Appearance of focal cortical dysplasia on serial MRI after maturation of myelination

Case report It is well known that magnetic resonance imaging (MRI) findings of focal cortical dysplasia (FCD) can change with maturation of myelination. In this paper, we report a patient with intractable epilepsy and negative MRI at the age of 2.5 years, after completion of myelination. Follow-up MRI at the age of 6 years revealed typical FCD findings in the right frontal lobe. During these 3.5 years, electroencephalogram (EEG) consistently depicted an area of irritation in accordance with de novo MRI findings. Intraoperative electrocorticogram showed frequent paroxysmal activity in the right frontal lobe; excision of the epileptogenic cortex resulted in a reduction in seizures. Conclusion It is possible that FCD becomes apparent on MRI even after maturation of myelination; thus, repeated MRI is recommended while EEG continues to demonstrate focal findings.     

Is excitation–contraction coupling impaired in myasthenia gravis?

OBJECTIVE: To investigate whether excitation-contraction (E-C) coupling of muscle is impaired in patients with myasthenia gravis (MG). METHODS: In 51 patients with generalized MG and 35 normal subjects, compound muscle action potentials (CMAPs) of the abductor pollicis brevis, and movement-related potentials using an accelerometer placed at the thumb tip were simultaneously recorded after median nerve stimulation at the wrist. The E-C coupling time (ECCT) was estimated by a latency difference between CMAP and movement-related potential. Antibodies against acetylcholine receptor (AChR), ryanodine receptor (RyR), and muscle specific receptor tyrosine kinase (MuSK) were measured by immunoassays. RESULTS: The mean ECCT was significantly longer in patients with MG (mean+/-SEM; 2.79+/-0.1 ms; p=0.002) than in normal controls (2.52+/-0.1 ms). Among MG patients, the mean ECCT was longer for patients with thymoma than for those without it (P=0.04), and was shorter for patients treated with FK506 (an immunosuppressant and also an enhancer of RyR related Ca(2+) release) than for those not receiving this treatment (p=0.04). ECCT had no significant correlation with anti-AChR, anti-RyR, or anti-MuSK antibodies. CONCLUSIONS: In MG, E-C coupling appears to be impaired, particularly in patients with thymoma, and FK506 possibly facilitates E-C coupling. SIGNIFICANCE: The functional implication of impaired E-C coupling is not established, but it may contribute to muscle weakness in patients with MG.     

Binding of plasminogen to hepatocytes isolated from injured mice liver and nonparenchymal cell-dependent proliferation of hepatocytes

Plasmin is an essential enzyme located in the pericellular microenvironment of liver cells during liver regeneration. Previously, we reported that liver regeneration ability was significantly increased in alpha2-antiplasmin gene knockout mice as compared to wild-type mice, but it was significantly decreased in plasminogen knockout mice, or Plg/alpha2-antiplasmin gene knockout mice. The present study aimed to demonstrate direct interaction between plasminogen and mouse hepatocytes in the process of liver regeneration. Using the isolated hepatocytes from mice we analyzed following subjects: binding capacity of plasminogen to hepatocytes, plasminogen activation in the presence of hepatocytes, and proliferation ability of hepatocytes cocultured with liver nonparenchymal cells. The isolated hepatocytes from plasminogen wild-type mice bound to immobilized plasminogen. The mouse hepatocytes enhanced plasminogen activation, and impaired the inhibitory effect of alpha2-antiplasmin. The proliferation ability of hepatocytes after liver injury was studied. In plasminogen wild-type and plasminogen knockout mice, the hepatocytes cocultured with nonparenchymal cells, which were obtained from mice without CCl4 injection, showed similar proliferation abilities. On the contrary, the proliferation ability of hepatocytes cocultured with nonparenchymal cells, which were obtained from CCl4-treated plasminogen knockout mice, was significantly impaired as compared to wild-type mice. These results indicate that the plasminogen-plasmin system on the surface of mouse hepatocytes plays an important role in liver regeneration.     

Observation of molecular changes of a necrotic tissue from a murine carcinoma by Fourier-transform infrared microspectroscopy.

