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1.
J Small Anim Pract ; 63(6): 486-491, 2022 06.
Article in English | MEDLINE | ID: mdl-34913482

ABSTRACT

Malignant pulmonary neoplasia associated with cystic airspaces is a well-recognised disease entity in humans. Two elderly dogs, previously diagnosed with a solitary emphysematous bulla, presented with non-specific clinical signs. At presentation, pulmonary auscultation was unremarkable. In both cases, thoracic CT demonstrated the transformation of the cystic airspace lesions characterised by a progressive increase of the solid component and reduction of the air component. Cytological evaluation and subsequent surgical excision followed by histopathology confirmed pulmonary carcinoma in both cases. These two cases represent the first demonstration of possible malignant transformation of pulmonary cystic airspace in dogs. Veterinarians should consider neoplastic transformation as a differential diagnosis in cases of cystic airspaces, particularly cases with features including thickening or irregularity of the wall, associated soft-tissue nodules or solid and non-solid tissue intermixed within clusters of multiple cystic airspaces. Ongoing monitoring of cystic airspace lesions through diagnostic imaging is recommended.


Subject(s)
Carcinoma , Cysts , Dog Diseases , Lung Neoplasms , Animals , Carcinoma/complications , Carcinoma/diagnosis , Carcinoma/surgery , Carcinoma/veterinary , Cysts/complications , Cysts/diagnostic imaging , Cysts/surgery , Cysts/veterinary , Dog Diseases/diagnostic imaging , Dog Diseases/surgery , Dogs , Lung , Lung Neoplasms/diagnosis , Lung Neoplasms/veterinary , Tomography, X-Ray Computed/methods , Tomography, X-Ray Computed/veterinary
2.
Br J Cancer ; 109(10): 2654-64, 2013 Nov 12.
Article in English | MEDLINE | ID: mdl-24136149

ABSTRACT

BACKGROUND: The DNA-repair gene DNA-dependent kinase catalytic subunit (DNA-PKcs) favours or inhibits carcinogenesis, depending on the cancer type. Its role in human hepatocellular carcinoma (HCC) is unknown. METHODS: DNA-dependent protein kinase catalytic subunit, H2A histone family member X (H2AFX) and heat shock transcription factor-1 (HSF1) levels were assessed by immunohistochemistry and/or immunoblotting and qRT-PCR in a collection of human HCC. Rates of proliferation, apoptosis, microvessel density and genomic instability were also determined. Heat shock factor-1 cDNA or DNA-PKcs-specific siRNA were used to explore the role of both genes in HCC. Activator protein 1 (AP-1) binding to DNA-PKcs promoter was evaluated by chromatin immunoprecipitation. Kaplan-Meier curves and multivariate Cox model were used to study the impact on clinical outcome. RESULTS: Total and phosphorylated DNA-PKcs and H2AFX were upregulated in HCC. Activated DNA-PKcs positively correlated with HCC proliferation, genomic instability and microvessel density, and negatively with apoptosis and patient's survival. Proliferation decline and massive apoptosis followed DNA-PKcs silencing in HCC cell lines. Total and phosphorylated HSF1 protein, mRNA and activity were upregulated in HCC. Mechanistically, we demonstrated that HSF1 induces DNA-PKcs upregulation through the activation of the MAPK/JNK/AP-1 axis. CONCLUSION: DNA-dependent protein kinase catalytic subunit transduces HSF1 effects in HCC cells, and might represent a novel target and prognostic factor in human HCC.


