Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome.

The regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.

Characteristic brain hypoperfusion by 99mTc-ECD single photon emission computed tomography (SPECT) in patients with the first-episode schizophrenia.

OBJECTIVE: In this study, we evaluated brain perfusion in patients with first-episode medicated schizophrenia using the new analytical method, statistical parametric mapping (SPM) applied to single photon emission computed tomography (SPECT). METHOD: We performed SPECT with 99-Tc-ethyl cysteinate dimer (99mTc-ECD) of the brain and magnetic resonance imaging (MRI) in patients with schizophrenia (n=30) and control subjects matched for age and gender (n=37). A voxel-by-voxel group analysis was performed using SPM2 (Z>3.0, P<0.001, uncorrected for multiple comparisons). RESULT: In comparison with control subjects, the volumes of the bilateral frontal areas were found to be decreased on MRI. Blood flow was found to be reduced in the bilateral temporal areas in the patients with schizophrenia on SPECT. CONCLUSION: In this study, patients with first-episode schizophrenia appeared to have significant bilateral temporal hypoperfusion, although temporal volumes were not significantly decreased in comparison with control subjects. Abnormality of temporal lobe blood flow in schizophrenia may show that functional changes occur earlier than structural changes, and may assist in the diagnosis of schizophrenia.

Jaw-opening dystonia (Brueghel's syndrome) associated with cavum septi pellucidi and Verga's ventricle - a case report.

Jaw-opening dystonia (oromandibular dystonia with jaw-opening; Brueghel's syndrome) is a rare condition, and only a limited number of cases have been reported in the literature. However, many patients may remain undiscovered or misdiagnosed, like a patient described previously. A case (40-year-old man) of jaw-opening dystonia (oromandibular dystonia with jaw-opening; Brueghel's syndrome) is reported. In this case, brain anomalies, cavum septi pellucidi and Verga's ventricle, were observed on magnetic resonance imaging of the brain. This case and a review of the literature indicate the presence of organic factors in the etiology of Brueghel's syndrome. The etiological relationship of brain anomalies in Bruegel's syndrome is discussed.

Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone.

We report the case of a 62-year-old man who was administered sodium valproate (VPA) and who subsequently developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). He had been taking VPA for treatment of idiopathic generalized tonic-clonic convulsions since he was 56 years old. After substituting VPA with zonisamide, the serum sodium level returned to normal. We consider this episode of SIADH to be the result of a combination of factors including a weakness of the central nervous system and the long-term administration of VPA.

Schizophrenia-associated idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome).

BACKGROUND: Idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome) is a benign hyperbilirubinemia found in the general population. There has been only 1 previous report of Gilbert's syndrome occurring in schizophrenic patients. The present study was conducted to determine the frequency of Gilbert's syndrome in schizophrenic patients relative to patients with other psychiatric disorders. METHOD: Plasma bilirubin concentrations of every patient admitted to the psychiatric hospital during a 3-year period were collected, and patients were examined to exclude all other causes of hyperbilirubinemia. In addition, the psychiatric symptoms of schizophrenic patients (ICD-10 criteria) with hyperbilirubinemia were evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Schizophrenic patients showed a significantly higher incidence of hyperbilirubinemia (p < .05) relative to patients suffering from other psychiatric disorders, and schizophrenic patients with hyperbilirubinemia showed significantly higher scores on the positive and general psychiatric subscales of the PANSS (p < .0001) than patients without hyperbilirubinemia. CONCLUSION: The apparently higher frequency of Gilbert's syndrome in schizophrenic patients may reflect a relationship between hyperbilirubinemia and schizophrenic psychosis. Hypothetical explanations, such as a possible genetic disposition for Gilbert's syndrome, an increased vulnerability of red cell membranes, and the role of estrogens in schizophrenic patients, are discussed.

Parkinson's disease associated with argyrophilic grains clinically resembling progressive supranuclear palsy: an autopsy case.

A 70-year-old male began to show akinesia, rigidity of extremities, finger tremor, disturbed vertical external ocular movement, and nuchal dystonia, which progressed slowly. Brain CT scan and magnetic resonance images showed slight atrophy of the frontal lobe and slight enlargement of the lateral ventricles. Hasegawa's dementia rating scale-revised version gave a moderate score of 11/30 points. He died of pneumonia at the age of 76. The clinical diagnosis was progressive supranuclear palsy (PSP). However, there were no neuropathological characteristics of PSP. Neuropathologically, Parkinson's disease was diagnosed. In addition, many argyrophilic grains (ArGs) in the gray matter were stained, especially in the insula, amygdala, hippocampus, parahippocampal gyrus, lateral occipitotemporal gyrus, and substantia nigra, by the Gallyas-Braak method. We consider that ArGs could modify the symptoms of Parkinson's disease and that Parkinson's disease with ArGs may show a PSP-like clinical course.

