Brain structural changes and neuropsychological impairments in male polydipsic schizophrenia

BACKGROUND: Polydipsia frequently occurs in schizophrenia patients. The excessive water loading in polydipsia occasionally induces a hyponatremic state and leads to water intoxication. Whether polydipsia in schizophrenic patients correlates with neuropsychological impairments or structural brain changes is not clear and remains controversial. METHODS: Eight polydipsic schizophrenia patients, eight nonpolydipsic schizophrenia patients, and eight healthy controls were recruited. All subjects underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural abnormalities were analyzed using a voxel-based morphometry (VBM) approach, and patients’ neuropsychological function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J). RESULTS: No significant differences were found between the two patient groups with respect to the clinical characteristics. Compared with healthy controls, polydipsic patients showed widespread brain volume reduction and neuropsychological impairment. Furthermore, the left insula was significantly reduced in polydipsic patients compared with nonpolydipsic patients. These nonpolydipsic patients performed intermediate to the other two groups in the neuropsychological function test. CONCLUSIONS: It is possible that polydipsia or the secondary hyponatremia might induce left insula volume reduction. Furthermore, this structural brain change may indirectly induce more severe neuropsychological impairments in polydipsic patients. Thus, we suggest that insula abnormalities might contribute to the pathophysiology of polydipsic patients

Age is not a limiting factor for brachytherapy for carcinoma of the node negative oral tongue in patients aged eighty or older

<p>Abstract</p> <p>Background</p> <p>To examine the role of brachytherapy for aged patients 80 or more in the trend of rapidly increasing number.</p> <p>Methods</p> <p>We examined the outcomes for elderly patients with node negative oral tongue cancer (T1-3N0M0) treated with brachytherapy. The 21 patients (2 T1, 14 T2, and 5 T3 cases) ranged in age from 80 to 89 years (median 81), and their cancer was pathologically confirmed. All patients underwent definitive radiation therapy, with low dose rate (LDR) Ra-226 brachytherapy (n = 4; median 70Gy), with Ir-192 (n = 12; 70Gy), with Au-198 (n = 1) or with high dose rate (HDR) Ir-192 brachytherapy (n = 4; 60 Gy). Eight patients also underwent external radiotherapy (median 30 Gy). The period of observation ranged from 13 months to 14 years (median 2.5 years). We selected 226 population matched younger counterpart from our medical chart.</p> <p>Results</p> <p>Definitive radiation therapy was completed for all 21 patients (100%), and acute grade 2-3 mucositis related to the therapy was tolerable. Local control (initial complete response) was attained in 19 of 21 patients (90%). The 2-year and 5-year local control rates were 91%, (100% for T1, 83% for T2 and 80% for T3 tumors after 2 years). These figures was not inferior to that of younger counterpart (82% at 5-year, n.s.). The cause-specific survival rate was 83% and the regional control rate 84% at the 2-years follow-up. However, 12 patients died because of intercurrent diseases or senility, resulting in overall survival rates of 55% at 2 years and 34% at 5 years.</p> <p>Conclusion</p> <p>Age is not a limiting factor for brachytherapy for appropriately selected elderly patients, and brachytherapy achieved good local control with acceptable morbidity.</p

Immunotoxin-Mediated Tract Targeting in the Primate Brain: Selective Elimination of the Cortico-Subthalamic “Hyperdirect” Pathway

Using a neuron-specific retrograde gene-transfer vector (NeuRet vector), we established immunotoxin (IT)-mediated tract targeting in the primate brain that allows ablation of a neuronal population constituting a particular pathway. Here, we attempted selective removal of the cortico-subthalamic “hyperdirect” pathway. In conjunction with the direct and indirect pathways, the hyperdirect pathway plays a crucial role in motor information processing in the basal ganglia. This pathway links the motor-related areas of the frontal lobe directly to the subthalamic nucleus (STN) without relay at the striatum. After electrical stimulation in the motor-related areas such as the supplementary motor area (SMA), triphasic responses consisting of an early excitation, an inhibition, and a late excitation are usually detected in the internal segment of the globus pallidus (GPi). Several lines of pharmacophysiological evidence suggest that the early excitation may be derived from the hyperdirect pathway. In the present study, the NeuRet vector expressing human interleukin-2 receptor α-subunit was injected into the STN of macaque monkeys. Then, IT injections were made into the SMA. In these monkeys, single-neuron activity in the GPi was recorded in response to the SMA stimulation. We found that the early excitation was largely reduced, with neither the inhibition nor the late excitation affected. The spontaneous firing rate and pattern of GPi neurons remained unchanged. This indicates that IT-mediated tract targeting successfully eliminated the hyperdirect pathway selectively from the basal ganglia circuitry without affecting spontaneous activity of STN neurons. The electrophysiological finding was confirmed with anatomical data obtained from retrograde and anterograde neural tracings. The present results define that the cortically-driven early excitation in GPi neurons is mediated by the hyperdirect pathway. The IT-mediated tract targeting technique will provide us with novel strategies for elucidating various neural network functions

Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Increased activation of the renin-angiotensin system (RAS) may be important in promoting coronary heart disease (CHD) and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor (<it>AGT1R</it>) and angiotensinogen (<it>AGT</it>) genotypes in type 2 diabetes.</p> <p>Methods</p> <p>Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). We analyzed single nucleotide polymorphisms (SNPs) associated with cardiovascular pathophysiology (including <it>AGT1R </it>T573C, <it>AGT1R </it>A1166C, and <it>AGT </it>M235T) and presence of renal dysfunction (eGFR<60 ml/min/1.73 m²) or history of CHD.</p> <p>Results</p> <p>The <it>AGT1R </it>1166 C-allele was associated with eGFR<60 ml/min/1.73 m²(multivariable OR 1.63 [1.01, 2.65]) in the HPFS men (n = 733) and in the combined dataset (n = 1566) (OR 1.42 [1.02, 1.98]). The <it>AGT1R </it>1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]). In NHS women (n = 833), <it>AGT </it>235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]). Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and <it>AGT1R </it>1166 C-allele (p = 0.008) and <it>AGT </it>M235T (p = 0.03) in models for CHD. No significant associations were seen between <it>AGT1R </it>T573 C-allele and renal dysfunction or CHD.</p> <p>Conclusion</p> <p>Polymorphisms in <it>AGT1R </it>and <it>AGT </it>genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between <it>AGT1R </it>1166 C-allele and <it>AGT </it>235T and CHD in type 2 diabetes.</p

Candida soluble cell wall β-glucan facilitates ovalbumin-induced allergic airway inflammation in mice: Possible role of antigen-presenting cells

<p>Abstract</p> <p>Background</p> <p>Although fungi have been implicated as initiating/deteriorating factors for allergic asthma, their contributing components have not been fully elucidated. We previously isolated soluble β-glucan from <it>Candida albicans </it>(CSBG) (Ohno et al., 2007). In the present study, the effects of CSBG exposure on airway immunopathology in the presence or absence of other immunogenic allergen was investigated <it>in vivo</it>, and their cellular mechanisms were analyzed both <it>in vivo </it>and <it>in vitro</it>.</p> <p>Methods</p> <p><it>In vivo</it>, ICR mice were divided into 4 experimental groups: vehicle, CSBG (25 μg/animal), ovalbumin (OVA: 2 μg/animal), and CSBG + OVA were repeatedly administered intratracheally. The bronchoalveolar lavage cellular profile, lung histology, levels of cytokines and chemokines in the lung homogenates, the expression pattern of antigen-presenting cell (APC)-related molecules in the lung digests, and serum immunoglobulin values were studied. <it>In vitro</it>, the impacts of CSBG (0–12.5 μg/ml) on the phenotype and function of immune cells such as splenocytes and bone marrow-derived dendritic cells (BMDCs) were evaluated in terms of cell proliferation, the surface expression of APC-related molecules, and OVA-mediated T-cell proliferating activity.</p> <p>Results</p> <p><it>In vivo</it>, repeated pulmonary exposure to CSBG induced neutrophilic airway inflammation in the absence of OVA, and markedly exacerbated OVA-related eosinophilic airway inflammation with mucus metaplasia in mice, which was concomitant with the amplified lung expression of Th2 cytokines and IL-17A and chemokines related to allergic response. Exposure to CSBG plus OVA increased the number of cells bearing MHC class II with or without CD80 in the lung compared to that of others. <it>In vitro</it>, CSBG significantly augmented splenocyte proliferation in the presence or absence of OVA. Further, CSBG increased the expression of APC-related molecules such as CD80, CD86, and DEC205 on BMDCs and amplified OVA-mediated T-cell proliferation through BMDCs.</p> <p>Conclusion</p> <p>CSBG potentiates allergic airway inflammation with maladaptive Th immunity, and this potentiation was associated with the enhanced activation of APCs including DC.</p

Twenty Years of SUGRA

A brief review is given of the developments of mSUGRA and its extensions since the formulation of these models in 1982. Future directions and prospects are also discussed.Comment: Invited talk at the International Conference BEYOND-2003, Schloss Ringberg, Germany, June 10-14, 2003; 21 pages, Late

Singular values of the Dirac operator in dense QCD-like theories

We study the singular values of the Dirac operator in dense QCD-like theories at zero temperature. The Dirac singular values are real and nonnegative at any nonzero quark density. The scale of their spectrum is set by the diquark condensate, in contrast to the complex Dirac eigenvalues whose scale is set by the chiral condensate at low density and by the BCS gap at high density. We identify three different low-energy effective theories with diquark sources applicable at low, intermediate, and high density, together with their overlapping domains of validity. We derive a number of exact formulas for the Dirac singular values, including Banks-Casher-type relations for the diquark condensate, Smilga-Stern-type relations for the slope of the singular value density, and Leutwyler-Smilga-type sum rules for the inverse singular values. We construct random matrix theories and determine the form of the microscopic spectral correlation functions of the singular values for all nonzero quark densities. We also derive a rigorous index theorem for non-Hermitian Dirac operators. Our results can in principle be tested in lattice simulations.Comment: 3 references added, version published in JHE