s‐Afadin binds more preferentially to the cell adhesion molecules nectins than l‐afadin

l‐Afadin was originally purified from rat brain as an actin filament (F‐actin)‐binding protein that was homologous to the AF‐6 gene product. Concomitantly, s‐afadin that did not show an F‐actin‐binding capability was copurified with l‐afadin. Structurally, s‐afadin lacks the C‐terminal F‐actin‐binding domain but has two short sequences that were not present in l‐afadin. The properties and roles of l‐afadin have intensively been investigated, but those of s‐afadin have poorly been understood. We show here an additional difference in their biochemical properties other than binding to F‐actin between l‐afadin and s‐afadin. Both l‐afadin and s‐afadin bound to nectins, immunoglobulin‐like cell adhesion molecules, whereas s‐afadin more preferentially bound to nectins than l‐afadin. The PDZ domain of l‐afadin and s‐afadin was essential for their binding to nectin‐3. The dilute domain of l‐afadin negatively regulated its binding to nectin‐3, but the deletion of the C‐terminal F‐actin‐binding domain of l‐afadin did not increase the binding of l‐afadin to nectin‐3. These results indicate that the s‐afadin‐specific C‐terminal inserts may be involved in its preference of binding to nectin‐3 and raise the possibility that there are proteins other than nectins that more preferentially bind s‐afadin than l‐afadin.     

Double ophthalmic arteries arising from the internal carotid artery

Rarely, the ophthalmic artery (OA) arises from the cavernous segment of the internal carotid artery (ICA) inferolaterally and enters into the orbit via the superior orbital fissure. This anomalous OA that originates from the inferolateral trunk is regarded as a persistent dorsal OA. Extremely rarely, both normal OA and persistent dorsal OA arise from the ICA. We report the first case of such double OAs, one of which arose from the cavernous segment of the ICA superolaterally and we believe that it originated from the meningohypophyseal trunk rather than the inferolateral trunk.     

Tal1/Scl gene transduction using a lentiviral vector stimulates highly efficient hematopoietic cell differentiation from common marmoset (Callithrix jacchus) embryonic stem cells

The development of embryonic stem cell (ESC) therapies requires the establishment of efficient methods to differentiate ESCs into specific cell lineages. Here, we report the in vitro differentiation of common marmoset (CM) (Callithrix jacchus) ESCs into hematopoietic cells after exogenous gene transfer using vesicular stomatitis virus-glycoprotein-pseudotyped lentiviral vectors. We transduced hematopoietic genes, including tal1/scl, gata1, gata2, hoxB4, and lhx2, into CM ESCs. By immunochemical and morphological analyses, we demonstrated that overexpression of tal1/scl, but not the remaining genes, dramatically increased hematopoiesis of CM ESCs, resulting in multiple blood-cell lineages. Furthermore, flow cytometric analysis demonstrated that CD34, a hematopoietic stem/progenitor cell marker, was highly expressed in tal1/scl-overexpressing embryoid body cells. Similar results were obtained from three independent CM ESC lines. These results suggest that transduction of exogenous tal1/scl cDNA into ESCs is a promising method to induce the efficient differentiation of CM ESCs into hematopoietic stem/progenitor cells.     

Correlation between preoperative mouth opening and surgical outcome after arthroscopic lysis and lavage in patients with disc displacement without reduction

Purpose: This study was designed to evaluate the efficacy of arthroscopic lysis and lavage for patients with limited mouth opening. The relationship between preoperative mouth opening and the surgical outcome was determined.Method: Fourteen patients with 16 internally deranged joints were treated by arthroscopic lysis and lavage. All had received 10.4 (7 to 19) months of nonsurgical treatment before arthroscopy. The preoperative magnetic resonance images showed anterior disc displacement without reduction in all treated joints.Results: Twelve of the 14 patients (86%) showed good reduction in pain and improved range of jaw movement on average follow-up of 28.5 (13 to 66) months. Two patients showed no improvement after arthroscopy and required open surgical procedures. The preoperative mouth opening of the successful group averaged 29.4 (22 to 35) mm, whereas the two failed cases had 10- and 19-mm openings, respectively (P < .05).Conclusion: Persistent limitation of mouth opening of more than 22 mm after nonsurgical treatment has a good prognosis when treated by arthroscopic lysis and lavage. However, those with greater limitation should probably have earlier surgical intervention.     

Functional dissociation between Kana and Kanji: agraphia following a thalamic hemorrhage

We report the case of a 61-year-old woman with a left thalamic hemorrhage causing agraphia of Kanji (morphograms). Single-photon emission computed tomography (SPECT) showed a decrease in the blood flow in the left thalamus from the superior temporal convolution to the parietal lobe, as well as in the frontal lobe while computed tomography showed no remarkable lesions in the cortex. The agraphia in this case may be due to the thalamic lesion itself, but the SPECT findings strongly suggest that a secondary cortical lesion may be involved in producing the higher cognitive disorder.     

