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Biomedical subjects

B C Wilson

Publications and source records attributed to B C Wilson.

At least 55 records · Page 3Linked to original sources

Magnetic resonance imaging of temperature changes during interstitial microwave heating: a phantom study.

Changes in magnetic resonance (MR) signals during interstitial microwave heating are reported, and correlated with simultaneously acquired temperature readings from three fiber-optic probes implanted in a polyacrylamide gel phantom. The heating by a MR-compatible microwave antenna did not interfere with simultaneous MR image data acquisition. MR phase-difference images were obtained using a fast two-dimensional-gradient echo sequence. From these images the temperature-sensitive resonant frequency of the 1H nuclei was found to decrease approximately by 0.008 ppm/ degree C. The method and results presented here demonstrate that noninvasive MR-temperature imaging can be performed simultaneously with interstitial microwave thermal treatment.

Biophysical Phenomena↗

Reduced response of the hypothalamo-pituitary-adrenal axis to alpha1-agonist stimulation during lactation.

To determine whether altered noradrenergic activation of the hypothalamo-pituitary-adrenal (HPA) axis contributes to the attenuated neuroendocrine response to stress observed during lactation, the effect of intracerebroventricular injection of the alpha1-agonist methoxamine (100 microg) was compared between virgin and lactating rats. Virgin rats showed significant increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml at 10 min and remaining significantly elevated for more than 120 min, but lactating rats showed no significant increase in corticosterone levels. Furthermore, methoxamine induced an increase in paraventricular nucleus (PVN) CRF messenger RNA expression in virgin, but not lactating, animals. Both groups of rats exhibited comparable elevations in plasma PRL after methoxamine treatment. Arginine vasopressin messenger RNA expression within the parvocellular PVN was greater in the lactating animals than in the virgin controls, but methoxamine injection was without further effect. Studies performed on ovariectomized virgin rats and ovariectomized rats receiving estradiol or progesterone replacement failed to reproduce the attenuated HPA responses seen after methoxamine treatment, although methoxamine-induced PRL levels were greatly increased by estradiol, probably arising from an effect on hormone synthesis. In vitro electrophysiological recordings of PVN neurons in hypothalamic slices from proestrous virgin and lactating rats showed that 45-52% of neurons in both groups exhibited excitatory responses to 10(-4) M methoxamine, but there was a differential response to 10(-5) M methoxamine, with PVN neurons from lactating animals failing to show a response. These data show a selective down-regulation of alpha1-mediated activation of the HPA axis in lactating animals. This may contribute to the attenuated stress-induced activation of the HPA axis during lactation.

Adrenergic alpha-Agonists↗

Changes in in vivo optical properties and light distributions in normal canine prostate during photodynamic therapy.

The optical absorption and transport scattering coefficients of normal prostate tissue have been measured in vivo in dogs. The measurements were made at 630 nm before and during treatment by Photofin photodynamic therapy using interstitial optical fiber fluence-rate detectors. Corresponding measurements were made ex vivo, at 1 week after treatment, in the contralateral lobe. The optical properties were derived by applying a diffusion theory model to the fluence rates measured at two different source-detector fiber distances. While the in vivo pretreatment and in vivo contralateral post-treatment absorption and scattering values are self-consistent and in agreement with published data, significant changes were observed in the light fluence rates, and hence in the derived optical properties, during light irradiation. The possible causes of such changes are considered, and the implications for light dosimetry in photodynamic therapy are discussed.

Animals↗

The effects of the HIV-1 envelope protein gp120 on the production of nitric oxide and proinflammatory cytokines in mixed glial cell cultures.

