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1.
Rev Sci Instrum ; 91(9): 093305, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-33003787

ABSTRACT

We have developed a novel discrimination methodology to identify ions in multispecies beams with similar charge-to-mass ratios, but different atomic numbers. After an initial separation by charge-to-mass ratios using co-linear electric and magnetic fields, individual ions can be discriminated by considering the linear energy transfer of ions irradiating a stimulable phosphor plate (Fujifilm imaging plate) by comparison with the Monte Carlo calculation. We apply the method to energetic multispecies laser-driven ion beams and use it to identify silver ions produced by the interaction between a high contrast, high intensity laser pulse; and a sub-micrometer silver foil target. We also show that this method can be used to calibrate the imaging plate for arbitrary ion species in the range of Z ≥ 6 with dE/dx > 0.1 MeV/µm without requiring individual calibration.

2.
Phys Rev Lett ; 124(8): 084802, 2020 Feb 28.
Article in English | MEDLINE | ID: mdl-32167312

ABSTRACT

Acceleration of particles from the interaction of ultraintense laser pulses up to 5×10^{21} W cm^{-2} with thin foils is investigated experimentally. The electron beam parameters varied with decreasing spot size, not just laser intensity, resulting in reduced temperatures and divergence. In particular, the temperature saturated due to insufficient acceleration length in the tightly focused spot. These dependencies affected the sheath-accelerated protons, which showed poorer spot-size scaling than widely used scaling laws. It is therefore shown that maximizing laser intensity by using very small foci has reducing returns for some applications.

3.
Cancer Chemother Pharmacol ; 71(1): 175-82, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23064956

ABSTRACT

The American Society of Clinical Oncology recently published a Clinical Practice Guideline entitled "Appropriate Chemotherapy Dosing for Obesity Adult Patients with Cancer." The panel recommended that full weight (actual weight)-based cytotoxic chemotherapy doses are used to treat obese patients with cancer, particularly when the goal of treatment is cure. However, no study has examined dosage calculation methods used for obese cancer patients in Japan. Here, we retrospectively studied the relationships between chemotherapy dose intensity, the occurrence of adverse events, and treatment outcomes in obese patients undergoing chemotherapy. Patients were divided into two groups: the actual BW group (BWg) was composed of patients receiving dosage amounts calculated using their actual BW (n = 64), and the ideal BWg was composed of patients receiving dosage amounts calculated using their ideal BW (n = 41). There were significant differences in the incidence of Grade 3/4 hematological toxicity in the actual and ideal BWg in solid tumor patients, but not in patients with hematological malignancies. In solid tumor patients with ≥30 body mass index (BMI), the incidence of Grade 3/4 hematological toxicity was significantly lower in the ideal BWg than in the actual BWg. Particularly, in patients with complications, incidence of Grade 4 hematological toxicity was significantly higher in the actual BWg than in the ideal BWg. These results suggest that the tumor type, degree of obesity, complications, and choice of chemotherapy regimen should be considered when determining chemotherapy dosage for obese patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Hematologic Neoplasms/drug therapy , Neoplasms/drug therapy , Obesity/complications , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Body Surface Area , Body Weight , Dose-Response Relationship, Drug , Drug Dosage Calculations , Female , Hematologic Neoplasms/pathology , Humans , Japan , Male , Middle Aged , Neoplasms/pathology , Retrospective Studies
4.
J Clin Neurosci ; 19(11): 1553-7, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22995760

ABSTRACT

NeuRobot, a micromanipulator system with a rigid neuroendoscope and three micromanipulators, was developed for less invasive and telecontrolled neurosurgery. This system can be used to perform sophisticated surgical procedures through a small, 10-mm-diameter, window. The present study was performed to evaluate the feasibility of using NeuRobot in neuroendoscopy. Four different intraventricular neurosurgical procedures were simulated in three fixed cadaver heads using NeuRobot: (1) fenestration of the floor of the third ventricle; (2) fenestration of the septum pellucidum; (3) biopsy of the thalamus; and (4) biopsy of the choroid plexus of the lateral ventricle. Each procedure required less than 2 min, and all procedures were performed accurately. After these surgical simulations, a third ventriculostomy was carried out safely and adequately in a patient with obstructive hydrocephalus due to a midbrain venous angioma. Our results confirmed that NeuRobot is applicable to lesions in which conventional endoscopic neurosurgery is indicated. Furthermore, NeuRobot can perform more complex surgical procedures than a conventional neuroendoscope because of its maneuverability and stability. NeuRobot will become a useful neurosurgical tool for dealing with lesions that are difficult to treat by conventional neuroendoscopic surgery.