PURPOSE: Our purpose is to develop infrared (IR) microspectroscopy as a new optical diagnostic tool to support conventional lightscopic techniques in investigating the viability of carcinoma tissues and to develop its use in the evaluation of the early effects of anticancer therapy by monitoring the IR spectra in the necrotic area. EXPERIMENTAL DESIGN: We evaluated the tissue which amassed for 4 weeks after the isotransplantation of mouse squamous cell carcinoma into the thigh of mice. The borders of the necrotic area of frozen tissue specimens were investigated by Fourier-transform IR microspectroscopy and conventional histological staining. RESULTS: A significantly higher accumulation of cholesterol was observed in the necrotic tissue of a carcinoma. The mechanism of this phenomenon is hitherto unrecognized. We proposed that the accumulated cholesterol may lie extracellularly as a result of the ruptured plasma and internal membranes after the swelling of the necrotic cells brought on by hypoxia. The analysis of the secondary structure of protein revealed that the amounts of beta-sheet increased significantly in striking contrast to the decreasing amounts of alpha-helix in a necrotic area of a carcinoma. It is plausible that this structural conversion of protein was because of lipid-autooxidation products, such as cholesterol oxide but not cholesterol itself, which possesses cell toxicity and could be generated in a necrotic area. CONCLUSIONS: We conclude that it will be possible to evaluate the efficacy of the clinical treatment of carcinoma by monitoring subtle biological changes of cholesterol absorbance in the early stage of necrosis because of anticancer treatment.     

Enhancement by neurotensin of hepatocarcinogenesis by N-nitrosomorpholine in Sprague-Dawley rats

The effect of neurotensin on hepatocarcinogenesis by N-nitrosomorpholine (NNM) was investigated in Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and alternate-day injections of neurotensin from the beginning until the end of the experiment. Preneoplastic and neoplastic lesions stained for placental type glutathione-S-transferase (GST-P) were examined histochemically. Administration of neurotensin significantly increased the percentage area and the number of GST-P-positive lesions, and the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that neurotensin enhances hepatocarcinogenesis and that this effect may be related to its effect in increasing cell proliferation in preneoplastic lesions.     

Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopamine neurons

A dopamine-derived neurotoxin, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol] was found to cause parkinsonian in rats and to deplete selectively dopamine neurons in the substantia nigra after infusion in the striatum. This isoquinoline occurs enantio-specifically in the nigra-striatum of human brains. The biosynthesis from dopamine is catalyzed by two enzymes, (R)salsolinol synthase and (R)salsolinol N-methyltransferase. The isoquinoline increases in the cerebrospinal fluid from parkinsonian patients, and the increase is ascribed to high activity of its synthesizing neutral (R)salsolinol N-methyltransferase, as shown by analyses in lymphocytes. The cell death caused by this neurotoxin in dopaminergic human neuroblastoma SH-SY5Y cells proved to be apoptotic. Apoptosis by this neurotoxin is mediated by intracellular sequential process, loss of mitochondrial membrane potential, activation of caspases and DNA fragmentation. These results are discussed in relation to the role of apoptosis in neurodegenerative diseases and the involvement of the endogenous toxin in the pathogenesis of Parkinson's disease.     

Nasal teratoma in a neonate associated with an acardiac amorphous twin

Nasopharyngeal teratomas are uncommon neoplasms found in neonates. A rare case of a teratoma arising from the nasal septum of a newborn associated with an acardiac amorphous twin is described. Antenatal ultrasonography suggested a fetal anomaly, for which a cesarean section was performed. Immediately after birth the tumor was excised, thereby eliminating life-threatening respiratory distress. The postoperative course was uneventful. Correspondence to: H. Takehara     

Chemical Modification of Natural Human Tumor Necrosis Factor-α with Polyethylene Glycol Increases Its Anti-tumor Potency

Natural human tumor necrosis factor-α (TNF-α) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG-modified TNF-a depended on the reaction time as well as the initial molar ratio of PEG to TNF-α. The specific activity of modified TNF-α was gradually reduced with increase in the degree of PEG-modification, but the plasma half-life of TNF-α was increased by up to 40-fold. Modified TNF-α showed approximately 100 times greater anti-tumor potency than unmodified TNF-α. Covalent attachment of PEG to TNF-α thus increased the bioavailability of TNF-α, and may facilitate its potential therapeutic use.     

Idiopathic benign paroxysmal positional vertigo with persistent vertigo/dizziness sensation is associated with latent canal paresis,endolymphatic hydrops,and osteoporosis

Objective

The aim of the present study was to examine the association of neuro-otological examination, blood test, and scoring questionnaire data with treatment-resistant intractability in idiopathic benign paroxysmal positional vertigo (BPPV) patients.