Earliest known hominin activity in the Philippines by 709 thousand years ago.

Over 60 years ago, stone tools and remains of megafauna were discovered on the Southeast Asian islands of Flores, Sulawesi and Luzon, and a Middle Pleistocene colonization by Homo erectus was initially proposed to have occurred on these islands1-4. However, until the discovery of Homo floresiensis in 2003, claims of the presence of archaic hominins on Wallacean islands were hypothetical owing to the absence of in situ fossils and/or stone artefacts that were excavated from well-documented stratigraphic contexts, or because secure numerical dating methods of these sites were lacking. As a consequence, these claims were generally treated with scepticism 5 . Here we describe the results of recent excavations at Kalinga in the Cagayan Valley of northern Luzon in the Philippines that have yielded 57 stone tools associated with an almost-complete disarticulated skeleton of Rhinoceros philippinensis, which shows clear signs of butchery, together with other fossil fauna remains attributed to stegodon, Philippine brown deer, freshwater turtle and monitor lizard. All finds originate from a clay-rich bone bed that was dated to between 777 and 631 thousand years ago using electron-spin resonance methods that were applied to tooth enamel and fluvial quartz. This evidence pushes back the proven period of colonization 6 of the Philippines by hundreds of thousands of years, and furthermore suggests that early overseas dispersal in Island South East Asia by premodern hominins took place several times during the Early and Middle Pleistocene stages1-4. The Philippines therefore may have had a central role in southward movements into Wallacea, not only of Pleistocene megafauna 7 , but also of archaic hominins.

Greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in a population of elderly Japanese men with relatively low dietary calcium intake: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study.

UNLABELLED: The effects of milk intake on bone health are not clear in elderly Asian men with low dietary calcium intake. This study showed that greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in community-dwelling elderly Japanese men. INTRODUCTION: The consumption of milk or dairy products is widely recommended for maintaining bone health regardless of gender or age. However, little evidence exists on the beneficial effects of milk intake on bone health in elderly Japanese men characterized with relatively low dietary calcium intake. Here we examined whether or not greater milk intake was associated with lower bone turnover, higher bone density, and stronger bone microarchitecture in community-dwelling elderly Japanese men. METHODS: Interviews were conducted to obtain information on medical history and lifestyle, including the amount of habitual milk intake, nutrient intake calculations based on a 1-week food diary, and measurements of areal bone mineral density (aBMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) by dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS) using DXA images at LS, and biochemical markers of bone turnover in sera. Participants with a history of diseases or medications that affect bone metabolism, or with missing data, were excluded from the analysis. RESULTS: The median intake of milk in the 1479 participants (mean age, 73.0 ± 5.1 years) was one glass of milk per day. Bone turnover markers showed a decreasing trend (p < 0.05) and aBMD at TH (p = 0.0019) and FN (p = 0.0057) and TBS (p = 0.0017) showed increasing trends with greater milk intake after adjusting for demographic and behavioral confounding factors. This association was attenuated after further adjusting for nutrient intake, in particular, calcium intake. CONCLUSIONS: Greater milk intake was associated with lower bone turnover, higher aBMD, and higher TBS in community-dwelling elderly Japanese men.

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN Interaction: Gamma-Ray Spectroscopy of _{Λ}

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

A pilot survey on obstetric complications in pregnant women with a history of repeated embryo implantation failure and those undergoing single local endometrial injury.

PURPOSE OF INVESTIGATION: To assess if a history of repeated implantation failure (RIF) or local endometrial injury (LEI) for RIF affects the pregnancy course in women who conceived in the subsequent in vitro fertilization (IVF)-embryo/blastocyst transfer (ET/BT) cycle. MATERIALS AND METHODS: Of 42 pregnant women with a history of three consecutive failed ET/BT cycles with negative pregnancy tests, 11 patients had a clinical pregnancy in the immediate subsequent ET/BT cycle following (the RIF group), whereas 31 patients had a clinical pregnancy in the subsequent ET/BT cycle following single curettage LEI in the proliferative phase of the preceding spontaneous cycle (the RIF/LEI group). Information on the obstetric complications were retrieved from medical records and compared with that of women who had a live birth in the first ET/BT attempt (the control group). Results: The clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were significantly higher in the RIF/LEI group than in the RIF group (p < 0.010). There were no significant differences in the incidence of pregnancy of unknown location, ectopic pregnancy, miscarriage, stillbirth, preterm birth, premature rupture of the membranes, placenta previa, placental abruption, preeclampsia, pregnancy-induced hypertension, gestational diabetes, fetal growth restriction, caesarean section, and blood transfusion were similar between the three groups (p > 0.31). CONCLUSION: In this pilot survey, neither a history of RIF nor LEI intervention for RIF increased the incidence of obstetric complications in the women who conceived in the subsequent ET/BT cycle.

