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1.
Eur J Histochem ; 54(3): e40, 2010.
Article in English | MEDLINE | ID: mdl-20839416

ABSTRACT

To evaluate the apoptosis involvement in the angiogenesis as a self-limiting process in patients with temporomandibular joint (TMJ) degenerated disc vessels, we assessed, by immunohistochemistry, the detection of TRAIL, its death receptor DR5 and caspase 3. TRAIL, its death receptor DR5 and caspase 3 expression were studied by immunohistochemistry in 15 TMJ discs displaced without reduction and in 4 unaffected discs. These apoptosis molecules were detected in the intima and media layers of newly formed vessels affected discs. In conclusion, vessels apoptosis activation in TMJ disc with ID could be regarded as a self-limiting process that try to leads to vessel regression; in this way an inhibition of angiogenic vessels may prove a key strategy in limiting pathological angiogenesis, by cutting off blood supply to tumors, or by reducing harmful inflammation.


Subject(s)
Apoptosis , Caspase 3/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , TNF-Related Apoptosis-Inducing Ligand/metabolism , Temporomandibular Joint Disc/pathology , Temporomandibular Joint Disorders/pathology , Adult , Female , Humans , Immunohistochemistry , Male , Middle Aged , Temporomandibular Joint Disorders/physiopathology
2.
Minerva Stomatol ; 59(3): 61-74, 2010 Mar.
Article in English, Italian | MEDLINE | ID: mdl-20357734

ABSTRACT

AIM: The aim of this retrospective study was to analyse the effectiveness of Andresen appliance in inducing an increased mandibular dimension and, above all, to test the "null" hypotesis that the patients' vertical skelettofacial morfology could influence this increase using the Ricketts' method of VERT. METHODS: Cephalometric records of 42 skeletal class II patients treated at the Orthodontic Department of Catania University were randomly selected. The sample was divided for vertical facial patterns, according to the facial classification method of Ricketts (VERT), into three groups: brachyfacial, mesiofacial and dolicofacial. Ten landmarks were located on the lateral cephalometric radiographs; growth in the horizontal-sagittal direction and in the vertical direction was evaluated using the measurements of total mandibular length (Co-Gn, Co-Pg, Ar-Pg, Ar-Gn), mandibular sagittal position (SNB, ANB) and mandibular ramus height (S-Go, Ar-Go, Co-Go). The intragroup comparisons were made using two tailed t-tests, while the intergroup comparisons were analyzed statistically using the Kruskal-Wallis test. RESULTS: The cephalometric values before (T0) and after (T1) treatment showed significant changes for the majority of the cephalometric variables in each group. Our findings demonstrated a statistically significant greater increase of mandibular dimension in the brachyfacial group, while similar results were found for mesiofacial and dolichofacial groups. CONCLUSION: The "null" hypothesis, that the skeletal pattern of subjects could influence the increase of mandibular dimension after Andresen treatment, had to be accepted: the brachyfacial patients showed a greater anterior mandibular displacement when compared to mesiofacial or dolichofacial group.


Subject(s)
Activator Appliances , Facial Bones/anatomy & histology , Malocclusion, Angle Class II/therapy , Mandible/growth & development , Child , Female , Humans , Male , Retrospective Studies , Time Factors
3.
J Endod ; 29(3): 180-3, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12669876

ABSTRACT

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a multifunctional cytokine. It is overexpressed in several conditions, which are characterized by vascular hyperpermeability and angiogenesis. In this investigation, we have evaluated the possibility that VEGF/VPF could be expressed in periapical lesions. We studied 17 periapical granulomas and 6 periapical cysts by immunohistochemistry. An immunopositive reaction for VEGF/VPF was observed in all 23 periapical lesions; however, the intensity of immunostaining by anti-VEGF antibody varied according to histopathological findings. In periapical granulomas without epithelium, almost all of the inflammatory cells were immunoreactive to anti-VEGF/VIP antibody. In periapical granulomas, which had rests of Malassez in them, some inflammatory cells were stained. On the other hand, epithelial cells always were stained by VEGF/VPF antibody, both in periapical lesions with epithelium and in radicular cysts. This study demonstrated that periapical lesions express VEGF/VPF, although with some differences in cell immunolabeling, which correlated to the lesions' stages of development. Initially, VEGF/VPF would assure angiogenesis and vascular hyperpermeability, resulting in accumulation of inflammatory cells, later it could be involved in cyst fluid accumulation. We hypothesize, therefore, that VEGF/VPF expression plays an important role in the pathogenesis of periapical granulomas and enlargement of radicular cysts by several mechanisms.


