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Biomedical subjects

C M Lang

Publications and source records attributed to C M Lang.

At least 19 recordsLinked to original sources
PubMed2001

Reinitiated expression of EJras transgene in targeted epidermal cells of transgenic rabbits by cottontail rabbit papillomavirus infection.

Transgenic rabbits carrying the EJras oncogene have been established in our laboratory (Am. J. Pathol. 155 (1999) 315). The expression of the ras gene is targeted to the epidermal keratinocytes using the upstream regulatory region (URR) of the cottontail rabbit papillomavirus (CRPV). All of the transgenic rabbits develop keratoacanthomas at multiple sites in the skin at 2-3 days after birth, and the tumors spontaneously regress in 1.5-2 months. With regression of the keratoacanthomas, the rabbits appear normal and EJras expression is undetectable in their skin. To determine if CRPV infection would reinitiate the expression of the EJras transgene and make the rabbits more sensitive to tumorigenesis, the rabbits were infected with CRPV at 2 months of age when the keratoacanthomas had regressed. This study shows that CRPV infection of the transgenic rabbit skin could shorten the latency required for CRPV papilloma initiation, and significantly increase the tumor growth and persistence rate compared with non-transgenic rabbits. Furthermore, EJras expression became detectable in the CRPV induced papillomas in transgenic rabbits, but not in the papillomas of non-transgenic rabbits. These results indicate that CRPV infection is able to reinitiate the expression of the CRPV URR controlled EJras oncogene carried by the transgenic rabbits and that the expression of EJras can enhance the tumorigenesis of CRPV infection.

Animals↗
PubMed2001

The academic paper.

Explore the source record for details and available documents.

Laboratory Animal Science↗
PubMed2000

In vivo effects of chronic treatment with [MET5]-enkephalin on hematological values and natural killer cell activity in athymic mice.

The role of endogenous opioids in immunological mechanisms was examined by subjecting athymic (nu/nu) mice to chronic injections of the opioid agonist [Met5]-enkephalin (MET) or continuous opioid receptor blockade with naltrexone (NTX). After 8 days of treatment, neither excess peptide nor deprivation of opioids from receptors had any effect on body weight, spleen index (spleen to body weight ratio), total and differential white blood cell counts, and natural killer (NK) cell activity in peripheral blood or splenic lymphocytes. At 28 days, chronic treatment with MET or NTX had no effect on any of these parameters with the exception of an elevation from controls in NK cell activity in peripheral blood in mice receiving NTX, and subnormal NK cell activity related to splenic lymphocytes in the MET group. These results suggest that chronic exposure to an opioid agonist, or persistent opioid receptor blockade, have little influence on a variety of immunological properties in athymic mice, suggesting that native opioids such as MET do not play a marked role in defense mechanisms in the athymic mouse.

Animals↗
PubMed2000

The opioid growth factor, [Met5]-enkephalin, inhibits DNA synthesis during recornification of mouse tail skin.

Opioid peptides serve as tonically active negative growth regulators in renewing and regenerating epithelia. To examine the involvement of opioids in renewal of the stratum corneum after tape stripping of tail skin, C57BL/6 J mice were given systemic injections of the potent opioid antagonist, naltrexone (NTX, 20 mg/kg i.p.) following injury. Blockade of opioid-receptor interaction by NTX for 4 h resulted in an elevation of 36-66% in basal cell DNA synthesis measured 24 h after injury. Injection of the endogenous opioid peptide, [Met5]-enkephalin (OGF, 10 mg/kg i.p.) 4 h before termination, suppressed radiolabelled thymidine incorporation in the basal cell layer by 37-46% at 24 h after wounding. The magnitude of the effects on DNA synthesis of OGF, but not NTX, depended on the timing of administration with respect to injury. OGF maximally depressed basal cell labelling (72%) when given 16 h after tape stripping. Concomitant administration of naloxone (10 mg/kg) with OGF blocked the inhibition of DNA synthesis; naloxone alone at the dosage utilized had no effect on cell labelling. Both OGF and its receptor, OGFr, were detected by immunocytochemistry in the basal and suprabasal cell layers, but not the cornified layer of tape stripped and uninjured tail skin. These results indicate: (a) a native opioid peptide and its receptor are expressed in epidermal cells of injured and uninjured mouse tail skin; (b) removal of the stratum corneum by tape stripping does not disrupt the function of the endogenous opioid growth system; (c) the proliferative response to wounding of the tail is tonically inhibited by the receptor-mediated action of an endogenous opioid peptide; and (d) DNA synthesis by basal cells can be elevated by disrupting opioid peptide receptor interactions.

Animals↗
PubMed1999

Development of keratoacanthomas and squamous cell carcinomas in transgenic rabbits with targeted expression of EJras oncogene in epidermis.