Although the neurotoxicity induced by the HIV envelope protein, gp120, has been demonstrated to require the presence of glial cells (microglia/astrocytes), the mechanisms for the gp120-induced neurotoxicity are not well understood. Moreover, the neurotoxic potencies of gp120s obtained from various HIV isolates are different. Since nitric oxide (NO) and proinflammatory cytokines (TNF-alpha, IL-1, IL-6) produced by glial cells have been involved in the neuropathogenesis of various diseases, this study examined the effects of gp120 obtained from two strains, HIV-1IIIB and HIV-1SF2, of the HIV-1 virus on the production of NO, TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 in murine primary mixed glial cell cultures. The glial cells exposed to HIV-1IIIB gp120 released NO, TNF-alpha, and IL-6 in a dose-dependent manner, whereas IL-1 alpha and IL-1 beta were undetectable. The cells exposed to HIV-1SF2 gp120 increased the release of IL-6 only. The gp120-induced effects were significantly enhanced by priming glial cells with IFN-gamma. To investigate the cellular sources and mechanisms of the gp120-induced IL-6 production, in situ hybridization with mRNA for IL-6 was performed in HIV-1IIIB gp120- or HIV-1SF2 gp120-stimulated microgliaenriched or astrocyte-enriched cultures. HIV-1IIIB gp120 or HIV-1SF2 gp120 induced the expression of IL-6 mRNA in both microglia-enriched and astrocyte-enriched cultures, indicating that both microglia and astrocytes produce IL-6, and that the transcriptional regulation is involved in the gp120-induced IL-6 production. Taken together, these results demonstrate that the production of NO, TNF-alpha, IL-1, or IL-6 from glial cells is differentially regulated by HIV-1IIIB gp120 and HIV-1SF2 gp120. These results may provide insights into the roles of NO and proinflammatory cytokines in the neurotoxicity of gp120s and the neuropathology of different strains of HIV-1 viruses.

Animals↗

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation.

Aminolevulinic Acid↗

Photodynamic therapy for malignant newly diagnosed supratentorial gliomas.

We report the use of photodynamic therapy (PDT) in the treatment of 20 patients with newly diagnosed malignant supratentorial gliomas. There were 10 males and 10 females; their mean age was 56 years and the mean Karnofsky score was 75. Eleven patients had glioblastoma multiforme (GBM) and 9 had malignant astrocytoma (MA). Intravenous porphyrin photosensitizer was administered 12-36 h prior to surgery and photoillumination. At operation all patients had the tumor subtotally resected followed by intraoperative cavitary photoillumination. Interstitial photoillumination using fibers with 2-cm diffusing tips supplemented the cavitary illumination in 3 patients. The total light energy delivered ranged from 570 to 4050 J (median = 1260 J). The energy density ranged from 15 to 110 J/cm2 (median = 32 J/cm2). All but two had postoperative radiation therapy (5000 cGy in 5 weeks). No untoward effects of radiation in conjunction with PDT were identified. There was 1 postoperative death and 1 patient had a persistent increase in postoperative neurological deficit. The median survival of these 20 patients with newly diagnosed malignant gliomas was 44 weeks with a 1- and 2-year survival of 40 and 15%, respectively. The median survival of these patients with newly diagnosed GBM was 37 weeks with a 1- and 2-year survival of 35 and 0%, respectively, and the median survival for MA was 48 weeks with a 1- and 2-year survival of 44 and 33%, respectively. Six patients with a Karnofsky score of > 70 who received a light dose of > 1260 J (mean energy density = 62 +/- 20 SEM J/cm2) had a median survival of 92 weeks with a 1- and 2-year survival of 83 and 33% respectively. Patients with malignant astrocytic tumors (GBM and MA) have a very poor prognosis. Nevertheless PDT is safe in newly diagnosed patients with supratentorial malignant gliomas who undergo postoperative radiation and appears to prolong survival in selected patients when an adequate light dose is used. Further improvement in survival may be expected with higher light doses.

Adult↗

Changing effect of i.c.v. IL-1 beta on vasopressin release in anaesthetized, female rats at different stages of lactation: role of prostaglandins and noradrenaline.

