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Biomedical subjects

William Jackson

Publications and source records attributed to William Jackson.

7 recordsLinked to original sources

Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition.

Our laboratory has demonstrated in the previous studies that dietary energy restriction (DER) inhibited the promotion of skin tumorigenesis and others have found that adrenalectomy may reverse that inhibition. The purpose of the research reported here was to determine if circulating corticosterone (CCS) may be the adrenal hormone responsible for DER prevention of skin carcinogenesis. Female SENCAR mice were initiated with 7,12-dimethylbenzanthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) in either sham-operated or adrenalectomized (ADX) mice fed ad libitum (AL) or energy restricted diets. DER was 60% of the AL calorie intake with the removal of energy from fat and carbohydrate. CCS, the main glucocorticoid hormone secreted by the murine adrenal gland, was added to the drinking water of AL/ADX and DER/ADX groups to determine the role of CCS in the DER inhibition of tumor development. In sham-operated groups, DER compared with AL-fed mice experienced significantly decreased papilloma incidence and multiplicity (P < 0.0001). ADX did not alter papilloma incidence or multiplicity in AL-fed mice but ADX partially reversed the inhibition of papilloma multiplicity and incidence in DER mice. CCS supplementation to both DER/ADX and AL/ADX mice resulted in reduced papilloma incidence and multiplicity. In DER/ADX mice, CCS dramatically reduced papilloma rates while in AL/ADX mice CCS reduced the papilloma rates to those seen in the DER sham group. DER significantly reduced carcinoma multiplicity mean counts per effective animal (P < 0.0001) compared with AL-fed groups in sham and ADX/CCS groups. DER/ADX mice lost the carcinoma multiplicity protection seen in sham/DER mice. CCS treatment of ADX mice significantly decreased total carcinoma (in situ and invasive) incidence rates per effective animal (P < 0.0003). ADX followed by CCS treatment in the DER mice resulted in the lowest carcinoma incidence and multiplicity. Thus, DER-inhibition of skin tumorigenesis was mediated at least in part through CCS. However, CCS was more effective in preventing papillomas and carcinomas in DER/ADX mice than in AL/ADX mice, suggesting that other factors may also be involved in the DER prevention of tumor formation.

Adrenal Glands↗

Defining the full therapeutic potential of recombinant growth factors in the post radiation-accident environment: the effect of supportive care plus administration of G-CSF.

Radiation accidents are uncontrolled and ill-defined, the exposure is nonuniform and may be partial body, forecasting a variable dose distribution and sparing of hematopoietic stem cells. We propose that the "best" treatment protocol available now for severely irradiated personnel with acute hematopoietic syndrome is the combination of supportive care and administration of recombinant cytokines as soon as possible after irradiation. Herein, we demonstrate the significant effect of G-CSF administration on lethally irradiated canines. G-CSF administered early and continuously after irradiation increased neutrophil recovery and survival over a lethal and supralethal dose range. The respective LD50/30 for the control, supportive care-alone cohorts of 338 cGy, was increased to 488 cGy with administration of G-CSF. Clearly, the use of supportive care and G-CSF enhanced recovery of myelopoiesis and survival after lethal doses of irradiation.

Animals↗

Inhibition of LPS-induced nitric oxide production in RAW cells by radioprotective thiols.

Nitric oxide (NO) is involved in producing damage after exposure to radiation and also in the toxicity associated with bacterial endotoxin (lipopolysaccharide, LPS). We have evaluated different radioprotective thiols for their effects on LPS-stimulated NO production in mouse macrophage cells, RAW 264.7. Our results indicate that although thiols inhibited NO production in general, the degree of inhibition depended upon the thiol compound. Long-chain aminothiols like WR-1065 [N-(2-mercaptoethyl)-1,3-diaminopropane] exerted a strong inhibition; but its parent drug, amifostine, which protects mice against radiation lethality, was not as effective as WR-1065. Diethyl dithiocarbamate, which is less effective than amifostine as a radioprotector, strongly inhibited NO production from macrophages. These results indicate that the radioprotective potential of sulfhydryl compounds is not related to its ability to inhibit NO production by macrophages and suggest that some of the thiol radioprotectors may effectively ameliorate the fatal symptoms of hypotensive shock, associated with endotoxin (LPS)-induced NO production.

Acetylcysteine↗

Benefits of early tracheostomy in severely burned children.