Activated ras genes have been frequently identified in both benign and malignant human tumors, including keratoacanthoma and squamous cell carcinoma. In this study, we developed two lines of transgenic rabbits in which the expression of EJras has been specifically targeted to the rabbit epidermal keratinocytes, using the upstream regulatory region of cottontail rabbit papillomavirus. All of the F1 transgenic progenies developed multiple keratoacanthomas at about 3 days after birth. The rabbits developed an average of 20 tumors, which usually reached the size of approximately 1 cm in diameter and then spontaneously regressed in about 2 months, similar to keratoacanthoma regression in humans. In addition, up to 18% of the rabbits then developed squamous cell carcinoma at about 5 months of age. The expression of EJras was detectable in all of the keratoacanthomas and squamous cell carcinomas. These results strongly support the involvement of the ras oncogene in both the initiation and regression of keratoacanthoma, and in the development of squamous cell carcinomas. These novel transgenic rabbits, with their consistent tumorigenic phenotype at an early age, high similarity to the human lesions, and easy accessibility for examination, manipulation, biopsy, and treatment, should provide a unique model system for studying ras activation-related tumor initiation, regression, and progression, and for evaluating antitumor therapies.

Animals↗
PubMed1999

The home inventory of dangers and safety precautions-2: addressing critical needs for prescriptive assessment devices in child maltreatment and in healthcare.

OBJECTIVE: This paper describes the development and preliminary validation of a prescriptive home danger and safety precaution instrument containing 14 epidemiological categories to be used in the design and evaluation of family-tailored injury prevention and safety interventions. METHOD: The HIDSP-2 evolved from application and revision of the previous home danger and safety precaution recognition and observation instruments. As part of this process, the suitability of the HIDSP-2 for use in a broad-based trial was evaluated with 29 low income parents exhibiting individual learning needs. Inter-rater reliability and stability of scores were examined. Internal consistency was examined for total dangers and precautions and for those categories in which there were sufficient items to do so. RESULTS: Administrative time was reduced while continuing usefulness in the identification and remediation of dangers and implementation of precautions was demonstrated. Stability of observation was high. Alphas as a measure of internal consistency was satisfactory for total danger and precautions separately; however, those for most individual categories were low. There was significant reduction in the number of dangers identified initially and significant improvement in the safety precautions implemented. CONCLUSIONS: The HIDSP-2 can assist healthcare, education, disability, and child protective service workers in the development of home safety plans for remediating home dangers and implementing precautions. While we see this instrument as eminently suitable for use in broad-based interventions and in epidemiological studies, further research must continue to examine the psychometric characteristics of the individual danger and precaution categories.

Accident Prevention↗
PubMed1998

Human melanoma metastasis is inhibited following ex vivo treatment with an antisense oligonucleotide to protein kinase C-alpha.

To determine whether alteration of PKC alpha expression would affect the metastatic potential of human melanoma cells, replicate cultures of C8161 cells were treated in vitro with a phosphorothioate antisense oligodeoxynucleotide (ODN) that specifically inhibits PKC alpha expression (ISIS-3521). Control C8161 cultures were treated with a scrambled sequence ODN, cationic liposomes or were left untreated. Northern blots demonstrated 70% inhibition of PKC alpha mRNA in ISIS-3521-treated cells compared to controls. Metastasis was suppressed by 75% when ISIS-3521-treated cells were injected intravenously into athymic mice. These results show that PKC alpha expression is important in the regulation of human melanoma metastasis.

Animals↗
PubMed1998

Diagnoses commonly missed in childhood. Long-term outcome and implications for treatment.

Psychiatric and developmental disorders with onset in early childhood are often missed and commonly overlooked by adult psychiatrists. These disorders have important continuities into adulthood and are powerful predictors of chronicity, comorbidity, and severity. It is essential that they are recognized and taken into account in the assessment and treatment of the adult patient.

Adolescent↗
PubMed1998

Rabbit genital tissue is susceptible to infection by rabbit oral papillomavirus: an animal model for a genital tissue-targeting papillomavirus.

Rabbit oral papillomavirus (ROPV) is a mucosatropic papillomavirus which naturally infects oral mucosal sites of domestic rabbits. In this study, we tested the hypothesis that rabbit genital mucosa is also susceptible to ROPV infection by using the athymic mouse xenograft system and adult immunocompetent rabbits. Subrenal xenografts of ROPV-infected rabbit vulvar and penile sheath tissues were strongly positive for ROPV infection by histologic, in situ hybridization, and Southern analyses. Direct inoculation of adult rabbit penises with infectious ROPV produced small raised lesions of approximately 1 by 1 by 1 mm that were ROPV positive by both in situ hybridization and Southern analyses and were also viral capsid antigen positive by immunohistological staining. Infection of rabbit genital tissues with ROPV may be a useful animal model for the study of genital tissue-targeting papillomaviruses.