Interleukin-1 beta stimulates oxytocin and vasopressin release in conscious, male rats and causes a rise in blood pressure. These experiments were done to : A) examine the effect of i.c.v. interleukin-1 beta (1 ng/microliter) on circulating levels of vasopressin in female rats at different stages of lactation and B) determine if alpha-adrenergic mechanisms and/or prostaglandins were involved as mediators. Urethane-anaesthetized nonlactating rats and rats at Day 7, 10, 20 and 26 of lactation were set up for arterial blood sampling and i.c.v. injections. One mL blood samples were obtained in one min periods before, and at 1, 2.5, 5, 10, 30, 60 and 120 min after the following treatments: i.c.v. treatment with either interleukin-1 beta (1 ng in 1 microliter PBS-BSA) or PBS-BSA (1 microliter) as a vehicle control; or i.c.v. treatment with interleukin-1 beta following pretreatment with either phentolamine (1.7 micrograms/microliter i.c.v.) or indomethacin (1 microgram/microliter i.c.v.). As blood was sampled, isotonic saline was infused (1 mL per min) and blood pressure was monitored to minimize any hypovolemic effects due to sampling. Extracted plasma was assayed using a specific vasopressin radioimmunoassay. Interleukin-1 beta i.c.v. stimulated the release of vasopressin above that elicited by PBS-BSA alone in non-lactating rats resulting in an approximate 1.2 to 2-fold increase in plasma hormone levels. Throughout the first half of lactation, vasopressin responsiveness to i.c.v. interleukin-1 beta treatment was markedly attenuated. In latter stages of lactation, the response recovered and resembled that of non-lactators around the time of weaning. Prostaglandins consistently mediate a stimulatory action of interleukin-1 beta on vasopressin release whereas alpha-adrenergic mechanisms mediate a depression of interleukin-1 beta-induced vasopressin release during the early to middle stages of lactation. It is possible that the depression in interleukin-1 beta-stimulation of vasopressin release in early to mid-lactation is conducive for nursing to occur and that the increase in vasopressin responsiveness towards the latter stages of lactation represents a component of the weaning process.

Anesthesia↗

The effects of ex vivo handling procedures on the near-infrared Raman spectra of normal mammalian tissues.

Recent studies in the literature have investigated the feasibility of tissue diagnostics based on Raman spectroscopy. The majority of these compare the ex vivo spectra of normal and diseased tissue. Due to the time lapse between tissue excision and spectroscopic examination, samples must be frozen or otherwise preserved to maintain their native biochemical states. In order to establish optimum procedures for ex vivo Raman spectroscopy of tissue, the effects of tissue drying, formalin fixing, snap freezing, tissue freezing in optimal cutting temperature (OCT) medium and extended post-thaw durations were studied to determine if any of these handling procedures introduced spectral artifacts. Experiments on representative tissues indicated that tissue heating due to the excitation light did not change the spectra significantly. With minor exceptions, OCT and formalin did not contaminate tissue spectra, so that samples stored for histological examination could also be studied with Raman spectroscopy. Tissue dehydration caused disruption of the protein vibrational modes, which caused spectral artifacts. It is concluded that ex vivo tissue samples should be frozen in OCT. Prior to spectral analysis, the tissue should then be acclimatized at room temperature in phosphate-buffered saline (PBS) and immersed in PBS during spectroscopic examination.

Adipose Tissue↗

Investigations of large vessel cooling during interstitial laser heating.

Interstitial laser heating of tissues is influenced by blood flow in the treatment region. Temperature gradients around large blood vessels may result in local underheating of tissues. A three-dimensional, time-dependent finite difference model of interstitial laser heating around large vessels is presented. A thermal conduction model was developed using a transport theory approximation for the energy distribution from an optical line source. Calculated transient temperature profiles and temperature reductions around 0.144 and 0.400 cm diam vessels show qualitative agreement with those measured in a series of tissue phantom studies. Experiments and calculations for a large vessel located approximately 1.0 cm from the optical source indicate that temperature reductions are less than 1 degree C at distances greater than approximately 1.0 cm from the vessel surface. The model also indicates that significant reductions in the extent of a thermal coagulation boundary can occur if a large vessel is situated inside the normal coagulation zone.

Blood Vessels↗

Long-term stimulation of nicotinic receptors is required to increase proenkephalin A mRNA levels and the delayed secretion of [Met5]-enkephalin in bovine adrenal medullary chromaffin cells.