Subject(s)
Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Carcinoma, Hepatocellular/pathology , DNA-Activated Protein Kinase/genetics , Liver Neoplasms/pathology , Nuclear Proteins/genetics , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation , Cell Survival/genetics , DNA-Binding Proteins/physiology , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Heat Shock Transcription Factors , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Predictive Value of Tests , Prognosis , Transcription Factors/physiology
3.
Nat Prod Res ; 27(17): 1521-7, 2013.
Article in English | MEDLINE | ID: mdl-22974401

ABSTRACT

Apium graveolens L. (wild celery), belonging to the family of Apiaceae, is a scaposus hemicryptophyte. Instead, the cultivate plant is an annual or biennial herb widely used as a spice and seasoning in food. A broad range of biological activities have been attributed to A. graveolens. These include antimicrobial activity, larvicidal activity, hepatoprotective activity, nematicidal and mosquito repellent potential and antihyperlipidaemic properties.In this study, the authors compare the composition of the volatile fractions of A. graveolens collected in natural populations in Portugal and Italy and evaluate their potential as antifungal agents.The composition of the volatile oils obtained by hydrodistillation and their antifungal activity are reported. The oils were analysed by gas chromatography-flame ionisation detector and gas chromatography-mass spectrometry methods and their composition were compared with that of the volatile extracts isolated by supercritical CO2. A chemical variability in the extracts depending on the origin of the plants and on the extraction method was observed. The results showed the presence of sedanenolide, neocnidilide and neophytadiene as main components. The minimal inhibitory concentration (MIC) and the minimal lethal concentration were used to evaluate the antifungal activity of the oils against Candida albicans, Candida tropicalis, Candida krusei, Candida guilliermondii, Candida parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, Trichophyton mentagrophytes, T. mentagrophytes var. interdigitale, Trichophyton verrucosum, Microsporum canis, Microsporum gypseum, Epidermophyton floccosum, Aspergillus niger, Aspergillus fumigatus and Aspergillus flavus. The oil from Italy rich in neophytadiene is the more active, with MIC values of 0.04-0.64 µL mL(-1). Our results show that A. graveolens volatile extracts may be useful in the clinical treatment of fungal diseases.


Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Apium/chemistry , Carbon Dioxide/chemistry , Chromatography, Supercritical Fluid/methods , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Apiaceae , Aspergillus/drug effects , Candida/drug effects , Candida albicans/drug effects , Microbial Sensitivity Tests , Trichophyton/drug effects
4.
Nat Prod Res ; 26(11): 993-1003, 2012.
Article in English | MEDLINE | ID: mdl-21902563

ABSTRACT

The essential oils and supercritical CO2 extracts of wild Smyrnium olusatrum L. growing in Sardinia (Italy) and in Portugal were investigated. For the study, oils were isolated from total plant aerial part (umbels containing seeds). The content of ß-phellandrene (67.3% vs. 42.7%) and α-pinene (31.9% vs. 1.2%), respectively, the main components of Portuguese and Italian essential oils, declined during the maturation stage of the umbels. Contrarily, some other important components, particularly curzerene, germacrene B, germacrone, alexandrofuran, 1-ß-acetoxyfurano-4(15)-eudesmene and 1-ß-acetoxyfurano-3-eudesmene, increased in fruiting umbels. The chemical composition of the Sardinian oil is rather different from those of other origin. The composition of the supercritical extracts and the essential oils is markedly different, particularly due to the high amount of furanosesquiterpenoids in the supercritical fluid extraction. The minimal inhibitory concentration (MIC) and the minimal lethal concentration were used to evaluate the antifungal activity of the oils against Candida albicans, Candida tropicalis, Candida krusei, Candida guillermondii, Candida parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, Epidermophyton floccosum, Aspergillus niger, Aspergillus fumigatus and Aspergillus flavus. The oils were particularly active against dermatophyte strains and C. neoformans, with MIC values in the range of 0.32-0.64 µL mL⁻¹.


Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Apiaceae/chemistry , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Fungi/drug effects , Gas Chromatography-Mass Spectrometry , Italy , Microbial Sensitivity Tests , Portugal
5.
Exp Clin Endocrinol Diabetes ; 119(10): 610-2, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21553366

