Cholelithiasis prevalence and risk factors in individuals with severe or profound intellectual and motor disabilities.

BACKGROUND: The prevalence and risk factors of cholelithiasis in individuals with severe or profound intellectual and motor disabilities (SPIMD) are poorly characterised. Thus, we aimed to investigate the prevalence and risk determinants of cholelithiasis in a cohort with SPIMD under medical care in a residential facility. METHODS: We categorised 84 patients in a residential hospital for persons with SPIMD into groups: those with (Group CL) and without (Group N) cholelithiasis. Gallstones were detected via computed tomography, ultrasonography or both. We evaluated gastrostomy status, nutritional and respiratory support, constipation, and bladder and kidney stones. Data were significantly analysed using univariate and multivariate logistic regression analyses. RESULTS: The prevalence rate of cholelithiasis in our SPIMD cohort was 27%. There were no significant differences in sex, age, weight, height, or Gross Motor Function Classification System between the two groups. However, more patients received enteral nutrition (39.13% vs. 6.56%; P = 0.000751) and were on ventilator support (56.52% vs. 19.67%; P = 0.00249) in Group CL than in Group N. Enteral nutrition [odds ratio (OR) 10.4, 95% confidence interval (CI) 1.98-54.7] and ventilator support (OR 20.0, 95% CI 1.99-201.0) were identified as independent risk factors for the prevalence of cholelithiasis in patients with SPIMD. CONCLUSIONS: Patients with SPIMD demonstrated an increased prevalence of cholelithiasis, with a notable association between nutritional tonic use and respiratory support. Therefore, to emphasise the need for proactive screening, it is crucial to devise diagnostic and therapeutic strategies specific to patients with SPIMD. Further investigation is essential to validate our findings and explore causative factors.

Baseline effective connectivity predicts response to repetitive transcranial magnetic stimulation in patients with treatment-resistant depression.

Repetitive transcranial magnetic stimulation (rTMS) has become a popular treatment option for treatment-resistant depression (TRD). However, suboptimal response rates highlight the need for improved efficacy through optimisation of treatment protocol and patient selection. We investigate whether the limbic salience network and its connectivity with prefrontal stimulation sites predict immediate and longer-term responsiveness to rTMS. Twenty-seven patients with TRD were randomly allocated to receive 16 sessions of either conventional rTMS or intermittent theta-burst (iTBS) over 4 weeks; delivered using connectivity profiling and neuronavigation to target person-specific dorsolateral prefrontal cortex (DLPFC). At baseline and 3-month follow-up, patients underwent clinical assessment and scanning session, and 1-month clinical follow-up. Resting-state fMRI data were entered into seed-based functional and effective connectivity analyses between right anterior insula (rAI) and DLPFC target, and independent components analysis to extract resting-state networks. Cerebral blood flow (CBF) was also assessed in the rAI. All brain measures were compared between baseline and follow-up, and related to treatment response at 1- and 3-months. Baseline fronto-insular effective connectivity and salience network connectivity were significantly positively correlated, while baseline rAI CBF was negatively correlated, with early (1-month) response to rTMS treatment but not sustained response (3-months), suggesting persistence of therapeutic response is not associated with baseline features. Connectivity or CBF measures did not change between the two time points. We demonstrate that fronto-insular and salience-network interactions can predict early response to rTMS in TRD, suggesting that these network nodes may be key regions toward developing rTMS response biomarkers.

Manganese-enhanced magnetic resonance imaging depicts brain activity in models of acute and chronic pain: A new window to study experimental spontaneous pain?

Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception. As a proof of concept that MEMRI is sensitive to the neural activity of spontaneous, intermittent behaviour, we studied a separate positive control group undergoing a voluntary running wheel experiment. In the pain models, pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWTs)) was measured at baseline and following either intra-articular injection of nerve growth factor (NGF, 10µg/50µl; acute pain model, n=4 rats per group), or the chondrocyte toxin monosodium iodoacetate (MIA, 1mg/50µl; chronic model, n=8 rats per group), or control injection. Separate groups of rats underwent a voluntary wheel running protocol (n=8 rats per group). Rats were administered with paramagnetic ion Mn2+ as soluble MnCl2 over seven days (subcutaneous osmotic pump) to allow cumulative activity-dependent neural accumulation in the models of pain, or over a period of running. T1-weighted MR imaging at 7T was performed under isoflurane anaesthesia using a receive-only rat head coil in combination with a 72mm volume coil for excitation. The pain models resulted in weight bearing asymmetry (NGF: 20.0 ± 5.2%, MIA: 15 ± 3%), and a reduction in PWT in the MIA model (8.3 ± 1.5g) on the final day of assessment before undergoing MR imaging. Voxel-wise and region-based analysis of MEMRI data did not identify group differences in T1 signal. However, MnCl2 accumulation in the VTA, right Ce amygdala, and left cingulate was negatively correlated with pain responses (greater differences in weight bearing), similarly MnCl2 accumulation was reduced in the VTA in line with hyperalgesia (lower PWTs), which suggests reduced regional activation as a result of the intensity and duration of pain experienced during the 7 days of MnCl2 exposure. Motor cortex T1-weighted signal increase was associated with the distance ran in the wheel running study, while no between group difference was seen. Our data suggest that on-going pain related signal changes identified using MEMRI offers a new window to study the neural underpinnings of spontaneous pain in rats.