The effects of nicotine on the transcriptional activity of the proENK gene, proenkephalin A (proENK) mRNA levels, and the secretion of [Met5]-enkephalin (ME) were studied in bovine adrenal medullary chromaffin (BAMC) cells. Nicotine (10 microM) caused an immediate secretion (within 1 hr) of ME followed by a delayed secretion (12-24 hr after treatment) into the medium. Posttreatment with the cholinergic antagonists, hexamethonium (1 mM) and atropine (1 microM), up to 6 hr after the nicotine treatment significantly inhibited the delayed secretion of ME induced by nicotine. However, nicotine-induced long-term secretion of ME was not affected when cholinergic antagonists were added 9 or 12 hr after the nicotine treatment. Long-term (24 hr) stimulation of BAMC cells with nicotine also increased proENK mRNA level. This nicotine-induced response was inhibited by posttreatment with cholinergic antagonists 0.5, 1, 3 and 6 hr after the nicotine treatment. As with the secretion experiments, these cholinergic antagonists did not affect the nicotine-induced responses when they were added at 9 and 12 hr. Posttreatment with nimodipine (1 microM), calmidazolium (1 microM) or KN-62 (5 microM) up to 6 hr after the nicotine treatment significantly inhibited the increases of the long-term secretion of ME and proENK mRNA level induced by nicotine. However, these agents were ineffective in blocking the long-term secretion of ME and proENK mRNA level induced by nicotine when BAMC cells were posttreated after 9 and 12 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Cross-resistance to cisplatin in cells resistant to photofrin-mediated photodynamic therapy.

This study shows that a Photofrin-induced photodynamic therapy-resistant variant (RIF-8A) of a radiation-induced fibrosarcoma-1 cell line (RIF-1) is cross-resistant to cis-diamminedichloroplatinum(II) (cisplatin). This is the first study to show cross-resistance to cisplatin in photodynamic therapy-resistant variants in vitro. Resistance does not appear to be the result of elevated glutathione levels since neither the resistant variant (RIF-8A) nor the parental line (RIF-1) varied in total glutathione levels. However, cisplatin-DNA adduct levels differed significantly between the two cell types. Immediately following a 1-h exposure to cisplatin (50 microM), RIF-1 cells contained 44.6 +/- 2.0 (SEM) pg platinum/micrograms DNA while RIF-8A cells contained 24.8 +/- 6.3 pg platinum/micrograms DNA. In addition, the resistant variant had decreased plasma and mitochondrial membrane potentials. The plasma and mitochondrial membranes of the resistant variant accumulated 3- and 3.6-fold less rhodamine 123, respectively. The difference in rhodamine 123 accumulation could not be attributed to elevated P-glycoprotein expression because both the parental line and the variant contained similar amounts of P-glycoprotein. In conclusion, alterations in the plasma and/or mitochondrial membrane potentials may provide cells with a survival advantage when challenged with either photodynamic therapy or cisplatin in vitro. This appears to be a novel mechanism of resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Pulsed photothermal radiometry in optically transparent media containing discrete optical absorbers.

A description of heat transport by conduction and radiation in inhomogeneous materials following absorption of a brief optical pulse is presented, and investigated experimentally using pulsed photothermal radiometry (PPTR). The model indicates that the role of radiation as an intramedium heat transfer modality increases with increasing temperatures and decreasing infrared (IR) absorption of the medium. However, for the range of conditions analysed in this study, conductive transfer dominates. Thus, the inclusion of radiation does not significantly perturb the internal temperature profiles, although it does influence the radiometric emission from the sample, and hence the PPTR signal. The thermal confinement effects described in this study may be relevant in photomedicine, for example in pulsed laser irradiation of tissues containing small absorbing targets.

Algorithms↗

Hepatic interstitial laser photocoagulation. An investigation of the relationship between acute thermal lesions and their sonographic images.

