[Clinical and prognostic analysis of opsoclonus-myoclonus-ataxia syndrome in children].

Objective: To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS). Methods: A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children's Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results: There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ²=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ²=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence (OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis (OR=11.64 (1.27-106.72), P=0.030). Conclusions: OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

[Expression of programmed cell death ligand 1 and clinicopathological and immunological characteristics in fumarate hydratase-deficient renal cell carcinoma].

Objective: To investigate the expression of programmed cell death ligand 1 (PD-L1), clinicopathologic features, immunohistochemical expression and molecular characteristics in fumarate hydratase (FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients. Methods: There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022. The clinical data, histological morphology, immunophenotype, PD-L1 expression and next-generation sequencing results were tabulated and analyzed. Results: There were 6 patients, all male, age ranged from 37 to 72 years (mean 45.7 years). Four cases were high-grade (WHO/ISUP grade3-4) with 2 or more histologic patterns, including papillary (most common), glandular, tubular, vesicular, ethmoid, nest-like, cystic and solid structures. Two cases were low-grade which showed nest-like, glandular, or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles. Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases, negative expression of FH in 5 cases, and positive expression of GATA3 in 5 cases. In high-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm2 and 130.5/mm2, respectively. PD-L1 combined positive scores (CPS) were 20, 50, 5 and 30, respectively. The Ki-67 proliferative index were 20%, 20%, 10% and 30%, respectively. In low-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm2 and 100.5/mm2, respectively. The PD-L1 CPS score was 1, and the Ki-67 proliferation index was 3%. High-throughput sequencing showed FH gene somatic mutation in 3 cases, FH gene germline mutation in 2 cases, and FH gene mutation was not detected in one case. Conclusion: FH-deficient renal cell carcinoma is more commonly high-grade than low grade. FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma, and GATA3 positivity is supportive of the diagnosis. The tumor infiltration of high-grade FH-deficient renal cell carcinoma shows an increase in CD4 and CD8 positive T-lymphocytes, and high expression of PD-L1; thus, anti-PD-L1 immunotherapy can be used as a treatment option.

[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

[Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants].

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.

Garlic skin induces shifts in the rumen microbiome and metabolome of fattening lambs.

Garlic (Allium sativum L.) and its constituents have been shown to modify rumen fermentation and improve growth performance. Garlic skin, a by-product of garlic processing, contains similar bioactive components as garlic bulb. This study aimed to investigate the effects of garlic skin supplementation on growth performance, ruminal microbes, and metabolites in ruminants. Twelve Hu lambs were randomly assigned to receive a basal diet (CON) or a basal diet supplemented with 80 g/kg DM of garlic skin (GAS). The experiment lasted for 10 weeks, with the first 2 weeks serving as the adaptation period. The results revealed that the average daily gain and volatile fatty acid concentration were higher (P < 0.05) in lambs fed GAS than those in the CON group. Garlic skin supplementation did not significantly (P > 0.10) affect the α-diversity indices, including the Chao1 index, the abundance-based coverage estimator value, and the Shannon and Simpson indices. At the genus level, garlic skin supplementation altered the ruminal bacterial composition by increasing (P < 0.05) the relative abundances of Prevotella, Bulleidia, Howardella, and Methanosphaera and decreasing (P < 0.05) the abundance of Fretibacterium. Concentrations of 139 metabolites significantly differed (P < 0.05) between the GAS and the CON groups. Among them, substrates for rumen microbial protein synthesis were enriched in the GAS group. The pathways of pyrimidine metabolism, purine metabolism, and vitamin B6 metabolism were influenced (P < 0.05) by garlic skin supplementation. Integrated correlation analysis also provided a link between the significantly altered rumen microbiota and metabolites. Thus, supplementation of garlic skin improved the growth performance of lambs by modifying rumen fermentation through shifts in the rumen microbiome and metabolome.

[Pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 antibody: two cases report and literature review].

