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C G Hurst

Publications and source records attributed to C G Hurst.

14 recordsLinked to original sources
PubMed1998

Sensitivity of cross-reacting antihuman antibodies in formalin-fixed porcine skin: including antibodies to proliferation antigens and cytokeratins with specificity in the skin.

Although no animal is a perfect skin model for the study of toxicological and therapeutic agents, structurally the pig may be superior to even non-human primates. Because our work involves effects of toxicological and therapeutic agents on the skin, we wanted to identify stains which may prove useful as well as determine cross-reactivity of some newer antihuman antibodies. We performed a battery of formalin-fixed skin from weanling pigs and minipigs. The battery of antibodies included LCA, CD3, OPD-4, CD34, UCHL-1, L-26, KP-1, MAC-387, Factor XIIIa, Leu-7, S-100 protein, HMB-45, GFAP, synaptophysin, neurofilament protein, ubiquitin, vimentin, type IV collagen, laminin, fibronectin, Factor VIII related antigen, Desmin-M, smooth muscle actin, cytokeratin 7, cytokeratin 20, AEI/AE3, CAM 5.2, EMA, GCDFP, Ki-67, and PCNA. Immunohistochemical stains for CD3, Leu-7, S-100 protein, type IV collagen, laminin, Factor VIII related antigen, GFAP, synaptophysin, neurofilament protein, ubiquitin, smooth muscle actin, vimentin, Desmin-M, cytokeratin 7, cytokeratin 20, AE1/AE3, CAM 5.2, Ki-67 and PCNA showed consistent cross-reactivity. In formalin-fixed tissue, only antibodies to lymphoreticular cells showed poor cross-reactivity. A high percentage of the remaining antibodies did show good cross-reactivity but with some interesting similarities and differences in specificity.

Animals↗
PubMed1997

Depth of morphologic skin damage and viability after one, two, and three passes of a high-energy, short-pulse CO2 laser (Tru-Pulse) in pig skin.

BACKGROUND: CO2 laser energy is absorbed by water, which is present in all tissue. The depth of penetration of CO2 lasers is narrow with minimal reflection, scatter, or transmission. However, thermal damage has limited the usefulness of conventional, continuous-wave CO2 lasers for debridement as demonstrated by wound healing studies. The development of high-energy CO2 lasers, with pulse durations that are less than the thermal relaxation time of tissue, have made vaporization of skin for resurfacing and wound debridement possible because of the decreased risk of thermal damage. OBJECTIVE: This study was performed to evaluate thermal damage produced by a CO2 laser. METHODS: Routine histopathologic examination and nitroblue-tetrazolium chloride (NBTC) staining were used to evaluate the depth of tissue damage and viability in weanling pig skin after one, two, and three passes of the laser. RESULTS: At a pulse energy of 300 mJ, with a pulse duration of 60 microseconds, one pass of the laser produced vaporization of the epidermis with minimal thermal damage. Two passes produced areas of denatured collagen with loss of viable cells in the superficial papillary dermis. Three passes extended the damage into the papillary dermis. CONCLUSION: Hyalinization of collagen appears to correspond well with the level of thermal damage as measured by NBTC staining. Our findings suggest that the energy necessary to vaporize the dermis may be greater than that needed to vaporize epidermis.

Animals↗
PubMed1997

Evaluation of cross-reacting anti-human antibodies in the euthymic hairless guinea pig model (HGP) suggests that the HGP may be a model for the study of proliferative skin disease.