Abnormalities in the effective connectivity of visuothalamic circuitry in schizophrenia.

BACKGROUND: Sensory-processing deficits appear crucial to the clinical expression of symptoms of schizophrenia. The visual cortex displays both dysconnectivity and aberrant spontaneous activity in patients with persistent symptoms and cognitive deficits. In this paper, we examine visual cortex in the context of the remerging notion of thalamic dysfunction in schizophrenia. We examined specific regional and longer-range abnormalities in sensory and thalamic circuits in schizophrenia, and whether these patterns are strong enough to discriminate symptomatic patients from controls. METHOD: Using publicly available resting fMRI data of 71 controls and 62 schizophrenia patients, we derived conjunction maps of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) to inform further seed-based Granger causality analysis (GCA) to study effective connectivity patterns. ReHo, fALFF and GCA maps were entered into a multiple kernel learning classifier, to determine whether patterns of local and effective connectivity can differentiate controls from patients. RESULTS: Visual cortex shows both ReHo and fALFF reductions in patients. Visuothalamic effective connectivity in patients was significantly reduced. Local connectivity (ReHo) patterns discriminated patients from controls with the highest level of accuracy of 80.32%. CONCLUSIONS: Both the inflow and outflow of Granger causal information between visual cortex and thalamus is affected in schizophrenia; this occurs in conjunction with highly discriminatory but localized dysconnectivity and reduced neural activity within the visual cortex. This may explain the visual-processing deficits that are present despite symptomatic remission in schizophrenia.

Shared white-matter dysconnectivity in schizophrenia and bipolar disorder with psychosis.

BACKGROUND: There is an appreciable overlap in the clinical presentation, epidemiology and treatment response of the two major psychotic disorders - schizophrenia and bipolar disorder. Nevertheless, the shared neurobiological correlates of these two disorders are still elusive. Using diffusion tensor imaging (DTI), we sought to identify brain regions which share altered white-matter connectivity across a clinical spectrum of psychotic disorders. METHOD: A sample of 41 healthy controls, 62 patients in a clinically stable state of an established psychotic disorder (40 with schizophrenia, 22 with bipolar disorder) were studied using DTI. Tract-based spatial statistics (TBSS) was used in order to study group differences between patients with psychosis and healthy controls using fractional anisotropy (FA). Probabilistic tractography was used in order to visualize the clusters that showed significant differences between these two groups. RESULTS: The TBSS analysis revealed five clusters (callosal, posterior thalamic/optic, paralimbic, fronto-occipital) with reduced FA in psychosis. This reduction in FA was associated with an increase in radial diffusivity and a decrease in mode of anisotropy. Factor analysis revealed a single white-matter integrity factor that predicted social and occupational functioning scores in patients irrespective of the diagnostic categorization. CONCLUSIONS: Our results show that a shared white-matter dysconnectivity links the two major psychotic disorders. These microstructural abnormalities predict functional outcome better than symptom-based diagnostic boundaries during a clinically stable phase of illness, highlighting the importance of seeking shared neurobiological factors that underlie the clinical spectrum of psychosis.

Dystonia-associated protein torsinA is not detectable at the nerve terminals of central neurons.