Subject(s)
Endothelial Growth Factors/analysis , Intercellular Signaling Peptides and Proteins/analysis , Lymphokines/analysis , Periapical Diseases/pathology , Protein Isoforms/analysis , Antibodies , Capillary Permeability , Coloring Agents , Cyst Fluid/cytology , Epithelial Cells/pathology , Epithelium/pathology , Fibroblasts/pathology , Fluorescent Dyes , Humans , Lymphocytes/pathology , Macrophages/pathology , Neovascularization, Pathologic/pathology , Periapical Granuloma/pathology , Periodontal Ligament/pathology , Plasma Cells/pathology , Radicular Cyst/pathology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
4.
Arch Oral Biol ; 48(3): 185-92, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12648555

ABSTRACT

A high density of blood vessels is found in specimens of temporomandibular joint (TMJ) disc at any stage of internal derangement of the joint, but the factors responsible for angiogenesis in the disc have not been described. The purpose here was to investigate, in human TMJ discs, the expression of vascular endothelial growth factor (VEGF), a multifunctional cytokine that contributes to angiogenesis. Specimens, free of significant morphological alterations and with varying degrees of disc tissue degeneration/regeneration, were studied by immunohistochemistry for VEGF in order to correlate immunohistochemical with histopathological findings. In normal discs and discs with minor pathological changes, fibroblast-like cells, fibrochondrocytes and chondrocyte-like cells were either not or only weakly immunostained by VEGF antibody. In disc specimens from internal derangement of the TMJ with significant tissue degeneration/regeneration, VEGF was consistently expressed. In these specimens, immunoreaction products for VEGF were observed both in the disc and in the endothelial cells of newly formed vessels. This VEGF immunolocalization is consistent with the stimulation of angiogenesis and the morphogenesis and differentiation of chondrocytes. Therefore VEGF expression by disc chondrocyte-like cells might reflect the action of the cytokine as an inducer of angiogenesis and as an autocrine signal for cells of the chondrogenic lineage.


Subject(s)
Endothelial Growth Factors/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Lymphokines/metabolism , Temporomandibular Joint Disc/metabolism , Temporomandibular Joint Disorders/metabolism , Adult , Chondrocytes/metabolism , Endothelium, Vascular/metabolism , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Neovascularization, Pathologic/metabolism , Temporomandibular Joint Disc/blood supply , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
5.
J Oral Maxillofac Surg ; 59(10): 1186-92, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11573179

ABSTRACT

PURPOSE: This study investigated histochemically the elastic fibers in human temporomandibular joint (TMJ) discs with varying degrees of tissue degeneration/regeneration to determine whether there are differences that correlate with the histologic findings. MATERIALS AND METHODS: Ten diseased human TMJ discs and 2 control specimens were studied histochemically by staining with Weigert's resorcin-fuchsin after oxidation with peracetic acid. This technique selectively stains elastic, elaunin, (pre-elastic), and oxytalan fibers. RESULTS: In TMJ discs with an abnormal collagen fiber arrangement, an increased number of oxytalan fibers could be observed, contrary to discs with scar-like tissue transformation in which oxytalan fibers were decreased in number. In discs showing tears and clefts, the oxytalan fibers run perpendicular to the defects, whereas elaunin and elastic fibers were mainly circumferentially arranged. In discs with chondroid metaplasia, elastic, elaunin, and oxytalan fibers were extensively detected. CONCLUSIONS: It is hypothesized that the elastic, elaunin, and oxytalan fibers found in severely damaged discs appear to ensure biomechanical compliance by reinforcing regions devoid of collagen bundles and thus function as shock absorbers of stretch and compression.