Subject(s)
Endoscopy/instrumentation , Micromanipulation/instrumentation , Neurosurgical Procedures/instrumentation , Biopsy/methods , Cadaver , Central Nervous System Venous Angioma/complications , Choroid Plexus/pathology , Endoscopy/methods , Humans , Hydrocephalus/etiology , Hydrocephalus/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Neuroendoscopy , Neurosurgical Procedures/methods , Robotics , Septum of Brain/surgery , Thalamus/pathology , Tomography, X-Ray Computed , Ventriculostomy/instrumentation , Ventriculostomy/methods
5.
Minerva Chir ; 67(3): 249-55, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22691829

ABSTRACT

AIM: The purpose of the present study was to determine whether in vivo electroporation could achieve selective blockade of apoptosis in a rat liver cirrhosis model. METHODS: A dimethylnitrosamine (DMN)-induced rat liver cirrhosis model was used. In vivo electroporation was performed after portal vein infusion of plasmid DNA. pFas-Fc plasmid DNA was used to block the apoptotic pathway. pUC/HGF and pCAGGS/EGFP were used as positive and negative controls, respectively. Liver collagen content was evaluated by hydroxyproline assay two weeks after gene transfer. Terminal deoxynucleotidyltransferase dUTP nick end-labeling was simultaneously performed in the liver to evaluate suppression of apoptosis. Survival analysis was performed using 10 rats that received the sFas gene, 10 that received the HGF gene, and 13 that received the GFP gene. RESULTS: The apoptotic cell index in the DMN-injected liver was significantly lower in rats that received the sFas gene compared with the negative control. The collagen content of the DMN-injected liver was also lower in rats that received the sFas gene compared with the negative control. There was no significant difference in the apoptotic cell index and collagen content of rats that received the sFas and HGF genes. Ten weeks after the initiation of DMN treatment, the survival rates with the sFas, HGF, and GFP genes were 56%, 100%, and 0, respectively. CONCLUSION: Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer improved the apoptotic cell index, hydroxyproline content, and survival rate. Soluble Fas gene therapy using in vivo electroporation can be a safe and efficient therapy for liver cirrhosis in rats.


Subject(s)
Apoptosis/genetics , DNA/administration & dosage , Electroporation , Gene Transfer Techniques , Liver Cirrhosis/genetics , Liver Cirrhosis/prevention & control , Animals , Infusions, Intravenous , Male , Plasmids , Portal Vein , Rats , Rats, Sprague-Dawley
6.
Int Angiol ; 30(5): 467-73, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21804487

