Deficits in spatial learning and motor coordination in ADAM11-deficient mice

BACKGROUND: ADAM11 is a member of the ADAM gene family and is mainly expressed in the nervous system. It is thought to be an adhesion molecule, since it has a disintegrin-like domain related to cell-cell or cell-matrix interactions. To elucidate the physiological functions of ADAM11, we generated ADAM11-deficient mice by means of gene targeting. RESULTS: ADAM11-deficient mice were apparently normal, and survived more than one year with no major histological abnormalities in the brain or spinal cord. Because ADAM11 is highly expressed in the hippocampus and cerebellum, we have examined ADAM11 mutant mice for learning using visual and hidden water maze tasks, and their motor coordination using a rotating rod task. Our results showed that their visual water maze task results are normal, but the hidden water maze and rotating rod task skills are impaired in ADAM11-deficient mice. CONCLUSION: Our results indicate that ADAM11 mutation does not affect cell migration and differentiation during development, but affects learning and motor coordination. Thus, ADAM11 might play an important signalling or structural role as a cell adhesion molecule at the synapse, and may thus participate in synaptic regulation underlying behavioural changes

Transport Barrier Analysis of LHD Plasmas in Gomparison with Neoclassical Models

Abstract In the local Electron Cyclotron Heating (ECH) experiments, high electron temperature plasmas have been olrtained in Compact Helical System (CHS), and recently in the Large Helical Device (LHD). The internal transport barrier (ITB) with strong positive radial electric field has been experimentally observed in CHS, which reduces neo-classical ripple transport and anomalous transport losses. The same physics picture; are expected in LHD high temperature plasmas. Several ion temperature profiles are assumed for analyzing LHD experimental data, and it is found that the experimentally obtained electron thermal transpc,rt coefficients seem to roughly agree with neoclassical ripple transport outside the ITB region. Howeler, around ITB region, about ten times higher than the neoclassical coefficients with strong ambipc'lar electric field prediction are obtained. The anomalous transport losses might be dominant and be redtLced by this strong electric field shear around the ITB region

Tumefactive multiple sclerosis requiring emergent biopsy and histological investigation to confirm the diagnosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tumefactive multiple sclerosis is a demyelinating disease that demonstrates tumor-like features on magnetic resonance imaging. Although diagnostic challenges without biopsy have been tried by employing radiological studies and cerebrospinal fluid examinations, histological investigation is still necessary for certain diagnosis in some complicated cases.</p> <p>Case presentation</p> <p>A 37-year-old Asian man complaining of mild left leg motor weakness visited our clinic. Magnetic resonance imaging demonstrated high-signal lesions in bilateral occipital forceps majors, the left caudate head, and the left semicentral ovale on fluid-attenuated inversion recovery and T2-weighted imaging, and these lesions were enhanced by gadolinium-dimeglumin. Tumefactive multiple sclerosis was suspected because the enhancement indistinctly extended along the corpus callosum on magnetic resonance imaging and scintigraphy showed a low malignancy of the lesions. But oligoclonal bands were not detected in cerebrospinal fluid. In a few days, his symptoms fulminantly deteriorated with mental confusion and left hemiparesis, and steroid pulse therapy was performed. In spite of the treatment, follow-up magnetic resonance imaging showed enlargement of the lesions. Therefore, emergent biopsy was performed and finally led to the diagnosis of demyelinating disease. The enhanced lesion on magnetic resonance imaging disappeared after one month of prednisolone treatment, but mild disorientation and left hemiparesis remained as sequelae.</p> <p>Conclusions</p> <p>Fulminant aggravation of the disease can cause irreversible neurological deficits. Thus, an early decision to perform a biopsy is necessary for exact diagnosis and appropriate treatment if radiological studies and cerebrospinal fluid examinations cannot rule out the possibility of brain tumors.</p

Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice

BACKGROUND: ADAM22 is a member of the ADAM gene family, but the fact that it is expressed only in the nervous systems makes it unique. ADAM22's sequence similarity to other ADAMs suggests it to be an integrin binder and thus to have a role in cell-cell or cell-matrix interactions. To elucidate the physiological functions of ADAM22, we employed gene targeting to generate ADAM22 knockout mice. RESULTS: ADAM22-deficient mice were produced in a good accordance with the Mendelian ratio and appeared normal at birth. After one week, severe ataxia was observed, and all homozygotes died before weaning, probably due to convulsions. No major histological abnormalities were detected in the cerebral cortex or cerebellum of the homozygous mutants; however, marked hypomyelination of the peripheral nerves was observed. CONCLUSION: The results of our study demonstrate that ADAM22 is closely involved in the correct functioning of the nervous system. Further analysis of ADAM22 will provide clues to understanding the mechanisms of human diseases such as epileptic seizures and peripheral neuropathy

Combination Therapy with Rituximab and Temozolomide for Recurrent and Refractory Primary Central Nervous System Lymphoma

High-dose methotrexate-based chemotherapy has extended survival in patients with primary central nervous system lymphoma (PCNSL). However, although salvage treatment is necessary in recurrent and refractory PCNSL, this has not been standardized. We herein describe the efficacy of a combination of rituximab and temozolomide (TMZ) in two consecutive patients with recurrent and refractory PCNSL. Based on the immunohistochemical study, case 1 had a non-germinal center B-cell-like (non-GCB) subtype, was positive for bcl-2 and negative for O6-methylguanine-DNA methyltransferase (MGMT). Case 2 was GCB subtype, bcl-2-, and MGMT+. Because of the positive expression of MGMT, interferon-beta was additionally given in case 2. Complete responses and partial responses were obtained after the third and fourth cycles of combination therapy, respectively. This was maintained for 12 months, with acceptable toxicity. The combination of rituximab and TMZ was effective in tumors with different immunohistochemical profiles. This combination therapy warrants further study in a larger population

Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

BACKGROUND: Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI) patients. CASE PRESENTATION: A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: < 0.7 pmol/l (1.1 – 6.9); Parathyroid hormone-related protein (PTHrP): 2.3 pmol/l (0.7 – 1.8). Ultrasound scan of urinary bladder showed mixed echogenicity, which was diagnosed as debris. CT of pelvis was interpreted as vesical abscess. Urine cytology: Transitional cells showing mild atypia. Bladder biopsy: Inflamed mucosa lined by normal urothelial cells. A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. CONCLUSION: This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs

Coral Ba/Ca Analysis Using ICP-OES With an Ultrasonic Nebulizer

The barium/calcium ratio (Ba/Ca) in coral skeletons has been used as a proxy to understand river floods and oceanic upwelling in the tropics and subtropics for the past centuries. Here, we establish a new method for Ba/Ca analysis using inductively coupled plasma optical emission spectrometry (ICP-OES), which has been widely used for coral proxy analyses and can save analysis time compared to other methods. We analyze Ba/Ca by combining an ultrasonic nebulizer with the intensity ratio calibration method to improve the signal intensity of Ba. Our method can determine Ba/Ca in samples with a Ca concentration of 9 mg/L with excellent analytical precision (<0.17 mu mol/mol) using ICP-OES