Presynaptic functions of the mammalian central neurons are regulated by a network of protein interactions. Synaptic vesicle recycling in and neurotransmitter release from the presynaptic nerve terminals are altered when a glutamate-deleting mutation is present in the torsinA protein (ΔE-torsinA). This mutation is linked with a hereditary form of the movement disorder dystonia known as DYT1 dystonia. Although torsinA expression is prevalent throughout the central nervous system, its subcellular localization - in particular with respect to presynaptic nerve terminals - remains unclear. This information would be useful in narrowing down possible models for how wild-type torsinA affects presynaptic function, as well as the nature of the presynaptic dysfunction that arises in the context of ΔE-torsinA mutation. Here we report on an analysis of the presynaptic localization of torsinA in cultured neurons obtained from a knock-in mouse model of DYT1 dystonia. Primary cultures of neurons were established from heterozygous and homozygous ΔE-torsinA knock-in mice, as well as from their wild-type littermates. Neurons were obtained from the striatum, cerebral cortex and hippocampus of these mice, and were subjected to immunocytochemistry. This analysis revealed the expression of both proteins in the somata and dendrites. However, neither the nerve terminals nor axonal shafts were immunoreactive. These results were confirmed by fluorogram-based quantitation. Our findings indicate that neither the wild-type nor the ΔE-torsinA mutant protein is present at substantial levels in the presynaptic structures of cultured neurons. Thus, the effects of torsinA, in wild-type and mutant forms, appear to influence presynaptic function indirectly, without residing in presynaptic structures.

Intra-arterial Administration of Fasudil Hydrochloride for Vasospasm Following Subarachnoid Haemorrhage: Experience of 90 Cases.

BACKGROUND: we investigated the clinical efficacy of intra-arterial administration of fasudil hydrochloride for cerebral vasospasm. METHOD: we reviewed 90 cases treated with intra-arterial administration of fasudil hydrochloride between August 1998 and April 2009 and investigated the clinical efficacy for cerebral vasospasm. FINDINGS: angiographic improvement of vasospasm was noted in all procedures. Eight had ischemic lesion on CT at discharge in Group A, which included 39 patients who presented angiographic and symptomatic vasospasm. However, 4 (50%) of these eight were recovered with a condition of GR. No patients showed ischemic lesion on CT in Group B, which included 51 patients who presented angiographic vasospasm without symptoms. Two (3.3%) of 59 patients who presented angiographic vasospasm without symptoms at the initial follow-up angiography had ischemic lesion on CT at discharge. The 1-year follow-up showed 78.9% of GR. No patient showed any adverse effects resulting from intra-arterial administration of fasudil hydrochloride. CONCLUSION: intra-arterial administration of fasudil hydrochloride was an effective and safe management technique for vasospasm.

CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function.

This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30-40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2-43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child-Pugh classification, was the only factor that differed significantly between reactions to treatment showing "non-enhanced" (Type A and B) and "enhanced" (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC.

Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan synthesis and expression of growth factor-related genes in human nucleus pulposus cell line.

Low-intensity pulsed ultrasound (LIPUS) stimulation has been shown to effect differentiation and activation of human chondrocytes. A study involving stimulation of rabbit disc cells with LIPUS revealed upregulation of cell proliferation and proteoglycan (PG) synthesis. However, the effect of LIPUS on human nucleus pulposus cells has not been investigated. In the present study, therefore, we investigated whether LIPUS stimulation of a human nucleus pulposus cell line (HNPSV-1) exerted a positive effect on cellular activity. HNPSV-1 cells were encapsulated in 1.2% sodium alginate solution at 1x10(5) cells/ml and cultured at 10 beads/well in 6-well plates. The cells were stimulated for 20 min each day using a LIPUS generator, and the effects of LIPUS were evaluated by measuring DNA and PG synthesis. Furthermore, mRNA expression was analyzed by cDNA microarray using total RNA extracted from the cultured cells. Our study revealed no significant difference in cell proliferation between the control and the ultrasound treated groups. However, PG production was significantly upregulated in HNPSV cells stimulated at intensities of 15, 30, 60, and 120 mW/cm(2) compared with the control. The results of cDNA array showed that LIPUS significantly stimulated the gene expression of growth factors and their receptors (BMP2, FGF7, TGFbetaR1 EGFRF1, VEGF). These findings suggest that LIPUS stimulation upregulates PG production in human nucleus pulposus cells by the enhancement of several matrix-related genes including growth factor-related genes. Safe and non-invasive stimulation using LIPUS may be a useful treatment for delaying the progression of disc degeneration.

Follow-up of Large Aneurysms Treated with Coil Embolization at an Acute Stage in Patients with Poor-Grade Subarachnoid Hemorrhage.