Subject(s)
Muscle Fibers, Skeletal/pathology , Temporomandibular Joint Disc/pathology , Temporomandibular Joint Disorders/pathology , Adult , Collagen , Contractile Proteins , Elastic Tissue/chemistry , Elastic Tissue/pathology , Elastin , Extracellular Matrix Proteins , Female , Histocytochemistry , Humans , Male , Microfibrils/pathology , Middle Aged
6.
J Endod ; 27(2): 89-92, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11491645

ABSTRACT

Heat shock protein (HSP) 27 is a member of the small HSP family that plays a part in the regulation of epithelial cell growth and differentiation, wound healing, apoptosis and cell protection against inflammatory cytotoxicity mediators. Thus the expression of HSP27 was investigated immunohistochemically in periapical granulomas with epithelial rests of Malassez and in radicular cysts. Anti-HSP27 mouse monoclonal antibody and peroxidase-labeled streptavidin-biotin standard technique were used to study the expression of HSP27. Proliferating epithelial cell rests, and islands of epithelium and epithelial lining of microcysts strongly reacted throughout all layers, whereas radicular cysts epithelial lining presented mainly a moderate suprabasal staining pattern. However both the proliferating epithelial cell rests and the radicular cysts shared an over-expression of HSP27 immunostaining intensity in coincidence with the presence of local infiltration of immune cells. HSP27 may play several roles in periapical lesions that include contributing to the migration of epithelial cell rests and an increased resistance both to necrotic and apoptotic cell deaths.


Subject(s)
Heat-Shock Proteins/analysis , Periapical Granuloma/metabolism , Periodontal Ligament/metabolism , Radicular Cyst/metabolism , Antibodies, Monoclonal , Apoptosis/physiology , Cell Differentiation/physiology , Cell Division/physiology , Cell Movement/physiology , Coloring Agents , Connective Tissue/metabolism , Connective Tissue/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Gene Expression Regulation , Heat-Shock Proteins/genetics , Humans , Immunoenzyme Techniques , Immunohistochemistry , Inflammation Mediators/physiology , Leukocytes/pathology , Periapical Granuloma/pathology , Periodontal Ligament/pathology , Radicular Cyst/pathology , Wound Healing/physiology
7.
Climacteric ; 2(1): 21-8, 1999 Mar.
Article in English | MEDLINE | ID: mdl-11910676

ABSTRACT

The objective of the study was to examine the direct and indirect influences of dispositional factors, namely optimism, health-related hardiness (HRH) and sense of coherence (SOC), on the symptom experiences of peri- and postmenopausal women. Indirect effects of dispositional factors were examined via attitudes to the menopause and coping (emotion-versus problem-focused). A survey methodology was employed to assess the research objective for 176 peri- and postmenopausal women recruited from menopause clinics and family planning centers in Queensland, Australia. Emotional stability of the subjects was statistically controlled to eliminate any possible confounding effect on symptom reporting. The results indicated that optimism and SOC affect menopausal health directly, as evidenced by fewer symptoms reported by women scoring highly on these dispositions. Any indirect effect of HRH, optimism and SOC appears to be exerted via problem-focused coping rather than emotion-focused coping or through attitudes. It was concluded that dispositional factors are important to the experience of the menopause and how women adapt to their midlife transition. Psychologists and professionals working in menopause clinics may need to promote feelings of optimism and a sense of coherence in menopausal women, to facilitate better adaptation to this important transitional phase in women's lives.


Subject(s)
Adaptation, Psychological , Affect , Menopause/psychology , Attitude to Health , Emotions , Female , Health Status , Hot Flashes , Humans , Irritable Mood , Middle Aged , Sleep Wake Disorders , Sweating
8.
Minerva Stomatol ; 48(11): 495-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10768008

