Mituhiro Osame

Cerebrotendinous xanthomatosis: Clinical and biochemical evaluation of eight patients and review of the literature

We present the clinical and laboratory findings of 8 patients with cerebrotendinous xanthomatosis. The clinical features consisted of a combination of bilateral Achilles tendon xanthomas, cataracts, low intelligence, pyramidal signs, cerebellar signs, convulsions, peripheral neuropathy, foot deformity, cardiovascular disease or atherosclerosis, EEG abnormality, and increased CSF protein. Increased cholesterol was present in the serum, CSF and red cell membrane of all 8 patients. The bile of one patient with late age onset of the disease showed an attenuated production of bile acids and bile alcohols. Three of the 7 had obstruction and/or marked narrowing of the coronary arteries. Data on 136 patients reported throughout the world are reviewed.

Neopterin in cerebrospinal fluid : a useful marker for diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis

Neopterin is a pyrazino-pyrimidine compound that is biosynthesized from guanosine triphosphate.’ Neopterin may be an in vitro indicator of activation of the immune system. Raised excretion of neopterin is related to the action of interferons on the T lymphocyte/macrophage axis.* Increased urinary neopterin levels occur in patients with malignancies and viral infections, as well as in patients with the acquired immunodeficiency syndrome (AIDS) and generalized lymphadenopathy.3-5 We have measured the levels of neopterin in human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic progressive myelopathy characterized clinically by a symmetric upper motoneuron disorder with urinary sphincter involvement and mild sensory disturbances, and serologically by the presence of antibodies against HTLV-I in serum and CSF.6 Methods. Twenty patients with HAM/TSP, 17 asymptomatic HTLV-I carriers, 6 patients with viral encephalitis, 30 patients with other neurologic disorders, including 6 cases of chronic MS, and 26 normal controls were analyzed. The assay for neopterin involved a pretreatment modified from that of Fukushima and N i ~ o n . ~ CSF and urinary neopterin levels were measured by high-pressure liquid chromatography (HPLC) with fluorometric detection. Each CSF sample (100 pl) was thawed and immediately acidified with 100 pl of ice-cold 0.1 N HCI and kept in ice. Then, 50 1 1 of a 1% 12/2% KI in 0.1 N HCl was added and allowed to react a t room temperature in the dark. After standing for 60 minutes, the mixture was neutralized with 50 1 1 of 1.5% ascorbic acid. The solution was centrifuged at high speed for 1 minute in a Beckmann microcentrifuge. For HPLC, a 100-p1 sample of the supernatant was injected over a C18 column (250 X 4.6 mm) with 7% methanol in water as the mobile phase. The neopterin assay was standardized with similarly treated authentic standards. Results. CSF neopterin values in controls (18.0 ? 5.3 pmol/ml, mean k SD) were in agreement with others. Extremely high values of CSF neopterin were found in patients with HAM/TSP (107.7 f 98.1; p < 0.001, Fisher’s exact test). Patients with viral encephalitides also showed high levels of neopterin in CSF. Other noninflammatory neurologic disorders such as MS, ALS, Parkinson’s disease, or cervical spondylosis showed CSF neopterin levels similar to those of the controls, with values below 30 pmol/ml (figure). Some cases of HAM show mild CSFpleocytosis. However, there was no significant correlation between cell counts and levels of neopterin in CSF. Urine samples were measured after being diluted 100 times. Urinary neopterin levels

Increased serum high mobility group box-1 level in Churg–Strauss syndrome THIS ARTICLE HAS BEEN RETRACTED

Churg–Strauss syndrome (CSS) is a rare form of systemic vasculitis occurring in patients with asthma and hypereosinophilia; however, its mechanisms involved in the severe tissue inflammation with vasculitis are poorly understood. High mobility group box 1 (HMGB1) protein, originally identified as a DNA binding protein, also has potent pro‐inflammatory and proangiogenic properties. In this study, we hypothesized that HMGB1 might be associated with CSS, and examined serum HMGB1 levels and compared those of asthma patients and healthy volunteers. We also investigated HMGB1 expression in the lesion, and eosinophil HMGB1 amount in CSS patients. We found that the serum HMGB1 levels in CSS patients were significantly higher than those of asthma patients and healthy volunteers. Eosinophils in the CSS lesion expressed HMGB1 and HMGB1 level in eosinophils from CSS patients was significantly higher than that of asthma patients, while there was no significant difference in HMGB1 levels in peripheral mononuclear cells. The serum HMGB1 level in CSS patients decreased after the steroid therapy, and showed significant positive correlations with several molecules, including soluble interleukin‐2 receptor, soluble thrombomodulin, and eosinophil cationic protein in sera. We propose that HMGB1 might contribute to the pathogenesis of CSS.

Polyneuropathy induced by m-tolyl methyl carbamate intoxication

SummaryA 55-year-old woman who attempted suicide by ingesting 200 ml of m-tolyl methyl carbamate (MTMC) is reported. She was comatose for 3 days and, upon recovery, had notable paraesthesia in her lower limbs and difficulty in walking. Neurological examination revealed sensorimotor polyneuropathy. Sural nerve biopsy revealed marked axonal degeneration with a moderate decrease of myelinated fibres.