OBJECTIVE: The role of tracheostomy in burn patients is controversial. Previous studies, primarily in adults, suggested that severely burned patients with tracheostomies have a higher incidence of tracheostomy site infections, mortality, and pneumonia. The purpose of this study is to determine the safety and efficacy of early tracheostomy in severely burned children. DESIGN: Case series study analyzing mechanical ventilation and sedation requirements before and 24 hrs after tracheostomy. SETTING: Regional pediatric burn center. PATIENTS: All children admitted to a regional pediatric burn center requiring tracheostomy from March 1, 1998, to October 1, 2001. METHODS: Data were recorded on patients' demographics, extent of burn, presence of inhalation injury, and mortality. Mechanical ventilation variables measured pretracheostomy (pre) and posttracheostomy (post) and included mode of ventilation, ventilator settings, peak inspiratory pressures, and arterial blood gases (Pao2, Paco2, pH, and oxygen saturation). Calculated variables included compliance, Pao2:Fio2 ratio, and minute ventilation. Tracheostomy-related variables recorded included the interval to tracheostomy insertion, the duration of tracheostomy, and tracheostomy complications. MAIN RESULTS: A total of 38 patients (with a mean age of 4.7 +/- 0.6 yrs and a mean total body surface area involvement of 54% +/- 4%, 63% with inhalation injury) underwent tracheostomy a mean of 3.9 +/- 0.7 days after admission. Overall mortality was 21%. There were no tracheostomy site infections, tracheostomy-related deaths, or tracheal stenoses in survivors. Peak inspiratory pressures were lower after tracheostomy (30.4 +/- 1.4 [pre] vs. 27.6 +/- 1.5 cm H2O [post]; p <.05), ventilatory volumes were higher (190 +/- 22 mL [pre] vs. 225.5 +/- 25 [post]; p <.05), compliance improved (10.5 +/- 1.4 [pre] vs. 15.1 +/- 2.3 mL/cm H2O [post]; p <.05), and the Pao2:Fio2 ratio improved (300.6 +/- 20 [pre] vs. 348.6 +/- 16 [post]). There was no difference in oxygenation, ventilation, minute ventilation, or pH after tracheostomy. CONCLUSIONS: Early tracheostomy in severely burned children is safe and effective. It provides a secure airway and may result in improvement in ventilator management for these children.

Adolescent↗

A whole body counting facility in a remote Enewetak Island setting.

The U.S. Department of Energy (DOE) has recently implemented a series of strategic initiatives to address long-term radiological surveillance needs at former U.S. test sites in the Marshall Islands. The plan is to engage local atoll communities in developing shared responsibilities for implementing radiation protection programs for resettled and resettling populations. As part of this new initiative, DOE agreed to design and construct a radiological laboratory on Enewetak Island, and help develop the necessary local resources to maintain and operate the facility. This cooperative effort was formalized in August 2000 between the DOE, the Republic of the Marshall Islands (RMI), and the Enewetak/Ujelang Local Atoll Government (EULGOV). The laboratory facility was completed in May 2001. The laboratory incorporates both a permanent whole body counting system to assess internal exposures to 137Cs, and clean living space for people providing 24-h void urine samples. DOE continues to provide on-going technical assistance, training, and data quality review while EULGOV provides manpower and infrastructure development to sustain facility operations on a full-time basis. This paper will detail the special construction, transportation and installation issues in establishing a whole body counting facility in an isolated, harsh environmental setting.

Body Burden↗

New strategies for the prevention of radiation injury: possible implications for countering radiation hazards of long-term space travel.

New strategies for the prevention of radiation injuries are currently being explored with the ultimate aim of developing globally radioprotective, nontoxic pharmacologics. The prophylactic treatments under review encompass such diverse pharmacologic classes as novel immunomodulators, nutritional antioxidants, and cytokines. An immunomodulator that shows promise is 5-androstenediol (AED), a well-tolerated, long-acting androstene steroid with broad-spectrum radioprotective attributes that include not only protection against acute tissue injury, but also reduced susceptibility to infectious agents, as well as reduced rates of neoplastic transformation. Other potentially useful radioprotectants currently under study include the nutraceutical vitamin E and analogs, a chemically-engineered cytokine, interleukin-1beta, and a sustained-release formulation of an aminothiol, amifostine. Results suggest that a new paradigm is evolving for the prophylaxes of radiation injuries, based on use of newly identified, nontoxic, broad-spectrum prophylactic agents whose protective action may be leveraged by subsequent postexposure use of cytokines with organ-specific reparative functions.

Animals↗