Morphological brain changes associated with Schneider's first-rank symptoms in schizophrenia: a MRI study

BACKGROUND: Schneider's first-rank symptoms involve an alienated feature of the sense of one's own mental or physical activity. To clarify the brain morphological basis for the production of these symptoms, volumes of the frontal and medial temporal regions and their clinical correlates were examined in patients with schizophrenia. METHOD: Twenty-two patients with schizophrenia and 44 age- and gender-matched healthy control subjects were included. All patients were in their psychotic episodes with definite Schneiderian symptoms, rated by using the Scale for Assessment of Positive Symptoms. Volumetric measurements of high-resolution magnetic resonance imaging were performed in the prefrontal area, cingulate gyrus, and precentral gyrus, and the medial temporal structures such as the amygdala, hippocampus, and parahippocampal gyrus. RESULTS: Patients had significantly decreased volumes in the cingulate gray matter and the amygdala compared to controls. In the patient group, Schneiderian symptom severity showed significant inverse correlations with volumes of the right posterior cingulate gray matter and of the left anterior parahippocampal gyrus. CONCLUSIONS: Schneiderian symptoms may be associated with morphological abnormalities in the limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus, which possibly serve the self-monitoring function and the coherent storage and reactivation of information.     

Requirement for IFN-gamma in IL-12 production induced by collaboration between v(alpha)14(+) NKT cells and antigen-presenting cells

Two cytokines IL-4 and IL-12 are known to determine the balance between T(h)1 and T(h)2 development. In addition to IL-4 production of V(alpha)14(+) NKT cells, they have recently been demonstrated to have the capacity to stimulate IL-12 production by antigen-presenting cells (APC). This study demonstrates that IFN-gamma is absolutely required for the NKT cell-stimulated IL-12 production. Culture of B cell-depleted spleen cells from C57BL/6 mice with alpha-galactosylceramide (alpha-GalCer) capable of selectively stimulating V(alpha)14/J(alpha)281(+) NKT cells resulted in the production of IL-12 together with IL-4. Whereas IL-4 production occurred in culture of IFN-gamma(-/-) C57BL/6 splenocytes, the same culture failed to generate IL-12 production. While IL-12 production induced during culture of V(alpha)14(+) NKT cells and APC depended on the interaction between CD40 ligand on NKT cells and CD40 on APC, the expression levels of these key molecules were comparable in cells from wild-type and IFN-gamma(-/-) mice. Addition of rIFN-gamma to alpha-GalCer stimulated IFN-gamma(-/-) splenocyte culture, and administration of rIFN-gamma to alpha-GalCer-injected IFN-gamma(-/-) mice resulted in the restoration of IL-12 production in vitro and in vivo. These results illustrate a mandatory role for IFN-gamma in V(alpha)14(+) NKT cell-stimulated IL-12 production by APC.     

Voxel-based morphometry of human brain with age and cerebrovascular risk factors

The objectives of this study were to evaluate the correlations of the volumes of the gray matter and white matter with age, and the correlations of the tissue probabilities of the gray matter and white matter with age and several cerebrovascular risk factors. We obtained magnetic resonance (MR) images of the brain and clinical information from 769 normal Japanese subjects. We processed the MR images automatically by correcting for inter-individual differences in brain size and shape, and by segmenting the MR images into the gray matter and white matter. Volumetry of the brain revealed a significant negative correlation between the gray matter volume and age, which was not observed between white matter volume and age. Voxel-based morphometry showed that age, systolic blood pressure, and alcohol drinking correlated with the regional tissue probabilities of the gray matter and white matter.     

Two cases of limited cutaneous nodular amyloidosis with primary Sj?gren's syndrome]

We described two female patients with primary Sj?gren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sj?gren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sj?gren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sj?gren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.     

Current status and problems of platelet function tests]

Platelet function tests have been utilized for a long time as a useful tool for the diagnosis of qualitative platelet disorders. However, recently reports suggest that platelet function tests currently available in routine laboratory do not necessarily reflect in vivo hemostatic states. First of all, bleeding time could sometimes be non-informative for the following reasons; 1) Duke method, the most popular method in Japan, has poor reproducibility, 2) there is no appropriate method for monitoring of aspirin ingestion, 3) prolongation of bleeding time does not correlate with the amount of blood loss during surgery. Platelet adhesion is still measured by the ability of platelets to be retained on glass beads. However, this test is unable to detect selectively platelet adhesion. Thus, the test in which platelets can exclusively adhere to subendothelial components such as collagen, may be required. Platelet aggregation has been mostly analyzed by the changes in light transmittance in platelet rich plasma (PRP) with a platelet aggregometer. However, this test totally depends on the platelet count in PRP or duration of time after taking blood from patients. Moreover, platelet aggregation in this system is optimally observed and is hardly detectable when the in vivo Ca++ concentration has been chelated. Furthermore, the test could not detect small platelet aggregates, thus being unable to measure the early phase of platelet aggregation. These observations suggest that more simple and specific tests should be developed and become available in routine laboratory.     

