Electrochemical hydrogen storage in MoS2 nanotubes.
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Biomedical subjects
Publications and source records attributed to N Kuriyama.
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Effective virus-mediated gene therapy for cancer will be facilitated by procedures that enhance the low level of gene transfer mediated by replication-deficient, recombinant viral vectors. We found recently that protease pretreatment of solid tumors is a useful strategy for enhancing virus-mediated gene transduction in vivo. In this study, we examined the potential of protease pretreatment to improve the efficacy of a gene therapy strategy for prodrug activation that depends on infection with a recombinant adenovirus encoding herpes simplex virus thymidine kinase (Ad-HSV-tk). Trypsin or a dissolved mixture of collagenase/dispase was inoculated into xenografts derived from the human glioblastoma multiforme-derived cell lines, U87 or U251. Ad-HSV-tk was administered 24 h after protease pretreatment, and animals were then treated for 10 days with ganciclovir (GCV). We found that protease pretreatment increased the efficacy of adenovirus mediated HSV-tk/GCV gene therapy in these experimental tumor models. Mice receiving Ad-HSV-tk/GCV after protease pretreatment demonstrated a significantly greater regression of tumors compared with those treated with Ad-HSV-tk/GCV alone. No adverse effects of protease pretreatment were observed. No signs of metastasis were seen either by histological inspection of lymph nodes or by a PCR-based analysis of selected mouse tissues to detect human tumor cells. Our findings indicate that protease pretreatment may be a useful strategy to enhance the efficacy of virus-mediated cancer gene therapy.
A key impediment to the development of effective virus-mediated gene therapy for cancer is the low level of gene transfer that occurs after the administration of recombinant viral vectors. Improving in vivo infection and transduction efficiency is an important goal for gene therapy. The limited distribution of gene delivery is particularly problematic when large vectors such as recombinant adenoviruses and retroviruses are used to mediate transgene delivery to solid tumors. To facilitate the spread of virus, we have investigated the potential of administering proteases prior to the intratumoral inoculation of recombinant replication deficient adenovirus. For these studies, we chose proteases that are active against collagen and the other extracellular matrix proteins found in primary brain tumor tissue, but are not widely expressed in normal brain. Various concentrations of a mixture of collagenase/dispase or trypsin were inoculated into xenografts of human glioblastoma multiforme-derived brain tumor cell lines U87, U251, and SF767. Subsequently, recombinant adenovirus encoding the beta-galactosidase gene was administered and tumor tissue was examined for evidence of virus infection. Both collagenase/dispase and trypsin enhanced virus infection, indicating that protease pretreatment may be a useful strategy for enhancing virus-mediated gene transduction for many in vivo applications.
As many as 40000 patients are newly diagnosed each year as having brain tumors. About half of these are metastatic foci of tumors originating outside the central nervous system, while the other half are primary tumors of central nervous system tissues. These are a diverse group of neoplasms. Currently, primary brain tumors are classified in a manner that reflects their histological appearance and location. The identification of cancer as a disorder of genes, however, has opened the possibility of classifying tumors according to the genetic alterations that underlie their pathogenesis and that regulate their malignant behavior. Two major classes of genes critical for the development of all types of cancer, including brain tumors, are now recognized: tumor suppressor genes, which encode genes that function to inhibit cell proliferation and tumor development, and oncogenes, which encode proteins that stimulate proliferation and mediate biological activities important for invasion, neoangiogenesis, immune escape, and other characteristics of malignancy. While in most cases the specific pathways regulating tumor characteristics such as tumor neoangiogenesis and tissue invasion remain to be defined, recognition of the genetic changes characteristic of individual tumor types should provide opportunities to develop more effective, less toxic therapies.
Churg-Strauss syndrome (CSS) is a disorder characterized by hypereosinophilia and systematic vasculitis occurring in individuals with bronchial asthma. We present a case of 24-year-old woman with CSS diagnosed by and followed with gastrointestinal fiberscopic examination and electroneuromyography. The duodenal biopsy showed granulomatous angiitis with eosinophilic infiltration, and the electroneuromyography showed peripheral nerve dysfunction. After steroid treatment, the duodenal erosion and ulcer were almost completely resolved. There was no improvement in electroneuromyography, but the patient was able to walk independently after intensive rehabilitative training.
The patient was a 23-year-old man. He had no history of trauma in the head and neck. When he was 20 years old (in 1992), he noticed muscle atrophy and weakness in the right hand. In a hospital, he had cervical MRI study and other examinations. The diagnosis was juvenile muscular atrophy of the upper limb (Hirayama's disease). After that the symptoms became worse in the bilateral forearms and hands. The neurological examination showed severe atrophy in bilateral C7 to Th1 innervated muscles, right pyramidal sign, mild superficial and deep sensory disturbance in the dermatome of C7-Th1, and right Horner's sign. Cervical MRI and myelography revealed the atrophy of cervical cord and intraspinal cavity formations from C5 to Th1. We concluded that chronic and intermittent compression to cervical cord with flexion position made the cavities during the clinical course because these cavities were not found in the MRI taken in 1992.