ABSTRACT

AIM: Endovascular aneurysm repair (EVAR) was first approved in Japan in 2007. In order to avoid the learning curve generally seen in the initial stages of implementation, we have aimed for procedural perfection. As the proximal type I endoleak (EL) is associated with a higher risk of late conversion and rupture, so we have treated the intraoperative type I EL scrupulously. The hostile neck, which is known to be a risk for perigraft leakage, is the focus of this study. We showed both the middle-term results of EVAR in our country and the possible necessity of intraoperative management for the hostile neck. METHODS: From a consecutive series of 134 patients who underwent EVAR of abdominal aortic aneurysms, 129 cases in which contrast agent was used intraoperatively were selected. All cases had at least 12-month follow-up postoperatively (12-40 months). Of the 129 selected cases, 49 cases (37%) that did not fulfill the commercially recommended criteria of the aneurysmal neck (length <15 mm and angle >60° of the aneurysm or >45° of the suprarenal aorta) were assigned to the off-label group. The other 80 cases were assigned to the on-label group. We carefully observed the completion angiography and when we found or suspected a type I EL, we performed a re-touch up, changed to a non-compliant balloon, and used a supportive device, such as a PalmazTM stent or aortic cuffs, in sequence. RESULTS: No postoperative type I ELs were detected within the follow-up period. Intraoperative type I ELs were detected more frequently in the off-label group (51%) than the on-label group (20%) (P<0.01). The rate of type I EL in the off-label group in terms of the neck length criteria (11/14 cases) was higher than that in the on-label group (30/115 cases) (P<0.01). In terms of the neck angle, patients in the off-label group had a greater tendency to develop the type I EL than those in the on-label group (18/42 vs. 23/87 cases) (P=0.06). CONCLUSION: Off-label usage regarding aneurysmal neck length and angle tends to be incomplete without additional procedures. Conversely, various techniques, including non-compliant balloon usage and aortic stenting or cuffs, produce good results for the intraoperative type I EL. We found a relationship between the neck condition and the intraoperative type I EL, and showed the importance of strictly obeying our simple algorithm against the proximal type I EL.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation , Endoleak/prevention & control , Endovascular Procedures , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/mortality , Aortography/methods , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/mortality , Endoleak/etiology , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Endovascular Procedures/mortality , Female , Humans , Japan , Kaplan-Meier Estimate , Male , Patient Selection , Prosthesis Design , Reoperation , Retrospective Studies , Stents , Survival Rate , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
7.
Eur J Vasc Endovasc Surg ; 40(5): 559-63, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20739201

ABSTRACT

OBJECTIVES: To verify the usefulness and limitation of intravascular ultrasound (IVUS) in endovascular aneurysm repair (EVAR). METHODS: A total of 112 consecutive patients, who underwent EVAR to treat abdominal aortic aneurysms, were examined retrospectively. Of these, 33 patients were assigned to the IVUS group because of renal failure, a suspected allergy to contrast agents or anatomical difficulties; the remaining 79 patients were assigned to the non-IVUS group. RESULTS: Patients in the IVUS group required fewer intra-arterial contrast agents (IACAs) than those in the non-IVUS group (67±34ml vs. 123±50ml; p<0.01). Blood loss and operation time were comparable between the two groups. No patients died within 30 days of the operation. Three major renal complications occurred in the non-IVUS group. Renal deterioration evaluated by chronic kidney disease (CKD) stage was found to a greater extent in the non-IVUS group. CONCLUSIONS: IVUS is a powerful auxiliary method in EVAR for reducing the required volume of contrast agents. The combination of IVUS and IACA usage showed good overall performance; thus, we propose the routine use of IVUS in EVAR procedures.


Subject(s)
Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/methods , Ultrasonography, Interventional , Aged , Aged, 80 and over , Female , Humans , Male , Retrospective Studies , Stents
8.
Int Angiol ; 25(4): 385-8, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17164745

ABSTRACT

AIM: A few studies have observed reduced vascular reserve measured by single photon emission computed tomography (SPECT) to be a risk factor for stroke in patients with carotid artery occlusion, but stenosis has been excluded from these former studies. This study has evaluated the prognosis of reduced vascular reserve in patients with stenosis, and the effect of carotid endarterectomy (CEA) on these patients. METHODS: Forty patients diagnosed as having >70% stenosis of the carotid artery at the University of Tokyo Hospital, between 2001 and 2004, underwent acetazolamide-stress SPECT test first. A resting SPECT study was performed on a different day from the stressed SPECT study. The patients were grouped as having reduced vascular reserve or normal vascular reserve from the SPECT results. Analysis of risk factors and the stroke-free curve analysis for reduced vascular reserve was performed. RESULTS: Of the 40 patients, 24 (60%) had reduced vascular reserve and 18 underwent CEA. The mean follow-up period was 21.5+/-15.5 months (mean+/-SD). Four strokes occurred during follow-up: in 1 patient with CEA and 3 without CEA. All stroke patients had reduced vascular reserve. The patients with reduced vascular reserve without any surgery had a significantly lower stroke-free rate compared with those with normal vascular reserve or reduced vascular reserve, but also receiving CEA. CONCLUSIONS: We propose performing SPECT tests in patients with severe carotid stenosis regardless of symptoms, and performing CEA on those with a reduction in vascular reserve.