SUMMARY: This study evaluated the clinical and angiographic outcome of large aneurysms treated with coil embolization at an acute stage in patients with poor-grade subarachnoid hemorrhage (SAH). Between July 1, 2001 and June 30, 2004, eight consecutive WFNS grade 5 patients with large aneurysms (15~23 mm) were treated with endovascular coil embolization within two days and followed for at least 30 months. There were three middle cerebral and five internal carotid artery aneurysms. No patients were treated by craniotomy and none survived without treatment. Two patients died of primary brain damage or cerebral vasospasm within one month. One patient died of pneumonia at 24 months. Four patients were alive with good recovery or moderate disability at the time of final follow-up (30~66 months). Angiography immediately after the procedure showed complete occlusion in three, neck remnant in four, and body filling in one patient. No complication was seen related to the procedure. Three aneurysms that were initially neck remnant developed body filling due to coil compaction. Two were re-treated with coils at six and 12 months and resulted in neck remnant. One patient refused re-treatment and died of re-bleeding. Endovascular coil embolization can be selected at an acute stage for the treatment of aneurysms in patients with poor-grade SAH without intraparenchymal hematoma even if the aneur-ysm is large. Serial follow up by MRA/angiography is necessary for at least 12 months.

Low-intensity pulsed ultrasound accelerates periodontal wound healing after flap surgery.

BACKGROUND AND OBJECTIVE: A study was conducted to evaluate the effects of low-intensity pulsed ultrasound on wound healing in periodontal tissues after mucoperiosteal flap surgery. MATERIAL AND METHODS: Bony defects were surgically produced bilaterally at the mesial roots of the mandibular fourth premolars in four beagle dogs. The flaps were repositioned to cover the defects and sutured after scaling and planing of the root surface to remove cementum. The affected area in the experimental group was exposed to low-intensity pulsed ultrasound, daily for 20 min, for a period of 4 wk from postoperative day 1 using a probe, 13 mm in diameter. On the control side, no ultrasound was emitted from the probe placed contralaterally. After the experiment, tissue samples were dissected out and fixed in 10% formalin for histological and immunohistochemical analyses. RESULTS: The experimental group showed that the processes in regeneration of both cementum and mandibular bone were accelerated by low-intensity pulsed ultrasound compared with the control group. In addition, the expression level of heat shock protein 70 was higher in the gingival epithelial cells of the low-intensity pulsed ultrasound-treated tooth. CONCLUSION: Our results suggest that osteoblasts, as well as cells in periodontal ligament and gingival epithelium, respond to mechanical stress loaded by low-intensity pulsed ultrasound, and that ultrasound accelerates periodontal wound healing and bone repair.

A double three-step theory of brain metastasis in mice: the role of the pia mater and matrix metalloproteinases.

The brain is frequently affected by the spread of lung cancer, and haematogenous metastasis is a common route to brain metastasis. We therefore developed an isogenic brain metastasis model of lung cancer to use the Lewis lung carcinoma cell line and analysed dynamics of neoplastic cells after extravasation. Histological analysis revealed two characteristic patterns: metastatic foci exhibiting an angiocentric pattern were designated 'perivascular proliferations'; neoplastic cells infiltrating the brain parenchyma were designated 'invasive proliferations'. Electron microscopic observation of perivascular proliferations showed that neoplastic cells were confined to the perivascular space. In invasive proliferations, however, fragments of collagen fibre were observed in the gaps between neoplastic cells, indicating that the neoplastic cells had disintegrated the pia-glial membrane. We analysed the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 by using both immunohistochemical analysis and real-time polymerase chain reaction analysis. MMP-2 expression was significantly higher in invasive proliferations. MMP-9 expression was significantly higher in day 7, but there was no significant difference in day 11. The pia-glial membrane and perivascular space are the barriers that neoplastic cells must overcome to infiltrate the brain. In conclusion, our findings suggest that brain metastasis requires two distinct processes.

Endovascular trapping for a giant aneurysm of the cervical internal carotid artery: a case report.

SUMMARY: We describe a case of giant cervical internal carotid aneurysm successfully treated by endovascular trapping. A 57-year-old woman with a history of maxillary contusion seven years before presented with pharyngeal discomfort during swallowing. MRI revealed a 4 cm mass in the right parapharyngeal space. A common carotid angiogram revealed a giant aneurysm with a wide neck originating from the cervical internal carotid artery; kinking of the internal carotid artery was noted at a point distal to the carotid bifurcation. Analysis of cerebral blood flow by SPECT during a balloon occlusion test showed no hypoperfusion areas, and the patient underwent endovascular trapping. There were no neurological or other complications after the procedure. A follow-up MRI revealed complete thrombosis of the aneurysm. Our results show that endovascular trapping for pseudoaneurysm of the cervical internal carotid artery can be a reliable and effective treatment in patients who tolerate a balloon occlusion test.