ABSTRACT

BACKGROUND: Clinical epidemiologic studies carried out in smokers versus non smokers support the concept that tobacco-related factor may affect the periodontal tissues and wound healing. METHODS: In this study, the role of nicotine on the integrin alpha 2 chain immunocytochemical expression, in human gingival fibroblasts (HGF) was investigated in vitro. The kinetic induction of this type of integrin on HGF in response to increasing percentage of nicotine was been characterized. A human gingival fibroblast strain, derived from a healthy individual with non-inflamed gingiva, was used in this study. The cells were then grown on acetylated microscope slides and fixed with cold ethanol, samples were then incubated for 16 to 19 hrs at 4 degrees C to anti-human alpha 2 integrin chain monoclonal antibody. RESULTS: In control cultures and in HGF treated with 0.025 microM nicotine the initial higher expression of alpha 2 chain decreased (grade 1 in both culture) while in HGF treated with 0.075 microM increased (grade 3). After 48 hours HGF exposed to 0.075 microM nicotine, increased further their expression of alpha 2 chain. CONCLUSIONS: The results obtained demonstrate a dose-time dependent nicotine influence on immunocytochemical expression of alpha 2 integrin chain. These data suggest that nicotine may promote a collagene breakdown via an increase of alpha 2 integrin chain expression.


Subject(s)
Fibroblasts/drug effects , Gingiva/drug effects , Integrins/analysis , Nicotine/adverse effects , Smoking/adverse effects , Cells, Cultured , Gingiva/metabolism , Humans , Immunoenzyme Techniques , Immunohistochemistry , Time Factors
9.
Aust N Z J Public Health ; 22(5): 547-51, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9744207

ABSTRACT

Past research on adults has found that the sensory appeal or taste of foods is a primary determiner of food consumption and how people think about food. The nomothetic nature of this research may have underestimated the impact of health considerations on food choice. This study compared 'nomothetic' and 'idiographic' modes of analysis in 1) determining the relative influence of palatability and perceived healthiness of foods, on preference for the food, and 2) assessing the relationship between palatability and evaluations of healthiness. Additionally, gender differences were examined in relation to within-person correlations between the concepts of preference, palatability and healthiness. Subjects (n = 139) rated 81 foods on preference, palatability and healthiness. Findings from both the idiographic and nomothetic analyses indicated that palatability rather than health considerations determined preferences in young adults. The within-person correlational analysis indicated a large number of persons, mostly female, who preferred unhealthy food. The sample was equally split in their evaluations of healthy food as palatable or not.


Subject(s)
Choice Behavior , Data Interpretation, Statistical , Food Preferences/psychology , Health Behavior , Nutritive Value , Taste , Adolescent , Adult , Female , Humans , Male , Sex Factors , Surveys and Questionnaires
10.
Minerva Stomatol ; 46(1-2): 39-43, 1997.
Article in Italian | MEDLINE | ID: mdl-9173215

ABSTRACT

The aim of this study was to provide a histomorphological analysis of some secondary cartilages of mandible and temporal bone as observed in human fetuses 18-22 weeks old. The behavior of cartilage was studied in both these regions, which were decalcified, cut at 10 mu, stained with Mallory staining and examined by optical microscopy. In mandible symphysis menti and condylar cartilage were described. The symphysis appeared to be formed by a fibrous cartilagineous structure surrounded by membranous bone. This structure seems be round in the caudal sections and ovoidal in the rostral sections with the major axis perpendicular to the mean sagittal plane. Meanwhile the condyle is formed by secondary cartilage which may be appreciated in this development stage 5 zona. Secondary cartilage was observed also in the temporal bone nearby the primitive glenoid fossa. The development and the importance of these cartilagineous structures are discussed.


Subject(s)
Cartilage/embryology , Mandible/embryology , Abortion, Spontaneous , Cartilage/anatomy & histology , Cartilage, Articular/anatomy & histology , Cartilage, Articular/embryology , Female , Gestational Age , Humans , Mandible/anatomy & histology , Mandibular Condyle/anatomy & histology , Mandibular Condyle/embryology , Pregnancy
11.
Minerva Stomatol ; 45(10): 441-9, 1996 Oct.
Article in Italian | MEDLINE | ID: mdl-9026688

ABSTRACT

The aim of this paper is to describe the development and growth of the middle-line cranial base synchondrosis and nasal septal cartilage of human fetuses. The sample consisted of 25 human fetuses aged from 9 weeks to 6 months. The samples were decalcified and processed in paraffin. Sections were cut at 10 mu and stained with Mallory staining. Histomorphological observation pointed out the presence and development of cranial base synchondrosis and nasal septal cartilage. As far as synchondrosis cell zone layers in endochondral growth sites are described moreover a caudorostral gradient in growth rate was observed. Functional connexions between the cartilaginous nasal capsule and the developing maxillae and premaxillae have been examined. The main connection was found to consist of the anterior septopremaxillary ligament running from the anterior border of the nasal septum posteroinferiorly to blend with premaxillary periosteum and interpremaxillary suture.