Neuro-ophthalmological abnormalities in HTLV-I associated myelopathy

To determine whether neuro-ophthalmological abnormality exists in HTLV-I Associated Myelopathy (HAM), 22 patients were examined using electrooculography and visual evoked potentials and compared with controls. Eleven cases had mild abnormalities in smooth pursuit movements. Of these 11 patients, four had transient diplopia or jerky eye movements. One patient had a delayed P100 latency in the visual evoked potentials. These data suggest that the central nervous system may also be involved in HAM.

Mechanisms of hyperpolarization induced by two cytokines, hTNFα and hIL-1α in neurons of the mollusc,Onchidium

Abstract The voltage and current responses induced by extracellular tumor necrosis factor (hTNFα) or interleukin-1 (hIL-1α) on the Be-1 and Es-1 neurons of theOnchidium ganglia were examined. Pressure-ejected hTNFα or hIL-1α produced an inhibitory, hyperpolarized effect in unclamped neurons. In the same neurons voltage-clamped at their resting potential levels, the same hTNFα or hIL-1α elicited an outward current having a time course similar to that of the hyperpolarization, associated with a decreased membrane conductance. The hTNFα- or hIL-1α-induced outward current did not reverse even at positive membrane potentials considerably above +100 mV in the absence of ouabain (a specific blocker of Na-pump). In the presence of ouabain, the hTNFα- or hIL-1α-induced current was reduced over a wide range of membrane potential, so that the current reversed at about +20 mV. Lowering the external Na+ concentration from 450 to 200 mM in the presence of ouabain, shifted the reversal potential from +20 to 0 mV, to near the shift value of 20.8 mV predicted by the Nernst equation for a Na+-selective conductance. Neither an increase nor a decrease of extracellular K+, Cl− or Ca2+, however, significantly altered the current induced by hTNFα or hIL-1α. These suggest that the hTNFα- or hIL-1α-induced hyperpolarization or outward current response is mediated by two mechanisms, a decrease in Na+ conductance and activation of the Na-pump.

Werner's syndrome associated with spastic paraparesis and peripheral neuropathy

A Werners syndrome patient with spastic paraparesis and polyneuropathy had slowing of central and peripheral nerve conduction. Sural nerve biopsy revealed a significantly higher frequency of demyelination and remyelination and a loss of myelinated fibers. These data suggest that the central and peripheral nervous systems are affected in Werners syndrome.

Schwartz-Jampel syndrome associated with von Willebrand's disease

SummaryWe report a very rare case of Schwartz-Jampel syndrome associated with von Willibrands disease. This association might be coincidental because of the different modes of inheritance of the two disorders. However, we speculate that there might be some link between the two disorders, for example in the locus of the affected gene.

Clinical investigation: increased serum stromal derived factor 1 alpha levels in pulmonary tuberculosis.

Pulmonary tuberculosis, a granulomatous disease, has few serological markers for its activity. Recently, an increased plasma level of stromal derived factor 1 alpha (SDF‐1α), which can induce strong chemotaxis of cells through its receptor CXCR4, was detected in patients with tuberculosis. In this study we investigated serum SDF‐1α levels and CXCR4 expression on peripheral blood mononuclear cells (PBMCs). Fifty‐five active tuberculosis patients, 30 resolved tuberculosis patients, 27 acute bronchitis patients and 8 healthy volunteers were examined. Histological expression of SDF‐1α in the tuberculosis lesion and CXCR4 expression of PBMCs were also analysed. Serum SDF‐1α levels in active tuberculosis patients were significantly higher than other groups. The sensitivity and specificity for the diagnosis of active tuberculosis was 88·5% and 85·3% (cutoff value = 650 pg/ml), respectively. CXCR4 expression levels on PBMCs showed a significant negative correlation with serum SDF‐1α levels. Inflammatory cells including multinuclear giant cells in the lesion expressed SDF‐1α. Measurement of serum SDF‐1α could be a useful screening marker for the identification of active pulmonary tuberuculosis. We propose that interaction of SDF‐1α and CXCR4 might be involved in the pathogenesis of pulmonary tuberculosis.

Depression of neuromuscular transmission in methylmercury-poisoned rats : a glass microelectrode and single fiber electromyography study

Changes in neuromuscular transmission were examined in methylmercury (MeHg)‐poisoned rats, given a total oral dose of 60 mg CH3HgCl at 5 mg/kg/day. A microelectrode study was done on the 21st day. The mean quantal content and mean values of the immediately available pool of ACh in the MeHg‐poisoned rats were reduced as compared to those in the control rats, but the mean values for the release probability of ACh did not differ significantly. Stimulation single fiber electromyography (SFEMG) was done on the biceps femoris muscle at 1,5, 10 and 20 Hz on the 28th day. Both a significant and consistent increase in jitter were found at increasing stimulation rates in the MeHg‐poisoned rats. The SFEMG findings suggest presynaptic involvement due to accelerated depletion of ACh. We confirmed that neuromuscular transmission is depressed in MeHg‐poisoned rats in vivo and in vitro.