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1.
Geobiology ; 9(5): 436-45, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21884364

ABSTRACT

The hydrothermally influenced sediments of Tutum Bay, Ambitle Island, Papua New Guinea, are ideal for investigating the chemolithotrophic activities of micro-organisms involved in arsenic cycling because hydrothermal vents there expel fluids with arsenite (As(III)) concentrations as high as 950 µg L(-1) . These hot (99 °C), slightly acidic (pH ~6), chemically reduced, shallow-sea vent fluids mix with colder, oxidized seawater to create steep gradients in temperature, pH, and concentrations of As, N, Fe, and S redox species. Near the vents, iron oxyhydroxides precipitate with up to 6.2 wt% arsenate (As(V)). Here, chemical analyses of sediment porewaters from 10 sites along a 300-m transect were combined with standard Gibbs energies to evaluate the energy yields (-ΔG(r)) from 19 potential chemolithotrophic metabolisms, including As(V) reduction, As(III) oxidation, Fe(III) reduction, and Fe(II) oxidation reactions. The 19 reactions yielded 2-94 kJ mol(-1) e(-) , with aerobic oxidation of sulphide and arsenite the two most exergonic reactions. Although anaerobic As(V) reduction and Fe(III) reduction were among the least exergonic reactions investigated, they are still potential net metabolisms. Gibbs energies of the arsenic redox reactions generally correlate linearly with pH, increasing with increasing pH for As(III) oxidation and decreasing with increasing pH for As(V) reduction. The calculated exergonic energy yields suggest that micro-organisms could exploit diverse energy sources in Tutum Bay, and examples of micro-organisms known to use these chemolithotrophic metabolic strategies are discussed. Energy modeling of redox reactions can help target sampling sites for future microbial collection and cultivation studies.


Subject(s)
Archaea/metabolism , Arsenic/metabolism , Bacteria/metabolism , Chemoautotrophic Growth , Hydrothermal Vents/microbiology , Iron/metabolism , Aerobiosis , Anaerobiosis , Arsenicals/metabolism , Bays/microbiology , Ferric Compounds/metabolism , Hydrothermal Vents/chemistry , Oxidation-Reduction , Papua New Guinea , Seawater/chemistry , Seawater/microbiology
2.
Int J Gynecol Cancer ; 16 Suppl 1: 111-7, 2006.
Article in English | MEDLINE | ID: mdl-16515577

ABSTRACT

The feasibility of applying magnetic resonance imaging (MRI) for conducting prospective studies of intraperitoneal (i.p.) tumor treatment response to chemotherapy and resultant effects on survival in human ovarian carcinoma/nude mouse orthotopic xenograft models was evaluated. Female nude mice were implanted i.p. with either NMP-1 or SKOV-3ip. human ovarian carcinoma cells on day 0. Initial T2-weighted magnetic resonance (MR) images of the abdomens of NMP-1-implanted mice were obtained on day 7 to confirm the presence of nascent tumors; similar confirmations were made on day 14 with mice bearing SKOV-3ip. xenografts. On the initial imaging days, a multiple-dose regimen of cisplatin (CDDP; qd7 x3) was commenced, using 4 or 6 mg/kg treatments with the NMP-1 model and using 6 mg/kg treatments with the SKOV-3ip. model. Mice were reimaged multiple times, 2 days following each CDDP injection and at later times as well, depending on host survival. The images for each mouse from the last imaging day (day 30 for NMP-1, day 44 for SKOV-3ip.) were used in a blinded fashion to attempt to visually distinguish control from treated mice and to determine whether MRI could predict a survival benefit. For SKOV-3ip. mice, ten out of ten mice were correctly segregated into the control or the CDDP treatment group based solely on these blinded, nonquantified MR results. In this model, the 6 mg/kg multiple-dose regimen achieved a modest response, improving life span by approximately 24%. However, for the NMP-1 mice, only six out of nine evaluable mice were correctly segregated into the control or one of the treatment groups by similar MRI criteria, a virtually random distribution; further, neither CDDP treatment regimen achieved a significant improvement in survival in this model. In another study, NMP-1-implanted mice were treated on day 7 after tumor implantation with a single injection of a hyaluronic acid-paclitaxel copolymer. Control and treated mice were MR imaged on day 28, which revealed marked reductions in tumor burden in treated mice, correlating well with a subsequently observed improved survival of approximately 40%. Our results suggest that MRI can be used to serially and noninvasively monitor treatment response and predict ongoing treatment effects on survival.


Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Magnetic Resonance Imaging , Ovarian Neoplasms/diagnosis , Paclitaxel/therapeutic use , Peritoneal Neoplasms/diagnosis , Animals , Cell Line, Tumor , Feasibility Studies , Female , Humans , Hyaluronic Acid/therapeutic use , Mice , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Polymers/therapeutic use , Predictive Value of Tests , Single-Blind Method , Tumor Burden , Xenograft Model Antitumor Assays
3.
Med Phys ; 31(2): 405-13, 2004 Feb.
Article in English | MEDLINE | ID: mdl-15000627

ABSTRACT

A catheter-based transurethral ultrasound applicator with angularly directional heating patterns has been designed for prostate thermal therapy and evaluated in canine prostate in vivo using MRI to monitor and assess performance. The ultrasound transducer array (3.5 mm diameter tubular transducers, 180 degrees active sectors, approximately 7.5 MHz) was integrated to a flexible delivery catheter (4 mm OD), and encapsulated within an expandable balloon (35 mm x 10 mm OD, 80 ml min(-1) ambient water) for coupling and cooling of the prostatic urethra. These devices were used to thermally coagulate targeted portions of the canine prostate (n = 2) while using MR thermal imaging (MRTI) to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. MRTI was based upon the complex phase-difference mapping technique using an interleaved gradient echo-planar imaging sequence with lipid suppression. MRTI derived temperature distributions, thermal dose exposures, T1-contrast enhanced MR images, and histology of sectioned prostates were used to define destroyed tissue zones and characterize the three-dimensional heating patterns. The ultrasound applicators produced approximately 180 degrees directed zones of thermal coagulation within targeted tissue which extended 15-20 mm radially to the outer boundary of the prostate within 15 min. Transducer activation lengths of 17 mm and 24 mm produced contiguous zones of coagulation extending axially approximately 18 mm and approximately 25 mm from base to apex, respectively. Peak temperatures around 90 degrees C were measured, with approximately 50 degrees C-52 degrees C corresponding to outer boundary t43 = 240 min at approximately 15 min treatment time. These devices are MRI compatible, and when coupled with multiplanar MRTI provide a means for selectively controlling the length and sector angle of therapeutic thermal treatment in the prostate.


Subject(s)
Prostatic Neoplasms/therapy , Ultrasonic Therapy , Ultrasonics , Urethra/pathology , Animals , Catheterization , Dogs , Echo-Planar Imaging , Heating , Hot Temperature , Humans , Magnetic Resonance Imaging , Magnetics , Male , Models, Statistical , Temperature , Time Factors , Transducers
4.
Int J Hyperthermia ; 20(1): 45-56, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14612313

ABSTRACT

The aim was to determine if water-cooled diffusing tips could produce larger and safer (better controlled) thermal lesions than non-cooled diffusing tips at 980 nm. Thermal lesions were induced in beef myocardium in vitro with and without water cooling using a 980 nm diode laser at various power levels. Seven intracerebral treatments were performed in six canines using water-cooled diffusing tips with four animals having intracerebral transmissible venereal tumours grown from inoculate. Magnetic resonance thermal imaging (MRTI)-based feedback software using a fast, radio frequency-spoiled gradient echo acquisition with two intersecting image planes was used for on-line monitoring and control of treatment and for the evaluation of in vivo laser lesion production. In cases where two-plane MRTI was employed, the maximum calculated temperature was compared in each plane. Using water-cooled tips and 400 micro m core diameter laser diffusing fibres in in vitro beef myocardium, power of up to 9.5 W was applied for 8 min without tip failure. Without cooling, tip failure occurred in under 4 min at 6 W, in under 2 min at 7 W and instantaneously at 8 W. Additionally, char accompanied lesions made with uncooled tips while cooled application resulted in only minimal char at only the highest thermal dose. Achieved lesion cross-sectional diameters in in vitro samples were up to 26.5 x 23.3 mm when water cooling was used. In canine brain and transmissible venereal tumours, up to 18.1 x 21.4 mm lesions were achieved. It is concluded that water cooling allows safe application of higher power to small core diameter diffusing tip fibres, which results in larger thermal lesions than can be achieved without cooling. Two-plane MRTI enhances on-line monitoring and feedback of thermal treatment.