ABSTRACT

Shwachman-Diamond syndrome is a rare clinical condition consisting of exocrine pancreatic dysfunction, various degree of pancytopenia, and metaphyseal dysplasia. The majority of Shwachman-Diamond syndrome cases result from mutations in the Shwachman-Bodian-Diamond Syndrome gene. To date, type 1 diabetes mellitus has only been reported in 4 independent cases presenting with Shwachman-Diamond syndrome, 3 of them with molecular confirmation of the diagnosis. We describe 2 unrelated patients with clinical and molecular features typical of Shwachman-Diamond syndrome and type 1 diabetes mellitus. In addition, we report the occurrence rate of type 1 diabetes mellitus in the Italian registry for Shwachman-Diamond syndrome, which is low (3.23%) but increased at least 30-fold over the type 1 diabetes mellitus occurrence rate in the general population. No evidence of a direct correlation between Shwachman-Diamond syndrome and type 1 diabetes mellitus have been reported, therefore the presence of both diseases in the same patient might be a chance association, however we suggest that the defects in immune regulation of Shwachman-Diamond syndrome might play a role in the development of type 1 diabetes mellitus.


Subject(s)
Bone Marrow Diseases/complications , Diabetes Mellitus, Type 1/complications , Exocrine Pancreatic Insufficiency/complications , Lipomatosis/complications , Bone Marrow Diseases/genetics , Bone Marrow Diseases/immunology , CD4-CD8 Ratio , Diabetes Mellitus, Type 1/etiology , Exocrine Pancreatic Insufficiency/genetics , Exocrine Pancreatic Insufficiency/immunology , Female , Heterozygote , Humans , Immune System/physiopathology , Infant , Italy/epidemiology , Lipomatosis/genetics , Lipomatosis/immunology , Male , Mutation , Prevalence , Proteins/genetics , Registries , Shwachman-Diamond Syndrome
6.
Gut ; 58(5): 679-87, 2009 May.
Article in English | MEDLINE | ID: mdl-19136513

ABSTRACT

BACKGROUND AND AIMS: Previous studies indicate unrestrained cell cycle progression in liver lesions from hepatocarcinogenesis-susceptible Fisher 344 (F344) rats and a block of G(1)-S transition in corresponding lesions from resistant Brown Norway (BN) rats. Here, the role of the Forkhead box M1B (FOXM1) gene during hepatocarcinogenesis in both rat models and human hepatocellular carcinoma (HCC) was assessed. METHODS AND RESULTS: Levels of FOXM1 and its targets were determined by immunoprecipitation and real-time PCR analyses in rat and human samples. FOXM1 function was investigated by either FOXM1 silencing or overexpression in human HCC cell lines. Activation of FOXM1 and its targets (Aurora Kinose A, Cdc2, cyclin B1, Nek2) occurred earlier and was most pronounced in liver lesions from F344 than BN rats, leading to the highest number of Cdc2-cyclin B1 complexes (implying the highest G(2)-M transition) in F344 rats. In human HCC, the level of FOXM1 progressively increased from surrounding non-tumorous livers to HCC, reaching the highest levels in tumours with poorer prognosis (as defined by patients' length of survival). Furthermore, expression levels of FOXM1 directly correlated with the proliferation index, genomic instability rate and microvessel density, and inversely with apoptosis. FOXM1 upregulation was due to extracellular signal-regulated kinase (ERK) and glioblastoma-associated oncogene 1 (GLI1) combined activity, and its overexpression resulted in increased proliferation and angiogenesis and reduced apoptosis in human HCC cell lines. Conversely, FOXM1 suppression led to decreased ERK activity, reduced proliferation and angiogenesis, and massive apoptosis of human HCC cell lines. CONCLUSIONS: FOXM1 upregulation is associated with the acquisition of a susceptible phenotype in rats and influences human HCC development and prognosis.


Subject(s)
Carcinoma, Hepatocellular/genetics , Extracellular Signal-Regulated MAP Kinases/genetics , Forkhead Transcription Factors/genetics , Liver Neoplasms/genetics , Animals , Carcinoma, Hepatocellular/pathology , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Forkhead Box Protein M1 , Forkhead Transcription Factors/physiology , Gene Expression Regulation, Neoplastic/genetics , Genes, cdc , Genetic Predisposition to Disease/genetics , Liver/pathology , Liver Neoplasms/pathology , Neovascularization, Pathologic/etiology , Rats , Rats, Inbred F344 , Transcriptional Activation , Up-Regulation
7.
Biochim Biophys Acta ; 1765(2): 126-47, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16216419

