The role of metalloelastase in immune complex-induced acute lung injury.

Matrix metalloproteases (MMPs) are a group of zinc-dependent endopeptidases that can degrade every component of the extracellular matrix. Under normal circumstances, the levels of MMPs are tightly regulated at both transcriptional and posttranscriptional levels. However, they are up-regulated in pathological states such as inflammation.

Role of stromelysin 1 and gelatinase B in experimental acute lung injury.

Matrix metalloproteinases (MMPs) are upregulated locally in sites of inflammation, including the lung. Several MMP activities are upregulated in acute lung injury models but the exact role that these MMPs play in the development of the lung injury is unclear due to the absence of specific inhibitors. To determine the involvement of individual MMPs in the development of lung injury, mice genetically deficient in gelatinase B (MMP-9) and stromelysin 1 (MMP-3) were acutely injured with immunoglobulin G immune complexes and the intensity of the lung injury was compared with genetically identical wild-type (WT) mice with normal MMP activities.

Constitutive expression of erbB2 in epidermis of transgenic mice results in epidermal hyperproliferation and spontaneous skin tumor development.

The erbB family of receptor tyrosine kinases, which consists of the epidermal growth factor receptor (EGFr/erbB1), erbB2 (neu), erbB3 and erbB4, has been shown to be important for both normal development as well as neoplasia. The expression of rat erbB2 was targeted to the basal layer of mouse epidermis with the bovine keratin 5 promoter. Overexpression of wild type rat erbB2 in the basal layer of epidermis led to alopecia, follicular hyperplasia and sebaceous gland enlargement as well as hyperplasia of the interfollicular epidermis.

Time-dependent inhibition of immune complex-induced lung injury by catalase: relationship to alterations in macrophage and neutrophil matrix metalloproteinase elaboration.

Rats were subjected to acute lung injury by the intra-alveolar formation of IgG immune complexes of bovine serum albumin (BSA) and anti-BSA. In this model of injury, complement activation occurs and large numbers of neutrophils invade the interstitium and alveolar space. In the present study, animals were treated with intratracheal catalase concomitantly with anti-BSA or after a lag period of 5-120 min.

Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion.

Transgenic mice overexpressing insulin-like growth factor-1 (IGF-1) in the basal layer of skin epidermis were generated using the bovine keratin 5 promoter (BK5). Neonatal transgenic mice were slightly smaller at birth and exhibited early ear unfolding, wrinkled and thickened skin, and slightly enlarged ears compared with nontransgenic littermates. Morphological evaluation of the skin revealed that persistent overexpression of IGF-1 in the basal layer of the epidermis resulted in epidermal hyperplasia, hyperkeratosis, and an increased labeling index that persisted in adult mice.

Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice.

Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2-3 months of age.

Enhancement of susceptibility to diverse skin tumor promoters by activation of the insulin-like growth factor-1 receptor in the epidermis of transgenic mice.

Insulin-like growth factor-1 (IGF-1) and its receptor are believed to play an important role in mitogenesis and neoplastic transformation. The purpose of this study was to further examine the role of IGF-1 during tumor promotion in mouse skin. HK1.

Papillomas at high risk for malignant progression arising both early and late during two-stage carcinogenesis in SENCAR mice.

The current study was designed to further establish that most papillomas produced in SENCAR mice during two-stage skin carcinogenesis are, in fact, premalignant lesions and to specifically determine the malignant conversion potential of papillomas that arise at different times during the carcinogenesis process. A method was established to physically map and monitor the lifespan of all papillomas produced in SENCAR mice during the course of an initiation-promotion experiment using DMBA as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The results from these experiments showed that in groups of mice initiated with either 0.

Altered expression of epidermal growth factor receptor ligands in tumor promoter-treated mouse epidermis and in primary mouse skin tumors induced by an initiation-promotion protocol.

Multiple epidermal growth factor receptor (EGFr) ligands have been identified, including transforming growth factor alpha (TGFalpha), heparin-binding epidermal growth factor (HB-EGF), amphiregulin (AR), and betacellulin (BTC). Previous work from our laboratory demonstrated that TGFalpha mRNA and protein are upregulated in epidermis during tumor-promoter treatment of mouse skin and in skin tumors produced by initiation-promotion regimens. The purpose of the study described here was to explore the role of other EGFr ligands in multistage skin carcinogenesis.

Severe follicular hyperplasia and spontaneous papilloma formation in transgenic mice expressing the neu oncogene under the control of the bovine keratin 5 promoter.