Objective: To investigate the clinical features and prognosis of pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 (GAD65) antibody. Methods: Clinical data of 2 patients diagnosed as autoimmune encephalitis associated with anti-GAD65 antibody at Department of Neurology, Beijing Children's Hospital in 2019 were analyzed retrospectively. A literature search with "anti-GAD65 antibody""encephalitis""epilepsy" or "cerebellar ataxia" as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to January 2020). The clinical features and prognosis of pediatric cases with complete clinical data were retrieved and summarized. Results: Two patients with positive anti-GAD65 antibody of serum and cerebrospinal fluid were both females. The onset age of case 1 was 57 months and her main clinical manifestations were fever and unconsciousness. The cranial magnetic resonance imaging (MRI) showed diffuse T2 weighted imaging (T2WI) abnormal signals, and the electroencephalogram (EEG) showed slow waves. The onset age of case 2 was 80 months and her main clinical manifestations of were recurrent focal seizures, memory loss, and headache. The MRI showed high T2WI signal in bilateral hippocampus, and the EEG showed abnormal discharge involving the temporal area. Both cases were treated with methylprednisolone and intravenous immunoglobulin, the short-term symptoms of them were both improved. They were followed up for 6 months and 1 year respectively, the case 1 recovered completely, and the case 2 still had focal seizures. Six English reports which included 6 cases were retrieved. Together with these 2 cases, a total of 8 cases were analyzed. The clinical symptoms included seizures (6 cases), memory loss (4 cases), loss of consciousness (3 cases), behavioral abnormalities (3 cases), cognitive impairment (2 cases), headache (2 cases), autonomic symptoms (1 case), ataxia (1 case), dysphagia (1 case), and aphasia (1 case). There were 5 cases with cranial MRI abnormalities in the acute phase or sub-acute phase, of whom 3 cases had the limbic system involvement, and 2 cases were mainly had extra limbic area involvement. Three cases had hippocampal atrophy or sclerosis during follow-up. All 8 patients were treated with immunotherapy. After immunotherapy, all patients had short-term improvement. Follow-up for 6 months to 6 years showed that 3 cases with extra limbic encephalitis improved to baseline levels, and 5 limbic encephalitis cases had poor outcomes, including 1 death and 4 cases still had focal epilepsy. Conclusions: Pediatric anti-GAD65 antibody associated autoimmune encephalitis is a rare but treatable disease, including limbic encephalitis and extra limbic encephalitis. The most common clinical manifestations are seizures and memory impairment. Early diagnosis and immunotherapy can improve the symptoms in a short time. But patients with limbic encephalitis often had refractory epilepsy in the chronic phase, and have a poor long-term outcome.

[Clinical observation on the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody and anti-N-methyl-D aspartate receptor in children].

Objective: To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS). Methods: The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children's Hospital from January 2011 to April 2019 were analyzed retrospectively. Results: A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases). Conclusions: MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.

[Primary skull base chondrosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of primary skull base chondrosarcoma. Methods: Nine cases of primary skull base chondrosarcoma were collected at the First Affiliated Hospital of Fujian Medical University, from January 2006 to June 2019, reviewed for the clinical and radiologic data and morphologic features, immunophenotype and molecular characteristics. Results: Among all the 9 cases, six were male, three were frmale, with average age 47 years, and median age 47 years; five cases were WHO gradeⅠ, and four were WHO grade Ⅱ. Microscopically, the tumor showed lobulated growth pattern with low-medium cellularity within a chondroid or mucoid background. The tumor cells showed mild-moderate atypia, with binucleated forms, and mitosis was rare or occasional. Immunohistochemistry (IHC) showed tumor cells were positive for S-100 protein, vimentin, SOX-9 and D2-40, and negative for Brachyury, CK, EMA and CK8/18; the Ki-67 index was low (1% to 5%). Molecular analysis showed IDH1 R132C mutation in four cases. Conclusions: Skull base chondrosarcoma is a rare cartilaginous malignant tumor with a good prognosis. Its characteristic morphologies, combined with IHC and molecular detection are helpful for the differential diagnosis.