Subject(s)
Brain Neoplasms/therapy , Hyperthermia, Induced/instrumentation , Laser Therapy , Magnetic Resonance Imaging/methods , Animals , Brain/pathology , Cattle , Dogs , Hyperthermia, Induced/methods , In Vitro Techniques , Muscles/injuries , Muscles/pathology , Necrosis , Neoplasms, Experimental/therapy , Venereal Tumors, Veterinary/therapy
5.
Proc Natl Acad Sci U S A ; 100(23): 13549-54, 2003 Nov 11.
Article in English | MEDLINE | ID: mdl-14597719

ABSTRACT

Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.


Subject(s)
Infrared Rays , Magnetic Resonance Spectroscopy/methods , Animals , Cell Line, Tumor , Female , Gold/chemistry , Humans , Hyperthermia, Induced , Magnetic Resonance Imaging , Mice , Mice, SCID , Models, Statistical , Nanotechnology , Neoplasms/therapy , Silicon/chemistry , Temperature
6.
Ann N Y Acad Sci ; 1009: 283-7, 2003 Dec.
Article in English | MEDLINE | ID: mdl-15028601

ABSTRACT

BU98008 (1-(4, 5-dihydro-1H-imidazol-2-yl)isoquinoline) is a novel isoquinoline derivative. Radioligand binding studies revealed it had high affinity for the I(1) receptor in rat kidney membranes but low affinity for the I(2) binding site and alpha(2)-adrenoceptor in rat brain membranes. Further evaluation of BU98008 in vivo revealed no effect on blood pressure following peripheral administration. These preliminary data suggest BU98008 may be an antagonist at I(1) receptors. Further evaluation following central administration must be performed before a hypotensive action can be excluded.


Subject(s)
Imidazoles/metabolism , Isoquinolines/metabolism , Receptors, Drug/metabolism , Adrenergic alpha-Agonists/pharmacology , Animals , Blood Pressure/drug effects , Body Temperature/drug effects , Brain/cytology , Brain/metabolism , Cell Membrane/metabolism , Clonidine/pharmacology , Heart Rate/drug effects , Imidazoles/chemistry , Imidazoles/pharmacology , Imidazoline Receptors , Isoquinolines/chemistry , Isoquinolines/pharmacology , Kidney/cytology , Kidney/metabolism , Ligands , Male , Radioligand Assay , Rats , Rats, Inbred SHR , Receptors, Adrenergic, alpha-2/metabolism , Receptors, Drug/antagonists & inhibitors
7.
J Med Primatol ; 30(2): 81-7, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11491408

ABSTRACT

The right cerebral hemisphere of 24 rhesus monkeys scheduled for necropsy at the completion of another project were studied histopathologically 1-30 days after a single dose of 60Co-irradiation. Histopathologically, inflammation and gliosis consistently occurred at specific time points but varied in severity between individuals. Multifocal hemorrhage, edema, and an acute neutrophilic inflammatory response were observed initially whereas perivascular accumulations of lymphocytes were observed in specimens at the end of the study. Microglia/macrophages were most prominent during the first week after irradiation, whereas astrocytes were reactive throughout the observation period. The early clinical manifestations of the central nervous system (CNS), because of brain irradiation in humans, correspond temporally with acute vascular responses, acute and subacute inflammatory cell responses, and subacute demyelination and reactive astrocytic and microglial responses observed in the rhesus monkey. Initial responses of the CNS to gamma-irradiation may have potential implications for the development of radiation-induced late injury of the CNS.


