Nonmechanical compact probe for cross-sectional velocity measurement based on differential laser Doppler velocimetry.

In this study, we propose and demonstrate a nonmechanical compact probe for cross-sectional velocity measurement based on differential laser Doppler velocimetry. The system introduces a method that combines simultaneous multipoint measurement using spatial encoding and nonmechanical scanning of measurement points, in which spatially encoded measurement points aligned along the transverse direction are scanned in the axial direction by changing the wavelength. The use of a waveguide-type LiNbO3 phase shifter array for serrodyne frequency shifting is feasible for the system based on fiber optics with an easily handled probe. To miniaturize the probe, a multimode fiber is introduced in the receiving optics and the parameters of the lens system in the transmitting optics are optimized. For the experiment, an eight-channel probe was assembled on an aluminum plate with an 8 cm × 8 cm area size. The experimental results reveal that the cross-sectional two-dimensional velocity distribution was successfully measured using the easily handled compact probe for the first time.

Report of decontamination at Tominari Elementary School.

On 19 April 2011, the Ministry of Education, Culture, Sports, Science, and Technology designated 13 elementary schools, including Tominari Elementary School in Date city, as high-dose schools that needed to restrict outdoor activities due to the effects of the accident at Fukushima Daiichi nuclear power plant. Approximately 1 week later, the municipal government took action to remove the topsoil from the school grounds, and the prohibition of outdoor activities at Tominari Elementary School was lifted. The school staff continued to work on decontaminating the surrounding areas using high-pressure washers and brushes. There were certain positive outcomes, but a more effective decontamination method was required. In July 2011, the municipal government started an environmental remediation project, both inside and outside the school buildings, with researchers and decontamination workers at Tominari Elementary School, involving members of the Parent-Teacher Association (PTA), local communities, and volunteers using various effective and specialised forms of decontamination. As a result, Tominari Elementary School was able to recommence swimming lessons at the end of the first semester, which had been thought to be impossible. This article will provide information about the importance of 'dialogue' for decontamination, how engagement of the experts gave members of the PTA and the local community a feeling of 'security and safety', and how the decontamination work was an ever-expanding collaborative work of a large number of people.

Hepatocyte growth factor incorporated into herpes simplex virus vector accelerates facial nerve regeneration after crush injury.

Hepatocyte growth factor (HGF) promotes regeneration of the central nervous system, but its effects on the peripheral nervous system remain unclear. This study was conducted to elucidate the effect of HGF on regeneration of the murine facial nerve after crush injury. To do so, a replication-defective herpes simplex virus vector that incorporated HGF was prepared (HSV-HGF). The main trunk of the facial nerve was compressed by mosquito hemostats, and HSV-HGF, control vector or medium was then applied to the compressed nerve. We found that mice in the HGF group required significantly fewer days for complete recovery from nerve compression. Furthermore, the amplitude of the evoked buccinator muscle compound action potential increased following HSV-HGF application. HGF expression in and around the compressed nerve was demonstrated by enzyme-linked immunoassay and immunohistochemistry. In addition, HSV-HGF introduction around the damaged nerve significantly accelerated recovery of function of the facial nerve. These data suggest a possible role of HGF in promoting facial nerve regeneration after nerve damage. Furthermore, this viral delivery method may be applied clinically for many types of severe facial palsy during facial nerve decompression surgery.

In situ visualization of ultraviolet-light-induced DNA damage repair in locally irradiated human fibroblasts.

We have developed a novel method that uses a microfilter mask to produce ultraviolet-induced DNA lesions in localized areas of the cell nucleus. This technique allows us to visualize localized DNA repair in situ using immunologic probes. Two major types of DNA photoproducts [cyclobutane pyrimidine dimers and (6-4) photoproducts] were indeed detected in several foci per nucleus in normal human fibroblasts. They were repaired at those localized sites at different speeds, indicating that DNA photoproducts remain in relatively fixed nuclear positions during repair. A nucleotide excision repair protein, proliferating cell nuclear antigen, was recruited to the sites of DNA damage within 30 min after ultraviolet exposure. The level of proliferating cell nuclear antigen varied with DNA repair activity and diminished within 24 h. In contrast, almost no proliferating cell nuclear antigen fluorescence was observed within 3 h in xeroderma pigmentosum fibroblasts, which could not repair either type of photolesion. These results demonstrate that this technique is useful for visualizing the normal nucleotide excision repair process in vivo. Interestingly, however, in xeroderma pigmentosum cells, proliferating cell nuclear antigen appeared at ultraviolet damage sites after a delay and persisted as late as 72 h after ultraviolet exposure. This result suggests that this technique is also valuable for examining an incomplete or stalled nucleotide excision repair process caused by the lack of a single functional nucleotide excision repair protein. Thus, the technique provides a powerful approach to understanding the temporal and spatial interactions between DNA damage and damage-binding proteins in vivo.