Comparison of non-vertebral fracture between minodronate and risedronate therapy in elderly female patients with Alzheimer disease.

OBJECTIVES: Minodronate is a nitrogen-containing bisphosphonate that is commercially available for the treatment of osteoporosis in Japan. Preclinical studies demonstrated that minodronate is at least 10 times more potent than alendronate in inhibiting bone resorption in vivo. A high incidence of fractures, particularly of the hip, represents an important problem in Alzheimer disease (AD) patients who are prone to falls and may have osteoporosis. METHODS: A total of 256 elderly patients with AD were assigned to daily treatment with 1.0 mg of minodronate or a daily treatment with risedronate combined with daily 1000 IU ergocalciferol and 1200 mg elemental calcium, and followed up for 12 months. RESULTS: At baseline, patients of both groups showed low 25-hydroxyvitamin D with compensatory hyperparathyroidism. Non-vertebral fractures occurred in 5 patients in the minodronate group and 7 patients in the risedronate group (5 hip fractures; one fracture each at the distal forearm and pelvis). There was no difference in risk of hip fracture between the two groups (p=.70; odds ratio=0.8). CONCLUSIONS: The study medications were well tolerated with relatively few adverse events and were equivalent in reducing the risk of a fracture in elderly patients with AD.

Taphonomy and chronosequence of the 709 ka Kalinga site formation (Luzon Island, Philippines).

The recently described site of Kalinga in the Philippines adds to our understanding of Early-Middle Pleistocene hominin behaviour. Yet, disentangling the natural from the anthropogenic modifications that have taken place in such an old archaeological site is challenging. In this paper we use a set of taphonomic tools at hand to rectify the distortion made by natural processes during the formation of the Kalinga site. From the description of the ribs completeness, surface damages and scattering in the excavation, one can reconstruct the butchery, transport and deposition sequence of the rhino carcass and its post-depositional disturbances and diagenetic evolution of the site. We conclude that the rhino and the stone artefacts potentially used to deflesh the carcass were transported by a mudflow from its butchery place over a few meters only and got stuck and mixed with an older faunal assemblage that was transported by a small stream.

Influences of entopeduncular nucleus stimulation upon electromyogram activity of masticatory muscles.

Influences of stimulation of the entopeduncular nucleus (Ep) upon electromyogram (EMG) activity of masticatory muscles were examined. In the rat lightly anesthetized with halothane, high frequency (HF) microstimulation (trains of 20, 333-Hz cathodal pulses at 30-60 microA) and GABA microinjection (0.2-0.6 microl of 10 mM GABA dissolved in physiological saline) were performed in the Ep by using a three-barreled microelectrode. EMG activity was recorded from the anterior digastrics and the anterior superficial masseter muscles by using two fine enamel-insulated copper wires. The EMG activity was also evoked by the GABA microinjection. The effect of the GABA microinjection was negated by the microinjection of bicuculline prior to the GABA microinjection. The EMG activity was classified into the tonic spike-type, burst-type, or mixed type on the basis of the waveform. In each rat, the location of the microelectrode tip was estimated by observing a series of serial frontal sections through the whole rostrocaudal extent of the Ep. The present data suggested that Ep neurons involved in elicitation of tonic spike-type activity in the jaw muscles might be located mainly in the rostral third of the Ep, and that Ep neurons implicated in provocation of burst-type activity in jaw muscles might be located in the caudal third of the Ep. Possible neuronal pathways from the Ep to motoneurons innervating the masticatory muscles were discussed. The present data shed new light on the control mechanisms of the basal ganglia upon jaw movements.

