A distinctive distribution of reactive astroglia in the precentral cortex in amyotrophic lateral sclerosis

Summary Morphological changes in astrocytes have been studied in the primary motor cortex of persons dying with or without amyotrophic lateral sclerosis (ALS). Glial fibrillary acidic protein (GFAP) and S-100 protein were used as immunohistochemical markers for reactive astroglia. In 12 brains of individuals without neurological disease glial cells showing moderate immunoreactivity for both GFAP and S-100 protein were uniformly distributed in the primary motor cortex in the upper regions of layer I and layer II. In 8 of 11 ALS cases, intensely immunoreactive cells were additionally found to occur and were scattered irregularly, mostly in layers II and III, but occasionally in layers IV and V. Clusters of these intensely positive cells occurred in patches about 200–400 m in diameter, each containing about 6 to >20 such cells. GFAP-positive astrocytes were seen in some of the 36 brains from persons with neurological problems other than ALS but the pattern was different. The abnormal appearance of clusters of positive astrocytes of the primary motor cortex may be intimately associated with the ALS disease process.Supported by a Grant-in-Aid from the Ministry of Education, Science and Culture (No. 8500736; H. K.) and grants from the Medical Research Council of Canada, Mrs. P. A. Woodward's Foundation and the B. C. Medical Services Foundation     

The Importance of Combined Antithrombotic Treatment for Capsular Warning Syndrome

Introduction

Capsular warning syndrome (CWS) is characterized by recurrent conventional episodes of motor and/or sensory deficits without cortical symptoms. The purpose of this case series study was to evaluate the safety and appropriate treatment for CWS to prevent the development of complete stroke.

A mathematical estimation of true cancer incidence using data from population-based cancer registries

BACKGROUND: Accurate cancer incidence data are needed to plan, monitor and evaluate national cancer control programs. In Japan, however, such information is not available owing to incomplete cancer registries. In order to attain incidence estimation adjusted to account for this incomplete information, we have developed a new method. METHODS: We developed a nonlinear regression model between observed incidence/mortality ratios and proportions of death certificate notification to observed incidence in various cancer registries. This model enables us to obtain the 'true incidence/mortality ratio', which, in the regression curve, is at zero point for the proportion of death certificate notifications. This is an ideal registration state without any missing cases. By multiplying it by the number of cancer mortalities from the National Vital Statistics, corrected cancer incidence can be estimated. RESULTS: Applying this method for the estimation of the Japanese cancer incidence in 1997, we obtained the 'true incidence/mortality ratios' of 2.074 for men and 2.587 for women. Cancer incidences in Japan for 1997 were thus estimated to be 346,000 for men and 280,000 for women. CONCLUSIONS: A new method is proposed to estimate the national cancer incidence after adjusting for completeness of cancer registries. This method enables us to more accurately estimate the cancer incidence in a country where several cancer registries exist with various degrees of completeness of registration.     

可溶化人羊膜液、绒毛膜液和全羊膜液对间充质干细胞增殖的影响

目的探讨可溶化人羊膜液(solubilized-amnion product,SAP)、绒毛膜液(solubilized-chorial product,SCP)、全羊膜液(amniotic fluid,AF)对羊膜间充质干细胞(human amniotic mesenchymal stem cells,h AMSC)的增殖影响。方法用物理化学方法提取可溶化羊膜液、绒毛膜液、全羊膜液,用CCK-8试剂盒检测不同浓度的羊膜液、绒毛膜液、全羊膜液对h AMSC的增殖作用。剥去38~40周孕妇剖腹产术后羊膜,用消化酶消化后制备h AMSC。结果 h AMSC在可溶化羊膜液、绒毛膜液中生长良好,细胞增殖明显大于对照组,且培养液中的浓度具有显著依存性。全羊膜液培养前期增殖效果不明显,但培养4 d后出现浓度依存性的细胞增殖效果。这些生物材料对Hep G2无明显效果。结论可溶化人羊膜液、绒毛膜液、全羊膜液对干细胞具有促进增殖生长作用,有望成为干细胞研究与再生医疗领域中的新型生物材料。     

Tyrosinase suppresses vasculogenic mimicry in human melanoma cells

Melanoma is a type of skin cancer that derives from melanocytes; this tumor is highly metastatic and causes poor clinical outcomes in patients. Vasculogenic mimicry (VM), a vascular-like network that is formed by tumor cells instead of endothelial cells, promotes the growth and metastasis of tumors by providing tumors with oxygen- and nutrient-containing blood. VM correlates with a poor prognosis in patients with melanoma, but the melanoma-specific mechanisms of VM are unknown. The present study revealed that treatment with the melanogenesis stimulators 3-isobutyl 1-methylxanthine (IBMX) and α-melanocyte-stimulating hormone (α-MSH) significantly inhibited VM in MNT-1 human pigmented melanoma cells. Tyrosinase (TYR), an essential enzyme in melanin production, was upregulated on treatment with α-MSH and IBMX, prompting an examination of the association between TYR and VM. A TYR inhibitor, arbutin, promoted VM in melanoma cells. Furthermore, CRISPR/Cas9-mediated knockout (KO) of TYR increased VM by melanoma cells. Notably, even in non-pigmented melanoma cells, TYR attenuated VM. Although re-expression of wild-type TYR suppressed VM in TYR-KO cells, T373K TYR, a frequently detected mutation in individuals with albinism, failed to inhibit VM. Overall, these results demonstrated that TYR negatively regulates VM, providing novel insights into the antioncogenic function of TYR in melanomas.     

Novel selective inhibitors for human topoisomerase I, BM2419-1 and -2 derived from saintopin

Compounds BM2419-1 and -2 were isolated from a culture broth of a fungus Paecilomyces sp. BM2419. It was shown that these novel compounds were artifacts derived from saintopin, a dual inhibitor of topoisomerase I and II by independent processes. In the human topoisomerase I inhibition assay using the recombinant Saccharomyces cerevisiae, BM2419-1 and -2 inhibited selectively the yeast growth dependent on human topoisomerase I induction with IC50 values of 0.3 ng/ml and 6.0 ng/ml, respectively.     

Double-blind studies of tolerance to praziquantel in Japanese patients with Schistosoma japonicum infections.

The first clinical trials of praziquantel against Schistosoma japonicum infections in Japan were planned to assess tolerance only. Three double-blind studies against placebo involving a total of 51 patients were conducted with dosages of praziquantel of 1 × 20 mg/kg body weight, 2 × 20 mg/kg, 3 × 20 mg/kg given on one day.     

Elderly onset Parkinson's disease complicated by dropped head syndrome that responded favorably to therapy*

An 86‐year‐old man presented with a 7‐year history of gait disturbance. He was admitted to hospital in April 2000, as he was experiencing difficulty eating due to progression of dropped head syndrome. Both standing and sitting, marked dropped head and kyphosis were observed. When supine, the patient was able to stretch his neck, and he could stand and walk with the aid of a walker. Rigidity and resting tremor were present predominantly in the lower limbs. Parkinson's disease was diagnosed, and L‐dopa and cabergoline were administered. Parkinsonism and dropped head syndrome improved in response to treatment. Cases involving Parkinson's disease are reportedly improved by L‐dopa, but exacerbated by dopamine agonists. Dropped head syndrome is thought to attributable to imbalances in the tonus of the anterior and posterior neck muscles. Dropped head in the present case may have been a complication of Parkinson's disease, since improvements occurred in response to L‐dopa.