Elevated expression of protease-activated receptor 1 via ΔNp63 down-regulation contributes to nodal metastasis in oral squamous cell carcinoma.

Protease-activated receptor 1 (PAR1) is known as a thrombin receptor. Recent studies have reported PAR1 expression in various malignancies; however, its role in oral squamous cell carcinoma (OSCC) requires clarification. A previous study showed that down-regulation of ΔNp63, a homolog of p53, augments PAR1 expression in OSCC. In the present study, the association of PAR1 expression with clinicopathological findings in OSCC was examined retrospectively. Expression of PAR1, thrombin, and ΔNp63 was examined immunohistochemically in OSCC specimens. Patients were divided into three groups based on the expression pattern of PAR1 at the invasive front: group A, PAR1-negative in both cancer and stromal cells; group B, positive in stromal cells but negative in cancer cells; group C, positive in both cancer and stromal cells. Histologically high-grade tumours were significantly more common in group C. Patients in group C had the highest incidence rate of nodal metastasis (P<0.001) and a lower survival rate (P=0.085) than those in the other groups. At the invasive front, in group C, thrombin was expressed but ΔNp63 expression was weak. These results indicate that increased PAR1 expression in both cancer and stromal cells could be a useful predictive marker of nodal metastasis and that ΔNp63 is involved in regulating PAR1 expression.

The influence of viscosity-enhancing agents on oral absorption of drugs.

The objective of this study was to evaluate the influence of viscosity-enhancing agents on oral absorption of metoprolol (MPL) and bisoprolol (BPL). Although the viscosity values were similar for MPL and BPL in hydroxypropyl methylcellulose (HPMC, 1.2 % (w/w)) and polyvinyl alcohol (PVA, 8.8 % (w/w)) solutions, the order of diffusion rate constants of the drugs in media were phosphate buffer solution (reference) > HPMC solution > PVA solution. In in vivo rat intestinal absorption experiments showed that the Cmax and AUC values of the drugs were lowest when they were administered into the rat jejunum in a PVA solution. In vitro binding studies showed that this may have been due to adsorption of the drugs to PVA molecules, resulting in decreased free fractions of the drugs. Our results indicated that intestinal absorption of the drugs in PVA solution was influenced both by decreased diffusion of the drugs and by interaction with PVA. Since various viscosity-enhancing agents are widely used as pharmaceutical and food additives, these findings may be of significance for understanding therapeutic efficacy and safety of oral drug products.

Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma.

Programmed cell death ligand 1 (PD-L1) and its receptor PD-1 are immune checkpoint molecules that attenuate the immune response. Blockade of PD-L1 enhances the immune response in a variety of tumours and thus serves as an effective anti-cancer treatment. However, the biological and prognostic roles of PD-L1/PD-1 signalling in oral squamous cell carcinoma (OSCC) remain to be elucidated. The purpose of this study was to examine the correlation of PD-L1/PD-1 signalling with the prognosis of OSCC patients to assess its potential therapeutic relevance. The expression of PD-L1 and of PD-1 was determined immunohistochemically in 97 patients with OSCC and the association of this expression with clinicopathological characteristics was examined. Increased expression of PD-L1 was found in 64.9% of OSCC cases and increased expression of PD-1 was found in 61.9%. Univariate and multivariate analysis revealed that increased expression of PD-L1 and PD-1 positively correlated with cervical lymph node metastasis. The expression of CD25, an activated T-cell marker, was negatively correlated with the labelling index of PD-L1 and PD-1. Moreover, the patient group with PD-L1-positive and PD-1-positive expression showed a more unfavourable prognosis than the group with PD-L1-negative and PD-1-negative expression. These data suggest that increased PD-L1 and PD-1 expression is predictive of nodal metastasis and a poor prognosis and is possibly involved in cancer progression via attenuating the immune response.

Fermi level pinning by gap states in organic semiconductors.