[Progressive cavitating leukoencephalopathy: four cases and literatures review].

Objective: To analyze the clinical and genetic features of progressive cavitating leukoencephalopathy (PCL). Method: The data of clinical and genetic features of 4 PCL patients diagnosed by Beijing Children's Hospital between January 2015 and January 2016 were analyzed. The cases with complete clinical data retrieved on literature search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to August 2016) by using search terms of"NDUFV1" ,"NDUFS1" , or"leukoencephalopathy" , were summarized. Result: There were three females and one male, two of which were compatriots. The age of onset ranged from 6 months to 15 months. All four children's first symptoms were motor development regression, and the developmental milestones were almost normal before the onset. Of the 4 patients, 3 had cognitive impairment, 1 had seizures, 4 had dystonia and pyramidal impairment, 2 had emaciation, and 1 had nystagmus. The lactate concentrations of 4 patients were normal in blood. One patient had lactaciduria in the urinary organic acid analysis. Cranial magnetic resonance imaging (MRI) of all patients showed leukoencephalopathy, involved in the corpus callosum, and three patients accompanied by cystic lesions. Follow up for 2-13 years showed that the physical and language development were improved. Genetic analysis revealed that mutations in NDUFS1 were found in three patients and NDUFV1 mutation was found in one patient. All six mutations (p.Arg377Cys and p. Arg377His in NDUFV1; p. Arg482Glyfs(*)5, p.Thr368Pro, p.Tyr454X and p. Asp565Gly in NDUFS1) are novel. Five English case reports including 10 PCL patients were collected. Together with this group of 4 cases, a total of 14 cases were involved. All 14 children patients had motor development regression, 11 cases had cognitive impairment and dystonia, 6 cases had pyramidal impairment, 5 cases had irritability, 4 cases had epilepsy and nystagmus, 3 cases had strabismus and swallowing difficulty. Cranial MRI showed patchy leukoencephalopathy with cavities, involved in the corpus callosum. Follow up for 19 months-15 years that the neurology development were improved slowly in all patients. Conclusion: NDUFS1 and NDUFV1 gene mutation screening should be performed firstly in patients with PCL clinical and imaging feature.

Genetic differentiation of chinese indigenous meat goats ascertained using microsatellite information.

To investigate the genetic diversity of seven Chinese indigenous meat goat breeds (Tibet goat, Guizhou white goat, Shannan white goat, Yichang white goat, Matou goat, Changjiangsanjiaozhou white goat and Anhui white goat), explain their genetic relationship and assess their integrity and degree of admixture, 302 individuals from these breeds and 42 Boer goats introduced from Africa as reference samples were genotyped for 11 microsatellite markers. Results indicated that the genetic diversity of Chinese indigenous meat goats was rich. The mean heterozygosity and the mean allelic richness (AR) for the 8 goat breeds varied from 0.697 to 0.738 and 6.21 to 7.35, respectively. Structure analysis showed that Tibet goat breed was genetically distinct and was the first to separate and the other Chinese goats were then divided into two sub-clusters: Shannan white goat and Yichang white goat in one cluster; and Guizhou white goat, Matou goat, Changjiangsanjiaozhou white goat and Anhui white goat in the other cluster. This grouping pattern was further supported by clustering analysis and Principal component analysis. These results may provide a scientific basis for the characteristization, conservation and utilization of Chinese meat goats.

Identification and pathogenicity of Vibrio ponticus affecting cultured Japanese sea bass, Lateolabrax japonicus (Cuvier in Cuvier and Valenciennes).