VLDL triglyceride kinetics in Wistar fatty rats, an animal model of NIDDM: effects of dietary fructose alone or in combination with pioglitazone.

The effects of dietary fructose alone or in combination with a new oral agent, pioglitazone, on VLDL-triglyceride (TG) turnover were studied in genetically obese Wistar fatty rats characterized by hyperinsulinemia (7,488 +/- 954 pmol/l), hyperglycemia, (22.5 +/- 1.4 mmol/l), and hypertriglyceridemia (4.39 +/- 0.54 mmol/l). They had an increased hepatic TG production (16.2 +/- 0.1 micromol/min; lean rats, 5.4 +/- 0.3 micromol/min) as well as a longer half-life of VLDL-TG from lean donors (8.8 +/- 1.4 min, lean recipients; 2.3 +/- 0.9 min). In addition, in lean recipients, the half-life of VLDL-TG from fatty donors was longer than that from lean donors (4.80 +/- 0.56 vs. 3.14 +/- 0.23 min). Although feeding fructose into fatty rats did not change plasma glucose and insulin levels, it produced a twofold increase in TG levels (8.74 +/- 1.15 mmol/l). This was associated with a 1.7-fold increase in TG production to 27.5 +/- 1.2 micromol/min, while no significant change was found in the half-life of lean VLDL-TG in fructose-fed fatty recipients (10.9 +/- 2.4 min) or in that of VLDL-TG from fructose-fed fatty donors in lean recipients (4.46 +/- 0.76 min). Daily administration of pioglitazone (3 mg/kg body weight) in fructose-fed fatty rats ameliorated glycemia and triglyceridemia to the level of lean rats (8.1 +/- 0.7 and 1.18 +/- 0.05 mmol/l, respectively) and insulinemia to a lesser extent (2,712 +/- 78 pmol/l). A fall in TG levels was associated with improvement of an impairment in the ability of fructose-fed fatty rats to remove lean VLDL-TG (half-fife: 2.6 +/- 0.6 min). Pioglitazone, however, produced no change in TG production (25.9 +/- 2.7 micromol/min), the half-life of VLDL-TG from fructose-fed fatty donors in lean recipients (4.17 +/- 0.38 min), or the activity of lipoprotein lipase and hepatic lipase in postheparin plasma. We conclude that in Wistar fatty rats 1) hypertriglyceridemia is attributed to TG overproduction and impaired TG catabolism, and the latter is due to changes in both VLDL, such that they are less able to be removed, and changes in the nature of Wistar fatty rats, such that they are less able to remove VLDL-TG; 2) fructose further increases hepatic TG production with a resultant deterioration in hypertriglyceridemia; 3) pioglitazone normalizes TG levels by altering the physiology of the Wistar fatty rats in a manner that increases their ability to remove VLDL-TG from the circulation.

Use of a 3D structure data base for understanding sequence-dependent conformational aspects of DNA.

The roll-twist-slide correlation in the DNA crystal structures that are collected in the Nucleic Acid Data Base is analyzed in order to obtain a general understanding of the effects of the nucleotide sequence on the 3D structure of a dinucleotide step. It is concluded that the differences between the pyrimidine bases and the purine bases in terms of their physical shapes are the major factors that determine the stereochemical characteristics of the steps through base to backbone and base to base interactions. The characteristics are further modulated by the differences between the A:T and G:C base-pairs, which can be explained by enhancement of the purine-pyrimidine asymmetry in the A:T base-pair.

Control of oro-facio-lingual movements by the substantia nigra pars reticulata: high-frequency electrical microstimulation and GABA microinjection findings in rats.