ABSTRACT

The different frequency of hepatocellular carcinoma (HCC) in humans at risk suggests a polygenic predisposition. However, detection of genetic variants is difficult in genetically heterogeneous human population. Studies on mouse and rat models identified 7 hepatocarcinogenesis susceptibility (Hcs) and 2 resistance (Hcr) loci in mice, and 7 Hcs and 9 Hcr loci in rats, controlling multiplicity and size of neoplastic liver lesions. Six liver neoplastic nodule remodeling (Lnnr) loci control number and volume of re-differentiating lesions in rat. A Hcs locus, with high phenotypic effects, and various epistatic gene-gene interactions were identified in rats, suggesting a genetic model of predisposition to hepatocarcinogenesis with different subset of low-penetrance genes, at play in different subsets of population, and a major locus. This model is in keeping with human HCC epidemiology. Several putative modifier genes in rodents, deregulated in HCC, are located in chromosomal segments syntenic to sites of chromosomal aberrations in humans, suggesting possible location of predisposing loci. Resistance to HCC is associated with lower genomic instability and downregulation of cell cycle key genes in preneoplastic and neoplastic lesions. p16(INK4A) upregulation occurs in susceptible and resistant rat lesions. p16(INK4A)-induced growth restraint was circumvented by Hsp90/Cdc37 chaperons and E2f4 nuclear export by Crm1 in susceptible, but not in resistant rats and human HCCs with better prognosis. Thus, protective mechanisms seem to be modulated by HCC modifiers, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.


Subject(s)
Carcinoma, Hepatocellular/genetics , Genetic Predisposition to Disease , Liver Neoplasms/genetics , Animals , Cell Transformation, Neoplastic/genetics , Humans
8.
J Fr Ophtalmol ; 28(6): 642-5, 2005 Jun.
Article in French | MEDLINE | ID: mdl-16141931

ABSTRACT

The authors report a case of a young patient with a recent decrease in unilateral vision. He had homozygote sickle cell disease with multiple general complications. Fundus examination was normal apart from a mild alteration of the macular reflect in the left eye, but fluorescein angiography showed multiple arteriolar macular occlusions, explaining the decrease in vision in the left eye. After erythropheresis, vision acuity improved and fluorescein angiography showed reperfusion. This case suggests that transfusional exchange may improve acute macular ischemia secondary to sickle cell disease.


Subject(s)
Anemia, Sickle Cell/complications , Macular Degeneration/etiology , Vision, Monocular , Acute Disease , Adolescent , Blood Transfusion , Erythropoiesis , Fluorescein Angiography , Humans , Macular Degeneration/diagnosis , Macular Degeneration/therapy , Male
9.
J Fr Ophtalmol ; 26(9): 905-10, 2003 Nov.
Article in French | MEDLINE | ID: mdl-14631274

ABSTRACT

PURPOSE: To report and analyze the circumstances of uveal melanoma detection. METHODS: The records of 143 consecutive patients diagnosed in the Ophthalmology Department of Gustave Roussy Institute between September 1994 and September 2001 were analyzed. The study included 66 females and 77 males, aged from 21 to 91 years (mean, 62.75 years). RESULTS: The first symptom was decreased visual acuity in 37% of cases. In 34.9%, there was no functional sign and a systematic fundus exam provided the diagnosis. Of the 143 patients, 18.8% presented alteration of the visual field or scotoma, 9.9% complained of phosphenes, 9% complained of metamorphopsia, and 6.5% complained of floaters. In 5.5% of cases, there was documented tumor growth. In 2%, the presence of extrascleral exteriorization was the first sign. At the time of diagnosis, anterior tumors tended to be significantly larger than posterior tumors (p<0.007). Smaller lesions were significantly associated with a systematic detection of the tumor (p<0.005). Liver metastasis occurred more frequently with ciliary body melanomas (p<0.001), which were more frequently the largest lesions. CONCLUSION: These results emphasize the importance of early detection of uveal melanoma. We recommended frequent fundus examination after pupil dilatation.