OBJECTIVES: The relationship between hepatic interstitial laser photocoagulation (ILP) lesions and their acute ultrasound images was evaluated. In addition, the natural history of ILP lesions in normal pig liver was documented. METHODS: Eighteen pigs underwent laparotomy and ultrasound-monitored ILP. In part 1 of the study, 12 pigs each had four separate exposures (1.50 W for 60, 100, 300, and 500 seconds) and were divided into four groups according to when they were killed (0, 3, 7, and 21 days). In part 2 of the study, six pigs each had two sequential exposures (1.60 W for 1,000 and then 500 seconds) at separate hepatic sites. Survival time was 3 days. Necropsy and histologic examination were performed in all animals. In 0- and 3-day survivors, actual thermal lesions were compared with "early" (immediately after ILP) and "late" (1 hour after ILP) ultrasound images. RESULTS: In the 300-, 500-, and 1,000-second exposures of parts 1 and 2, thermal lesions were overestimated or approximated by early ultrasound and were underestimated or approximated by late ultrasound. Analysis of variance showed statistically significant differences between thermal lesions and their early and late ultrasound images (F = 18.6, P < .001, no interactions). Time-growth characteristics of ILP lesions were reasonably consistent on ultrasound; exceptions were identifiable 200 seconds into the exposure. In part 2, ultrasound changes were minimal in five of six 500-second (second sequential) technically satisfactory exposures. Thermal lesions were seen at necropsy. All lesions healed by formation of granulation tissue and collagen. CONCLUSIONS: During ILP, early ultrasound images frequently overestimate actual thermal lesions. Ultrasound-monitored ILP of tumors may be most effective if, on early ultrasound, echogenic changes extend beyond the tumor margins. Late ultrasound images underestimate or approximate thermal lesions. Their value in clinical ILP should be investigated. It is unclear why ultrasound images of proven thermal lesions were not seen during 5 of 6 otherwise satisfactory 500-second ILP exposures performed immediately after 1,000-second exposures.

Animals↗

Optical and thermal characterization of natural (Sepia officinalis) melanin.

The optical properties and the thermal diffusivity of natural cuttlefish (Sepia officinalis) melanin have been measured. The optical absorption and scattering properties of melanin particles were determined at 580 nm and 633 nm, using photometric and photothermal techniques. For the photometric studies, the absorption and the transport scattering coefficients were determined from the measurements of diffuse reflectance and transmittance. The scattering anisotropy was obtained from an additional measurement of the total attenuation coefficient and independently obtained by goniometry. For photothermal studies, pulsed photothermal radiometry was used to deduce the absorption and transport scattering coefficients via a model based on optical diffusion theory. Pulsed photothermal radiometry was also used to provide the thermal diffusivity of solid melanin pressed pellets.

Animals↗

Hepatic interstitial laser photocoagulation: demonstration and possible clinical importance of intravascular gas.

PURPOSE: To investigate gas formation during hepatic interstitial laser photocoagulation (ILP). MATERIALS AND METHODS: In vitro, ILP was performed with a neodymium yttrium aluminum garnet laser on a piece of liver in a water bath. In vivo, nine pigs underwent 24 ultrasound (US)-monitored ILP procedures. Fiber tips were more than 1 cm from (n = 16) or adjacent to (n = 8) intrahepatic veins. The gas production seen on US images was graded on a scale of 0 to 4. Precordial Doppler US was performed in all cases. RESULTS: In vitro, smoke bubbles emanated from the vessels during ILP. In vivo, US showed intravascular gas production during nine of 15 exposures of at least 500 seconds duration. Gas production scores of 2 or more were recorded for nine exposures. Intracardiac gas was identified on eight precordial Doppler US recordings. All animals survived. CONCLUSION: Gas was detected in the heart during some ILP exposures. Patients with a probe-patent foramen ovale (24% prevalence) could be at risk for paradoxic air embolus during ILP.

Animals↗

Role of the subfornical organ in the relaxin-induced prolongation of gestation in the rat.

The role of the subfornical organ in the timing of birth in the rat was investigated. Animals with radiofrequency lesions of the subfornical organ made on day 12 of pregnancy gave birth significantly earlier (P < 0.05) than intact and control-lesioned rats. Animals with lesions made on day 19 of pregnancy gave birth within control times. In addition, the natural fall in plasma relaxin observed at the end of gestation in rats was prevented by i.v. infusion of porcine relaxin (4.2 micrograms/h for 5 days from day 19 of gestation), which maintained plasma relaxin levels at approximately 100 ng/ml. This rate of infusion was selected because the resultant circulating levels of relaxin reflect plasma concentrations observed on day 20 of pregnancy in rats. The effect of lesion of the subfornical organ was then studied on the timing of birth in relaxin-infused rats. Intact animals and rats with control lesions receiving an infusion of relaxin had significantly (P < 0.05) prolonged pregnancies compared with intact saline-infused controls. However, the timing of birth of rats with lesions of the subfornical organ receiving an infusion of relaxin was not significantly (P > 0.05) different from that in intact saline-infused controls. The results support the hypothesis that the subfornical organ appears to mediate the central effects of relaxin and may have a natural role in the events that lead to delivery in the rat.

Animals↗