Animals↗
PubMed1998

Fatal trematodiasis in research turtles.

During a 5-year period, 16 freshwater turtles (Trachemys scripta elegans and Chrysemys picta) that were purchased for research purposes died spontaneously. Clinical signs of disease included lethargy, constant swimming, swimming sideways, hemiplegia, and ulcerative lesions on the carapace. At necropsy, subcutaneous edema, hepatic necrosis, pancreatic necrosis, splenic necrosis, and intestinal parasites were identified. Histologically, trematode eggs were seen within the liver, brain, spleen, kidney, myocardium, lung, pancreas, testes, and bladder, and were associated with granulomatous reactions. The size and distribution of the eggs were consistent with Spirorchis sp. infection, although adults could not be found to confirm the species. Spirorchid flukes are 1 to 2 mm long and inhabit the heart and blood vessels where they produce eggs. Spirorchis parvus are capable of invading various tissues, including pancreas and the central nervous system. The pathogenicity of the flukes seems to be related to widespread deposition of the eggs, which may block small blood vessels within the intestines, causing necrosis and bacteremia. Antemortem diagnosis is made by direct examination of fecal smears for eggs. Postmortem diagnosis is accomplished by examination of tissues for adult parasites and microgranulomas associated with the fluke eggs. The parasite requires a snail intermediate host to complete its life cycle. Intramuscular or oral administration of praziquantel is reported to be an effective treatment.

Animals↗
PubMed1997

Chronic exposure to the opioid antagonist naltrexone during pregnancy: maternal and offspring effects.

The role of endogenous opioids in pregnancy and parturition, and the influence exerted on prenatal and postnatal features of the offspring, were studied in rats. Females received daily injections of 50 mg/kg naltrexone (NTX), a dosage found to block opioids from interacting with opioid receptors for 24 h, throughout pregnancy. No effects on the length of gestation, course of pregnancy, litter size, or the viability of the mother or offspring were noted. The body weights, crown-rump lengths, and wet and dry weights of the brain, heart, kidney, liver, and skeletal muscle (triceps surae) in neonates delivered by NTX-treated rats were substantially elevated compared to newborn animals of saline-injected mothers. Offspring exposed to NTX during prenatal life were larger in body weight and length, and organ wet and dry weights on postnatal days 10 and 21. By weaning (day 21 ), body weights of NTX-exposed rats were 36% greater than controls, and increases were observed in the wet weights of brain (18%), heart (42%), kidney (38%), lungs (22%), liver (44%), and triceps surae (246%). These data lead us to hypothesize that native opioids are important growth-inhibiting, tonically active regulators of prenatal ontogeny, and that events occurring in prenatal life are determinants to postnatal outcome insofar as somatic development.

Animals↗
PubMed1997

Opioid receptor blockade during prenatal life modifies postnatal behavioral development.

The ontogeny of physical characteristics, spontaneous motor, and sensorimotor behaviors of preweaning rats, as well as ambulation and emotionality at weaning (day 21) were studied in rats exposed to 50 mg/kg naltrexone (NTX) or saline (controls) daily throughout gestation by maternal administration; all animals were cross-fostered to untreated mothers at birth. Morphine challenge tests and nociceptive measures revealed that this dosage of opioid antagonist blocked opioid receptors for 24 h. At birth and weaning, animals in the NTX group weighed 12 and 20%, respectively, more than control offspring. The age at which a specific physical characteristic, spontaneous motor behavior, or reflex initially appeared and the age at which 100% of the animals demonstrated a particular characteristic/behavior often were accelerated in animals prenatally exposed to NTX. The frequency of ambulation was subnormal in the NTX group, and the frequency and/or incidence of rearing, grooming, wet-dog shakes, and defecation were reduced from normal levels in these opioid antagonist-exposed rats. These results imply that interactions of endogenous opioid systems during embryogenesis are determinants of somatic, physical, and behavioral development in postnatal life.

Animals↗
PubMed1997

Experimental pneumonia virus of mice infection of guineapigs spontaneously infected with Bordetella bronchiseptica.

Guineapigs that were intranasally inoculated with pneumonia virus of mice (PVM) seroconverted to PVM by 11 days post-infection. During the course of study (2-60 days post-infection) no gross or histologic lesions were identified within the lungs that could be attributed to PVM infection. Mild rhinitis and tracheitis were found in most animals and acute purulent bronchopneumonia in two animals, which may have resulted from spontaneous subclinical Bordetella bronchiseptica infection. Viral and bacterial respiratory diseases of the guineapig are briefly reviewed.

Animals↗
PubMed1996

Transgenic mice expressing the thymus leukemia antigen fail to control cutaneous herpes simplex virus infection.