To provide direct evidence for substantia nigra pars reticulata (SNr) control of oro-facio-lingual muscle activity, high-frequency electrical microstimulation (mainly trains of 20, 333-Hz cathodal pulses at 40-60 microA) and GABA microinjection (1-5 microl of 10 mM GABA in saline) were carried out using a three-barreled microelectrode at the same SNr site in lightly anesthetized, chronically decorticated rats (n=39). Decortication eliminated the possibility that SNr microstimulation might activate corticofugal fibers descending in the adjoining cerebral peduncle. When the most ventral layer of the SNr was approached, high-amplitude electromyographic (EMG) activity of up to 6 mV with a distinctive waveform appeared synchronously with electrical stimuli in the anterior digastric, masseter, genioglossus, and levator labii superioris muscles. This EMG activity was evoked bilaterally, with an ipsilateral predominance. Eye movements, mostly rotation of the eyeball vertically down in the orbit, were noted. Infrequent blinking was also noted. Histologic examination localized the effector site to the middle third of the mediolateral extent of the caudal SNr corresponding to between 5.8 mm (level of the oculomotor nerve) and 6.5mm (caudal end of the SNr) caudal to bregma; and to the ventralmost peripeduncular region of the SNr corresponding to 7.7 mm to 8.0 mm beneath the cortical surface. We referred to this site as the substantia nigra pars reticulata oro-facio-lingual (SNr-ofl) region. GABA injection produced tonic EMG discharge with consistent amplitude in all of the four muscles studied. The GABA effect was negated by a preceding microinjection of the GABA-A receptor antagonist bicuculline, whereas saline control injection had no effect. Changes in amplitude of evoked EMG activity according to location of the stimulating microelectrode reflected somatotopic organization of the SNr-ofl region. This extremely localized electrical and receptor microstimulation in the SNr produced synchronized powerful contraction of jaw, tongue, and facial muscles with different neural innervation. These findings advance our understanding of the mechanisms of the SNr concerning oro-facio-lingual movements.

A transcription frame-based analysis of the genomic DNA sequence of a hyper-thermophilic archaeon for the identification of genes, pseudo-genes and operon structures.

An algorithm for identifying transcription units, independently regulated genes and operons, and pseudo-genes that are not expected to be expressed, has been developed by combining a system for predicting transcription and translation signals, and a system for scoring the triplet periodicity in ORF candidates. By using the algorithm, the 1.09 Mb sequence that covers approximately 60% of the genome of Pyrococcus sp. OT3 has been analyzed. The identified ORFs show the expected biological and physical characteristics, while the rejected ORF candidates do not. Frequent use of operon structures for transcription, and gene duplication followed by mutation or termination of the duplicated genes, are discussed.

Convergence of cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain.

Because of the likely involvement of central convergence of afferent inputs in mechanisms underlying referred pain, the activity of single neurones was recorded in the cat's trigeminal (V) subnucleus caudalis (medullary dorsal horn) to test for the presence and extent of convergent inputs to the neurones. In chloralose-anaesthetized or decerebrate unanaesthetized cats, electrical stimuli were applied to afferents supplying facial skin, oral mucosa, canine and premolar tooth pulp, laryngeal mucosa, cervical skin and muscle, and jaw and tongue muscles, and tactile and noxious mechanical and thermal stimuli were applied to skin and mucosa. Considerable proportions of caudalis neurones which could be functionally classified on the basis of their cutaneous receptive field properties as low-threshold mechanoreceptive (LTM), wide-dynamic-range (WDR), or nociceptive-specific (NS) neurones, could be excited by electrical stimulation of several of these afferent inputs. Extensive convergence of afferent inputs, including inputs from skin or mucosal areas outside the neuronal oral-facial receptive field delineated by natural stimuli, was a particular feature of the units classified as cutaneous nociceptive neurones (i.e., WDR and NS). On the basis of antidromic activation, 15% of these WDR and NS neurones were shown to have a direct projection to the contralateral thalamus. The findings question the use of terminology and classifications of somatosensory neurones based only on the cutaneous receptive field properties of the neurones since distinctions between the different neuronal populations become less obvious when properties other than those related to cutaneous afferent inputs are taken into account. Moreover, the observations of extensive convergence of different types of afferents, which was especially apparent in cutaneous nociceptive neurones, also suggest a role for these neurones in mediating deep pain and in spread and referral of pain.

Aberrant expression of bcl-2 gene family in Down's syndrome brains.