Subject(s)
Carotid Stenosis/diagnostic imaging , Carotid Stenosis/physiopathology , Stroke/etiology , Tomography, Emission-Computed, Single-Photon , Aged , Carotid Stenosis/complications , Female , Humans , Male , Predictive Value of Tests , Prognosis , Regional Blood Flow , Risk Factors
9.
Acta Neurochir Suppl ; 98: 63-6, 2006.
Article in English | MEDLINE | ID: mdl-17009702

ABSTRACT

BACKGROUND: To perform less invasive neurosurgery, a telecontrolled micromanipulator system has been developed and applied to clinical situations. Basic experiments for telesurgery have also been conducted. METHOD: A cadaver head was used to carry out surgical simulation of the opening of the sylvian fissure and third ventriculostomy. After obtaining permission from the Ethical Committee of Shinshu University School of Medicine, part of the recurrent meningioma in a 45-year-old man was removed. As basic experiment for telesurgery, surgical simulation was also conducted in a rat brain with the operating console transported to a hospital 40 km distant from the University. FINDINGS: Opening of the sylvian fissure and third ventriculostomy were accurately performed. Tumour removal in a patient with recurrent meningioma was safely achieved. Surgical simulation in the rat brain was accurately and correctly carried out, operated on from a hospital 40 km distant. CONCLUSIONS: The NeuRobot, telecontrolled micromanipulator system, can be used as a tool for less invasive neurosurgery.


Subject(s)
Cerebellar Neoplasms/surgery , Meningioma/surgery , Minimally Invasive Surgical Procedures/instrumentation , Neurosurgical Procedures/instrumentation , Robotics , Telemedicine/instrumentation , Animals , Cadaver , Cerebellar Neoplasms/secondary , Equipment Design , Humans , Male , Meningioma/secondary , Middle Aged , Pia Mater/surgery , Rats
10.
Int Angiol ; 25(1): 35-9, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16520722

ABSTRACT

AIM: The prevalence of carotid stenosis is reported to be high among patients with arteriosclerosis, but the hazards of carotid stenosis and the benefits of carotid endarterectomy (CEA) on long-term event-free survival are still unknown. The aim of this prospective study was to screen preoperative patients with arterial disease for carotid stenosis, and to determine whether CEA had any effect on stroke during the postoperative follow-up period. METHODS: From 1999 to 2003, 406 consecutive preoperative patients with arterial disease underwent routine carotid duplex scan. Patients with known carotid stenosis and those due to undergo operation in emergency were excluded from the study. CEA was performed before or simultaneously with vascular surgery if necessary. The prevalence and risk factors for carotid stenosis were studied, and the patients were followed up for stroke or death. RESULTS: Among the 406 patients examined, 19.4% had greater than 50% stenosis and 11.3% had greater than 70% stenosis. The risk factors for carotid stenosis were having occlusive arterial disease (P=0.0001), and history of stroke (P=0.0038). Long-term follow-up study revealed that patients with greater than 70% carotid stenosis without CEA had a higher tendency for stroke or death, but the stroke rate in patients with severe stenosis who underwent CEA remained low, as in patients with less than 70% stenosis. CONCLUSIONS: Patients with greater than 70% carotid stenosis, diagnosed before arterial operation who did not undergo CEA, had a higher risk for stroke during the postoperative follow-up period. However, their risk could be reduced by performing CEA before or simultaneously with scheduled vascular surgery.


Subject(s)
Aorta, Abdominal/pathology , Arterial Occlusive Diseases/complications , Endarterectomy, Carotid , Stroke/prevention & control , Aged , Aged, 80 and over , Analysis of Variance , Carotid Artery, Internal/pathology , Carotid Artery, Internal/surgery , Carotid Stenosis/complications , Carotid Stenosis/surgery , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Risk Factors , Severity of Illness Index , Stroke/etiology , Survival Analysis , Treatment Outcome
11.
Opt Express ; 14(22): 10785-9, 2006 Oct 30.
Article in English | MEDLINE | ID: mdl-19529488

ABSTRACT

We demonstrated all-optical label storing and switching for 40 Gb/s optical packets by using all-optical signal processing of multimode interference bistable laser diode optical flip-flops. The stored optical labels in the optical flip-flop controlled an all-optical switch to forward the injected optical packets. The 40 Gb/s optical packets were successfully switched in the all-optical scheme with 11-dB extinction ratio. Error-free operation for the output packets from the switch was also obtained with 1.3-dB power penalty. The presented all-optical packet switching has the advantages of ultrafast switching and transparency of data rate and format, suitable for the future optical networks.

