Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.     

Phenotypic and Genotypic Lineage Switch of a Lymphoma with Shared Chromosome Translocation and T-Cell Receptor γ Gene Rearrangement

A case of non-Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T-cell type, pleomorphic small cell lymphoma developed, followed by B-cell type, diffuse centroblastic/centrocytic lymphoma, and finally T-zone lymphoma without follicles again developed, from which AST-1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B-cell tumor, the second relapsed T-cell tumor and AST-1 cell line. Furthermore, T-cell receptor (TCR) γ gene rearrangement bands of the same size were observed in the first relapsed B-cell tumor and the second relapsed T-cell tumor as well as AST-1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR δ/α gene complex, was observed in the second relapsed tumor and AST-1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR δ/α gene complex was studied. The result showed that two rearrangements of TCR α gene detected with J_α probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST-1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.     

Protodioscin isolated from fenugreek (Trigonella foenumgraecum L.) induces cell death and morphological change indicative of apoptosis in leukemic cell line H-60, but not in gastric cancer cell line KATO III

Protodioscin (PD) was purified from fenugreek (Trigonella foenumgraecum L.) and identified by Mass, and 1H- and 13C-NMR. The effects of PD on cell viability in human leukemia HL-60 and human stomach cancer KATO III cells were investigated. PD displayed strong growth inhibitory effect against HL-60 cells, but weak growth inhibitory effect on KATO III cells. Morphological change showing apoptotic bodies was observed in the HL-60 cells treated with PD, but not in KATO III cells treated with PD. Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 75.2, 96.3, and 100% after a 3-day treatment with 2.5, 5, and 10 microM PD, respectively. The fragmentation by PD of DNA to oligonucleosomal-sized fragments, that is a characteristic of apoptosis, was observed to be both concentration- and time-dependent in the HL-60 cells. These findings suggest that growth inhibition by PD of HL-60 cells results from the induction of apoptosis by this compound in HL-60 cells.     

Mutational screening of APP gene in patients with early-onset Alzheimer disease utilizing mismatched PCR-RFLP

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS-1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early-onset Alzheimer disease.     

Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo: clinical significance of fibronectin and fibronectin receptor expressed in human glioma tissues

In order to clarify the role of fibronectin in glioma invasion in vivo, we analyzed the relationship between fibronectin-stimulated cell migration and adhesion in 14 primary glioma cells and the expression of fibronectin and the fibronectin receptor in the corresponding tumor tissues. The tumors comprised nine glioblastomas (GB) and five anaplastic gliomas (AG) consisting of two astrocytomas, two oligoastrocytomas and one ependymoma. All glioma cells tested in the primary cell culture were found to migrate to fibronectin in a dose-dependent manner. The extent of cell migration to fibronectin was not significantly different for the GB and AG groups. On the other hand, cell adhesion to fibronectin in the AG was much stronger than that in the GB group. Immunohistochemistry demonstrated that fibronectin positively stained in the extra-cellular matrix (ECM) in eight cases and that the fibronectin receptor was positive in tumor cell membranes in 10 cases. In addition, cellular fibronectin isoforms containing ED-A and ED-B sequences were found to be immunolocalized in the tumor cells and the ECM of GB. These isoforms were also specifically expressed in tumor vessels within tumor tissues, but not in those within normal brain tissues. Cell migration tended to be expressed more strongly by glioma cells derived from tumor tissues in which fibronectin was posi-tively immunolocalized in the ECM than from tissues with negative fibronectin in the ECM. Four glioma cells derived from GB whose tumor cells did not positively stain for fibronectin receptors migrated much less extensively to fibronectin than other glioma cells whose tissues showed positive staining for the fibronectin receptor. Of these four GB, two had loss of heterozygosity in the locus of fibronectin receptor b1 gene. These results suggest that fibronectin deposited in the extracellular matrix of tumors, which can be derived from both plasma and the tumor cell itself, strongly promotes the migration of glioma cells, and that expression of the fibronectin receptor may play a critical role in the biological behavior of the tumor cells, particularly in fibronectin-stimulated cell migration in vivo.© Kluwer Academic Publishers 1998     