Down's syndrome (DS) patient brains are known to develop prematurely the same degenerative changes as those seen in Alzheimer's disease (AD). On the assumption that the apoptotic mechanism is involved in the neuronal loss in DS, we have investigated the expression of the bcl-2 gene family in DS brains and found marked alterations. The most prominent changes were in the temporal lobes where neuronal loss was greatest. Our findings suggest that a apoptotic process is involved in the neuronal loss in DS.

Structural analysis of nucleic acids by precise denaturing gradient gel electrophoresis: II. Applications to the analysis of subtle and drastic mobility changes of oligo- and polynucleotides.

Precise denaturing gradient gel electrophoresis was effectively applied to various kinds of oligo- and polynucleotides. The analyses on oligonucleotides revealed that every oligonucleotide has its own characteristic normalized mobility profile (NMP), which can be used to identify, characterize and classify the molecules. The precise system also enabled us to obtain unequivocally the mobility transitions corresponding to the melting of hairpin structures of oligonucleotides, single-stranded (ss) DNAs, and RNAs. Another application to co-migration and separate migration experiments demonstrated that there were significant binding interactions between two species of ss molecules of similar mobility, even when they have little complementarity with each other. When the precise temperature gradient gel electrophoresis was applied to double-stranded DNAs, it could be confirmed with high reliability that the mobility transitions observed correspond to cooperative meltings and strand dissociations. Through these experiments, mu m, a parameter defined as a mobility transition point, was shown to be effective to deal with those phenomena quantitatively.

Response characteristics of primary periodontal mechanoreceptive neurons in the trigeminal mesencephalic nucleus to trapezoidal mechanical stimulation of a single tooth in the rat.

The response characteristics of primary periodontal mechanoreceptive neurons in the trigeminal mesencephalic nucleus (MeNV) were studied by changing the rate and magnitude of trapezoidal pressure applied to the upper incisor in very lightly anesthetized rats. Using a metal microelectrode in the MeNV either for recording or for stimulation, the projection site of primary afferents in the anterior superior alveolar nerve innervating the upper incisor was determined. Its stereotaxic coordinates were 1.0--2.0 mm posterior to the interaural plane and 1.2--1.3 mm lateral to the mid-sagittal plane, corresponding to the caudal part of the MeNV. From this site of 19 animals, single unitary activity from 41 primary periodontal mechanoreceptive neurons was recorded, which were identified by: (1) the constant, brief latency of 1.0--4.0 ms (2.0 +/- 0.6 ms, mean +/- S.D.) from the onset of single tooth tapping; (2) the wave forms of their unitary spike responses; and (3) the ability to follow faithfully trains of repetitive stimuli applied to the anterior superior alveolar nerve at rates of more than 100 Hz for 2 s. The responses of the identified primary mechanoreceptive neurons in the MeNV were tested for repetitive tapping and trapezoidal pressure to the ipsilateral upper incisor. The highest frequency of one-to-one following was observed in repetitive tapping at 100 Hz. All of the 27 tested neurons exhibited such very rapid adaptation as to show only on-off responses to trapezoidal pressures, and did not respond at all unless the pressures were applied more rapidly than 0.6 Newtons/s (N/s). In most of these neurons, the number of evoked spikes was greater in on-responses than in off-responses, and the number and frequency of spikes were increased with an increase in the rate of pressure application. But in several neurons only one spike was triggered even when the pressures were applied at the rate of more than 83.1 N/s.

Functional properties of the primary motor cortex and ventral premotor cortex in the monkey during a visually guided jaw-movement task with a delay period.

This study investigated single neuronal activity in the face area of the primary motor cortex (MI) and ventral part of the premotor cortex (PMv) while a monkey performed a visually guided jaw-movement task with a delay period. When the monkey executed the jaw movements, 48 MI and 53 PMv neurons showed statistically significant activities time-locked to jaw movements and were defined as movement-related neurons. The activities of movement-related neurons could be classified into phasic, phasic-tonic and tonic patterns based on the changes in discharge rate. Most of the neurons exhibiting phasic and phasic-tonic activities probably contributed to the initiation of jaw movements, since they exhibited transient responses immediately after the onset of the go-cue indicating the jaw movement. In contrast, the sustained activity of the movement-related neurons exhibiting phasic-tonic and tonic activities may be involved in controlling and/or maintaining jaw position. Sustained activity was also detected during the delay period in 4 MI and 29 PMv neurons and these neurons were defined as set-related neurons. It is thought that these set-related neurons are involved in the preparation for the subsequent jaw movement, since the masticatory muscles showed no significant changes during the delay period. These findings suggest that the MI may be involved predominantly in the initiation and control of jaw movements, and that the PMv may be involved in motor preparation, and may play a role as a higher-order motor area related to the initiation and control of jaw movements.