TL-transgenic mice expressing the thymus leukemia antigen demonstrate a lack of viral clearance following cutaneous HSV infection of the footpad. In this study, both uninfected and HSV-infected TL-transgenic mice demonstrate increased concentrations of IL-4 as well as decreased concentrations of IFN-gamma which may possibly underlie the impairment of viral clearance. Furthermore, lymphocytes from HSV-infected nontransgenic mice, adoptively transferred into HSV-infected TL-transgenic mice, promoted viral clearance and led to an increase in IFN-gamma production. Transgenic mice which were subcutaneously injected with IFN-gamma in the right footpad were also capable of clearing the viral challenge; however, clearance was restricted solely to the right footpad. These studies support the possibility of perturbations in the immune system of TL-transgenic mice and effectively demonstrate the utility of this model system in the study of HSV clearance, persistence, and potential spontaneous reactivation. Moreover, the TL-transgenic animals may provide a useful model system for additional studies requiring a host system skewed toward a Th2 phenotype.

Adoptive Transfer↗
PubMed1996

Immortalization of inbred rabbit keratinocytes from a Shope papilloma and tumorigenic transformation of the cells by EJ-ras.

An immortalized cell line of keratinocytes, named SPG1-3, was established from a papilloma induced from cottontail rabbit papillomavirus (CRPV)-infected inbred rabbit skin. The cells have reached 60 passages in culture and are still growing well, but they are not tumorigenic in athymic mice. Although CRPV DNA was present as extrachromosomal episomes in the papilloma from which the cell line was derived from a single colony of keratinocytes, there was no CRPV DNA detectable in the cells. Three sub-cell lines of SPG1-3EJ, SPG1-3EJ1 and SPG1-3EJ2 were then established from the EJ-ras transfected SPG1-3 cells. All of the three sub-lines contained both EJ-ras DNA and a 1.2 kb transcript of EJ-ras, and they are malignantly tumorigenic in athymic mice. These data indicate that CRPV genome and its expression might be essential for the initiation and maintenance of neoplasia, but not for the maintenance of immortalization of the tumor-derived cells. In addition, some oncogenes such as EJ-ras may play an essential role in tumorigenic and malignant conversion of the immortalized cells. These cell lines derived from inbred rabbit skin may provide a useful in vitro system for better understanding of the oncogenic processes of papillomavirus-involved neoplastic progression by transfecting the cells with CRPV genes and serial transplantation to the inbred rabbits for studying host immune responses to the viral oncogenic potential.

Animals↗
PubMed1996

Inhibition of human colon cancer by intermittent opioid receptor blockade with naltrexone.

Nude mice inoculated with human colon cancer (HT-29) and receiving 0.1 mg/kg naltrexone (NTX) beginning immediately after tumor cell injection exhibited a marked retardation in tumorigenicity. This dosage of NTX, which blocked opioid receptors for 6-8 h/day, resulted in a delay of 2.4-fold in tumor appearance compared to control subjects. At the time (10 days) when all control mice had tumors, 80% of the mice in the 0.1 mg/kg NTX group had no signs of neoplasia. Binding capacity, but not affinity, of [3H][Met5]-enkephalin was reduced 85% of control levels in tumor tissue from mice of the 0.1 NTX group. Plasma, but not tumor tissue levels of [Met5]-enkephalin were elevated (2.5-fold) in contrast to control values. These results suggest that daily intermittent opioid receptor blockade with NTX provokes the interaction of opioids and receptors in the interval following drug availability, with opioids serving to inhibit tumorigenicity of human colon cancer.

Animals↗
PubMed1996

Optic neuropathy following simulation of orbital hemorrhage in the nonhuman primate.

The goal of the study was to determine, using a nonhuman primate (NHP) model, the minimum duration of elevated intraocular pressure (IOP) (induced by an inflated catheter) necessary to produce significant visual system deficits. In Old World monkeys (Macaca mulatta), a catheter was placed retrobulbarly in one orbit and inflated with saline for either 180 min (10 monkeys) or 240 min (six monkeys subjects). Baseline color fundus photographs, monochromatic photography, fluorescein angiography, and IOP measurements were performed preoperatively and at either 2, 4, or 6 weeks postoperatively on both eyes of each monkey prior to killing and histological analysis. Optic neuropathy was demonstrated in eight of these NHPs. In the two most severe cases (240 min inflation condition), complete nerve fiber atrophy with central retinal artery occlusion was observed. Sector nerve fiber atrophy, extending from the temporal disc to beyond the macula, was noted in the other six monkeys, five of which were in the 180 min inflation condition. Thus, optic neuropathy, sufficient to produce visual loss, was noted following increased IOP (> or = 50 mm Hg) for 180 min or 240 min. These data emphasize the need for timely intervention to mitigate the potential detrimental effects of retrobulbar hemorrhage when it occurs in humans.

Animals↗