which sent their collaterals into the Vmo had the P fiber passing through the tract of the trigeminal motor nerve. The average size of somata and mean diameters of U fibers and main collaterals from C fiber were significantly larger in SA neurons than FA neurons. The average size of fiber varicosities became smaller in the following nuclei, Vmo, Vsup, Vp, Vint and Vo.r, but not significant between the two functional types. The functional role of the periodontal Vmes afferents to jaw reflexes was discussed particularly with respect to their central projection sites in the brainstem nuclei.

Masticatory motoneurons were identified electrophysiologically and stained with horseradish peroxidase (HRP). The masseter motoneurons could be divided into 3 groups on the basis of their dendritic morphology. In contrast, the digastric or mylohyoid motoneurons showed a similar dendritic configuration. These neurons had much developed dendritic trees in the dorsomedial than ventrolateral direction. The first group of the masseter motoneurons had their dendritic trees which extended radially in all directions with a slight preference to project rostrally. These somata were located in the center of the subdivision containing the masseter motoneurons. In the second group, their dendritic arbores had a polarity extending hemispherically. These neuronal somata were located in the medial, ventral, and lateral regions of the subdivision. For the masseter motoneurons in the two groups and jaw-opening motoneurons, the dendritic swellings were frequently observed in the distal branches. The third group had their dendritic trees which were much simpler in configurations with less tapering or branching than those of other neurons examined. Furthermore, a wide variety of dendritic spines and appendages, and no dendritic swellings, observed in the third group were distinct from other neurons stained. The dendritic trees of the jaw-closing and -opening motoneurons were confined to the individual subdivisions. There were no instances in which axon collaterals were observed for well-stained 16 axons.