12.
Int Angiol ; 24(4): 340-8, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16355091

ABSTRACT

AIM: The purpose of this study was to investigate the long-term results of combined iliac endovascular intervention and infrainguinal surgical revascularization. METHODS: A retrospective review of 39 infrainguinal bypasses combined with iliac endovascular intervention in 35 patients over a 16-year period was performed (Combined group). These results were compared to those of 43 infrainguinal bypasses performed with suprainguinal bypass operation in 39 patients (Surgical group), who had iliac lesions not amenable to angioplasty/stenting. There was no significant difference in the preoperative limb ischemic symptoms between them. RESULTS: Although the proportion of patients with coronary artery disease in the Combined group was significantly higher than that in the Surgical group, there was a trend toward lower morbidity/mortality in the Combined group compared with the Surgical group (8.6% vs 15.4%; P=0.3706). No significant differences in the rates of clinical and hemodynamic improvement and limb salvage rate were observed between the two groups. The primary patency rate of infrainguinal bypass at 1, 3, and 5 years was 83.2%, 80%, and 71.2% in the Combined group, and 97.1%, 89.9%, and 80.5% in the Surgical group, respectively. The secondary patency rate at 1, 3, and 5 years was 91.9%, 91.9%, and 76.3% in the Combined group, and 97.1%, 89.9%, and 84.6% in the Surgical group, respectively. Importantly, there was no significant difference in the primary/secondary patency rates between the two groups (Kaplan-Meier, log-rank test, primary patency, P=0.116; secondary patency, P=0.4407). CONCLUSIONS: Infrainguinal surgical reconstruction combined with iliac endovascular procedure may reduce operative risk, and further, long-term patency is comparable to that in the Surgical group.


Subject(s)
Arterial Occlusive Diseases/surgery , Iliac Artery , Vascular Surgical Procedures/methods , Aged , Aged, 80 and over , Angiography , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/physiopathology , Follow-Up Studies , Humans , Inguinal Canal , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome , Vascular Patency/physiology
13.
Int Angiol ; 24(4): 391-4, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16355100

ABSTRACT

A rare case of a persistent sciatic artery (PSA) in a patient with aneurysms of the internal carotid artery and abdominal aorta is presented. A 70-year-old man was referred with intermittent claudication of the right lower extremity. Angiography and computed tomography demonstrated that this symptom was due to occlusion of the PSA. On preoperative examinations, aneurysms of the extracranial internal carotid artery and abdominal aorta were incidentally discovered, and then surgically treated prior to the management of PSA. Systemic examinations must be performed in patients with PSA in order to scrutinize associated anomalies or vascular disease.


Subject(s)
Aneurysm/complications , Aortic Aneurysm, Abdominal/complications , Carotid Artery, Internal , Femoral Artery/abnormalities , Intermittent Claudication/complications , Aged , Aneurysm/diagnostic imaging , Aneurysm/surgery , Angiography , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Diagnosis, Differential , Femoral Artery/diagnostic imaging , Follow-Up Studies , Humans , Intermittent Claudication/diagnostic imaging , Intermittent Claudication/surgery , Male , Tomography, X-Ray Computed , Vascular Surgical Procedures/methods
14.
Water Sci Technol ; 49(5-6): 173-9, 2004.
Article in English | MEDLINE | ID: mdl-15137421

ABSTRACT

In order to develop a new type of anaerobic digestion process equipped with a nitrogen removal function, denitrification of nitrate nitrogen (NO3-N) in anaerobic acidogenesis of organic fraction of municipal waste (OFMSW) was investigated by two semi-continuous reactors. Reactor 1 and Reactor 2 were fed by 3% and 7% of solids concentration of synthetic garbage, respectively. Generation of nitrogen gas (N2) and ammonium nitrogen (NH4-N) was simultaneously observed in the low load of nitrate (NO3-N) (below 0.68 g NO3-N/L). In Reactor 1, ammonium nitrogen generation decreased as the addition of nitrate increased. Finally, the increase of the addition of nitrate resulted in the increase of acetic acid production.