Subject(s)
Central Nervous System/pathology , Central Nervous System/radiation effects , Radiation Injuries/veterinary , Animals , Autopsy/veterinary , Disease Models, Animal , Female , Humans , Inflammation , Macaca mulatta , Macrophages , Microglia , Radiation Injuries/pathology , Radiotherapy/adverse effects
8.
Int J Radiat Oncol Biol Phys ; 50(4): 1013-20, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11429229

ABSTRACT

PURPOSE: To obtain clinically useful quantitative data on the extent and kinetics of recovery of occult radiation injury in primate spinal cord, after a commonly administered elective radiation dose of 44 Gy, given in about 2 Gy per fraction. METHODS AND MATERIALS: A group of 56 rhesus monkeys was assigned to receive two radiation courses to the cervical and upper thoracic spinal cord, given in 2.2 Gy per fraction. The dose of the initial course was 44 Gy in all monkeys. Reirradiation dose was 57.2 Gy, given after 1-year (n = 16) or 2-year (n = 20) intervals, or 66 Gy, given after 2-year (n = 4) or 3-year (n = 14) intervals. Two animals developed intramedullary tumors before reirradiation and, therefore, did not receive a second course. The study endpoint was myeloparesis, manifesting predominantly as lower extremity weakness and decrease in balance, occurring within 2.5 years after reirradiation, complemented by histologic examination of the spinal cord. The data obtained were analyzed along with data from a previous study addressing single-course tolerance, and data from a preliminary study of reirradiation tolerance. RESULTS: Only 4 of 45 monkeys completing the required observation period (2-2.5 years after reirradiation, 3-5.5 years total) developed myeloparesis. The data revealed a substantial recovery of occult injury induced by 44 Gy within the first year, and suggested additional recovery between 1 and 3 years. Fitting the data with a model, assuming that all (single course and reirradiation) dose-response curves were parallel, yielded recovery estimates of 33.6 Gy (76%), 37.6 Gy (85%), and 44.6 Gy (101%) of the initial dose, after 1, 2, and 3 years, respectively, at the 5% incidence (D(5)) level. The most conservative estimate, using a model in which it was assumed that there was no recovery between 1 and 3 years following initial irradiation and that the combined reirradiation curve was not necessarily parallel to the single-course curve, still showed an overall recovery equivalent to 26.8 Gy (61%). The spinal cords of symptomatic monkeys consistently revealed a mixture of white matter necrosis and vascular injury, but the majority of spinal cords of asymptomatic animals did not exhibit overt lesions detectable by light microscopy. CONCLUSION: Combined analysis with the data of the previous studies yielded firm evidence that the spinal cord has a large capacity to recover from occult radiation injury induced by a commonly prescribed elective dose. This finding strengthens the rationale for selective use of radiotherapy to treat second primary tumors arising in previously irradiated tissues or late recurrences. However, some caution should be exercised in applying quantitative experimental data, because the length of follow-up in these experiments was limited to 2-2.5 years after reirradiation, whereas human myelopathy cases occasionally occur after longer latency. Because there is a large variation in long-term recovery among tissues, the tolerance of other tissues at risk should also be taken into account in prescribing therapy.


Subject(s)
Radiation Injuries, Experimental/physiopathology , Spinal Cord/radiation effects , Animals , Cervical Vertebrae , Dose-Response Relationship, Radiation , Female , Macaca mulatta , Radiation Tolerance , Radiobiology , Thoracic Vertebrae , Wound Healing/physiology
9.
J Med Primatol ; 30(1): 56-60, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11396864

ABSTRACT

This report outlines a comparison of renal weight and volume and selected skeletal parameters to sex in 22 adult male and 156 adult female rhesus macaques. Means and standard deviations for kidney weight and volume, body weight, and radiographic measurements for both males and females are reported. Ninety-five percent confidence intervals and P-values for the mean differences between the sexes for these parameters were also compiled. Male monkeys were larger, but had kidneys of similar size to those of the females. Joint distributions of the radiographic measurements of the first lumbar vertebra and the skull showed that males were larger in both measurements. The distributions of these parameters were clearly separate in males and females, while joint distributions of kidney weight and volume for males and females overlapped almost completely. We found that, regardless of age, sex, weight, or skeletal size, all normal adult rhesus monkeys generally have similar-sized kidneys.