We measure the gap density of states and the Fermi level position in thin-film transistors based on pentacene and dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) films grown on various surfaces using Kelvin probe force microscopy. It is found that the density of states in the gap of pentacene is extremely sensitive to the underlying interface and governs the Fermi level energy in the gap. The density of gap states in pentacene films grown on bare silicon dioxide (SiO(2)) was found to be larger by 1 order of magnitude compared to that in pentacene grown on SiO(2) treated with hexamethyldisilazane and larger by 2 orders of magnitude compared to that of pentacene grown on aluminum oxide (AlO(x)) treated with a self-assembled monolayer (SAM) of n-tetradecylphosphonic acid (HC(14)-PA). When DNTT was grown on HC(14)-PA-SAM-treated AlO(x), the gap density of states was even smaller, so that the Fermi level pinning was significantly reduced. The correlation between the measured gap density of states and the transistor performance is demonstrated and discussed.

Motor neuron disease with dementia combined with degeneration of striatonigral and pallidoluysian systems.

This study concerns an autopsy case of motor neuron disease with dementia (MND-D) that exhibited unusual clinical and neuropathological findings. The patient was a Japanese man without any relevant family history who was 60 years old at the time of death. His clinical manifestation included character change at the age of 54, followed by frozen gait, dysarthria and bradykinesia and he was diagnosed with Parkinson's disease. He gradually developed spastic paresis and died of respiratory failure 6 years after onset of the illness. Neuropathological examinations showed prominent degeneration in the striatonigral and pallidoluysian systems in addition to the neuronal loss and microvacuolation in the second to third layers of the frontal and temporal cortex, the involvement of the upper and lower motor neuron systems and the presence of ubiquitinated neuronal inclusions. To our knowledge, five cases of motor neuron disease (MND) combined with pallido-nigro-luysian atrophy (PNLA) have been reported previously, but the present case is the first report of MND-D combined with the degeneration of the striatonigral and pallidoluysian systems. Such an association may represent more than a coincidental occurrence, and it suggests that MND-D is not simply a disease of the motor neuron system but a multisystem degeneration.

Constituents of holothuroidea. 10. Isolation and structure of a biologically active ganglioside molecular species from the sea cucumber Holothuria leucospilota.

Three ganglioside molecular species, HLG-1 (1), HLG-2 (2), and HLG-3 (3) have been obtained from the lipid fraction of the chloroform/methanol extract of the sea cucumber Holothuria leucospilota. The structures of these gangliosides have been determined, on the basis of chemical and spectroscopic evidence, as 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (1), 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->4)-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (2) and 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-neuraminosyl)-(2-->4)-(N-aetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moieties were composed of heterogeneous phytosphingosine, sphingosine and 2-hydroxy fatty acid units. Compounds 2 and 3 represent new ganglioside molecular species. These three ganglioside molecular species showed neuritogenic activity toward the rat pheochromocytoma cell line, PC-12 cell, in the presence of NGF (nerve growth factor).

Selective recognition of consecutive G sequence in double-stranded DNA by a zinc(II)-macrocyclic tetraamine complex appended with an anthraquinone.

