Usefulness of a dose distribution analysis system with a common scanner

Although one-dimensional densitometry has been widely performed for linac dosimetry, it is a time-consuming, labor-intensive procedure. We studied a new densitometry system (DD-System) that consists of a personal computer and common flatbed-type scanner, with regard to its usefulness for daily QC checks in comparison with conventional densitometry. The spatial resolution of the DD-System is very high, and its accuracy of measurements of field size and flatness are equivalent to those of a conventional system at an optical density <2.0. Although the performance of the image scanner limits the maximum optical density of our system, this system can acquire high-resolution two-dimensional dose distributions quickly and easily. In conclusion, the DD-System is very useful for reducing the amount of time and effort required in daily QC activities. We consider this system applicable to the analysis of complicated dose distributions in this era of IMRT.     

Identification of the main aroma compounds in dried seeds of Brassica hirta

The composition of the volatile oil from Sinapis Semen, dried seeds of Brassica hirta (Cruciferae), have been investigated using capillary GC and GC/MS. The important odor-active compounds in the oil were also detected by means of GC-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). The oil was found to contain 68 components, representing 95.36% of the total oil. The main constituents were 4-hydroxy-benzeneacetonitrile (29.63%), palmitic acid (14.55%), linoleic acid and oleic acid (9.67%). The AEDA and GC-O analyses showed that heptanal, phenylethylalcohol, (2E)-octenal and (2E, 4E)-dodecadienal are to a large extent responsible for the characteristic flavor of Sinapis Semen.     

Successful in vivo blockade of CD25 (high-affinity interleukin 2 receptor) on T cells by administration of humanized anti-Tac antibody to patients with psoriasis

BACKGROUND: Daclizumab is a humanized antibody to the alpha-subunit (CD25) of the interleukin 2 (IL-2) receptor that blocks normal IL-2 binding to this receptor. Because IL-2 is a major stimulus for T-cell growth, blockade of the IL-2 receptor could be useful in treating T-cell-mediated (autoimmune) diseases. OBJECTIVE: Our purpose was to determine whether adequate concentrations of antibody were achieved in circulating blood and in psoriatic skin lesions to saturate CD25 receptors. We also intended to measure clinical effect and safety of this agent when used alone (without other immunosuppressive drugs) in psoriasis. METHODS: Nineteen patients with psoriasis in two centers received daclizumab at an initial dose of 2 mg/kg, then 1 mg/kg at weeks 2, 4, 8, and 12. To determine whether CD25 was blocked in vivo, flow cytometric studies measured (1) expression of CD25 on CD3(+) T cells derived from blood and (2) immuno-histochemistry measures of CD25(+) cells done on pretreatment and posttreatment biopsy specimens. Patients were followed up clinically with photographs and Psoriasis Area and Severity Index scores. RESULTS: This study showed a consistent blockade of CD25 in peripheral blood and tissue during the first 4 weeks of therapy while the dosing was every 2 weeks. Variable desaturation of receptors began after 4 weeks, which correlated with a reversal in disease improvement. Patients with a pretreatment Psoriasis Area and Severity Index score of less than 36 showed a mean reduction in severity by 30% at 8 weeks (P =.02). During the 16 weeks of treatment, a 44.8% decrease in expression of the IL-2 receptor alpha-subunit was found. The absolute T-cell counts were calculated and showed no significant changes during the course of the study. No significant adverse events were produced by daclizumab during this study. CONCLUSION: We therefore conclude that daclizumab is a well-tolerated agent that blocks CD25 expression in peripheral blood and skin. Furthermore, it may be useful in treating psoriasis in some patients.     

Close Association between Fas Ligand (FasL; CD95L)-positive Tumor-associated Macrophages and Apoptotic Cancer Cells along Invasive Margin of Colorectal Carcinoma: A Proposal on Tumor-Host Interactions

Anti-tumor immune responses are considered to be one of the key host reactions in human colorectal cancer, with T cells as important effector cells. For the induction of tumor-specific immunity, processing of cancer cells and pruning of T cells by antigen-presenting cells are important. The present study was designed to clarify the relationship between Fas ligand (FasL; CD95L) expression and apoptotic cancer cells. Immunohistochemistry using frozen sections taken from 58 patients with colorectal cancer revealed that stromal cells composed mainly of tumor-associated macrophages expressed FasL, leaving cancer cells negative for FasL. These macrophages were abundantly distributed along the invasive margin. In situ hybridization revealed that these macrophages as well as cancer cells expressed FasL mRNA, whereas macrophages in the normal colon mucosa rarely expressed FasL. Apoptotic cancer cells recognized by monoclonal antibody M30 CytoDEATH were localized not only in cancer cell nests, but also in the stroma along the invasive margin showing a dissociated pattern, which was particularly evident in the areas of FasL⁺ macrophages. Furthermore, these macrophages, phenotypically similar to dendritic cells, occasionally contained M30⁺ apoptotic cancer cells in the cytoplasm. Clinicopathologic analyses in 123 cases revealed 1) a positive correlation between the degree of dissociated M30⁺ apoptotic cancer cells and the number of macrophages along the invasive margin and 2) an inverse association between the degree of dissociated M30⁺ apoptotic cancer cells and the occurrence of hematogenous metastasis after surgical resection of the primary tumor. In conclusion, the present study shows the impor- tance of FasL⁺ activated macrophages as one of the host defense mechanisms against cancer cell spread in human colorectal cancer.     