Development of diffusion-weighted image using a 0.3T open MRI.

The purpose of this study was to develop a new technique for diffusion-weighted MRI (DWI) with a low-field scanner. DWI is becoming important for assessment of acute stroke. Until recently DWI required expensive technology. We developed multishot-DWI sequence for 0.3T open type MR imager. We prospectively studied forty patients on this 0.3T MRI and compared this DWI to single-shot-DWI by 1.5T-MRI. Group A: Twenty-four patients with acute cerebral infarctions detected by 1.5T-DWI were re-examined using 0.3T-DWI within 24 hours. Sixteen patients with acute cerebral infarctions detected by 0.3T-DWI were re-examined using 1.5T-DWI within 24 hours. In 22 (92%) of 24 cases, 0.3T-DWI showed high signal. In the other two patients, motion artifact distorted 0.3T-DWI. Group B: In all 16 patients, all infarctions detected by 0.3T-DWI showed high signal on 1.5T-DWI. These preliminary data show that, as long as the patient is able to keep still, multishot-DWI can be acquired successfully on a 0.3T open type MRI system.

Phase I study of a weekly schedule of fixed-dose paclitaxel and escalating doses of cisplatin for recurrent or unresectable gastric cancer in Japan.

The authors objective was to determine the toxicities and maximum tolerated dose of a dose-dense schedule of fixed-dose paclitaxel and escalating doses of cisplatin in patients with recurrent or unresectable carcinoma of the stomach. On days 1, 8, 15, 29, 36, and 43, patients received a fixed dose of paclitaxel (80 mg/m2 over 1 hour after a short premedication) followed by a 30-minute infusion of cisplatin at dose levels of 7, 15, 20, and 25 mg/m2. Six patients were treated at each dose level, except for the dose of 25 mg/m2 cisplatin. All the patients were assessed for toxicity and 17 patients (81%) were evaluated for response. The cisplatin dose could be escalated to 25 mg/m2. At the dose of 80 mg/m2 paclitaxel and 25 mg/m2 cisplatin, all 3 patients developed dose-limiting toxicity of the gastrointestinal tract. There were no treatment-related deaths. Leukopenia grades 3 or 4 was seen in 5 patients (11.1%), but infectious complications were not encountered. Other toxicities were mild and easily managed. Weekly paclitaxel at a dose of 80 mg/m2 infused over 1 hour, followed by an infusion of 20 mg/m2 cisplatin is recommended for further study in patients with recurrent or unresectable gastric cancer.

Rupture of a large vertebral artery aneurysm following proximal occlusion.

SUMMARY: Proximal occlusion of the vertebral artery is regarded as a safe and effective method of treating aneurysms of the vertebral artery or the vertebrobasilar junction unsuitable for treatment by neck clipping. Complications known to develop after this procedure include ischemic lesions of the perforators and other areas. There are only a limited number of reports on early rupture of aneurysm following proximal occlusion of the vertebral artery for the treatment of unruptured aneurysm. We recently encountered a case of large aneurysm of the vertebral artery identified after detection of brainstem compression. This patient underwent proximal occlusion of the vertebral artery with a coil and developed a fatal rupture of the aneurysm ten days after proximal occlusion. The patient was a 72-year-old woman who had complained of dysphagia and unsteadiness for several years. An approximately 20 mm diameter aneurysm was detected in her left vertebral artery. She underwent endovascular treatment, that is, her left vertebral artery was occluded with coils at a point proximal to the aneurysm. Her initial post-procedure course was uneventful. However, she suddenly developed right-side hemiparesis nine days after procedure. At that time, CT scan suggested sudden thrombosis of the aneurysm. Right vertebral angiography revealed a small part of the aneurysm. She was treated conservatively. Ten days after the procedure, she suffered massive subarachnoid haemorrhage. Both the present case and past reports suggest that proximal occlusion of the vertebral artery is effective in treating relatively large aneurysms unsuitable for treatment by neck clipping or trapping. However, when the bifurcation of the posterior inferior cerebellar artery (PICA) is distal to the occluded point in cases where the PICA bifurcates from the aneurysm or the neck region, blood supply to the aneurysm may persist because anterograde blood flow to the PICA may be preserved. Therefore, clinicians must consider the possibility of aneurysm rupture after proximal occlusion in the following cases: 1) when the aneurysm is large or giant, but non-thrombosed; 2) when thrombosis occurs soon after the procedure; 3) when postoperative angiography shows partial filling of the aneurysm with contrast agent through the contralateral vertebral artery of basilar artery or the cervical muscle branches.