Transgenic mice were developed to explore the role of the erbB2 during epithelial homeostasis and tumorigenesis, through targeted expression of the neu oncogene (neu*). Expression of a neu* cDNA was targeted to the basal layer of skin epidermis as well as other epithelial tissues of transgenic mice via the bovine keratin 5 promoter. Two transgenic founders were obtained that were morphologically distinguishable from non-transgenic littermates by their visibly thickened skin and patchy hair growth by day 3 after birth.

Association of a murine chromosome 9 locus (Psl1) with susceptibility to mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.

It has been known for many years that there are dramatic differences in the susceptibility of mouse stocks and strains to two-stage skin carcinogenesis and that these differences are due the animals' responsiveness to tumor-promoting agents. In earlier studies using several inbred mouse strains, we found that susceptibility to skin tumor promotion by phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) is a multigenic trait. To extend this work, we conducted a genome scan of (C57BL/6 x DBA/2)F1 x C57BL/6 mice previously scored for sensitivity to skin tumor promotion by TPA.

Analysis of the ability of 12-O-tetradecanoylphorbol-13-acetate to induce epidermal hyperplasia, transforming growth factor-alpha, and skin tumor promotion in wa-1 mice.

Wa-1 mutant mice possess a defect in the production of transforming growth factor-alpha (TGF-alpha) that leads to a phenotype characterized by wavy hair and curly whiskers. In light of recent evidence indicating the importance of TGF-alpha in epithelial tumorigenesis, this study characterizes the responsiveness of wa-1 mice to skin tumor promotion by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). The responsiveness of wa-1 mice to TPA was compared with that of SENCAR and C57BL/6 mice, representing mouse lines highly sensitive and resistant to skin tumor promotion, respectively.

Altered expression of insulin-like growth factor I and its receptor during multistage carcinogenesis in mouse skin.

We examined the possible role of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-Ir) during multistage carcinogenesis in mouse skin. For this purpose, the expression of both IGF-I and IGF-Ir was investigated in mouse skin during tumor promoter treatment and in primary papillomas and squamous cell carcinomas (SCCs) obtained from SENCAR mice treated with standard initiation-promotion regimens. IGF-I transcripts were not detectable or only weakly detectable in normal SENCAR mouse epidermis by northern or reverse transcription (RT)-polymerase chain reaction (PCR) analysis, respectively, whereas IGF-I transcripts (primarily a 7.

Elevation of transforming growth factor-alpha mRNA and protein expression by diverse tumor promoters in SENCAR mouse epidermis.

The study presented here was designed to further investigate the role of transforming growth factor-alpha (TGF alpha) in skin tumor promotion by examining the ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) and several non-phorbol ester promoters to alter TGF alpha mRNA and protein levels in mouse epidermis. Total RNA was isolated from SENCAR mouse epidermis at various times after single topical treatments with TPA (3.4 nmol), chrysarobin (220 nmol), okadaic acid (2.

[Cochleovestibular hypofunction syndrome of infrequent origin. Thrombosis of venous endotracheal sinuses].

First appearance of the lateral sinus and jugular gulf thrombosis use to be a neurologic syndrome including headache, vomiting, convulsions, hydrocephalus, etc. We present a case in which the first and only symptom was the classic triad of Médière's disease: vertigo, tinnitus and hearing loss. We also discuss the radiological study, treatment and the literature review.

Loss of mouse epidermal protein kinase C isozyme activities following treatment with phorbol ester and non-phorbol ester tumor promoters.

The present study has examined changes in activities and levels of four protein kinase C (PKC) isozymes (PKC alpha, PKC beta, PKC gamma and PKC delta) detectable in mouse epidermal preparations following both single and multiple treatments with 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, PKC epsilon and PKC eta protein levels were monitored by immunoblotting following TPA application. Finally, PKC isozyme activity profiles were also examined in epidermal preparations from mice treated with single applications of two non-phorbol ester tumor promoters: chrysarobin (CHRY) and okadaic acid (OA).

[Principal serotypes of Salmonella identified in 10703 strains in Mexico from 1982 to 1993].

From 1982 to 1993, 10703 Salmonella strains from The National Network of Diarroheal Laboratories of Mexico were sent to the Enteric Bacteriology Laboratory of INDRE. The strains were confirmed by serology and 119 different Salmonella serotypes were found. The most frequent serotypes were as follows: S.

Altered expression of the epidermal growth factor receptor and transforming growth factor-alpha during multistage skin carcinogenesis in SENCAR mice.