Animal models have an important role in cutaneous research. The guinea pig has proven to be a useful model in a wide spectrum of these cutaneous studies; however, its usefulness is often compromised by the need for depilation. A euthymic hairless guinea pig (HGP) model avoids the problems associated with depilation. Morphologically, as in human skin, these animals have a multi-cell-layer epidermis. Proliferation kinetic studies, as well as documentation of the degree of immunologic cross-reactivity between available antibodies to human cutaneous antigens, could extend the usefulness of this animal model. We performed a battery of anti-human antibodies on formalin fixed tissue, to a variety of antigens present within the skin and on inflammatory cells. These included CD3, UCHL-1, OPD4, L-26, KP-1, Factor XIIIa, S-100 protein, cytokeratin (AE1, AE3 and CK1), CAM 5.2, vimentin, CD 34, Factor VIII, fibronectin, SM actin, collagen IV, laminin, Bcl-2, p53, Ki-67, and PCNA. Cross-reacting antibodies included: CD3, S-100 protein, cytokeratin (AE1, AE3 and CK1), vimentin, Factor VIII, SM actin, collagen IV, p53, Ki-67, and PCNA. Although this battery of antibodies is limited, the markedly increased staining of Ki-67 and PCNA within keratinocytes in the epidermis as compared to normal human skin reflects a high proliferative rate. In addition, positive staining for p53, Ki-67, and PCNA may be useful in studying effects on cell cycle kinetics and apoptosis.

Actins↗
PubMed1997

Immunohistochemical studies of basement membrane proteins and proliferation and apoptosis markers in sulfur mustard induced cutaneous lesions in weanling pigs.

Sulfur mustard (2,2-dichlorodiethyl sulfide, HD) is a chemical warfare agent that is a threat to both troops and civilians. The focus of HD research has been on intracellular adduct formation leading to apoptosis and/or necrosis in cutaneous lesions. However, there is work which suggests that HD may have a more direct effect on the basement membrane zone. Immunohistochemical staining to desmosomal proteins, cellular fibronectin, laminin 1, laminin 5, collagen IV, collagen VII, p53, Bcl-2, and PCNA was performed on weanling pig skin exposed to vesicating doses of HD, GB3, an antibody to laminin 5, showed a progressive decrease with loss of expression during the time period of clinical vesiculation. The other basement membrane proteins showed no change or inconsistent changes. PCNA, and p53 staining increased in the overlying epidermis in areas of vesiculation without significant necrosis. Bcl-2 positive cells were decreased or absent after exposure. This study implicates laminin 5 as the main basement membrane protein affected acutely by HD exposure. The patterns of staining of PCNA, Bcl-2, and p53 within the epidermis suggest that apoptosis and cellular necrosis both may play a role in cell death secondary to HD.

Animals↗
PubMed1997

CO2 laser debridement of sulphur mustard (bis-2-chloroethyl sulphide) induced cutaneous lesions accelerates production of a normal epidermis with elimination of cytological atypia.

Sulphur mustard (bis-2-chloroethyl sulphide; HD) exposure acutely produces lesions that vary from mild erythema, to blister formation, to necrosis. When blisters occur, with or without necrosis, healing of the lesions is delayed. Weanling pigs exposed to a mild erythema-producing dose of HD and to a moderate erythema-producing dose that consistently gave microblister formation were treated with CO2 laser (Tru-Pulse) debridement at 6, 24 or 48 h after exposure. The histopathological features observed at 14 days after exposure in control skin and skin exposed to both HD doses were compared with the features observed in CO2 laser-debrided skin in non-exposed and HD-exposed skin sites. The overlying epidermis in the non-laser treated lesions was thin, with cytological atypia and squamoid changes within the basal cell layer, as well as scattered apoptotic/necrotic keratinocytes. An increased inflammatory infiltrate and necrobiotic changes in the dermis were seen at the higher HD dose. All laser-treated lesions appeared identical, with a thick, differentiated epidermis and a well-formed basal cell layer. There was minimal inflammatory infiltrate. In the papillary dermis there were increased stromal cells. Laser debridement of mild clinical lesions induced by HD produced a more functional epidermis by 14 days as well as clearing the epidermis of damaged keratinocytes.

Animals↗
PubMed1997

Increased smooth muscle actin, factor XIIIa, and vimentin-positive cells in the papillary dermis of carbon dioxide laser-debrided porcine skin.