Subject(s)
Choroid Neoplasms/diagnosis , Melanoma/diagnosis , Uveal Neoplasms/diagnosis , Adult , Age Distribution , Aged , Aged, 80 and over , Choroid Neoplasms/complications , Choroid Neoplasms/epidemiology , Ciliary Body , Diagnosis, Differential , Female , France/epidemiology , Humans , Liver Neoplasms/secondary , Male , Melanoma/complications , Melanoma/epidemiology , Middle Aged , Ophthalmoscopy , Phosphenes , Prognosis , Retrospective Studies , Scotoma/etiology , Sex Distribution , Time Factors , Uveal Neoplasms/complications , Uveal Neoplasms/epidemiology , Vision Disorders/etiology , Visual Acuity , Visual Fields
10.
J Fr Ophtalmol ; 26(7): 720-4, 2003 Sep.
Article in French | MEDLINE | ID: mdl-13130260

ABSTRACT

INTRODUCTION: This study aimed to describe the clinical characteristics of uveitis presenting de novo in the elderly. The study design was a description of a retrospectively identified case series. PATIENTS: The records of 193 patients with uveitis referred to Bicêtre Hospital's department of ophthalmology between January 1995 and January 2000 were reviewed. Among these patients, the records of 57 patients with uveitis de novo beginning after age 60 were analyzed. RESULTS: Idiopathic uveitis accounted for the majority of cases. Whereas herpes viruses were the most frequent specific diagnosis, presumed sarcoidosis and birdshot choroidopathy were also identified as diagnostic entities of uveitis presenting for the first time in the elderly. Only three cases of masquerade syndrome were identified, two cases of intraocular lymphoma, and one metastasis of a visceral melanoma. CONCLUSION: Masquerade syndromes are not the leading cause of uveitis in the elderly. Idiopathic uveitis and herpes viruses are the most common etiology found.


Subject(s)
Uveitis/epidemiology , Aged , Autoimmune Diseases/genetics , Diagnosis, Differential , Eye Neoplasms/diagnosis , Eye Neoplasms/secondary , Female , France/epidemiology , HLA-B27 Antigen/analysis , HLA-B27 Antigen/genetics , Herpesviridae Infections/complications , Humans , Lymphoma/diagnosis , Male , Melanoma/diagnosis , Melanoma/secondary , Middle Aged , Retrospective Studies , Sarcoidosis/complications , Uveitis/diagnosis , Uveitis/etiology , Uveitis/virology
11.
P. R. health sci. j ; 21(4): 351-354, Dec. 2002.
Article in Spanish | LILACS | ID: lil-356227

ABSTRACT

The high prevalence of violence in children and youth has been a great concern among diverse sectors of our society. Considered as a complex public health problem, the Centers of Disease Control and Prevention (CDC) of Atlanta, Georgia, has financed local and national projects geared to its prevention. This work describes the process in which the Developing Centers of Youth Violence Prevention from the University of Puerto Rico and the University of Southern California collaborated in the development of core competencies for health professionals in youth violence prevention. This two Developing Centers are projects funded by the CDC.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Violence/prevention & control
12.
J Fr Ophtalmol ; 25(6): 599-603, 2002 Jun.
Article in French | MEDLINE | ID: mdl-12223947

ABSTRACT

PURPOSE: To report the treatment strategies and visual acuity outcomes of chronic postoperative endophthalmitis. MATERIAL: and methods: The authors reviewed the records of 15 patients presenting 3 or more weeks after cataract surgery with intraocular inflammation and treated at Bicêtre Hospital from 1992 to 1998. Group I included 6 consecutive patients treated with vitrectomy and intravitreal antibiotic injection (vancomycin and cefazolin). Group II included 9 consecutive patients treated with intravitreal antibiotic injection (vancomycin and ceftazidime) and irrigation of the capsular bag (vancomycin). The minimum follow-up period was 1 year. RESULTS: In group I, 2 patients had recurrent inflammation. In these patients, the capsular bag and the intraocular implant were removed. In 1 patient there was culture-proven Corynebacterium and in 1 patient a Staphylococcus epidermidis was found. Final visual acuity was 20/40 or better in 5 patients and 20/100 in 1 patient. Visual acuity improved in all cases. In group II no recurrence was seen in the 12-20 months of follow-up. In 2 patients there was proven Staphylococcus epidermidis and in one patient Propionibacterium acnes was found. Final visual acuity was 20/40 or more in 3 patients, 20/100 or more in 4 patients and less than 20/200 in 2 patients. Visual acuity improved in 8 cases. CONCLUSIONS: Intravitreal antibiotic injection with vitrectomy and intravitreal antibiotic injection with antibiotic irrigation of the capsular bag are both effective in the treatment of delayed chronic postoperative endophthalmitis; however, with the second approach, there is minimal surgical trauma and the intraocular implant is retained.