Subject(s)
Cartilage/embryology , Nasal Septum/embryology , Skull Base/embryology , Gestational Age , Humans , Osteogenesis , Staining and Labeling/methods , Tissue Fixation/methods
12.
Psychol Rep ; 79(1): 225-6, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8873809

ABSTRACT

The period after the birth of a child may be characterized by occasions of physical exhaustion. Mothers who self-reported having experienced postnatal depression in the past year and physical exhaustion were examined.


Subject(s)
Depression/psychology , Puerperal Disorders/psychology , Adolescent , Adult , Female , Humans , Middle Aged
13.
Adolescence ; 31(124): 883-901, 1996.
Article in English | MEDLINE | ID: mdl-8970661

ABSTRACT

Australia's "sporting nation" image has been challenged by adolescents' decreasing involvement in active leisure pursuits. A significant number of adolescents experience leisure boredom and dissatisfaction, which have been implicated in drug use and delinquency. Researchers have largely ignored the multivariate nature of adolescent leisure experiences. This North Queensland, Australian adolescent leisure study explored the extent to which adolescent leisure experiences were mediated by individual and situational variables. Seventy-five Cairns and 65 Atherton high school students (66 males and 74 females) were surveyed from grades 8, 10, and 12 (ages 12 to 19), during normal class periods. The Self-Rating Scale (SPS) measure of self-esteem, Sensation-Seeking Scale Form II (SSS), Leisure Boredom Scale (LBS), and a time-use inventory yielded quantitative data. Urban adolescents reported less leisure satisfaction. Participation was highest for passive leisure and lowest for active leisure. Urban adolescents reported higher social leisure, while rural adolescents engaged in more passive leisure. For both Cairns and Atherton, the heaviest substance users were those who scored low on self-esteem and high on sensation-seeking. Atherton adolescents who scored low on self-esteem but high on sensation-seeking, reported the most crime involvement. Methodological issues and implications are discussed and suggestions made for future research.


Subject(s)
Boredom , Leisure Activities , Psychology, Adolescent , Self Concept , Sensation , Adolescent , Analysis of Variance , Attitude , Australia , Crime/statistics & numerical data , Female , Humans , Male , Risk-Taking , Rural Population , Substance-Related Disorders/etiology , Urban Population
14.
Psychol Rep ; 75(3 Pt 1): 1339-43, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7892402

ABSTRACT

The self-esteem of 69 women attending weight-loss centres was examined in relation to attitudes towards body and weight, actual weight, number of diets undergone and weight fluctuations. Rosenberg's Self-esteem Scale was used to measure self-esteem. Attitudes towards the body and weight were assessed using Freedman's Body-Love Questionnaire. The Body Mass Index was used as a weight-range classification for the women. Body image was assessed using the silhouette chart of Bell, Kirkpatrick, and Rinn. Women with stable weight had the highest self-esteem. The number of diets undertaken was associated with lowered self-esteem. High scores on evaluation of appearance were positively correlated with scores on self-esteem. No association was found between self-esteem and either eating restraint or significant others' attitudes. There was good agreement between the women's perceptions of their own bodies and independent raters' perceptions indicating a lack of body-image distortion for this non-eating-disordered group.


Subject(s)
Body Image , Diet, Reducing/psychology , Self Concept , Weight Loss , Adult , Body Mass Index , Female , Humans , Middle Aged , Personality Inventory
15.
Psychol Rep ; 73(2): 555-61, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8234608

ABSTRACT

This study compared professional and volunteer counsellors on a number of key variables in the progression to burnout, namely, stressors, strain, defensive coping, social support, Type A personality, and breakdown. Job stressors unique to each group were identified but there was overwhelming evidence for professionals and volunteers belonging to a homogeneous counselling population as evidenced by similarity across major constructs. Path analysis supported theoretical formulations on burnout by Maslach and Cherniss, and gave support to Lin, Dean, and Ensel's argument that social support may act as a buffer to burnout.


