Infection of Mycobacterium bovis bacillus Calmette-Guérin in antibody-mediated gamma delta T-cell-depleted mice.

To evaluate the hypothesis that gamma delta T cells participate in protective immunity against mycobacterial infection, we depleted gamma delta T cells from mice by administration of anti-T-cell receptor (TCR)gamma delta monoclonal antibody (mAb) and analysed protection against Mycobacterium bovis bacillus Calmette-Guérin (BCG). The gamma delta T-cell-depleted mice did not show any exaggerated bacterial multiplication compared with control mice. In contrast, alpha beta T-cell-depleted mice, which were administrated anti-TCR alpha beta mAb before BCG infection, showed a depressed protective immunity. These results suggest that gamma delta T cells are not essential for coping with a primary BCG infection.     

Escherichia coli infection induces only fetal thymus-derived gamma delta T cells at the infected site

Intraperitoneal infection of mice with Escherichia coli induced activated TCR gamma delta T cells in the peritoneal cavity. We provide evidence that the E. coli-induced gamma delta T cells are derived only from the fetal thymus on the following grounds. The gamma delta T cells were not induced in athymic nude mice and irradiated bone marrow-transferred mice which lack fetal thymus-derived T cells. However, E. coli infection of fetal thymus-grafted nude mice did induce fetal thymus-derived gamma delta T cells. These results suggest that the fetal thymus-derived gamma delta T cells colonize the periphery during early ontogeny, and are maintained until adult age. The E. coli-induced gamma delta T cells express only the Vdelta1 gene. Vgamma6 was predominantly expressed whereas anti-Vgamma1 and anti-Vgamma4 monoclonal antibodies stained less than 3 % of the cells. Direct sequencing of PCR products revealed that Vgamma6 and Vdelta1 genes expressed by the E. coli-induced gamma delta T cells were invariant sequences identical to those expressed in the fetal thymus. The antigen (Ag) specificity of a T cell hybridoma expressing the fetal type Vgamma6 / Vdelta1(+) TCR could not be identified as the cells failed to respond to lipopolysaccharide, E. coli Ag, mycobacterial heat shock protein 65, or isopentenyl pyrophosphate. These results suggest that the Vgamma6 / Vdelta1(+) gamma delta T cells derived from fetal thymus can participate in immune responses against bacterial infection through recognition of a novel class of Ag which is not yet identified.     

Multimodality language mapping in patients with left-hemispheric language dominance on Wada test

Objective

We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test.

Methods

We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions.

Results

Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p < 0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p < 0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation.

Conclusions

Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance.

Significance

Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients.     

A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth

Disrupted-in-schizophrenia 1 (DISC1) is a gene disrupted by a (1;11) (q42.1;q14.3) translocation that segregates with major psychiatric disorders in a Scottish family. To investigate how DISC1 confers susceptibility to psychiatric disorders, we previously identified fasciculation and elongation protein zeta-1 and Kendrin as DISC1-interacting molecules in a yeast two-hybrid screen of a human brain complementary DNA library. Here, we have further identified a novel DISC1-interacting protein, termed DISC1-Binding Zinc-finger protein (DBZ), which has a predicted C(2)H(2)-type zinc-finger motif and coiled-coil domains. DBZ was co-immunoprecipitated with DISC1 in lysates of PC12 cells and rat brain tissue. The domain of DISC1 interacting with DBZ was close to the translocation breakpoint in the DISC1 gene. DBZ messenger RNA (mRNA) was expressed in human brains, but not in peripheral tissues. In situ hybridization revealed high expression of DBZ mRNA in the hippocampus, olfactory tubercle, cerebral cortex and striatum in rats. Because this pattern of localization was similar to that of the pituitary adenylate cyclase (PAC(1)) receptor for pituitary adenylate cyclase-activating polypeptide (PACAP), which has recently been implicated in neuropsychological functions, we examined whether DISC1/DBZ interaction was involved in the PACAP signaling pathway. PACAP upregulated DISC1 expression and markedly reduced the association between DISC1 and DBZ in PC12 cells. A DISC1-binding domain of DBZ reduced the neurite length in PC12 cells after PACAP stimulation and in primary cultured hippocampal neurons. The present results provide some new molecular insights into the mechanisms of neuronal development and neuropsychiatric disorders.     