In the study presented here, we examined the possible role of the transforming growth factor-alpha (TGF alpha)/epidermal growth factor receptor (EGFR) system during multistage carcinogenesis in mouse skin. In this regard, the expression (mRNA and protein) of both TGF alpha and EGFR was examined in primary papillomas and squamous cell carcinomas (SCCs) obtained from SENCAR mice treated with standard initiation-promotion regimens and compared with the levels of expression in normal epidermis. The level of a 4.

Role of the epidermal growth factor receptor and transforming growth factor alpha in mouse skin carcinogenesis.

The mouse skin model of multistage carcinogenesis continues to serve as a major in vivo model for studying the sequential and stepwise evolution of the cancer process by chemical and physical carcinogens. The initiation stage of mouse skin carcinogenesis involves genetic damage in the form of DNA adducts or initiator-induced DNA base changes. These changes ultimately lead to mutations in critical target genes of epidermal stem cells.

Comparison of 12-O-tetradecanoylphorbol-13-acetate and teleocidin for induction of epidermal hyperplasia, activation of epidermal PKC isozymes and skin tumor promotion in SENCAR and C57BL/6 mice.

The present study compared the ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin to induce sustained epidermal hyperplasia, activate partially purified epidermal protein kinase C (PKC) isozymes and promote skin tumors in SENCAR and C57BL/6 mice. Teleocidin was less effective than TPA on a molar basis for inducing sustained epidermal hyperplasia, promoting skin tumors and activating partially purified epidermal PKC isozymes in vitro when examined using SENCAR mice. In contrast, teleocidin was more effective than TPA on a molar basis for inducing sustained epidermal hyperplasia, approximately equi-effective for promoting skin tumors and significantly less effective for activating PKC isozymes in vitro when examined using C57BL/6 mice.

Functions of an adult sickle cell group: education, task orientation, and support.

Although psychosocial concerns of patients with sickle cell disease have been described, these descriptions are based primarily on experience with adolescents and children. In addition, there is an absence of reports on sickle cell groups specifically designed for adult patients. This article reports on the development of an adult sickle cell support group and provides a description of the psychosocial factors most prevalent in patients' lives.

Further identification of protein kinase C isozymes in mouse epidermis.

In the current study, the protein kinase C (PKC) isozymes present in mouse epidermis have been identified using immunological and chromatographic methods. Six PKC isozymes, PKC alpha, PKC beta, PKC gamma, PKC delta, PKC epsilon, and PKC zeta, were identified in unfractionated epidermal preparations by protein immunoblotting. The subcellular distribution and presence of these isozymes was further verified by hydroxyapatite (HA) chromatography with the exception of PKE epsilon, which could not be detected following HA chromatography.

Further analysis of c-Ha-ras mutations in papillomas initiated by several polycyclic aromatic hydrocarbons and papillomas from uninitiated, promoter-treated skin in SENCAR mice.

In this study we analyzed the mutations in c-Ha-ras from skin papillomas initiated with benzo[a]pyrene (B[a]P), 7-methylbenz[a]anthracene (7-MBA), and 10-fluoro-7-methylbenz[a]anthracene (10-F-7-MBA) and from papillomas induced by treatment with tumor promoter alone. Among the papillomas induced by treatment with tumor promoter alone, 56% (nine of 16) had mutations in c-Ha-ras. These mutations were found primarily in codon 61 and included both A182-->T and A182-->G mutations.

Further genetic analyses of skin tumor promoter susceptibility using inbred and recombinant inbred mice.

To explore further the genetics of susceptibility to skin tumor promotion in inbred mice, several aspects of responsiveness to 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined in C3H/He mice and segregating crosses between this mouse strain and C57BL/6 mice as well as BXD and BXH recombinant inbred (RI) strains. Dose-response relationships were established for skin tumor promotion by TPA following initiation with 7,12-dimethylbenz[a]anthracene in C3H/He and B6C3F1, as well as several other mouse stocks and strains included for comparison. The relative responsiveness to TPA skin tumor promotion was: SENCAR much greater than DBA/2 greater than C3H/He approximately B6D2F1 greater than B6C3F1 much greater than C57BL/6.

Induction of epidermal ornithine decarboxylase activity in mouse skin exposed to biogenic silica fibers.

The present study demonstrates that biogenic silica fibers (BSF), previously shown to promote skin tumors in mice and more recently to promote the induction of mesotheliomas when injected into the pleural cavity of rats, rapidly induces epidermal ornithine decarboxylase (ODC) activity in SENCAR mice following topical application. The time course for induction of epidermal ODC by BSF was very similar to that observed following topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). Maximal ODC activity was observed 4-6 h following treatment with BSF.