Subject(s)
Burnout, Professional/psychology , Counseling , Volunteers/psychology , Adaptation, Psychological , Adult , Defense Mechanisms , Female , Humans , Male , Middle Aged , Social Support , Type A Personality , Workload/psychology
16.
Am J Med Genet ; 47(5): 660-78, 1993 Oct 01.
Article in English | MEDLINE | ID: mdl-8266994

ABSTRACT

The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders combining defects of craniofacial and limb development. The predominantly preaxial form is called Nager AFD, the predominantly postaxial form of AFD (POADS) is also known as the Genée-Wiedemann or Miller syndrome. The former appears to be about twice as common as the latter with well-documented autosomal dominant and recessive occurrences in both conditions. Only 1 AD occurrence of POADS is known, but 5 sets of sibs are suggestive of AR inheritance. Heterogeneity of apparently nonsyndromal AFD of both types is powerful support for the hypothesis that the AFDs are polytopic field defects arising during blastogenesis. Six other previously described forms of AFD include the AFD syndrome of Kelly et al. (AR), the Rodríguez or Madrid form of AFD (AR or XLR), the Reynolds or Idaho form of AFD (AD), the Arens or Tel Aviv type of AFD (AF?), the presumed AR AFD syndrome of Richieri-Costa et al., and the AD Patterson-Stevenson-Fontaine syndrome. Here we review the AFDs and report on a previously apparently undescribed autosomal or X-linked dominant form of AFD with mental retardation in a Sicilian mother and her 4 sons.


Subject(s)
Genes, Dominant , Mandibulofacial Dysostosis/genetics , X Chromosome , Adolescent , Adult , Child , Cytogenetics , Female , Fetal Growth Retardation/genetics , Genetic Linkage , Hand Deformities, Congenital/genetics , Humans , Intellectual Disability/genetics , Male , Pedigree , Syndrome
17.
Minerva Ginecol ; 44(7-8): 345-8, 1992.
Article in Italian | MEDLINE | ID: mdl-1407636

ABSTRACT

Our pelviscopic operative series from 1986 to June 1991 is reported. Nowadays our group performs 70% of female genital benign lesions by the pelviscopic technique. Infect laparotomy has been abandoned in case of benign ovarian cyst while the pelviscopic myomectomy rate is about 69%. Our results show that this kind of management is safe and also undeniable advantages such as morbidity reduction, shorter hospital stay, less social cost, quick return to work and renewing of the method make the indications more and more every day.


Subject(s)
Hysterectomy , Laparoscopy , Laparotomy , Female , Humans , Hysterectomy/methods , Laparotomy/trends , Uterine Diseases/surgery , Uterine Neoplasms/surgery
18.
J Cell Physiol ; 148(3): 380-90, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1655815

ABSTRACT

We have shown in previous studies that metastatically-competent variant subpopulations (B5, C1) derived from a non-metastatic murine mammary adenocarcinoma (SP1) have a pronounced growth advantage over their non-metastatic tumor cell counterparts in primary tumors. As a result, primary tumors can be progressively overgrown by cells having the competence to spread elsewhere in the body. This occurs despite any evidence to indicate an intrinsic in vivo growth rate advantage of the metastatic cells when grown as isolated populations. This suggested that cell-cell interactions between metastatic and non-metastatic tumor populations may be involved in the metastatic cell growth dominance process. Evidence was therefore sought for growth factors released by SP1 cells which could preferentially stimulate the B5 or C1 variants and thereby mediate this cell-cell interaction process. We found that cocultures of SP1 and C1 or B5 cells with irradiated C1, B5, or SP1 "feeder" cells showed significant stimulation of C1 and B5 by SP1 "feeder" cells. Cell growth stimulation in response to EGF, TGF-alpha, TGF-beta 1, bFGF, PDGF, NGF, IGF-1, or IGF-2 demonstrated that only TGF-beta 1 could duplicate this effect. A repeat of the coculture experiment in the presence of specific neutralizing anti-TGF-beta antibodies was therefore undertaken and this was found to markedly reduce the stimulation of C1 or B5 cells by irradiated SP1 cells. Conditioned media from the SP1 and C1 cell lines was quantitated for TGF-beta activity and contained 4.5 ng/ml and 2.0 ng/ml, respectively. However, the majority of the TGF-beta released by SP1 cells was found to be spontaneously active, whereas 70% of the TGF-beta released by C1 cells was in its latent form. Scatchard analysis revealed approximately four times the number of TGF-beta receptors, of similar type and affinity, present on C1 as compared with SP1 cells. The in vitro results support the hypothesis that active TGF-beta released by SP1 cells may stimulate the proliferation of metastatic variant cells in a paracrine like fashion. In vivo evidence for this was obtained by showing that coinjection of irradiated SP1 cells could selectively stimulate tumor growth of viable C1 cells and this effect was markedly diminished by neutralizing polyclonal anti-TGF-beta antibodies. Taken together, the results suggest a novel role for TGF-beta in clonal evolution of malignant tumor growth and as a molecular mediator of tumor cell-tumor cell interactions involved in facilitating tumor progression.