Central sites involved in lateral hypothalamus conditioned neural responses to acoustic cues in the rat

1. Unit activity in the lateral hypothalamus (LHA) of the rat was recorded during discrimination learning of cue-tone stimuli (CTS) predicting glucose (CTS1+) or intracranial self-stimulation (ICSS) (CTS2+) as positive reinforcement or electric shock (CTS1-) or tail pinch (CTS2-) as negative reinforcement. The same action, licking, was used as the behavioral response to all stimuli. Procaine hydrochloride, a local anesthetic, was microinjected into the ventral tegmental area (VTA) and the amygdala (AM). LHA neuron responses and licking were analyzed to investigate the afferent input pathway(s) responsible for LHA neural responses to conditioning CTSs in positive reinforcement and to identify the central site involved in CTS learning. Although the animals were restrained, there was no respiratory, cardiac rate, or blood pressure evidence of stress. The headholder was specially designed in our laboratory to avoid pain or discomfort to the animal. The subjects would often, after the first few sessions, voluntarily enter into position in the apparatus, presumably to obtain the reward available during the experiments. 2. In positive reinforcement, a rat was rewarded by 5 microliters of glucose or ICSS when it licked a spout. The rat licked for glucose after CTS1+ or for ICSS after CTS2+. In negative reinforcement, an aversive stimulus, either electric shock or tail pinch, was applied if the rat did not lick the spout. The electric shock and tail pinch were maintained weak enough to produce an avoidance ratio less than 20-30%, averaged in all trials. The rat licked to avoid electric shock after CTS1- or tail pinch after CTS2-. 3. Of 271 LHA neurons analyzed, 202 (74.5%) responded to either or both rewarding and aversive stimuli. The number of neurons that responded to only rewarding stimuli was relatively large (105/271), and the number that responded similarly to both rewarding and aversive stimuli was small (29/271). The effects of both glucose and ICSS, and the effects of both electric shock and tail pinch, were usually similar in neurons analyzed for both rewarding and aversive stimulation. Of 271 neurons, 173 responded differentially to rewarding and aversive stimuli. 4. Neural and behavioral responses were recorded before, during, and after local anesthesia of the VTA in 15 rats and of the AM in 14 rats. Injections of 0.3-0.8 microliters of 5% procaine hydrochloride or 0.9% saline were made at a rate of 0.3 microliters/min through guide cannulae chronically implanted in the VTA and AM, ipsilateral to the recording and ICSS sites in 29 rats that self-stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of amygdalar and lateral hypothalamic neurons to visual information processing of food and nonfood in monkey

Visual information processing was investigated in the inferotemporal cortical (ITCx)-amygdalar (AM)-lateral hypothalamic (LHA) axis which contributes to food-nonfood discrimination. Neuronal activity was recorded from monkey AM and LHA during discrimination of sensory stimuli including sight of food or nonfood. The task had four phases: control, visual, bar press, and ingestion. Of 710 AM neurons tested, 220 (31.0%) responded during visual phase: 48 to only visual stimulation, 13 (1.9%) to visual plus oral sensory stimulation, 142 (20.0%) to multimodal stimulation and 17 (2.4%) to one affectively significant item. Of 669 LHA neurons tested, 106 (15.8%) responded in the visual phase. Of 80 visual-related neurons tested systematically, 33 (41.2%) responded selectively to the sight of any object predicting the availability of reward, and 47 (58.8%) responded nondifferentially to both food and nonfood. Many of AM neuron responses were graded according to the degree of affective significance of sensory stimuli (sensory-affective association), but responses of LHA food responsive neurons did not depend on the kind of reward indicated by the sensory stimuli (stimulus-reinforcement association). Some AM and LHA food responses were modulated by extinction or reversal. Dynamic information processing in ITCx-AM-LHA axis was investigated by reversible deficits of bilateral ITCx or AM by cooling. ITCx cooling suppressed discrimination by vision responding AM neurons (8/17). AM cooling suppressed LHA responses to food (9/22). We suggest deep AM-LHA involvement in food-nonfood discrimination based on AM sensory-affective association and LHA stimulus-reinforcement association.     

Antigenic variation of the Epstein–Barr virus nuclear antigen EBNA1 as revealed by monoclonal antibodies

The Epstein–Barr virus (EBV) nuclear antigen EBNA1 plays an essential role in the replication of EBV episomes in latently infected cells and is the only viral protein that is consistently expressed in all programs of latent EBV gene expression. In this study, four monoclonal antibodies (MoAbs) directed to a region (amino acid residues 442–530) of EBNA1 were generated. Competitive enzyme-linked immunosorbent assay (ELISA) experiments using biotinylated MoAbs showed that they recognized distinct epitopes. Reactivity of these MoAbs with various laboratory EBV strains and field EBV isolates was shown to be heterogeneous in that EBNA1 from certain strains (isolates) was recognized and that from others was not. All four MoAbs showed such heterogeneous reactivity, and moreover, each MoAb showed a distinct spectrum of reactivity with these EBV strains (isolates). These results demonstrate an extensive structural variation in this region of EBNA1 as predicted by previous sequencing studies. These MoAbs will be useful as probes to dissect this structural heterogeneity of EBNA1.