AIMS: To rapidly determine the causative agent of mass death in Lateolabrax japonicus in Zhelin Bay of Guangdong Province in China in April 2004. METHODS AND RESULTS: Thirty-six strains, numbered sequentially from RP01 to RP36, were isolated from six diseased fish. All of the strains were identified as being of the same vibrio species according to the results of universal primer PCR combined with DGGE (UPPCR-DGGE). RP30 was one of these strains that was randomly selected and analysed by using a morphological, physiological and biochemical plate, Biolog GN2 Microplate System and API 20E system. Furthermore, RP30' 16S rDNA was sequenced and aligned in Genbank. Its virulence to Lateolabrax japonicus (Cuvier in Cuvier and Valenciennes) was also tested. RP30 is most closely related to four Vibrio ponticus strains (99.3% similarity). LD50s were 2.5 (x103 CFU per fish for intraperitoneal inoculation (IP) and 3.2 (x103 CFU per fish for intramuscular inoculation (IM), respectively. CONCLUSIONS: The investigated pathogenic agent of Lateolabrax japonicus (Cuvier in Cuvier and Valenciennes) was V. ponticus. SIGNIFICANCE AND IMPACT OF THE STUDY: UPPCR-DGGE is very helpful in epidemiologic investigation. Interestingly, this is the first report that V. ponticus infects cultured marine fish. DGGE was likewise first introduced to epidemiologic investigation of fish disease.

Investigation of seven Vibrio virulence genes among Vibrio alginolyticus and Vibrio parahaemolyticus strains from the coastal mariculture systems in Guangdong, China.

AIMS: To investigate the distribution of the virulence of two Vibrio species among different strains obtained from the mariculture systems on the coast of Guangdong in China and the correlation between the virulence strains and the virulence genes among Vibrio alginolyticus. METHODS: Besides three strains, 72 V. alginolyticus strains and seven Vibrio parahaemolyticus strains were examined by PCR or semi-nested PCR for the virulence genes (tlh, trh, tdh, toxR, toxRS, ctxA, VPI). Additionally, the virulence of 18 V. alginolyticus strains was tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Virulence genes homologous to those in the V. parahaemolyticus and Vibrio cholerae are widely distributed among V. alginolyticus and V. parahaemolyticus in the coastal mariculture systems in Guangdong, China. Some of the V. alginolyticus strains are pathogenic to aquatic animals, and might have derived their virulence genes from V. parahaemolyticus or V. cholerae, representing a possible reservoir of these genes. However, there is no correlation between presence and absence of the virulence genes used to investigate V. alginolyticus and its virulent strains. In this report, we also show that tlh is distributed among V. alginolyticus.

Galectin-1 as a potential therapeutic agent for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects almost selectively motor neurons in the central nervous system. Most ALS patients die within five years of onset. One of the neuropathological features of ALS is an "axonal spheroid," a large swelling of a motor axon within the anterior horn of the spinal cord; this abnormal structure seems to be related to the pathogenesis of motor neuron degeneration in ALS. In 2001, using biochemical and immunohistochemical methods, we found an accumulation of galectin-1 in ALS spheroids. By immuno-electron microscopy, the galectin-1 accumulated in the spheroids was observed to be closely associated with neurofilaments. Furthermore, we observed a marked depletion of galectin-1 in the skin of ALS patients; another abnormality frequently observed in ALS. These findings, therefore, suggest that galectin-1 may be involved in the pathogenesis of ALS. It is known that an oxidized form of galectin-1 promotes axonal regeneration; however, it is not known whether oxidized galectin-1 has a beneficial or an adverse effect on the pathophysiology of ALS. To examine this issue, we administered oxidized galectin-1 to transgenic mice with H46R mutant SOD1, an ALS model mouse. The results showed that the administration of oxidized galectin-1 improved the motor activity, delayed the onset of symptoms, and prolonged the survival of the galectin-1-treated mice. Furthermore, the number of remaining motor neurons in the spinal cord was more preserved in the galectin-1-treated mice than in the non-treated mice. We conclude that galectin-1 could be a candidate agent for the treatment of ALS.