Subject(s)
Cell Communication , Cell Division , Growth Substances/pharmacology , Receptors, Cell Surface/physiology , Transforming Growth Factor beta/physiology , Adenocarcinoma/pathology , Animals , Antibodies , Cell Division/drug effects , Cell Line , Culture Media, Serum-Free , DNA Replication/drug effects , Female , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred DBA , Mice, Nude , Neoplasm Metastasis , Radioligand Assay , Receptors, Transforming Growth Factor beta , Thymidine/metabolism , Transforming Growth Factor beta/immunology , Transforming Growth Factor beta/pharmacology
19.
Biochem Biophys Res Commun ; 175(2): 697-705, 1991 Mar 15.
Article in English | MEDLINE | ID: mdl-2018512

ABSTRACT

Transient transfection of simian kidney (COS) cells with a recombinant plasmid encoding human preproendothelin-1 resulted in the production of biologically active endothelin-1. Conditioned medium from human preproendothelin-1 transfected cells demonstrated a significant increase in immunoreactive endothelin and big endothelin which co-eluted, when analyzed by reverse phase HPLC, with synthetic endothelin-1 and big endothelin-1, respectively. In addition, biological activity was confirmed by both inhibition of [125I]endothelin-1 binding to rat cerebellar and renal medullary membrane endothelin receptors and in vitro vasoconstriction of rabbit aorta. This is the first demonstration that human preproendothelin-1 is capable of being processed to a vasoactive form in a heterologous system and suggests that human preproendothelin-1 transfected COS cells may provide a useful model system for the study of endothelin biosynthesis.


Subject(s)
Endothelins/genetics , Animals , Biological Assay , Chlorocebus aethiops , Cloning, Molecular , DNA/genetics , Genetic Vectors , Humans , In Vitro Techniques , Rabbits , Recombinant Proteins , Transfection , Vasoconstriction
20.
Eur J Pharmacol ; 194(1): 115-7, 1991 Feb 26.
Article in English | MEDLINE | ID: mdl-1647960

ABSTRACT

The aim of the present study was to determine the effect of a calcium channel blocker on renal function, urinary endothelin excretion and endothelin receptor number in rats. Administration of cyclosporine resulted in a significant impairment of renal function when measured by either [14C]inulin or 24 h creatinine clearances. This nephrotoxicity was associated with statistically significant (P less than 0.05) increases in urinary endothelin excretion and renal endothelin receptor number. Treatment with nifedipine attenuated cyclosporine A-induced renal dysfunction and reduced urinary endothelin excretion. The data provide further evidence of a role for endothelin in cyclosporine A-induced nephrotoxicity.


Subject(s)
Cyclosporins/toxicity , Endothelins/urine , Kidney Diseases/prevention & control , Kidney/metabolism , Nifedipine/pharmacology , Receptors, Cell Surface/metabolism , Animals , Blood Urea Nitrogen , Creatinine/blood , Glomerular Filtration Rate/drug effects , In Vitro Techniques , Kidney/drug effects , Kidney Diseases/chemically induced , Kidney Diseases/physiopathology , Male , Membranes/drug effects , Membranes/metabolism , Rats , Rats, Inbred Strains , Receptors, Cell Surface/drug effects , Receptors, Endothelin
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