BACKGROUND: Pulsed carbon dioxide (CO2) laser debridement is now being used as therapy for photodamaged skin. It has been proposed that the long duration of erythema and a tissue scaffold, which results from tightening of the collagen helix induced by the laser heat, may lead to tightening of sagging skin and skin creases of lesser magnitude. METHODS: Weanling pigs exposed to mild and moderate erythema producing doses of sulfur mustard (bis-2-chloroethyl sulfide; HD) were treated with the CO2 laser (Tru-Pulse) at 6, 24, and 48 hours after exposure. In addition to histologic examination of laser-debrided and nondebrided biopsy specimens obtained at 14 days after exposure, immunohistochemical staining with antibodies to smooth muscle actin, Factor XIIIa, vimentin, and CD3 was performed. RESULTS: CO2 laser debridement of the HD-exposed skin resulted in clearing of the cytologic atypia induced by this chemical carcinogen and reduced the inflammatory infiltrate. In addition laser debridement resulted in increased numbers of stromal cells within the papillary dermis, which showed immunohistochemical staining for smooth muscle actin, Factor XIIIa, and vimentin. CONCLUSIONS: CO2 laser debridement is effective in clearing the epidermis of cytologically damage cells in HD as well as solar-damaged skin. In addition CO2 laser debridement may result in tightening of sagging skin and produce a decrease in skin creases initially, by inducing increased stromal cells within the papillary dermis, with prominent contractile actin filaments. The collagen produced by these stromal cells may subsequently maintain these improvements in the photoaged skin.

Actins↗
PubMed1996

Cutaneous histopathologic features in weanling pigs after exposure to three different doses of liquid sulfur mustard.

Sulfur mustard (2,2' dichlorodiethyl sulfide, HD) is a chemical warfare agent that is easily produced, and may be used against civilian populations as well as against military troops. However, good therapeutic and prophylactic measures await a better understanding of the pathophysiology of lesions produced by this agent. Because the skin remains is one of the principal routes for HD exposure and damage, the study of HD-induced skin lesions is of major interest. Blister formation is a characteristic of HD-induced skin lesions in humans. Attempts have been made to find an animal model that produces cutaneous microblisters after exposure to the naturally occurring liquid as well as vaporized HD. Weanling pigs were exposed to three different doses of liquid HD. Histopathologic findings showed microblister formation as well as variable apoptosis and/or necrosis of epidermal keratinocytes and vascular endothelium. Pig skin is morphologically similar to human skin. In the pig, the epidermal lipids, the density of hair follicles, the presence of sweat glands, the proliferation kinetics, and the antigenicity are all closer to human skin than are rodent models. All these features may be important in lesions induced by HD, and may mean that the pig is a superior model for studying the pathophysiology of HD-induced cutaneous lesions.

Animals↗
PubMed1995

Sulfur mustard: its continuing threat as a chemical warfare agent, the cutaneous lesions induced, progress in understanding its mechanism of action, its long-term health effects, and new developments for protection and therapy.

Although sulfur mustard (SM) has been used as a chemical warfare agent since the early twentieth century, it has reemerged in the past decade as a major threat around the world. SM is an agent that is easily produced even in underdeveloped countries and for which there is no effective therapy. This agent is a potential threat not only on the battlefield but also to civilian populations. The skin and other epithelial surfaces are the first targets as this agent is absorbed, and reactions within the skin are the subject of active research into the mechanism of action of this alkylating agent. The depletion of glutathione, generation of reactive oxygen species, and the formation of stable DNA adducts remain theoretic and demonstrated by-products of SM exposure implicated in the disease produced. However, new findings related to the effects of SM on the basement membrane zone; interest in delayed healing of the lesions induced; the inflammatory mediators, enzymes, and cytokines that result; and cellular typing of the inflammatory infiltrate will increase our understanding of the pathophysiology of the lesions caused by SM. In addition, the recent development of a topical skin protectant for SM and for other chemical warfare agents may have broad applications within dermatology.