Expansion of Lung Vα14 NKT Cells by Administration of α-Galactosylceramide-pulsed Dendritic Cells

NKT cells, a novel murine lymphoid lineage bearing an invariant T cell receptor encoded by Vα14 and Jα281 gene segments, recognize a specific ligand glycolipid, α-galactosylceramide (α-GalCer) in a CDld-dependent manner. Recent research has revealed that activated Vα14 NKT cells have dramatic antitumor effects against a wide variety of tumor cell lines in vivo and in vitro. Here, we demonstrate strong in vivo antitumor effects brought about by treatment with α-GalCer-pulsed dendritic cells in comparison with in vitro -activated Vα14 NKT cells. Furthermore, we show a significant expansion of endogenous Vα14 NKT cells in the lung following the administration of α-GalCer-pulsed dendritic cells. The feasibility of immunotherapy with α-GalCer-pulsed dendritic cells is discussed.     

HLA associations in otosclerosis in Japanese patients

Otosclerosis is a disease of the otic capsule that is caused by abnormal resorption and redeposition of bony tissue. Sixty-two unrelated Japanese patients exhibiting clinical otosclerosis were typed for HLA-A, -B,-C antigens. Twenty-one of the patients were also typed for DR antigens. The frequency of HLA-Aw33 was significantly higher in otosclerosis patients than in the control group (24.2% vs 9.5%). This finding suggests that the presence of HLA-Aw33 antigens may be related to an increased susceptibility to otosclerosis or to its clinical outcome.     

Surgical treatment of metastatic tumor in the lung

This paper is to reconsider and reorganize surgical indication of metastatic tumor in the lung in accordance with the recent progress of medicine, which was based on the patients experienced at National Cancer Center Hospital. Among several criteria proposed by Thomford in 1965, three items: 1) the patient is a good risk for surgery, 2) the primary malignancy is controlled, 3) the lung is the only one site for metastatic lesion, remain to be true even today. In addition, another three conditions must be recognized in selecting patients: 1) Biological behavior of the tumor varies in different histology and different site of the primary lesion. 2) When the tumor is susceptible to chemotherapy, surgical indication can be widen. 3) The tumors located in bilateral lung, which used to be surgically contraindicated, can be successfully removed with simultaneous thoracotomy via sternotomy.     

Effects of 1-ethyl-4-(2-morpholinoethyl)-3, 3-diphenyl-2-pyrrolidinone hydrochloride hydrate (doxapram) on the transmural stimulation and reactiontonicotine of the isolated guinea pig heart atrium]

It has been reported that doxapram exhibits a remarkable stimulating effect on respiration in humans and various experimental animals. The present experiment was an attempt to investigate whether or not doxapram inhibits an atrial arrest induced by transmural stimulation and exogenously applied nicotine. Doxapram and dimorpholamine used as comparative agents showed transient and slightly positive responses followed by a negative one in the atrium preparation. Transmural stimulation under a condition of 30 V intensity with 0.3 msec duration at a frequency of 10 Hz for 2 sec caused an atrial arrest for about 3 sec followed by negative chronotropic and inotropic responses, and a positive one. All responses caused by transmural stimulation were hardly affected by pretreatment with doxapram at a concentration of 10(-5) g/ml or less, while dimorpholamine at a high concentration (10(-5)g/ml) showed an inhibition of atrial arrest and following negative responses. Negative chronotropic and inotropic responses caused by an application of nicotine were significantly inhibited by pretreatment with doxapram or dimorpholamine. Both doxapram and dimorpholamine at higher concentrations also inhibited the positive responses of the atrium caused by nicotine. Neither doxapram nor dimorpholamine affected the ACh-induced responses. NA-induced responses were uneffected by pretreatment with doxapram, while the responses were slightly potentiated by dimorpholamine. The action mechanisms of doxapram and dimorpholamine are discussed.