Neostriatal stimulation activates tongue-protruder muscle, but not tongue-retractor or facial muscles: an electrical and chemical microstimulation study in rats.

Whether electrical microstimulation of a rat's striatal jaw region (SJR) in fact induced tongue or facial muscle activity in addition to jaw muscle activity was tested. Microstimulation of SJR-evoked EMG activity in a jaw-opener (anterior digastricus) and tongue-protruder (genioglossus). No activity was evoked in jaw-closers (temporalis or masseter), tongue-retractor (hyoglossus) or in facial muscles. In addition, the EMG effect could still be induced after extensive ablation of the neocortex; it was reproduced by microinjection of 50 mM kainic acid into SJR. The effective sites were histologically localized to a small central striatal region adjoining the anterior commissure. These findings may be of considerable value in understanding the striatal mechanism of orolingual dyskinesia involving involuntary jaw and tongue movements.

Dopamine receptor antagonists increase markedly the quantity of retrograde transport of HRP in the rat masseteric motoneuron.

Horseradish peroxidase (HRP) was injected, bilaterally, into the rat masseter muscle, subsequent to an intramuscular or intraperitoneal injection of one of five dopamine antagonists (chlorpromazine and haloperidol as the D1 and D2 receptor antagonist, SCH 23390 as the specific D1 receptor antagonist, sulpiride and domperidone as the specific D2 receptor antagonist). Control rats received an injection of a corresponding vehicle solution. After a survival period of 16 h, the brainstem was cut into 60 microns cryosections and processed with the TMB technique. The amount of retrogradely transported HRP was quantitatively measured in terms of the amount of HRP reaction product present in the motoneuron by the method which we have developed using an image processing system combined with a light microscope and a TV camera. Chlorpromazine, haloperidol, SCH 23390 and sulpiride significantly raised the quantity of retrograde transport of HRP. On the contrary, domperidone which can not penetrate the blood-brain barrier showed no significant change in the amount of the retrograde transport. In addition, an intravenous injection of chlorpromazine (8 mg/kg) was found to increase the amplitude of monosynaptic masseteric reflex EMG activity evoked by stimulations of the mesencephalic trigeminal nucleus. These results suggest that a possible regulatory system involving the dopamine receptor in the uptake and retrograde transport of HRP from axon terminals to cell bodies of the masseteric motoneuron exists in higher order neurons which make synaptic contact with the motoneuron.

Innervation of the tooth pulp by the mesencephalic trigeminal nucleus in the cat: a retrograde horseradish peroxidase study.

HRP was applied to the tooth pulp of 8 cats. Six were subjected to postoperative administration of the anti-inflammatory drug, prednisolone, whereas the remaining two were not. In all prednisolone-treated cats, labeled neurons were found in both the mesencephalic trigeminal nucleus and trigeminal ganglion, ipsilaterally. On the other hand, no labeled neurons were observed in the mesencephalic nucleus in cats receiving no steroid.

Further observation of Japanese Creutzfeldt-Jacob disease with widespread amyloid plaques.

An autopsy case of Creutzfeld-Jacob disease with widespread amyloid plaques is reported. A 45-year-old Japanese man, whose father had died of a similar disease, had a 5-year illness characterized by progressive cerebellar signs. Mental changes and brain-stem signs developed in the late stage. Myoclonus frequently occurred. Akinetic mutism ensued. The autopsy revealed spongiform encephalopathy with widespread amyloid plaques and extensive degeneration of the white matter. This disease, Western Gerstmann-Sträussler-Scheinker disease and panencephalopathic type of Creutzfeld-Jacob disease are discussed.