Subject(s)
Bacteria, Anaerobic/physiology , Bioreactors , Nitrogen/isolation & purification , Refuse Disposal/methods , Water Pollutants/isolation & purification , Gases/analysis , Nitrates/analysis , Quaternary Ammonium Compounds/analysis
15.
Calcif Tissue Int ; 70(6): 488-95, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12016462

ABSTRACT

26,27-hexafluoro-1a,25-dihydroxyvitamin D3 (F6-D3) has been reported to be 5-10 times more potent than 1a,25-dihydroxyvitamin D3[1,25(OH)2D3] in biological systems in vivo and in vitro. However, the effect of F6-D3 on bone formation has yet to be clarified. In the present study, we investigated the effect of F6-D3 on SV40-transfected human fetal osteoblastic cells (SV-HFO) and found it to be about 100 times greater than that of 1,25(OH)2D3 in stimulating calcification. F6-D3 was also about 100 times more effective than 1,25(OH)2D3 in enhancing the expression of mRNA for alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In the presence of 10?8 M F6-D3 and 10?6 M 1,25(OH)2D3, the calcification began on day 9 and increased up to day 19. Expression of mRNA for ALP and OCN reached a maximum on day 4 and thereafter declined. On the other hand, when osteoblastic cells were incubated with a low level of [1b-3H]-F6-D3- or [1b-3H]-1,25(OH)2D3, each radioactive peak could not be detected. However, on the incubation of osteoblastic cells and radioactive substrate in the presence of ketoconazole, a selective inhibitor of CYP24, a clear peak for each substrate was detected. This suggested that F6-D3 as well as 1,25(OH)2D3 is metabolized by CYP24. Osteoblastic cells were incubated with 10?8 M[1b-3H]-F6-D3 or 10?8 M[1b-3H]-1,25(OH)2D3 for 4, 9, and 14 days. A small peak of 1,25(OH)2D3 was observed and thereafter its level decreased. In addition, two unknown peaks increased when the culture period was extended. In the case of F6-D3, peaks of F6-D3 and 26,27-hexafluoro-23-oxo-1a,25(OH)2D3(23-oxo-F6) were clearly detected, the latter being about 4 times higher than the former. Both peaks was retained up to day 14. The amount of unlabeled F6-D3 and 23-oxo-F6 calculated from the specific radioactivity in the cells may be similar to the amount of 1,25(OH)2D3 and its metabolites. The strong activity of F6-D3 in stimulating calcification may be due to the fact that F6-D3 is much more potent than 1,25(OH)2D3 in enhancing the expression of mRNA for ALP, OCN, and OPN and that the amount of F6-D3 and 23-oxo-F6 accumulated in the cells is much greater than that of 1,25(OH)2D3 and its metabolite.


Subject(s)
Calcification, Physiologic/drug effects , Calcitriol/analogs & derivatives , Calcitriol/pharmacology , Osteoblasts/drug effects , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Blotting, Northern , Cell Line, Transformed , Cell Transformation, Viral , Dose-Response Relationship, Drug , Fetus , Humans , Hydroxyproline/metabolism , Osteoblasts/metabolism , Osteocalcin/genetics , Osteocalcin/metabolism , Osteopontin , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sialoglycoproteins/biosynthesis , Sialoglycoproteins/genetics , Staining and Labeling
16.
Br J Ophthalmol ; 86(5): 581-6, 2002 May.
Article in English | MEDLINE | ID: mdl-11973258

