Keiko Otani

Oral signs as indicators of possible osteoporosis in elderly women

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.

Physiological and morphological characteristics of cat masticatory motoneurons--intracellular injection of HRP.

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)

Physiological and morphological characteristics of periodontal mesencephalic trigeminal neurons in the cat — intra-axonal staining with HRP

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 Probsts 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.

Central terminations of periodontal mechanoreceptive and tooth pulp afferents in the trigeminal principal and oral nuclei of the cat.

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 that 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Morphology of central terminations of low-threshold trigeminal primary afferents from facial skin in the cat — intra-axonal staining with HRP

Intra-axonal recording and horseradish peroxidase (HRP) injection techniques were employed to examine 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 sparse and widespread arbors characterized by a string-like appearance, while the Vo collaterals were more stringy. Facial lip afferents were characterized by a great difference in collateral morphology between FA and SA type.(ABSTRACT TRUNCATED AT 400 WORDS)

Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes.

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 Akaikes 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.

Morphology of masticatory motoneurons stained intracellularly with horseradish peroxidase

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.

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

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]

Investigation on circular asymmetry of geographical distribution in cancer mortality of Hiroshima atomic bomb survivors based on risk maps: analysis of spatial survival data

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.

Workshop Report on Atomic Bomb Dosimetry--Review of Dose Related Factors for the Evaluation of Exposures to Residual Radiation at Hiroshima and Nagasaki.

AbstractGroups 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 59th 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.