A zinc (II) complex with a macrocyclic tetraamine appended with an anthraquinone ((9,10-anthraquinon-2-yl)methyl-1,4,7,10-tetraazacyclododecane, ZnL, anthraquinonyl-cyclen) selectively recognizes consecutive G sequence in double-stranded DNA. The affinity of the Zn2+-anthraquinonyl-cyclen to consecutive dG groups in DNA was disclosed by comparison of K(app) values (=[DNA-bound ZnL]/[uncomplexed ZnL][uncomplexed nucleobase in DNA]) determined by the UV spectrophotometric titrations at pH 8, I=0.1 (NaNO3), and 25 degrees C for poly(dG) x poly(dC) (K(app) = 1.5 x 10(5) M(-1)), poly(dG-dC)2 (2.8 x 10(4) M(-1)), poly(dA-dT)2 (4.3 x 10(4) M(-1)), and calf thymus DNA (2.8 x 10(4) M(-1)). The corresponding K(app) values with the Zn2+-free ligand were 5.3 x 10(3) M(-1), 7.4 x 10(3) M(-1), 7.4 x 10(3) M(-1), and 5.9 x 10(3) M(-1), respectively. The selective recognition of consecutive G sequence was concluded from the DNase I footprinting of SV40 early promotor DNA fraction (197 bp) containing a TATA box and six GC boxes. The present finding is in remarkable contrast to the previous selective T-recognition by Zn2+-cyclen complexes appended with acridine, quinoline(s), and naphthalene(s) [J. Am. Chem. Soc. 121 (1999) 5426]. While the Zn2+-acridinyl-cyclen inhibited TATA binding protein from interacting with a TATA box consensus DNA [J. Inorg. Biochem. 79 (2000) 253], the present Zn2+-anthraquinonyl-cyclen inhibited the Sp1 transcriptional factor protein from interacting with a GC box-consensus DNA.

Neurons and extracellular neurofibrillary tangles in the hippocampal subdivisions in early-onset familial Alzheimer's disease: a case study.

We have investigated morphometrically unaffected neurons, intracellular neurofibrillary tangles (I-NFT) and extracellular neurofibrillary tangles (E-NFT) in eight subdivisions of the hippocampal cortex in two cases of early-onset familial Alzheimer's disease (FAD) and six cases of early-onset sporadic Alzheimer's disease (SAD). The hippocampal subdivisions examined included: CA4, CA3, CA2, CA1, prosubiculum, subiculum and presubiculum (PRE), parasubiculum (PARA) and entorhinal cortex (ENT). CA3, CA2 and CA1 in the FAD cases showed more severe neuronal loss and much greater E-NFT formation than in the SAD cases, while ENT in both the FAD cases showed less neuronal loss and less E-NFT formation. These data suggest that the cornu ammonis is affected more severely than the ENT in the FAD cases. These observations indicate that hippocampal pathology in the FAD cases is qualitatively as well as quantitatively different from that in sporadic cases. These results provide further evidence for pathological heterogeneity in AD, although the number of FAD cases examined is very small.

Effects of serotonergic agents on the up-regulation of dopamine D2 receptors induced by haloperidol in rat striatum.

We examined the modulatory effect of serotonergic activities on haloperidol-induced up-regulation of dopamine D2 receptors in rat striatum. Chronic treatment with haloperidol (0.1, 0.5 mg/kg, i.p., 3 weeks) increased the number of dopamine D2 receptors, while no increase was observed with the atypical antipsychotic drugs clozapine (10 mg/kg) and trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1 H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (ORG 5222; 0.25 mg/kg). Chronic treatment with 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), a nonselective serotonin (5-hydroxytryptamine, 5-HT) receptor agonist (2.5 mg/kg), or with citalopram, a 5-HT reuptake inhibitor (10 mg/kg), potentiated the haloperidol (0.1 mg/kg)-induced up-regulation of dopamine D2 receptors, while that with (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist (0.1 mg/kg) had no influence on the dopamine D2 receptor up-regulation. Coadministration of ritanserin (1 mg/kg), a 5-HT2A/2C receptor antagonist, with a low dose of haloperidol (0.1 mg/kg), but not with a high dose of the agent (0.5 mg/kg) attenuated the dopamine D2 receptor up-regulation, Drug occupation of 5-HT2A and dopamine D2 receptors in vivo examined using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was 69.8% and 45.1%, respectively, after the acute administration of haloperidol (0.1 mg/kg) plus ritanserin (1 mg/kg). This profile, that 5-HT2A receptors are highly occupied compared with dopamine D2 receptors, was similar to that of clozapine or ORG 5222. These results suggest that potent 5-HT2A receptor antagonism versus weak dopamine D2 receptor blockade may be involved in the absence of up-regulation of dopamine D2 receptors after chronic treatment with clozapine or ORG 5222.