Elevated levels of free putrescine and N1-acetylspermidine in cyst fluids of malignant brain tumours.

The contents of free and conjugated polyamines in cyst fluids of brain tumours were analysed. The putrescine and N1-acetylspermidine levels in cyst fluids of malignant brain tumours were significantly higher than those of benign tumours. The free spermidine levels in malignant and benign tumours were about the same, while the total spermidine levels were higher in malignant than those in benign tumours. These results suggest that polyamine levels in cyst fluids reflect the altered polyamine metabolism in brain tumours.     

Psychiatric Symptoms and Subthalamic Nucleus Stimulation in Parkinson's Disease. A Retrospective Study in Our Japanese Patients

Objectives. With respect to postoperative activities of daily living (ADL), we retrospectively investigated associated psychiatric symptoms that influenced beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese patients with Parkinson disease (PD). Materials and Methods. Twenty‐five patients underwent bilateral STN stimulation. Pre‐ and 3 months after the surgery, their parkinsonian symptoms were evaluated with Unified Parkinson Disease Rating Scale (UPDRS) and Schwab‐England (S‐E) ADL scale. Stepwise multiple analysis was performed to determine the factors affecting postoperative ADL. Results. Eleven out of 25 patients manifested drug‐induced psychosis preoperatively, although their mean dosage of levodopa was small (366.4 ± 152.7 mg). Disease duration positively affected the severity of the patients’ psychiatric symptoms. Postoperative S‐E score showed a significant improvement compared to the pretreatment baseline in both of “on” and “off” medication states, as all their cardinal motor symptoms were significantly ameliorated. Preoperative scores for thought disorder and axial disability negatively impact on the postoperative S‐E score in “on” state (p < 0.01). Preoperative score for intellectual impairment was only a significant predictor of worse postoperative ADL in “off” state. Conclusions. The markedly lower dose of levodopa may suggest ethnic characteristics of our Japanese patients with respect to tolerance for antiparkinsonian medications. Preoperative manifestation of drug‐induced psychosis and cognitive dysfunction were the major factor that strikingly suppressed daily activities after STN stimulation.     

Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women

A high total homocysteine (tHcy) level during pregnancy is a risk factor for adverse perinatal outcomes, such as fetal growth restriction and preeclampsia. Caffeine is assumed to increase tHcy levels by acting as a vitamin B₆ antagonist. The objective of this study was to examine a relationship between circulating tHcy levels and dietary caffeine and vitamin B₆ intakes in pregnant Japanese women. A total of 321 healthy women with singleton pregnancies were recruited in metropolitan Tokyo, from June to December 2008, resulting in the final number included in the study as 254. Dietary caffeine intakes did not correlate with plasma tHcy levels. When we analyzed the data according to caffeinated beverages, caffeinated tea consumption was positively associated with plasma tHcy levels only among the women with a high intake of vitamin B₆, after controlling for confounding factors (P = 0.029). No correlation between coffee consumption and plasma tHcy levels was found. Pregnant Japanese women might need to cut down the consumption of caffeinated tea as well as take sufficient vitamin B₆ in order to prevent the tHcy levels from increasing.     