Subject(s)
Cataract Extraction/adverse effects , Endophthalmitis/therapy , Postoperative Complications/therapy , Corynebacterium Infections/diagnosis , Corynebacterium Infections/therapy , Endophthalmitis/diagnosis , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/therapy , Follow-Up Studies , Humans , Inflammation , Retrospective Studies , Time Factors , Visual Acuity
13.
J Fr Ophtalmol ; 25(4): 399-403, 2002 Apr.
Article in French | MEDLINE | ID: mdl-12011745

ABSTRACT

PURPOSE: To investigate the outcome of irradiation of complicated choroidal hemangiomas in Sturge-Weber syndrome. PATIENTS AND METHODS: The charts of 6 patients (7 eyes) with Sturge-Weber syndrome and choroidal hemangiomas were reviewed. An exudative retinal detachment was the indication for treatment in all cases. The mean age of the 6 patients was 13 years (range, 4 to 20 years). The minimum follow-up time was 1 year. Patients were checked for initial and final best-corrected visual acuity, fundus examination, fluorescein angiography, and tumor thickness on B-scan ultrasonography. The patients were treated with radiotherapy. A total dose of 20 Grays was applied to 7 eyes: 2 with a circumscribed choroidal hemangioma underwent proton therapy and 5 with diffuse hemangioma were treated by external beam irradiation. RESULTS: Complete resolution of the subretinal fluid was achieved in all cases with the tumor height decreased. Visual acuity improved to 1 line or more in 5 eyes and remained stable in 2 eyes. Two cases that underwent proton therapy developed radiation retinopathy. CONCLUSION: External beam radiation is an effective and safe option in the management of choroidal hemangiomas complicated by retinal detachment. Based on our experience, proton therapy should be reserved for sporadic circumscribed choroidal hemangioma.


Subject(s)
Choroid Neoplasms/radiotherapy , Hemangioma/radiotherapy , Sturge-Weber Syndrome/radiotherapy , Adolescent , Child , Child, Preschool , Female , Humans , Male , Radiotherapy/adverse effects , Radiotherapy Dosage , Treatment Outcome
14.
J Fr Ophtalmol ; 25(10): 1032-5, 2002 Dec.
Article in French | MEDLINE | ID: mdl-12527827

ABSTRACT

Diffuse uveal melanocytic proliferation is a rare paraneoplastic syndrome resulting in rapid bilateral visual loss in patients with systemic carcinoma, caused by proliferation of benign melanocytes within the choroid and the ciliary body. More often visual impairment is due to retinal detachment and cataract. The authors report two cases of presumed diffuse uveal melanocytic proliferation. The first patient was a 74-year-old man with a history of colic carcinoma and hemangioendothelioma of the liver who presented with bilateral multiple nevi of the choroid and extrascleral melanic nodule. The second patient was a 59-year-old woman who presented bilateral multiple nevi of the choroid and a history of carcinoma of the thyroid treated by thyroidectomy 2 years before. There was no evidence of systemic melanoma in either patient. Our two patients showed slow progression with no visual impairment and a longer survival than those described in the literature.