ABSTRACT

AIMS: To evaluate a new delivery system of 5-fluorouracil (5-FU) using 5-fluorocytosine (5-FC) as a prodrug and cytosine deaminase induced in vitro and in vivo. METHODS: Fibroblastic cells from rabbit Tenon's capsule were cultured. The cells were exposed to 5-FU and 5-FC with or without cytosine deaminase induced by recombinant adenovirus. In the in vitro study, cell proliferation and DNA synthesis were assessed by MTS, BrdU assay. The effect of 5-FC removal after the treatment of 5-FC and cytosine deaminase induction was also assayed. In the in vivo study cells with or without cytosine deaminase induction were transplanted into the subconjunctival space of mice, followed by eye drops of 1000 microg/ml of 5-FC three times a day. The mice were sacrificed at days 1, 5, and 10, then the cells transplanted were evaluated. RESULTS: Cell proliferation was inhibited by exposure to 5-FU in a dose dependent manner; however, up to 1000 microg/ml of 5-FC did not affect cell proliferation. Cell proliferation was inhibited by exposure to 5-FC in a time dependent manner with induction of cytosine deaminase following infection of recombinant adenovirus. When 5-FC was removed 3 or 6 days after the treatment, the cells grew again. The effect was reproduced in the in vivo model of subconjunctival cellular proliferation although 5-FC was administrated as eye drops. There were no cases with corneal erosion. CONCLUSION: Cell proliferation was inhibited by co-exposure of 5-FC and cytosine deaminase. This new delivery system may merit controlled delivery of 5-FU after filtering surgery.


Subject(s)
Antimetabolites/administration & dosage , Drug Delivery Systems/methods , Fluorouracil/administration & dosage , Nucleoside Deaminases , Prodrugs/administration & dosage , Animals , Cell Division/drug effects , Cells, Cultured , Cytosine Deaminase , DNA/biosynthesis , Fibroblasts/drug effects , Flucytosine/administration & dosage , Rabbits
17.
Clin Exp Immunol ; 126(2): 259-65, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11703369

ABSTRACT

Although increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) has been demonstrated in inflammatory sites of various diseases, its role in colitis remains unknown. In this study, we examined whether MAdCAM-1 is involved in the pathogenesis of granulomatous colitis induced by peptidoglycan-polysaccharide (PG-PS). Experimental colitis was induced by intramural injection of PG-PS to rat colon. After 3 weeks the colon was removed and the mucosal inflammation was assessed. The area of MAdCAM-1-positive venules and the subsets of infiltrating cells were determined in colonic mucosa by immunohistochemistry. In another experiment, monoclonal antibody against MAdCAM-1 was administered intraperitoneally to examine its attenuating effect on colitis. The intramural injection of PG-PS induced significant colonic inflammation with granuloma formation. The submucosa was drastically thickened with the infiltration of CD4 positive lymphocytes and ED-1 positive macrophages. Intense MAdCAM-1 expression was observed on endothelium of the submucosal venules in inflamed mucosa. Administration of anti-MAdCAM-1 antibody significantly attenuated the PG-PS-induced colonic damage and cell infiltration. Enhanced expression of MAdCAM-1 was demonstrated in venular endothelium of the inflamed colon in PG-PS-induced colitis. The attenuating effect of anti-MAdCAM-1 suggests the importance of the MAdCAM-1-dependent process in the formation of chronic granulomatous colitis.


Subject(s)
Cell Adhesion Molecules/physiology , Crohn Disease/etiology , Crohn Disease/immunology , Immunoglobulins/physiology , Intestinal Mucosa/immunology , Mucoproteins/physiology , Animals , Antibodies, Monoclonal/pharmacology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , Cell Adhesion Molecules/antagonists & inhibitors , Cell Movement , Chronic Disease , Crohn Disease/chemically induced , Crohn Disease/pathology , Endothelium, Vascular/immunology , Endothelium, Vascular/pathology , Female , Immunohistochemistry , Intestinal Mucosa/blood supply , Intestinal Mucosa/pathology , Mucoproteins/antagonists & inhibitors , Peptidoglycan/toxicity , Polysaccharides/toxicity , Rats , Rats, Inbred Lew
18.
Respiration ; 68(5): 506-8, 2001.
Article in English | MEDLINE | ID: mdl-11694814