Divergent effects of lithium and sodium valproate on brain-derived neurotrophic factor (BDNF) production in human astrocytoma cells at therapeutic concentrations

Mood stabilizers such as lithium (Li) or valproic acid (VPA) are used in the therapy of bipolar disorders, but the mechanisms by which these medicines work is unclear. Recently, neuroprotection has attracted attention as a potential action for VPA and Li. The close spatial relationship of the pre- and post-synapse with an astrocyte process within a 'tripartite synapse' suggests that mood stabilizer actions on astrocytes may be important. Therefore, we examined the effect of Li and VPA, at therapeutic concentrations, on brain-derived neurotrophic factor (BDNF) production in cultured human astrocytoma cells over an extended period of exposure. Released (extracellular) and intracellular BDNF was measured with sandwich-ELISA. Intracellular BDNF mRNA was also quantified using RT-PCR. VPA treatment potentiated the level of extracellular BDNF, whereas Li reduced it. Furthermore, VPA caused increased intracellular levels of BDNF protein and mRNA, while exposure to Li led to no significant differences compared to control cells. We suggest the possibility that VPA and Li have divergent effects on astrocyte BDNF production. Mood stabilizers play an essential role in regulating BDNF not only in neurons, but also in astrocytes. These findings could form the basis of a new astrocyte-targeted approach towards developing effective medications to treat bipolar disorders.     

TU-100 exerts a protective effect against bacterial translocation by maintaining the tight junction

Purpose

We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT.

Methods

Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected.

Results

CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1β and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1β and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1.

Conclusions

TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway.

     

A practical prediction model for early hematoma expansion in spontaneous deep ganglionic intracerebral hemorrhage

Objective

Early hematoma expansion is a known cause of morbidity and mortality in patients with intracerebral hemorrhage (ICH). The goal of this study was to identify clinical predictors of ICH growth in the acute stage.

Materials and methods

We studied 201 patients with acute (<6 h) deep ganglionic ICH. Patients underwent CT scan at baseline and hematoma expansion (>33% or >12.5 ml increase) was determined on the second scan performed within 24 h. Fourteen clinical and neuroimaging variables (age, gender, GCS at admission, hypertension, diabetes mellitus, kidney disease, stroke, hemorrhagic, antiplatelet use, anticoagulant use, hematoma density heterogeneity, hematoma shape irregularity, hematoma volume and presence of IVH) were registered. Additionally, blood pressure was registered at initial systolic BP (i-SBP) and systolic BP 1.5 h after admission (1.5 h-SBP). The discriminant value of the hematoma volume and 1.5 h-SBP for hematoma expansion were determined by the receiver operating characteristic (ROC) curves. Factors associated with hematoma expansion were analyzed with multiple logistic regression.

Results

Early hematoma expansion occurred in 15 patients (7.0%). The cut-off value of hematoma volume and 1.5 h-SBP were determined to be 16 ml and 160 mmHg, respectively. Hematoma volume above 16 ml (HV > 16) ([OR] = 5.05, 95% CI 1.32–21.36, p = 0.018), hematoma heterogeneity (HH) ([OR] = 7.81, 95% CI 1.91–40.23, p = 0.004) and 1.5 h-SBP above 160 mmHg (1.5 h-SBP > 160) ([OR] = 8.77, 95% CI 2.33–44.56, p = 0.001) independently predicted ICH expansion. If those three factors were present, the probability was estimated to be 59%.

Conclusions

The presented model (HV > 16, HH, 1.5 h-SBP > 160) can be a practical tool for prediction of ICH growth in the acute stage. Further prospective studies are warranted to validate the ability of this model to predict clinical outcome.     

Ageing of the vibratory tissue of human vocal folds

Sixty-four human larynges ranging in age between 70 and 104 years were investigated histologically. The results were incorporated into our previous data for younger age groups. Discussion was focused on the mucosa around the vocal fold edge. The following tendencies were observed with ageing: (1) the membranous vocal fold shortens in males; (2) the mucosa thickens in females; (3) the cover of the vocal fold thickens in females; (4) edema develops in the superficial layer of the lamina propria in both sexes; (5) the intermediate layer of the lamina propria thins and its contour becomes deteriorated in males; (6) elastic fibers in the intermediate layer become less dense and atrophy in males; (7) the deep layer of the lamina propria thickens in males; (8) collagenous fibers in the deep layer become denser and fibrotic in males. The degree of these geriatric changes vary from individual to individual.