Subject(s)
Bone and Bones/anatomy & histology , Kidney/anatomy & histology , Macaca mulatta/anatomy & histology , Animals , Biometry , Body Weight , Female , Male , Sex Factors
10.
Contemp Top Lab Anim Sci ; 40(1): 33-5, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11300674

ABSTRACT

An adult domestic female pig (Sus scrofa) exhibited clinical signs of right-sided Horner's syndrome after experimental placement of a woven aortic stent followed by aortic catheterization. The clinical signs included a miotic pupil, ptosis of the upper eyelid, prolapse of the nictitating membrane, and enophthalmos. Necropsy revealed a large mass in the right midcervical region that encased or was in contact with the carotid artery, internal jugular vein, and vagus nerve. Closer evaluation of the mass revealed that it was a small piece of surgical suture material that was embedded within the lumen of the carotid artery. This extrinsic material served as a nidus for an inflammatory reaction involving the vagus nerve.


Subject(s)
Carotid Arteries/surgery , Foreign-Body Reaction/veterinary , Horner Syndrome/veterinary , Iatrogenic Disease/veterinary , Swine Diseases/etiology , Animals , Aorta/surgery , Carotid Arteries/pathology , Female , Horner Syndrome/etiology , Stents , Swine , Swine Diseases/pathology , Vagus Nerve/pathology
11.
Urol Res ; 29(5): 345-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11762797

ABSTRACT

This study characterized the VX2 bladder cancer model in rabbits and tested the feasibility of treating bladder cancer by extravesical cryosurgery. After the growth characteristics of the VX2 bladder tumor model were determined, the VX2 tumor was inoculated into rabbits at the dome of the bladder. One week later, three freeze/thaw cycles were followed by immediate surgical repair. The control group underwent a sham operation without freezing. When the VX2 tumor is injected into the bladder wall, invasion and central necrosis occurred within I week, lymphatic metastases by 2 weeks, and lung metastases by 3 weeks after inoculation. By 4 weeks, all control rabbits had large VX2 tumors in their bladders and advanced lung metastases. Nine of the ten rabbits in the cryosurgical group had mild to moderate degrees of lung metastases, and six of them had relatively small local recurrences. One rabbit had no tumor in the bladder and only microscopic lung metastasis. The extravesical approach to cryosurgery employing bladder inversion is well tolerated. Cryosurgery exhibits modest efficacy in treating local tumors and delaying lung metastasis in this aggressive tumor model.


Subject(s)
Carcinoma, Squamous Cell/surgery , Cryosurgery , Urinary Bladder Neoplasms/surgery , Urologic Surgical Procedures , Animals , Carcinoma, Squamous Cell/pathology , Cryosurgery/standards , Rabbits , Urinary Bladder/surgery , Urinary Bladder Neoplasms/pathology
13.
Urology ; 56(1): 155-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10869658

ABSTRACT

OBJECTIVES: To evaluate the biosafety and in vivo biodistribution of intravesical instillation of an adenovirus that contains human p53 gene. Mutations of p53, which are found in as many as 40% of transitional cell carcinomas, are associated with a poor prognosis and resistance to chemotherapy and radiation therapy. Restoration of wild-type p53 status by means of adenoviral-mediated therapy may enhance apoptosis and improve the response to therapy, but the issues of biosafety and toxicity have not yet been addressed. METHODS: Adenovirus-p53 (1 x 10(8), 1 x 10(9), and 5 x 10(9) pfu/mL) and luciferase reporter gene (5 x 10(9)) were instilled into the bladders of anesthetized female BALB/c mice. The mice were killed on days 1, 3, 6, and 13, and representative samples of the bladder, ureter, kidney, adrenal gland, ovary, liver, heart, and lung were removed for histologic evaluation. RESULTS: No histologic signs of toxicity were found. The hematologic and biochemical profiles of the mice were normal, with the exception of a transient elevation in liver function tests on day 1 in the three treatment groups. CONCLUSIONS: Intravesical instillation of adenovirus-p53 was well tolerated; the bladder urothelium appeared to prevent systemic dissemination. The results of these experiments support the safety of intravesical gene transfer by intravesical instillation.