We reported a 67-year-old woman with bilateral caudate head infarcts. She developed sudden mutism followed by abulia. She was admitted to our hospital 2 months after ictus for further examination. She showed prominent abulia and was inactive, slow and apathetic. Spontaneous activity and speech, immediate response to queries, spontaneous word recall and attention and persistence to complex programs were disturbed. Apparent motor disturbance, gait disturbance, motor aphasia, apraxia and remote memory disturbance were not identified. She seemed to be depressed but not sad. Brain CT and MRI revealed bilateral caudate head hemorrhagic infarcts including bilateral anterior internal capsules, in which the left lesion was more extensive than right one and involved the part of the left putamen. These infarct locations were thought to be supplied by the area around the medial striate artery including Heubner's arteries and the A1 perforator. Digital subtraction angiography showed asymptomatic right internal carotid artery occlusion. She bad had hypertension, diabetes mellitus and atrial fibrillation and also had a left atrium with a large diameter. The infarcts were thought to be caused by cardioembolic occlusion to the distal portion of the left internal carotid artery. Although some variations of vasculature at the anterior communicating artery might contribute to bilateral medial striate artery infarcts, we could not demonstrate such abnormalities by angiography. Bilateral caudate head infarcts involving the anterior internal capsule may cause prominent abulia. The patient did not improve by drug and rehabilitation therapy and died suddenly a year after discharge.
Maximum production of alkaline serine protease by Bacillus alcalophilus subsp. halodurans KP 1239 was achieved after 24 h cultivation, at an initial pH of 7.6, on a medium containing 1.0% sodium citrate, 0.3% yeast extract, and 0.3% KH2PO4. The enzyme was purified to crystalline form from culture broth. The enzyme was most active at 60 degrees C and at pH 11.5. The molecular weight, isoelectric point and sedimentation coefficient in water at 20 degrees C were estimated as 29,000, 8.8 and 3.3S, respectively. The N-terminal amino acid sequence was Ala-Gln-Ser-Val-Pro-Trp-Gly-Ile-Ser-Arg-Val-Gln-Ala-Pro-Ala-Ala- His-Asn-Arg-Gly-. The enzyme shared its antigenic determinants with B. alcalophilus ATCC 21522 serine protease, but not with the subtilisins Carlsberg and BPN'.
In order to assess tissue blood flow quantitatively under various temperature conditions, we have developed a new blood-flow measurement apparatus based on the thermal diffusion method. This new method is hardly affected by environmental temperature, by means of using the thermal clearance curve with its baseline corrected before each measurement. Fundamental studies concerning the measurement of human skin blood flow were carried out in the finger. The results obtained were as follows. 1) The gradient of the thermal clearance curve did not show significant changes under various temperature conditions. This result indicated that the effects of environmental temperature on the thermal clearance curve were almost removed. 2) A highly positive correlation was obtained between the thermal conductivity of various materials similar to human skin in thermal conductivity and the gradient of the thermal clearance curve from a probe placed on a plate of each material. 3) There was linear relationship between the water flow and the gradient of the thermal clearance curve in various water flows of a micro-circulation model. The gradient of the thermal clearance curve obtained for each water flow had good reproducibility. 4) The gradient of the thermal clearance curve changed in parallel with the finger ischemia and hyperemia induced by inflation of a tourniquet. There was good reproducibility in continuous measurements. 5) A highly significant positive correlation was obtained between finger blood flow measured by the inhaled hydrogen clearance method and the gradient of the thermal clearance curve, indicating that it was possible to assess finger blood flow quantitatively by the gradient of the thermal clearance curve. The weak point in the former thermal diffusion method, where the baseline was unstable as a result of environmental temperature, was removed. It was concluded that this new thermal diffusion method using the thermal clearance curve, which was calibrated previously by the hydrogen clearance method, enabled us to measure finger blood flow noninvasively at various temperatures. This method will be useful for diagnosis and research in various medical fields.
Using an improved system for measuring skin blood flow by the thermal clearance curve, the change of the skin blood flow in the finger (finger blood flow) of the workers using vibratory tools induced by 10 degrees C cold water immersion for 10 min was observed in order to clarify the pathogenesis of vibration-induced white finger (VWF) from the aspect of peripheral circulatory function and simultaneously to demonstrate the efficiency of the system. The subjects constituted a group of 10 workers with VWF (VWF group) and 10 healthy workers without a history of hand-arm symptoms (control group). Ages and years of exposure to vibration in the two group were almost equal. The results were as follows. 1) While the finger blood flow in the control group was remarkably decreased at 1 min after the immersion, the decrease in the VWF group was low as compared with that in the control group. This result shows that vasoconstriction just after the immersion in VWF patients is not as great as that in the control group. 2) The finger blood flow in the control group at 5 min after the immersion was increased. In contrast no increase in the VWF group was observed. These results showed that cold-induced vasodilatation (CIVD) in VWF patients diminished. 3) An increase of the finger blood flow at 1 min after stopping the immersion was observed in the VWF group. These results suggest that the property of reaction to cold in VWF patients is not excessive vasoconstriction as has been hypothesized, but the diminution of CIVD. Apart from 10 workers of VWF group, observing the change of the finger blood flow in a case in which VWF was provoked by the immersion, the author found an abnormal decrease of the finger blood flow at 5 min after the immersion. This finding supports the hypothesis that the diminution of CIVD plays an important role in VWF attack as well. Concerning the characteristics of peripheral circulatory function in VWF patients, it can therefore be considered that its reaction in VWF attack is vasospasms, while the reaction to cold is the diminution of CIVD in the non-attack phase. The cold water immersion test using the system was recognized to be useful for diagnostic examination because the estimation of finger blood flows at both measuring points, 1 min and 5 min after the immersion, could fairly well discriminate VWF patients from healthy workers.(ABSTRACT TRUNCATED AT 400 WORDS)