Reversible pitch perception deficit caused by carbamazepine.

Carbamazepine (CBZ) is an antiepileptic drug frequently used to treat a variety of neurologic diseases or symptoms. In addition, the drug is used as a mood stabilizer in patients with affective or schizophrenic disorders. Among its adverse effects, auditory disturbance is described rarely. In this report, we describe a 25-year-old woman who noted falsely higher pitch perception after starting CBZ treatment for schizoaffective disorder. We also review the literature reporting CBZ-associated abnormal pitch perception.

Dementia of Alzheimer type with and without multiple lacunar infarctions: evaluation of white matter lesions.

The white matter lesions in dementia of Alzheimer type (DAT) with and without multiple lacunar infarctions were studied relative to a normal control group. The frequency and distribution of white matter (WM) lesions in DAT (22 cases; mean age +/- standard deviation (SD), 88.1 +/- 5.8), DAT with multiple lacunar infarctions (DAT + CVD, 18 cases; mean age +/- SD, 87.8 +/- 6.0), and in a normal control group (17 cases; mean age +/- SD, 85.2 +/- 4.8) were evaluated. The frequency of myelin pallor (frontal, parietal and occipital lobes) was significantly higher in the DAT + CVD group than in the other groups (DAT and controls). There was no significant difference in the frequency of myelin pallor between the DAT and control groups. Therefore, it was concluded that the WM lesions in DAT are the result of ischemia rather than wallerian degeneration.

A case of small cerebral cyst and pericentric inversion of chromosome 9 that developed schizophrenia-like psychosis.

A case of schizophrenia-like psychosis (psychotic disorder not otherwise specified according to the DSM-IV criteria) with pericentric inversion on chromosome 9 [inv.(9) (p11; q13)] is reported. In this case, a minor brain anomaly, a small cyst in the left subcortex, was observed on magnetic resonance imaging of the brain. In the clinical course, prominent chronic hallucinations were observed; however, there was no evidence of the disorganization of personality, delusion, and deterioration in level of functioning that are usually seen in schizophrenia. This case and a review of the literature indicate that the pericentric region of chromosome 9 might be a potential areas of interest for the aetiology of psychiatric disorders. The phenotype-karyotype relationship of pericentric inversion on chromosome 9 and its relationship to psychosis are discussed.

A case of seizures 1 week after the cessation of interferon-alpha therapy.

We report on a 60-year-old woman with a history of bipolar mood disorder who had seizures and developed a delirious state 1 week after the cessation of interferon-alpha (IFN-alpha) for chronic hepatitis C. The IFN-alpha was administered to the patient for 7 weeks (266 million IU). One week after the cessation of IFN-alpha therapy, the patient had four generalized tonic-clonic seizures over a 2-day period and developed a delirious state for 2 months. We consider these seizures and delirious state to be related to IFN-alpha.

Increased expression of Wnt-1 in schizophrenic brains.

The regulated expression of Wnt-1, one member of the wingless/Wnt pathway, in the brain is critical for many neurodevelopmental processes. Recently, it has been reported that the wingless/Wnt pathway participates in a complex behavioral phenomenon and suggested that this pathway's molecules are candidate genes for neuropsychiatric disorders. Thus, we investigated the expression of Wnt-1 in the hippocampal region, which is believed to be closely involved in the pathophysiology of schizophrenia, of postmortem brains from 10 schizophrenic and 10 control individuals. Immunohistochemical analysis with polyclonal antibodies recognizing Wnt-1 revealed immunoreactivity primarily in the pyramidal cell layer, particularly in CA3 and CA4 regions. We observed a significant elevation in the number of Wnt-1-immunoreactive neurons in the great majority of schizophrenic brains relative to that in controls. The expression of Wnt-1 may be related to cell adhesion, synaptic rearrangement, and plasticity. Therefore, the increase in Wnt-1 immunoreactivity in schizophrenic hippocampi suggests an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings suggest an abnormality of the wingless/Wnt pathway present in the schizophrenic brain and may support the 'neurodevelopmental hypothesis' of schizophrenia.

Mechanisms of fine-surface-texture discrimination in human tactile sensation.

