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.     

Treatment of ras-induced cancers by the F-actin-bundling drug MKT-077

A rhodacyanine dye called MKT-077 has shown a highly selective toxicity toward several distinct human malignant cell lines, including bladder carcinoma EJ, and has been subjected to clinical trials for cancer therapy. In the pancreatic carcinoma cell line CRL-1420, but not in normal African green monkey kidney cell line CV-1, it is selectively accumulated in mitochondria. However, both the specific oncogenes responsible for its selective toxicity toward cancer cells, and its target proteins in these cancer cells, still remain to be determined. This study was conducted using normal and ras-transformed NIH 3T3 fibroblasts to determine whether oncogenic ras mutants such as v-Ha-ras are responsible for the selective toxicity of MKT-077 and also to identify its targets, using its derivative called "compound 1" as a specific ligand. We have found that v-Ha-ras is responsible for the selective toxicity of MKT-077 in both in vitro and in vivo. Furthermore, we have identified and affinity purified at least two distinct proteins of 45 kD (p45) and 75 kD (p75), which bind MKT-077 in v-Ha-ras-transformed cells but not in parental normal cells. Microsequencing analysis has revealed that the p45 is a mixture of beta- and gamma-actin, whereas the p75 is HSC70, a constitutive member of the Hsp70 heat shock adenosine triphosphatase family, which inactivates the tumor suppressor p53. MKT-077 binds actin directly, bundles actin filaments by cross-linking, and blocks membrane ruffling. Like a few F-actin-bundling proteins such as HS1, alpha-actinin, and vinculin as well as F-actin cappers such as tensin and chaetoglobosin K (CK), the F-actin-bundling drug MKT-077 suppresses ras transformation by blocking membrane ruffling. These findings suggest that other selective F-actin-bundling/capping compounds are also potentially useful for the chemotherapy of ras-associated cancers.     

Primary ureteral tumor in the residual ureter: a report of two cases]

Two cases of primary ureteral tumor in the residual ureter are reported. One was in a 40-year-old woman who had undergone simple nephrectomy for renal tuberculosis 6 years earlier. The other was in a 59-year-old man 11 years after ureterostomy for hydronephrosis. They presented with hematuria. Cystoscopic examination revealed a ureteral tumor out of the residual ureteral orifice. Computed tomographic scan showed a perivesical mass attached to the urinary bladder. It is useful for examination of ureteral stump's condition. We performed ureterectomy. The pathological study revealed the former high grade transitional cell carcinoma with squamous cell carcinoma and lymph nodes metastasis and the latter low grade transitional cell carcinoma. They have been free of disease for 5.5 years and 1.75 years, respectively. These cases are the nine and tenth reports of primary ureteral tumor of the ureteral stump in the Japanese literature.     

The effect of sequential multiple grafting of syngeneic newborn thymus on the immune functions and life expectancy of aging mice

Enhancement of the immune functions and extension of the mean life expectancy were successfully performed in aging mice by sequential multiple grafting of syngeneic newborn thymus. In the first experiment, 2-month-old female C57BL/6 mice were grafted with either syngeneic newborn thymus or newborn spleen every 2 months, 5 or 6 times. A significant enhancement of T cell dependent immune functions were observed in the group sequentially grafted with newborn thymus, in comparison to that grafted with multiple sequential newborn spleen or with a single newborn thymus and that without a graft. In the second experiment, the same sequential grafting protocol was performed in middle aged mice at monthly interval for 4-5 consecutive months and the immune functions and survival rate were compared between the experimental and control groups. The immune functions were only partially rejuvenated, but an extension of the mean remaining life expectancy was observed in the experimental group (312 +/- 38 days) as compared with control (214 +/- 42 days), although maximal life-span was the same in both groups (1100 days).     

Infectious but non-leukemogenic Friend leukemia virus obtained after prolonged cultivation in vitro

A non-leukemogenic strain of Friend leukemia virus (FLV) propagated in vitro interfered with infection by murine sarcoma virus (Moloney) (MSV) and acted as a helper of defective MSV. This suggests that the non-leukemogenic strain of FLV is infectious. After prolonged propagation in vitro, the leukemogenicity of a highly leukemogenic strain of FLV gradually decreased, while the infectivity assayed by interference with MSV infection remained unchanged.     

Dysregulation of T-cell function in the elderly : scientific basis and clinical implications

The function of the immune system is to maintain body integrity by defending against infections, cancers, autoimmune diseases and inflammation-related chronic diseases. The immune response is known to become defective with aging, leading to decreased longevity and appearance of age-related disease. The most important changes occur in T-cell immunity, and are manifested particularly as altered clonal expansion of cells of limited antigen specificity. The causes of these alterations are multifactorial, and include thymic involution, T-cell subset changes and signal transduction alterations. The clinical consequences of these changes are not well defined, except for their extremely important negative impact on defence against infections, especially by new pathogens, and decreased responses to vaccination. Considering the public health consequences of decreased immune competence in old age, strategies for immune response modulation are desirable to decrease the health burden for the elderly and improve their quality of life.     