Alteration of the langerhans islets in pancreatic cancer patients

Summary An abnormal glucose metabolism occurs in up to 80% of pancreatic cancer patients shortly or a few months before the first clinical admission. Reasons for this abnormality are obscure. We investigated immunohistochemically the pattern of islets in 14 pancreatic cancer specimens and used 14 chronic pancreatitis samples and 10 normal pancreata as controls. To study the topographical relationship of these islets to the cancer, islets in four different arbitrary zones within and around the cancer were evaluated. Ten out of 14 cancer specimens showed a significant loss of β cells (p<0.005) and eight of them also showed a significant increase of α cells (p<0.005), all of them from hyperglycemic patients. Most affected islets were found within zone 1 (intratumoral) and zone 2 (peritumoral), to a lesser extent in zone 3 (acini close to tumor) and none in zone 4 (acini remote from tumor). No comparable changes were found in chronic pancreatitis patients. The incidence of 72% with alteration of islets in our material correlates with the frequency of abnormal glucose levels in human pancreatic cancer patients. Our findings support the notion that islet cell abnormalities is likely caused by substances released from cancer cells.     

Independent predictors of neuronal adaptation in human primary visual cortex measured with high-gamma activity

Neuronal adaptation is defined as a reduced neural response to a repeated stimulus and can be demonstrated by reduced augmentation of event-related gamma activity. Several studies reported that variance in the degree of gamma augmentation could be explained by pre-stimulus low-frequency oscillations. Here, we measured the spatio-temporal characteristics of visually-driven amplitude modulations in human primary visual cortex using intracranial electrocorticography. We determined if inter-stimulus intervals or pre-stimulus oscillations independently predicted local neuronal adaptation measured with amplitude changes of high-gamma activity at 80-150 Hz. Participants were given repetitive photic stimuli with a flash duration of 20 μs in each block; the inter-stimulus interval was set constant within each block but different (0.2, 0.5, 1.0 or 2.0 s) across blocks. Stimuli elicited augmentation of high-gamma activity in the occipital cortex at about 30 to 90 ms, and high-gamma augmentation was most prominent in the medial occipital region. High-gamma augmentation was subsequently followed by lingering beta augmentation at 20-30 Hz and high-gamma attenuation. Neuronal adaptation was demonstrated as a gradual reduction of high-gamma augmentation over trials. Multivariate analysis demonstrated that a larger number of prior stimuli, shorter inter-stimulus interval, and pre-stimulus high-gamma attenuation independently predicted a reduced high-gamma augmentation in a given trial, while pre-stimulus beta amplitude or delta phase had no significant predictive value. Association between pre-stimulus high-gamma attenuation and a reduced neural response suggests that high-gamma attenuation represents a refractory period. The local effects of pre-stimulus beta augmentation and delta phase on neuronal adaptation may be modest in primary visual cortex.     

Undercarboxylated osteocalcin concentration in postmenopausal women receiving hormone therapy daily and on alternate days

OBJECTIVE: Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K status. The authors examined the difference in serum ucOC concentrations in postmenopausal women receiving hormone therapy (HT) daily and on alternate days, and assessed the association between ucOC and triglyceride concentrations, which are related to the transport of vitamin K. DESIGN: Seventy-three postmenopausal women were recruited for this study. Thirty-seven women received 0.625 mg of conjugated equine estrogens (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) daily, and 36 women received 0.625 mg of CEE and 2.5 mg of MPA on alternate days. The concentrations of serum ucOC, bone turnover markers, lipid profiles, and hormones were measured before and after 12 months of HT. RESULTS: The ucOC concentration in women taking HT daily was significantly (P < 0.01) lower than that in women taking HT on alternate days. Serum ucOC concentrations during HT showed a significant (P < 0.01) inverse correlation with estradiol concentrations during HT. Serum estradiol concentrations during HT showed a significant (P < 0.01) positive correlation with triglyceride concentrations during HT. Furthermore, ucOC concentrations during HT showed a significant (P < 0.05) inverse correlation with triglyceride concentrations in women receiving HT. CONCLUSIONS: The effect of HT on alternate days on ucOC concentration was weaker than the effect of HT daily. In addition, ucOC concentration after 12 months of HT daily might be decreased due to the conversion of ucOC to carboxylated OC by the effect of vitamin K through increased triglyceride levels induced by oral CEE.