The purpose of this study was to evaluate the ability of touch to discriminate fine-surface textures and to suggest possible mechanisms of the discriminations. Two experiments were performed. In experiment 1, aluminum-oxide abrasive papers were adopted as stimuli, and psychometric functions and difference thresholds were determined in fine-surface-texture discrimination tasks. The grit values of abrasive papers were 400, 600, 1200, 2000, 3000, 4000, and 8000; corresponding average particle sizes were 40, 30, 12, 9, 5, 3, and 1 micron, respectively. Ten subjects participated in experiment 1. The difference thresholds obtained in experiment 1 were between 2.4 and 3.3 microns. In experiment 2, the tasks were discriminations of ridge height. The cross sections of the etched ridges were rectangular and the ridge heights were 6.3, 7.0, 8.6, 10.8, 12.3, 18.5, and 25.0 microns. Six subjects participated in experiment 2. The difference thresholds in experiment 2 were between 0.95 and 2.0 microns. It was reasoned, based on the Weber fraction values calculated from the difference thresholds and on the limit of neural information-processing ability of humans, that the subjects discriminate fine roughness only from the amplitude information presented in surface unevenness.

GTP-dependent modification of a 21-kDa substrate with NAD+ in bovine brain soluble fraction is not ADP-ribosylation of small G-protein but tailing of tRNA.

Labeling of 21-kDa material was observed when bovine brain soluble fraction was incubated with [adenylate-32P]NAD+ in the presence of GTP. The 21-kDa substrate, slightly smaller than C3 substrate in size, was labeled even without C3 exoenzyme. GTP could be replaced by nucleoside triphosphates other than ATP while ATP inhibited the GTP-induced labeling of 21-kDa substrate. After incubation of the soluble fraction with [adenylate-32P]NAD+ in the presence of GTP, [32P]ADP and [32P]ATP were detected in addition to [32P]AMP and [32P]ADP-ribose while only the last two nucleotides were observed without GTP. The 21-kDa substrate was labeled with [alpha-32P]ATP even in the absence of GTP, suggesting adenylylation rather than ADP-ribosylation. The labeled 21-kDa substrate, was extractable by phenol, disappeared with RNase treatment but not with tryptic digestion. Alkaline treatment of the phenol extract yielded an equal mixture of 3'-[32P]CMP and 2'-[32P]CMP. From these results we concluded that the 21-kDa labeling is a result of tRNA tailing with [alpha-32P]ATP generated from the [32P]AMP moiety of [adenylate-32P]NAD+. Results from reconstitution experiments using enzymes and tRNA purified from bovine brain soluble fraction, which are involved in this pathway, confirmed our conclusion.

Immunohistochemical localization of ADP-ribosylarginine hydrolase in rodent CNS.

Polyclonal antibodies were generated against ADP-ribosylarginine hydrolase (AAH), using recombinant fusion protein of rat AAH and glutathione-S-transferase as a immunogen, and affinity-purified. Western blotting showed that the antibodies recognized in mouse brain homogenate a single protein with a molecular mass of 38 kDa, the expected size for mouse AAH. An analysis using the antibodies revealed that heavy labelings were apparent in various brain regions. In the cerebral cortex, pyramidal cells in layers III and V were the most heavily labeled. In the hippocampal formation, labeling was present on the pyramidal neurons and granule cells. The most heavily immunostained cell type was the pyramidal neuron of CA3. In the cerebellum, Purkinje cells were the most heavily labeled. Less intense staining was present over the granule cells. In the basal ganglia, neurons in the caudate nucleus and large multipolar cells in the amygdaloid complex were immunoreactive. Heavy labeling was seen in many midbrain and brainstem nuclei. Neurons in the habenula and ependymal cells were stained heavily. On Western blot analysis of rat cerebrospinal fluid (CSF), the anti-AAH antibodies recognized a protein with a molecular mass of 38 kDa. This is apparently the first evidence of a widespread but distinctive distribution of AAH in neurons of mouse brain and the presence of extracellular AAH in rat CSF.

Quantitative comparison between serum components and somatic cells in bovine quarter milk.

Quantitative comparisons between serum components and somatic cells in 202 bovine quarter milks collected at 3 dairy farms were conducted. Detection of serum components was carried out by an immunological technique, and cell counts were calculated by Breed's method. A high correlation (r = 0.77) between cell counts and gamma-globulin contents was demonstrated, while correlation between cell counts and serum albumin was not close (r = 0.45). In a comparison between cell counts and gamma-globulin contents, 19 (65.4%) out of 29 milks containing over 500,000 cells/ml had gamma-globulin less than 1.138 mg/ml, which was also seen in 97% of 172 milks having less than 500,000 cells/ml. From these results, it was suggested that the gamma-globulin content of milk might be of use for differentiating normal milk from abnormal ones.