Quantitation and visualization of ultraviolet-induced DNA damage using specific antibodies: application to pigment cell biology.

The major types of DNA damage induced by sunlight in the skin are DNA photoproducts, such as cyclobutane pyrimidine dimers (CPDs), (6-4)photoproducts (6-4PPs) and Dewar isomers of 6-4PPs. A sensitive method for quantitating and visualizing each type of DNA photoproduct induced by biologically relevant doses of ultraviolet (UV) or sunlight is essential to characterize DNA photoproducts and their biological effects. We have established monoclonal antibodies specific for CPDs, 6-4PPs or Dewar isomers. Those antibodies allow one to quantitate photoproducts in DNA purified from cultured cells or from the skin epidermis using an enzyme-linked immunosorbent assay. One can also use those specific antibodies with in situ laser cytometry to visualize and measure DNA photoproducts in cultured cells or in the skin, using indirect immunofluorescence and a laser-scanning confocal microscope. This latter method allows us to reconstruct three-dimensional images of nuclei containing DNA photoproducts and to simultaneously examine DNA photoproducts and histology in multilayered epidermis. Using those techniques, one can determine the induction and repair of these three distinct types of DNA photoproducts in cultured cells and in the skin exposed to sublethal or suberythematous doses of UV or solar simulated radiation. As examples of the utility of these techniques and antibodies, we describe the DNA repair kinetics following irradiation of human cell nuclei and the photoprotective effect of melanin against DNA photoproducts in cultured pigmented cells and in human epidermis.

Development of systemic sclerosis in a patient with systemic lupus erythematosus and topoisomerase I antibody.

We describe a patient with systemic lupus erythematosus (SLE) associated with topoisomerase I (topo I, Scl-70) antibody, a specific marker for systemic sclerosis (SSc). SSc patients who produce this antibody have severe cutaneous and visceral involvement, and eventually have a poor prognosis. It is rare to find this antibody in patients with other collagen diseases. Only four SLE patients have been reported in the English language literature who were topo I antibody-positive but had no clinical evidence of scleroderma. The serum of our patient with SLE had precipitating topo I antibody from the onset of his disease. Twelve years after the onset of SLE, he developed proximal scleroderma and pulmonary fibrosis. This case reconfirms the prognostic significance of topo I antibody as a predictive marker, and indicates that SLE patients with topo I antibody require careful follow-up for future development of scleroderma.

[Enhancement of antitumor effect of MMC on Walker 256 by intra-arterial administration of noradrenaline in hyperthermia].

We performed a study of hyperthermia while injecting 0.05% of Noradrenaline following MMC for 10 minutes into the feeding artery of Walker-256 carcinosarcomas implanted 6 days earlier into the s.c. dorsum side of hindpaw of Wistar rats. The tumor growth rates on the 6th day after treatment by warning tumor in hot water (40 degrees C, 44 degrees C) for 10 minutes with or without Noradrenaline, were 0.7 +/- 0.6, 2.1 +/- 0.9 (40 degrees C) and 0.2 +/- 0.3, 0.0 +/- 0.0 (44 degrees C), respectively. The data suggested that tumor ischemia induced by a vasoconstrictive drug may enhance the antitumor effect in low grade warning therapy (40 degrees C). An injection of warmed physiological saline (50 degrees C) may heat the tumor vessels on the tumor surface and showed enhanced antitumor effects as a from of hyperthermia. The target area of the tumor for hyperthermia can be considered to be the tumor vessels on the tumor surface.

[Enhancement of Walker-256 antitumor effect by intra-arterial administration of TNF before using mitomycin C].

Intraarterial administration of TNF showed enhanced antitumor effects on Walker-256 implanted in the dorsum side of the Wistar rat hindpaw than by its intravenous injection. Using MMC immediate after TNF can have an improved antitumor effects.

[Thermochemotherapy of unresectable pancreatic carcinoma (hot water and intra-arterial chemotherapy using noradrenaline)].

A 86-year-old man with unresectable pancreatic carcinoma was treated with thermochemotherapy. In most of the body and tail affected by the tumor, which did not show any cytotoxic damage after intraarterial chemotherapy, an enhanced antitumor effect was achieved by hyperthermia, which heated the tumor using hot water in a balloon placed on the pancreas, and which was delivered through a vinyl tube leading out of the body for 40 minutes while administration of antitumor agents mixed with noradrenaline was simultaneously given into the celiac artery. In this case, we observed that using noradrenaline with contrast material injected into the celiac artery it was possible to delineate the tumor area by computed tomography of the pancreas.