ABSTRACT

BACKGROUND: There is no information on serial pharmacokinetic assessment in the lungs after administration of aerosolized pentamidine. OBJECTIVE: The present study was performed to evaluate the elimination of aerosolized pentamidine from bronchial airways following inhalation. METHODS: We used 4 sheep with tracheotomies in the present study. Pentamidine (300 mg) was administered by inhalation to each animal. Serial bronchial washing to obtain epithelial lining fluid (ELF) was performed 1, 7, 10, 14, 21 and 28 days after administration of aerosolized pentamidine in each animal. The pentamidine concentration in the supernatant of ELF was measured by high-performance liquid chromatography. RESULTS: The maximal pentamidine level on the first day (12 h after inhalation) was 616.5 +/- 238.2 ng/ml (mean +/- SE) in ELF. The pentamidine levels rapidly decreased within 2 weeks (8.9 +/- 1.2 ng/ml at 14 days), followed by slow elimination (8.9 +/- 0.8 ng/ml at 28 days). Thus, inhaled pentamidine showed a rapid clearance from the bronchial wall within the first 2 weeks. CONCLUSIONS: These findings may be useful in designing and interpreting future studies of aerosolized pentamidine in patients who are receiving inhaled pentamidine, especially for those with failure of prophylaxis for Pneumocystis carinii pneumonia.


Subject(s)
Antifungal Agents/pharmacokinetics , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Pentamidine/pharmacokinetics , Administration, Inhalation , Animals , Antifungal Agents/blood , Models, Animal , Pentamidine/blood , Sheep , Time Factors
19.
Bioresour Technol ; 80(3): 227-31, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11601547

ABSTRACT

The effect of the iron concentration in the external environment on hydrogen production was studied using sucrose solution and the mixed microorganisms from a soybean-meal silo. The iron concentration ranged from 0 to 4,000 mg FeCl2 l(-1). The temperature was maintained at 37 degrees C. The maximum specific hydrogen production rate was found to be 24.0 ml g(-1) VSS h(-1) at 4,000 mg FeCl2 l(-1). The specific production rate of butyrate increased with increasing iron concentration from 0 to 20 mg FeCl2 l(-1) and decreased with increasing iron concentration from 20 to 4,000 mg FeCl2 l(-1). The maximum specific production rates of ethanol (682 mg g(-1) VSS h(-1)) and butanol (47.0 mg g(-1) VSS h(-1)) were obtained at iron concentrations of 5 and 3 mg FeCl2 l(-1), respectively. The maximum hydrogen production yield of 131.9 ml g(-1) sucrose was obtained at the iron concentration of 800 mg FeCl2 l(-1). The maximum yields of acetate (389.3 mg g(-1) sucrose), propionate (37.8 mg g(-1) sucrose), and butyrate (196.5 mg g(-1) sucros) were obtained at iron concentrations of 3, 200 and 200 mg FeCl2 l(-1), respectively. The sucrose degradation efficiencies were close to 1.0 when iron concentrations were between 200 and 800 mg FeCl2 l(-1). The maximum biomass production yield was 0.283 g VSS g(-1) sucrose at an iron concentration of 3,000 mg FeCl2 l(-1).


Subject(s)
Fermentation , Hydrogen/metabolism , Iron/metabolism , Acetates/metabolism , Biodegradation, Environmental , Butyrates/metabolism , Kinetics , Models, Chemical , Propionates/metabolism , Sewage , Sucrose/metabolism , Temperature
20.
Neurosci Lett ; 310(2-3): 129-32, 2001 Sep 14.
Article in English | MEDLINE | ID: mdl-11585584

ABSTRACT

The renal sympathetic nerve activity (RNA) response to gravitational changes induced by parabolic flight was examined in chronically instrumented conscious rats. Two types of RNA responses were found. In six out of 12 rats, the RNA did not respond during the 2 G period, but immediately fell to background levels on entry into microgravity (microG), then recovered to the 1 G control level during continued microG (shutdown obvious group). In the other six rats, the RNA increased to 158+/-13% at the end of the 2 G period, increased further to 195+/-22% on entry into microG, then gradually recovered to that seen at 1 G (shutdown obscure group). The mean arterial pressure in the shutdown obvious group was significantly higher and the heart rate tended to be higher than in the shutdown obscure group, suggesting that the baseline sympathetic tone in the shutdown obvious group was higher than in the shutdown obscure group. These results suggest that the RNA response to parabolic flight might be affected by the baseline sympathetic tone.


Subject(s)
Hypergravity , Kidney/innervation , Sympathetic Nervous System/physiology , Weightlessness Simulation , Animals , Blood Pressure/physiology , Consciousness , Heart Rate/physiology , Male , Rats , Rats, Sprague-Dawley
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