[TCR alpha beta + CD4- CD8- T cells among the peripheral blood mononuclear cells of myasthenia gravis patients].

We investigated the occurrence of TCR alpha beta + CD4- CD8- mononuclear cells (DN alpha beta T cells) and TCR gamma delta + CD3+ mononuclear cells (gamma delta T cells) among the peripheral blood mononuclear cells of 22 myasthenia gravis patients (MG) and 22 controls in order to examine whether extrathymic T cell subpopulations might be responsible for the pathogenesis of MG. The differences between the mean percentages of both DN alpha beta T cells and gamma delta T cells in the MG patients (DN alpha beta T cells: 0.53 +/- 0.51%, gamma delta T cells: 3.45 +/- 2.79%) and the controls (DN alpha beta T cells: 0.32 +/- 0.16%, gamma delta T cells: 3.81 +/- 2.36%) were not significantly different. However, higher DN alpha beta T cells ratios (1.48 approximately 1.84%) were noted in three MG patients. Thymectomy and subsequent thorough dissection of the anterior mediastinum 3 years after thymectomy had no effect on the symptoms of one patient, a 25-year-old woman without thymoma. The other two patients, a 45-year-old man and a 41-year-old woman without thymoma, had recurrences despite long-term remissions (14 years and 30 years, respectively) after thymectomy. Examination of DN alpha beta T cells, which are probably generated extrathymically without negative selection, may play an important role in understanding the pathogenesis in these three cases of MG.

Pathology of the cerebellar dentate nucleus in sporadic olivopontocerebellar atrophy: a morphometric investigation.

The pathology of the cerebellar dentate nucleus was investigated by morphometric methods in three patients with sporadic olivopontocerebellar atrophy (sOPCA), and the results were compared to specimens from three subjects without neurological disease (controls). The size of dentate neurons; the number of small and large neurons (50-199 microns2 and larger than 200 microns2, respectively) at rostral, middle, and caudal levels; nerve cell density; total volume of the gray band; and total nerve cell number, were estimated with an image analyzer applied to serial 20-microns-thick sections of one celloidin-embedded cerebellar hemisphere. The number of small neurons in patients with sOPCA was significantly increased at the rostral level while the number of large neurons showed large inter-individual variations. Dentate neurons also showed various qualitative changes such as atrophy and hypertrophy. The nerve cell density in the dentate nucleus was 1.7 times higher in the patients than in the controls. However, the total volume of the gray band was reduced to one-half of that in controls. There were no differences in the total nerve cell number between the patients and controls. This reduction in size of the dentate gray matter in patients with sOPCA may result from the disappearance of afferent nerve fibers originating from Purkinje cells, inferior olivary neurons, and pontine neurons.

[The effect of plasmapheresis with high-dose intravenous methylprednisolone therapy on cytokine synthesis of peripheral blood monocyte from patients with myasthenia gravis].

We studied interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2) production by peripheral blood monocyte (PBM) from 7 patients with myasthenia gravis (MG) receiving plasmapheresis (PP) (PP therapy only, one patient; PP+high dose intravenous methylprednisolone therapy (pulse therapy: pu therapy), 6 patients) to evaluate the effects of PP therapy on cytokine synthesis of PBM from MG patients. Immediately after PP, PBM IL-2 production decreased and PBM IL-1 beta production increased. In a patient receiving PP only, PBM IL-2 production increased again and PBM IL-1 beta production maintained the high value through the next day. But in 6 patients receiving PP+pu therapy, PBM IL-2 production maintained significantly (p < 0.01) through the next day compared with a patient receiving PP only. In four patients receiving repeated PP+pu therapy, as PBM IL-2 production gradually reduced, the severity of MG improved. These findings suggest that PP in MG had the effects of down-regulation of PBM IL-2 production and up-regulation of PBM IL-1 beta production, and that PP+pu therapy combined with PP suppresses the enhanced PBM IL-1 beta synthesis in MG patients.