Subject(s)
Adenoviridae , Genes, p53 , Genetic Therapy/methods , Adenoviridae/enzymology , Adenoviridae/isolation & purification , Administration, Intravesical , Animals , Female , Genetic Therapy/adverse effects , Humans , Luciferases/metabolism , Mice , Mice, Inbred BALB C/blood
14.
Ultrason Imaging ; 21(3): 201-15, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10604801

ABSTRACT

Elastography has been shown to be successful in mapping the relative mechanical attributes of normal as well as abnormal tissues. In this study, the histological characteristics of freshly excised normal canine prostates were used to explain consistently depicted elastographic features. The elastograms of the transverse cross-sections across the urethra demonstrated a consistent symmetry of the gland as well as clear anatomic structures. These include a central portion of the gland surrounding the urethra and a peripheral gland. The central gland was consistently softer than the peripheral gland. At the level of the verumontanum, depicted as a small stiff ridge, the lumen of the urethra was consistently demonstrated as an inverted soft 'u' or 'v' shaped area. The network of branching-fibrous connective tissue septa was depicted by the elastogram as linear features, which converged on the urethra. In the anterior side of the gland, the fibromuscular stroma was seen as a circumscribed hard tissue. In the sagittal view, the elastogram suggested a stiff peripheral zone surrounding a softer central zone, which is traversed by the urethra depicted as soft tissue.


Subject(s)
Prostate/diagnostic imaging , Prostate/physiology , Animals , Dogs , Elasticity , Image Processing, Computer-Assisted , In Vitro Techniques , Male , Prostate/cytology , Ultrasonography
15.
Ultrasound Med Biol ; 25(7): 1099-113, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10574342

ABSTRACT

The elastographic visualization and evaluation of high-intensity focused ultrasound (HIFU)-induced lesions were investigated. The lesions were induced in vitro in freshly excised canine livers. The use of different treatment intensity levels and exposure times resulted in lesions of different sizes. Each lesion was clearly depicted by the corresponding elastogram as being an area harder than the background. The strain contrast of the lesion/background was found to be dependent on the level of energy deposition. A lesion/background strain contrast between -2.5 dB and -3.5 dB was found to completely define the entire zone of tissue damage. The area of tissue damage was automatically estimated from the elastograms by evaluating the number of pixels enclosed inside the isointensity contour lines corresponding to a strain contrast of -2.5, -3 and -3.5 dB. The area of the lesion was measured from a tissue photograph obtained at approximately the same plane where elastographic data were collected. The estimated lesion areas ranged between approximately 10 mm2 and 110 mm2. A high correlation between the damaged areas as depicted by the elastograms and the corresponding areas as measured from the gross pathology photographs was found (r2 = 0.93, p value < 0.0004, n = 16). This statistically significant high correlation demonstrates that elastography has the potential to become a reliable and accurate modality for HIFU therapy monitoring.


Subject(s)
Hyperthermia, Induced/instrumentation , Liver/pathology , Ultrasonic Therapy/instrumentation , Animals , Dogs , Elasticity , Equipment Design , Magnetic Resonance Imaging/instrumentation , Transducers
16.
J Vasc Interv Radiol ; 10(9): 1207-18, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10527198