Identification of peptides containing T-cell epitopes of Japanese cedar (Cryptomeria japonica) pollen allergen (Cry j 1) in dogs.

Japanese cedar (Cryptomeria japonica, CJ) pollen has been known to cause atopic dermatitis in dogs in Japan. However, since the mechanism of the CJ antigen recognition is not well understood in dogs, it is difficult to develop effective immunotherapy for atopic dermatitis caused by sensitization to CJ pollen. In order to aim at development of a peptide immunotherapy, we tried to identify T-cell epitopes of a major allergen of CJ pollen, Cry j 1, in dogs sensitive to CJ pollen allergen. Peripheral blood mononuclear cells (PBMCs) obtained from 22 dogs experimentally sensitized to CJ pollen allergen and 5 atopic dogs sensitive to CJ pollen allergen were used for mapping of T-cell epitopes of Cry j 1 using 35 kinds of synthesized overlapping peptides of Cry j 1. Reactive peptides were identified based on the results of blastogenic responses of PBMCs against the peptides when the stimulation indices were beyond 2.0. Three reactive peptides were identical in a relatively high population of experimental dogs, which were Nos. 8 (p71-90) (41%), 10 (p91-110) (50%), and 11 (p101-120) (41%). It was considered that these synthesized peptides should contain T-cell epitopes of Cry j 1 in the dogs. However, there were no reactive peptides identical among the five atopic dogs spontaneously sensitive to CJ pollen. The population of dogs experimentally sensitized to CJ pollen antigen will be used in order to investigate effects of a peptide immunotherapy using the reactive peptides. The results in atopic dogs sensitive to CJ pollen antigen will also provide useful information on necessity to develop a tailor-made immunotherapy using reactive peptides in each dog.

[Retinal hazard from blue light emitting diode].

PURPOSE: To compare the effect of exposure time from a blue(460 nm) light emitting diode(LED) on the morphology of the outer retina and determine conditions where damage occurs. MATERIALS AND METHODS: Young adult rhesus monkeys were anesthetized, and received blue LED exposure from a modified slit-lamp. A 3 mm beam of 0.85 mW was imaged onto the retina through a lens positioned before the cornea and exposure damage was determined at time intervals for 12 to 90 min. Fundus photography, fluorescein angiography(FAG), retinal tomography(HRT), and s-cone electororetinogram(S-ERG) were recorded at baseline, 2, and 30 days. RESULTS: Two days after 40 min exposure, there was a grey, discolored region, which was over-fluorescent in FAG, and an incresse in HRT and S-ERG corresponding to the site which was exposed to LED light. In histological examination at 30 days, the LED had caused produced a marked disruption of the disks of photoreceptor cells, damaged retinal pigment epithelium(RPE) apical villi, and a loss of RPE melanin after 90 min exposure. CONCLUSION: A threshold level was found around 40 min. This morphological damage may impair function and continuous exposure to blue light is potentially dangerous to vision.

Telomere length and telomerase activity in canine mammary gland tumors.

OBJECTIVE: To measure telomere length and telomerase activity in naturally occurring canine mammary gland tumors. SAMPLE POPULATION: 27 mammary gland tumor specimens obtained during resection or necropsy and 12 mammary gland tissue specimens obtained from healthy (control) dogs. PROCEDURE: Telomere length in tissue specimens was measured by use of restriction endonuclease digestion and Southern blot analysis. Telomerase activity was measured by use of a telomeric repeat amplification protocol assay. RESULTS: Telomere length in mammary gland tumors ranged from 11.0 to 21.6 kilobase pairs (kbp; mean +/- SEM, 14.5+/-0.5 kbp) but did not differ among tumor types. Telomeres in mammary gland tumors were slightly shorter than in normal tissue specimens, but telomere length could not be directly compared between groups, because mean age of dogs was significantly different between groups. Age was negatively correlated with telomere length in control dogs but was not significantly correlated with length in affected dogs. Telomerase activity was detected in 26 of 27 mammary gland tumors and in 4 of 12 normal tissue specimens. However, telomerase activity and telomere length were not correlated in tumor specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Telomere length is maintained in canine mammary gland tumors regardless of the age of the affected dog. Measurement of telomere length may be a useful tool for monitoring the in vivo effects of telomerase inhibitors in dogs with tumors.