Delirium associated with Joseph disease.

Three Japanese patients with Joseph disease from different families developed sleep disturbance, followed by delirium at the middle to end stage. Brain CT scans of the three patients showed brainstem tegmental atrophy. EEG revealed slowing of background activity. Two necropsy cases showed degeneration of the reticular formation, raphe nuclei and locus ceruleus in the brainstem tegmentum in addition to the common pathological findings of Joseph disease. The clinicopathological correlation between the delirium and the brainstem tegmental atrophy in Joseph disease is discussed.

[A study on the pharmacological properties of atypical antipsychotic drugs: in vivo dopamine and serotonin receptor occupancy by atypical antipsychotic drugs in the rat brain].

In vivo occupancy by typical or atypical antipsychotic drugs of dopamine D-1, D-2 and serotonin (5-HT)2 receptors in the membranes and slices of the rat brain was measured using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist at these receptor sites. In the membranes, the occupancy of D-1 receptors in the striatum by all tested drugs except cis-flupenthixol was minimal. Typical antipsychotic drugs such as chlorpromazine (10 mg/kg), haloperidol (1 mg/kg), cis-flupenthixol (1 mg/kg) and zotepine (5 mg/kg) occupied predominantly D-2 receptors in the striatum. Among atypical antipsychotic drugs, sulpiride (30 mg/kg) and amperozide (1 mg/kg) had no effect on the EEDQ-induced reduction in D-1, D-2 or 5-HT2 receptors, whereas clozapine (10 mg/kg), fluperlapine (10 mg/kg), risperidone (1 mg/kg), setoperone (0.25 mg/kg) and ORG 5222 (0.25 mg/kg) occupied mainly 5-HT2 receptors in the frontal cortex. In the slices, the occupancy by all tested drugs of D-1 receptors in the striatum, nucleus accumbens and substantia nigra was minimal with the exception of clozapine which showed about 30% occupancy in the substantia nigra. Typical antipsychotic drugs, chlorpomazine (10 mg/kg) and haloperidol (1 mg/kg) occupied predominantly D-2 receptors in the striatum and the nucleus accumbens. On the other hand, atypical antipsychotic drugs, clozapine (10 mg/kg) and risperidone (1 mg/kg), occupied mainly 5-HT2 receptors in the frontal cortex. These results suggest that there is a certain group of atypical antipsychotic drugs characterized by high occupancy of 5-HT2 receptors and low or minimum occupancy of D-2 receptors. These characteristics may be relevant to their weak potency in producing extrapyramidal side effects in man or catalepsy in rodents. Although we could find no clear regional differences in receptor occupancies by these antipsychotic drugs, further study are needed to elucidate this issue.

Dopamine D1, D2 and serotonin2 receptor occupation by typical and atypical antipsychotic drugs in vivo.

In vivo occupation of dopamine D1 and D2 and serotonin (5-HT)2 receptors by typical and atypical antipsychotic drugs (APD) was examined using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, which nonselectively and irreversibly inactivates these receptor sites. APD were classified as typical or atypical based on their capacity to induce extrapyramidal side effect in humans and/or catalepsy in laboratory rodents. Pretreatment of rats with typical APD (haloperidol, 0.25-3 mg/kg; chlorpromazine, 5-10 mg/kg; cis-flupenthixol, 1 mg/kg; zotepine, 5 mg/kg; nemonapride, 0.5-2 mg/kg) potently reversed the N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline-induced D2 receptor inactivation in rat striatum. In contrast, some atypical APD or its candidates (clozapine, 5-30 mg/kg; fluperlapine, 10 mg/kg; risperidone, 0.25-3 mg/kg; setoperone, 0.025-0.25 mg/kg; ORG 5222, 0.25 mg/kg) showed considerable occupation of 5-HT2 receptors in cerebral cortex with smaller or negligible occupation of D2 and D1 receptors. Pretreatment with the other atypical APD (sulpiride, 30 mg/kg; amperozide, 1 mg/kg) had no effect on these three receptors, although at higher doses, sulpiride (60 mg/kg) and amperozide (5 mg/kg) slightly but significantly reversed D2 and 5-HT2 receptor inactivation, respectively. It was concluded that a certain group of atypical APD is characterized by high occupancy of 5-HT2 receptor with lower or minimal occupancy of D2 and D1 receptors in vivo. The relevance of these characteristics of atypical APD was discussed in relation to extrapyramidal side effects and the therapeutic effects on schizophrenia.

Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy--an immunocytochemical and Gallyas silver impregnation study.

A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities.

Pathology of the cerebellar dentate and interpositus nuclei in Joseph disease: a morphometric investigation.

Cerebellar dentate and interpositus nuclei pathology was studied morphometrically in 3 patients with Joseph disease compared to 3 control subjects. Size of neurons, number of small neurons (cell body area: 50-199 microns 2) and large neurons (cell body area: 200 microns 2 or greater) at the rostral, medial and caudal levels, neuronal cell density, total volume of the gray bands, and total neuronal cell number were evaluated in the dentate, emboliform, and globose nuclei, using an image analyzer, after making horizontal serial 20-microns thick sections of a unilateral cerebellar hemisphere embedded in celloidin. The number of large neurons in Joseph disease was around 20% of that in the controls at each level in the individual nucleus (P less than 0.05 or P less than 0.01). In contrast, the number of small neurons was significantly reduced only at the caudal level of the dentate nucleus (P less than 0.05). The neuronal cell density was decreased within the nuclei. The total volume of the gray bands was reduced to about 70% within the nuclei (P less than 0.05 or P less than 0.01). The total number of neurons was decreased to about a third, a half, and a third within the dentate (P less than 0.001), emboliform (P less than 0.01), and globose nuclei (P less than 0.001), respectively. The principal pathologic change of the dentate and interpositus nuclei in Joseph disease was severe loss of neurons, with significant loss of the large neurons, indicating that Joseph disease is a type of cerebellar efferent system disorder.

[Cytoskeletal proteins abnormalities in olivopontocerebellar atrophy].

A highly sensitive silver technique for glial cytoplasmic inclusions in olivopontocerebellar atrophy (OPCA) was applied to 15 subjects with neurodegenerative disorders including 4 patients with OPCA, 4 patients with Joseph disease and with 3 normal control subjects, and the argyrophilic structures in the OPCA cases were immunocytochemically examined. As a result, the argyrophilic structures were found in the OPCA cases and Alzheimer cases. The argyrophilic structures included the white matter oligodendroglia, and neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus. The pontocerebellar tracts and the surrounding white matter of the inferior olivary nucleus contained a small number of argyrophilic nerve fibers with a hollow structure, which were interpreted as myelin. Immunocytochemistry demonstrated that the oligodendroglia in the white matter had immunoreactivities to an paired helical filament (PHF), microtubule associated protein 5 (MAP5), tau and ubiquitin antiserum, and the astroglia in the white matters had an immunoreactivity to a MAP5 antiserum. In the putamen, pontine nucleus and inferior olivary nucleus, in addition to the immunoreactivities observed in the oligodendroglia, the neurons were immunoreactive for PHF, MAP5, tau and ubiquitin antisera, and the astroglia had the same immunoreactivities as the neurons except for being tau negative in the putamen. The nerve fibers in the pontocerebellar tract and inferior olivary nucleus capsule were strongly positive for myelin basic protein and negative for PHF antiserum. These findings indicate that the Gallyas positive argyrophilia in the OPCA subjects is closely associated with PHF or tau.