ABSTRACT

PURPOSE: Studies were conducted in rabbits to evaluate two new liquid polymeric compounds developed for selective arterial embolization. MATERIALS AND METHODS: The compounds consisted of cellulose acetate NF (Embolyx C) or ethylene-vinyl alcohol copolymer (Embolyx E) dissolved in anhydrous dimethyl sulfoxide (DMSO) containing 30% tantalum powder. Acute renal embolization was performed to determine an optimal method of administration and level of embolization. Kidneys were embolized with and without flow around the catheter. DMSO was also injected in the same manner. Tissue sections were examined radiographically and microscopically. Tumor embolization was performed to evaluate the efficacy of the polymers and compare their embolic effects with polyvinyl alcohol (PVA) particles and gelatin sponge (Gelfoam) powder. An embolic agent, saline, or DMSO was injected into the deep femoral artery feeding an intramuscular VX2 carcinoma. Animals were followed up for 3 weeks. RESULTS: Viscosity and administration technique affected polymer distribution and depth of penetration. Embolization with the test polymers was quicker and more easily achieved than with PVA or Gelfoam, and no recanalization occurred. Both polymers were as effective as PVA particles for tumor ablation, but DMSO caused some vascular damage. CONCLUSION: Although use of DMSO has some drawbacks, the results of this study warrant further investigation of the Embolyx polymers for tumor embolization.


Subject(s)
Biocompatible Materials/chemistry , Cellulose/analogs & derivatives , Embolization, Therapeutic/instrumentation , Polyvinyls/chemistry , Angiography , Animals , Cellulose/chemistry , Dimethyl Sulfoxide/chemistry , Evaluation Studies as Topic , Gelatin Sponge, Absorbable/chemistry , Hemostatics/chemistry , Kidney/blood supply , Kidney/diagnostic imaging , Materials Testing , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/therapy , Polyvinyl Alcohol/chemistry , Rabbits , Solvents/chemistry
17.
Strahlenther Onkol ; 175(9): 437-43, 1999 Sep.
Article in German | MEDLINE | ID: mdl-10518977

ABSTRACT

BACKGROUND: Radiosensitivity of the spinal cord makes both curative first-line treatment of numerous malignancies and re-irradiation of recurrent or second tumors more difficult. This review discusses recent advances in basic research that alter the view on the pathogenesis of radiation myelopathy, possibly offering strategies for prevention and/or therapy. RESULTS: Available data of developmental neurobiology and preclinical studies of demyelinating diseases revealed interesting insights into oligodendrocyte development, intercellular signaling pathways, and myelination processes. Current findings suggest that administration of cytokines could increase proliferation of oligodendrocyte progenitor cells, enhance their differentiation, upregulate synthesis of myelin constituents, and promote myelin regeneration in the adult central nervous system (Table 1). Other compounds might also be able to modulate progression of pathogenic processes that eventually lead to radiation myelopathy. This offers several possible biological prevention and/or treatment strategies, which currently are being investigated in animal studies (Table 2). CONCLUSION: Technical options as well as optimization of fractionation parameters should be given priority in the attempt to reduce iatrogenic neurotoxicity. However, rational biological strategies could offer a new perspective for many patients.


Subject(s)
Radiation Injuries/therapy , Spinal Cord/radiation effects , Adult , Animals , Cytokines/therapeutic use , Humans , Nerve Regeneration/drug effects , Nerve Regeneration/radiation effects , Oligodendroglia/drug effects , Oligodendroglia/radiation effects , Prognosis , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Radiation Tolerance
18.
Radiat Oncol Investig ; 7(4): 193-203, 1999.
Article in English | MEDLINE | ID: mdl-10492160

ABSTRACT

This article discusses recent advances in basic research that alter the view of the pathogenesis of radiation myelopathy and summarizes the available data from developmental neurobiology and preclinical studies on demyelinating diseases. These studies have produced interesting insights into oligodendrocyte development, intercellular signaling pathways, and myelination processes. Current findings suggest that administration of cytokines as platelet-derived growth factor and basic fibroblast growth factor could increase proliferation of oligodendrocyte progenitors, enhance their differentiation, up-regulate synthesis of myelin constituents, and promote myelin regeneration in the adult central nervous system (CNS). Other compounds might also be able to modulate the progression of pathogenic processes that lead to myelopathy. In addition, several possible biological prevention or treatment strategies, for example stimulation of endogenous cellular regeneration and glial cell transplantation, are discussed. Rationally designed animal experiments pursuing such strategies could further elucidate the pathogenesis of radiation-induced CNS damage.