Fish drug analysis—Phish-pharm: A searchable database of pharmacokinetics data in fish

Information about drug residues and pharmacokinetic parameters in aquatic species is relatively sparse. In addition, it is difficult to rapidly compare data between studies due to differences in experimental conditions, such as water temperatures and salinity. To facilitate the study of aquatic species drug metabolism, we constructed a Fish Drug/Chemical Analysis Phish-Pharm (FDA-PP) database. This database consists of more than 400 articles that include data from 90 species (64 genera) of fish. Data fields include genus, species, water temperatures, the average animal weight, sample types analyzed, drug (or chemical) name, dosage, route of administration, metabolites identified, method of analysis, protein binding, clearance, volume of distribution in a central compartment (Vc) or volume of distribution at steady-state (Vd), and drug half-lives (t((1/2))). Additional fields list the citation, authors, title, and Internet links. The document will be periodically updated, and users are invited to submit additional data. Updates will be announced in future issues of The AAPS Journal. This database will be a valuable resource to investigators of drug metabolism in aquatic species as well as government and private organizations involved in the drug approval process for aquatic species.     

Detection of peripheral microemboli through collateral circulation by Doppler ultrasound monitoring-report of 2 cases

It is possible for a proximal arterial source to lead to distal atheroembolism even in the presence of chronic occlusive disease. However, no monitoring technique has been established regarding detection of peripheral emboli through the collateral circulation in the lower limbs. We report a 60-year-old woman and a 73-year-old man with iliac stenosis and complete occlusion of the ipsilateral superficial femoral artery in whom Doppler ultrasound successfully detected microembolic signals (MES) at the tibioperoneal trunk during percutaneous transluminal angioplasty (PTA) and stent placement. By means of continuous Doppler ultrasound monitoring, 29 MES were successfully detected immediately after PTA or stent placement (MESp) and 64 MES were detected immediately after the contrast medium administration (MESc). MESc generated significantly higher intensities (median 28, range 7 to 38) as opposed to MESp (median 21, range 5 to 35, p = 0.017). In addition, the intensity of MES after prestent PTA (n = 8, 25 dB, 12-35 dB) and stenting (n = 18, 22 dB, 9-35 dB) was significantly higher than that of MES after poststent PTA (n = 3, 13 dB, range; 5-16 dB), respectively (p = 0.041, p = 0.034). Iliac PTA and stent placement were successful. Ankle/brachial pressure index and the symptoms improved in both patients, who showed no embolic symptoms after the procedure. This study suggested that it was possible to detect peripheral microemboli through the collateral circulation by Doppler ultrasound monitoring and that this technique would be helpful to investigate the mechanism of embolization in patients with PTA and stent placement.     

Opposing effects of isoflurane and sevoflurane on neurogenic pulmonary edema development in an animal model

BACKGROUND: The current study was undertaken to investigate the effects of pretreatment with isoflurane and sevoflurane on the development of neurogenic pulmonary edema in an animal model. METHODS: Rats were exposed to room air (control), 1.5% isoflurane, or 2.5% sevoflurane for 4 h. They were then anesthetized with intraperitoneal injections of pentobarbital sodium, and fibrinogen and thrombin were injected into the cisterna magna to induce neurogenic pulmonary edema. RESULTS: Consecutive injections of fibrinogen and thrombin caused increases in blood pressure, with the peak values obtained in the isoflurane and sevoflurane groups being lower than the control values. The incidence of significant neurogenic pulmonary edema was 58%, 100%, and 8% in the control, isoflurane, and sevoflurane groups, respectively. The lung water ratio, an index of severity of edema, was 4.86 +/- 0.78, 6.15 +/- 0.64, and 4.40 +/- 0.32 in the control, isoflurane, and sevoflurane groups, respectively. Furthermore, immunohistochemical staining for vascular endothelial growth factor demonstrated an increase of expression in the rat lungs exposed to isoflurane. Treatment with an anti-vascular endothelial growth factor antibody during exposure to isoflurane completely inhibited the effect of isoflurane to promote neurogenic pulmonary edema in this model. CONCLUSION: Exposure to 1.5% isoflurane enhances the development of neurogenic pulmonary edema development in this animal model, most likely via release of vascular endothelial growth factor from bronchial epithelial cells, an effect not observed with sevoflurane.