Humans↗
PubMed1995

Histopathologic features seen in sulfur mustard induced cutaneous lesions in hairless guinea pigs.

Sulfur mustard (SM), a chemical warfare agent first used early in the 20th century, has re-emerged in the past decade as a major threat around the world. At present, there are no effective therapeutic measures for SM exposure. Because the skin as well as other interface epithelial surfaces are the first tissues effected as this agent is absorbed, reactions within the skin are an area of active research into the mechanism of action of this alkylating agent. The euthymic hairless guinea pig has been used as the animal model for the study of SM induced injuries because of morphologic similarity of its skin to human skin, with a multiple layer epidermis, and because this animal has a normal immune system. We reviewed 102 biopsy specimens from 51 animals exposed to three different dose times of saturated SM vapor. Histopathologic evidence exists for increased programmed cell death as well as cellular necrosis, subepidermal blister formation, and delayed re-epithelialization secondary to problems with adhesion. Information obtained from this study adds to the body of information important in the investigation of the mechanisms of action of SM.

Animals↗
PubMed1991

Pyridostigmine used as a nerve agent pretreatment under wartime conditions.

OBJECTIVE: To determine the adverse effects of pretreatment with pyridostigmine bromide for nerve agent exposure during wartime. DESIGN: A retrospective study. SETTING: Southwest Asia. PARTICIPANTS: Personnel who provided medical support to the XVIII Airborne Corps. These medical officers supplied information pertaining to symptoms and disposition of 41,650 soldiers who received pyridostigmine at the onset of hostilities of Operation Desert Storm. INTERVENTION: Pyridostigmine bromide, 30 mg orally, was self-administered every 8 hours while under the threat of nerve agent attack (for 1 to 7 days). MAIN OUTCOME MEASURE: Physiologic changes attributable to pyridostigmine that resulted in need for medical attention, discontinuation of the drug, hospitalization, and/or evacuation from Southwest Asia. RESULTS: About half of the population noted physiologic changes that were not incapacitating, such as increased flatus, abdominal cramps, soft stools, and urinary urgency. Approximately 1% of the soldiers believed they had effects that warranted medical attention, but fewer than 0.1% had effects sufficient to discontinue the drug. Nonincapacitating symptoms often occurred; however, military mission performance was not impaired. CONCLUSION: While under the threat of nerve agent attack, pyridostigmine can be administered to virtually all soldiers.

Chemical Warfare Agents↗
PubMedDate not supplied

Sulfur mustard-increased proteolysis following in vitro and in vivo exposures.

The pathologic mechanisms underlying sulfur mustard (HD)-induced skin vesication are as yet undefined. Papirmeister et al. (1985) postulate enhanced proteolytic activity as a proximate cause of HD-induced cutaneous injury. Using a chromogenic peptide substrate assay, we previously reported that in vitro exposure of cell cultures to HD enhances proteolytic activity. We have continued our investigation of HD-increased proteolytic activity in vitro and have expanded our studies to include an in vivo animal model for HD exposure. In vitro exposure of human peripheral blood lymphocytes (PBL) to HD demonstrated that the increase in proteolytic activity is both time- and temperature-dependent. Using a panel of 10 protease substrates, we established that the HD-increased proteolysis was markedly different from that generated by plasminogen activator. The hairless guinea pig is an animal model used for the study of HD-induced dermal pathology. When control and HD-exposed PBL and hairless guinea pig skin where examined, similarities in their protease substrate reactivities were observed. HD-exposed hairless guinea pig skin biopsies demonstrated increased proteolytic activity that was time-dependent. The HD-increased proteolytic response was similar in both in vitro and in vivo studies and may be useful for elucidating both the mechanism of HD-induced vesication and potential treatment compounds.

Animals↗