Subject(s)
Demyelinating Diseases/etiology , Radiation Injuries/etiology , Radiotherapy/adverse effects , Spinal Cord Diseases/etiology , Spinal Cord/radiation effects , Animals , Cell Differentiation , Cytokines/therapeutic use , Demyelinating Diseases/drug therapy , Demyelinating Diseases/metabolism , Humans , Myelin Sheath/metabolism , Radiation Injuries/drug therapy , Radiation Injuries/metabolism , Spinal Cord Diseases/drug therapy , Spinal Cord Diseases/metabolism
19.
Gene Ther ; 6(3): 393-402, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10435089

ABSTRACT

A recombinant adenovirus with deleted E1 and E3, and E4-inactivated by replacing the E4 promoter with a synthetic promoter composed of a minimal TATA box and five consensus yeast GAL4-binding site elements was developed and used to express the human tumor suppresser gene p53. The toxicity and immunogenicity of this vector and vector-mediated p53 gene expression in vivo were studied in immunocompetent C3H and C57BL/6 mice. Expression of the late viral gene product, hexon protein, was observed in C3H and C57BL/6 mice injected with E4 wild-type adenovirus constructs Adv-cmv-beta-Gal (BG), Adv-cmv-hp53 (WT), and empty E1- vector Adv-E4 (EW) 3 to 28 days after injection, but was undetectable in mice treated with E4 modified empty E1- vector Adv-GAL4 (EG) or Adv-cmv-hp53-GAL4 (G4). Expression of the p53 gene was observed in both WT- and G4-injected C3H and C57BL/6 mouse livers from days 3 to 28. Ten weeks after injection, p53 gene expression was still detected in G4-treated C57BL/6 mice at similar levels, but was not detectable in WT-treated mice. Vector-induced liver toxicity was evaluated by analyzing serum transaminases (SGOT and SGPT) activities. In all cases, SGOT and SGPT activities were markedly decreased in EG-treated C3H and C57BL/6 mice compared with those in EW-treated mice on days 3, 7 and 14 after injection. In C57BL/6 mice, the total anti-adenoviral CTL activities were two- to three-fold higher in animals treated with EW vector than in those treated with EG vector. These results suggest that inactivation of the E4 promoter efficiently diminished the viral replication and the late viral gene expression, reduced host immune response and consequently reduced toxicity and prolonged the duration of transgene expression in vivo.


Subject(s)
Adenoviridae/genetics , Adenovirus Early Proteins/genetics , Capsid Proteins , Genes, p53 , Genetic Vectors/administration & dosage , Adenoviridae/immunology , Adenovirus E1 Proteins/genetics , Adenovirus E2 Proteins/genetics , Adenovirus E3 Proteins/genetics , Adenovirus E4 Proteins/genetics , Animals , Capsid/genetics , Gene Deletion , Gene Expression , Genetic Vectors/toxicity , Humans , Liver/metabolism , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Promoter Regions, Genetic/genetics , T-Lymphocytes, Cytotoxic/immunology
20.
J Med Primatol ; 28(2): 67-72, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10431696

ABSTRACT

In this study, the normal distribution of renal weight and volume was determined and the correlation between the weight and volume and various skeletal measurements taken from radiographs and at necropsy was assessed. Values from 136 female monkeys with complete data (including all bone, radiographic, and kidney measurements) were analyzed. The mean kidney weight was 13 g with a standard deviation (SD) of 2 g. The mean kidney volume was 12 ml, SD 2 ml. The estimation of kidney weight and volume from bone length, age, or body weight was not reliable according to statistical analysis of our data. We did find that all apparently normal adult female rhesus monkeys typically have similar sized kidneys. This information is useful in that it reduces concerns about consistency in experimental subjects.


Subject(s)
Kidney/anatomy & histology , Macaca mulatta/anatomy & histology , Animals , Body Weight , Clavicle/diagnostic imaging , Female , Humerus/diagnostic imaging , Kidney/physiology , Organ Size , Radiography , Reference Values , Skull/diagnostic imaging
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