太空发育鸡胚的前庭感受器细胞形态学研究

为了探讨太空微重力对鸡胚前庭感觉上皮细胞的形态发育的影响 ,选取在航天飞机 (STS-2 9)发育鸡胚和地面发育鸡胚各两只 ,利用计算机显微测量技术分别测量椭圆囊和球囊的毛细胞、支持细胞核的切面面积、周长、形状系数。太空发育鸡胚的球囊支持细胞核的切面面积、周长显著大于地面组 ,形状系数无差异 ;太空发育鸡胚的椭圆囊支持细胞核的切面面积、周长、形状系数以及椭圆囊和球囊毛细胞的切面面积、周长与地面发育鸡胚相比无明显差异。微重力可能对球囊支持细胞核的体积发育有影响 ,对椭圆囊和球囊的毛细胞以及椭圆囊支持细胞核的形态发育无影响。     

Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells

Dendritic cell-like cells (Mo-DCs) generated from peripheral blood monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used as tools to treat cancer patients (DC-vaccines). Because Mo-DCs have multiple antigen presentation-related functions, including phagocytosis, migration, cytokine production, and T cell stimulation, establishment of a method for simultaneously evaluating the various functions of Mo-DCs is important. We developed a new in vitro three-dimensional two-layer collagen matrix culture model that consists of a collagen gel containing Mo-DCs as the lower layer and a collagen gel containing necrotic GCTM-1 tumor cells and/or T cells as the upper layer. We used this system to observe simultaneously multiple functions of Mo-DCs by phase-contrast or fluorescence microscopy and to assess IL-12 secretion during more than 2 weeks of culture. We also observed interactions between Mo-DCs and necrotic GCTM-1 or T cells on an individual cell basis by time-lapse videomicroscopy. In addition, we collected Mo-DCs from the collagen gels by collagenase treatment and analyzed the expression of antigen presentation-related molecules such as HLA-DR, CD80, CD83, and CD86 on Mo-DCs. This model may be a useful tool for evaluation of the various functions of Mo-DCs used as DC vaccines and for studies of the complex behaviors of Mo-DCs in vivo.     

Clostridium perfringens foodborne outbreak due to braised chop suey supplied by chafing dish

On February 13, 2002, a public health center in Hiroshima Prefecture, Japan, was notified that many individuals living at the Japan Maritime Self-Defence Force base had symptoms resembling those of food poisoning. Self-administered questionnaires requesting information regarding meal consumption and symptoms were distributed to all 281 members at the base. A case of the illness was defined as a member who had had watery or mucousy stool, or loose stool with abdominal cramps, more than twice a day after consuming dinner on February 12. Control of the illness was defined as a member with no symptoms. The dinner on February 12 was significantly associated with the illness (Mantel-Haenszel odds ratio: 3.59, 95% confidence interval: 1.06-12.20). A case-control study showed that, among the food supplied at dinner on February 12, the braised chop suey was significantly associated with the illness (odds ratio: 12.30, 95% confidence interval: 1.90-521.00). The braised chop suey had been stored in a chafing dish. An environmental investigation indicated that Clostridium perfringens (C. perfringens) in the chafing dish proliferated under an inappropriate heat-retention temperature, and the contaminated braised chop suey could have caused the food poisoning. This study demonstrated that the recommended heat-retention temperature (over 65 degrees C) should be confirmed thoroughly.     

Effects of running exercise during recovery from hindlimb unloading on soleus muscle fibers and their spinal motoneurons in rats

The effects of hindlimb unloading and recovery with or without running exercise on morphological and metabolic properties of soleus muscle fibers and their spinal motoneurons in rats were investigated. Ten-week-old rats were hindlimb suspended for 2 weeks and thereafter were rehabilitated with or without voluntary running exercise for 2 weeks. A decreased percentage of type I fibers and atrophy of all types of fibers were observed after hindlimb unloading. In addition, decreased oxidative enzyme activity of all types of fibers was observed after hindlimb unloading. In contrast, an improvement in the decreased percentage of type I fibers, decreased fiber cross-sectional area, and decreased fiber oxidative enzyme activity was observed after recovery with running exercise, but not without running exercise. There were no changes in the number, cell body size, or oxidative enzyme activity of motoneurons innervating the soleus muscle after hindlimb unloading or recovery with or without running exercise. These results indicate that running exercise is beneficial for the recovery of the decreased percentage of type I fibers and the atrophy and decreased oxidative enzyme activity of all types of fibers in the soleus muscle induced by hindlimb unloading and that there are no changes in morphological or metabolic properties of spinal motoneurons innervating the soleus muscle following decreased or increased neuromuscular activity.