[Intra-arterial infusion chemotherapy combine with noradrenalin administration (an improved antitumor effect using a cancerous blood vessel].

We have performed experimental and clinical studies to observe whether higher concentrations of drugs are selectively delivered into tumor tissues through the tumor vessels and improved chemotherapy results were obtained by using noradrenaline in intraarterial chemotherapy. Noradrenaline administered into the tumor-feeding artery may enhance drug delivery into the tumor tissue and show improved chemotherapy results on Walker-256 formed tumor vessels. These advantages of using vasoconstrictive agents may be considered to be derived from the high injection pressure caused by increased vascular resistance and various other factors induced in abnormal microcirculation of the tumor vessels. MMC concentration in Walker-256 (weight 0.2 to 0.39 g) after intraarterial administration of 10 mg of MMC in 2.5 ml of physiological saline were 2.20 +/- 1.26 mcg/g (n = 11) in the noradrenaline group and 0.52 +/- 0.22 mcg/g (n = 13) in the MMC alone group. The 90-day survival ratio for intraarterial injection of 0.25 mg/kg of MMC and 2 mcg of noradrenaline was 42.9% (6/14), a result equivalent to a dose range of between 0.50 mg/kg and 0.75 mg/kg without the use of any vasoactive drug. The median survival periods for stomach cancer (Stage 4) after non-radical surgery by means of intraarterial chemotherapy with and without noradrenaline were, respectively, 12 months (n = 8) and 5.8 months (n = 6), with statistical significance (P greater than 0.05). Effective histological changes estimated microscopically by Takahashi's criteria of preoperative treatment in 31 stomach cancer patients were found in 11 patients (36.7%) with primary tumor and 12 patients (52.2%) with metastatic lymph nodes. A partial response rate of 54.5 (6/11) for hepatic tumor (Stages 3 to 4 according to was achieved with the use of the Ariel's classification) following regimen: intravenous injection of 70 mg/body of CDDP on the first day, followed by intraarterial injection of 0.1 to 0.4 mg/kg of MMC and 0.1 to 0.6 mg/kg of ADM together with 0.3 to 1.0 mg of noradrenaline in 40 to 100 ml of physiological saline for 3 to 20 minutes within one week after the first treatment. Most of the complications were due to hemorrhage from ulceration of the intestinal canal because of mucosal damage caused by the high concentration of anti-cancer drugs induced by noradrenaline. Decrease of hemoglobin of more than 1.0 g/dl was found in 19 out of 31 patients (61.3%) who received no treatment for bleeding, and in one out of 13 patients (7.7%) who was administered 200 mg of cimetidine twice a day for one week.

[Intra-arterial chemotherapy with nor-adrenaline. Experimental study 1 (enhancement of anti-tumor effect and tumor vessels)].

We have performed studies to observe whether the administration of nor-adrenaline during intraarterial chemotherapy has the possibility of increasing the permeability of tumor vessels and thus enhancing the anti-cancer effects. The tumor model was Walker-256, which was implanted into the dorsum side of the hindpaw of Wistar rats. Tumors were divided into those in which tumor vessels were not apparent after two days (D-2 group), and those in which vessels appeared after four and six days (D-4 and 6 group). Vascular permeability within the tumors was measured quantitatively using Evans Blue (EB) uptake volume in the tumor after intraarterial injection of 10 mg of EB with nor-adrenaline (nor-ad group) or the same dose of EB alone (control group). The mean values for the nor-ad group/control groups were calculated as the permeability activity of vessels enhanced by administration of nor-adrenaline in the D-2 to 6 group. The permeability activity of the D-2 group was 0.8, while that of the D-4 and 6 group was 2.5. The 90-day survival ratio was not improved in the D-2 group (P greater than 0.1), but was improved in the D-4 and 6 group (P less than 0.005) by intraarterial administration of 0.5 mg/kg of MMC with 2 mcg of nor-adrenaline, compared with the same dose of MMC alone. Therefore, the use of nor-adrenaline in intraarterial chemotherapy was observed to increase the permeability of tumor vessels and improve the treatment results.

[The case studies on oral administration of tegafur encapsulated with slow releasing granule (SF-SP) for three rectal patients].

Three rectal cancer patients with partial response (PR) were obtained by oral administration of 800-1200 mg/day of SF-SP. One of them showed I-A grade and other I-B in Karnofsky evaluation.

[Intra-arterial chemotherapy combined with noradrenaline--histopathological effect in stomach cancer].

The histological evaluation of intraarterial administration of MMC, adriamycin and noradrenalin as a preoperative treatment was performed in 24 gastric patients. The effective histological changes estimated microscopically by the Takahashi's criteria were found in 9 (37.5%) patients with the primary tumor and in 8 (50.0%) patients with the metastatic lymph nodes.