Subject(s)
Melanocytes/pathology , Paraneoplastic Syndromes/pathology , Uvea/pathology , Aged , Cell Division , Female , Humans , Male , Middle Aged
15.
Hepatology ; 33(5): 1110-7, 2001 May.
Article in English | MEDLINE | ID: mdl-11343238

ABSTRACT

Hepatocarcinogenesis sensitivity (Hcs1, 2) and resistance (Hcr1-3) loci have been identified by linkage analysis on rat chromosomes 7 and 1, and 10, 4, and 8, respectively. Cytogenetic studies documented deletions on chromosomes 3 and 6 of neoplastic rat hepatocytes. Hepatocellular carcinomas (HCCs) were produced in F1 hybrid rats between Long-Evans (LE) and Fisher 344 (F344) rats. Scanning of the above chromosomes for loss of heterozygosity (LOH) showed allelic imbalance (AI) at multiple regions on chromosomes 6, 7, and 10q. Detailed deletion mapping of chromosome 10 localized a putative suppressor Hcr1 gene to within a 3.2-cM interval flanked by D10Rat51 and D10Rat121. Two other distinct regions with frequent AIs were found inside the Hcr1 locus, at marker loci including DNaseI and Mrp genes, and in a segment including 4 consecutive markers (D10Rat64, D10Rat182, D10Rat113, D10Rat216). In 40% of HCCs, AI was seen at the p53 locus. AI on chromosome 7 occurred at the Hcs1 locus, where is located c-myc, which is amplified in HCCs, suggesting allelic gain. Most AIs occurred in poorly/moderately differentiated carcinomas, and a few events were seen in well-differentiated tumors on chromosomes 7 and 10. These data suggest that alteration of a cluster of oncosuppressor genes on 10q is important for HCC progression. The existence of AI on segments of rat chromosomes 6, 7, and 10, syntenic to chromosomal segments of human HCCs where chromosomal gains or deletions occur, suggests a commonality of some molecular events in the pathogenesis of HCCs in rats and humans. Our map provides information toward cloning putative oncosuppressor genes associated with this carcinoma.


Subject(s)
Carcinoma, Hepatocellular/genetics , Chromosome Mapping , Chromosomes/genetics , Liver Neoplasms/genetics , Loss of Heterozygosity , Transcription Factors/genetics , Animals , Genes, Tumor Suppressor/genetics , Genetic Predisposition to Disease , Genetic Testing , Rats , Rats, Inbred Strains
16.
Carcinogenesis ; 22(2): 301-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11181452

ABSTRACT

Dehydroepiandrosterone (DHEA) inhibits glucose 6-phosphate dehydrogenase (G6PD) activity and growth of preneoplastic lesions in various tissues, but its administration may also enhance tumorigenesis by genotoxic carcinogens. We have investigated in single preneoplastic liver lesions, induced in diethylnitrosamine-initiated rats by the resistant hepatocyte protocol, the mechanisms underlying these opposite DHEA effects. Administration of DHEA (0.45% in the diet) for 10 and 26 weeks and of its analog 16alpha-fluoro-5-androsten-17-one (FA, 0.25%) for 10 weeks, starting 4 weeks after initiation, induced an apparent decrease in the number of glutathione S:-transferase (placental) (GST-P)-positive lesions and an increase in lesion volume. DHEA administration for 38 weeks enhanced hepatocellular carcinoma multiplicity. Depending on the rise in the number of slowly growing, remodeling GST-P-positive lesions induced by DHEA and FA, overall DNA synthesis decreased slightly in these lesions at 14 weeks, but increased in uniform lesions. Labeling index (LI) in single uniform lesions at 14 weeks ranged between very low (not different from normal liver) to high (>10-fold normal liver). DHEA and FA induced broad increases in lesions with a high LI, which showed a higher number of cells overexpressing c-Ha-ras and/or c-fos than those with a lower LI. High G6PD activity was inhibited by DHEA and FA in only approximately 50% of preneoplastic lesions. These data indicate selection in rats subjected to long-term DHEA and FA treatments of a subpopulation of GST-P-positive cells with high growth and progression potentials. Overall effects of these compounds depends on the relative numbers of lesions in which inhibition of DNA synthesis can counteract their transforming effect.


Subject(s)
Carcinoma, Hepatocellular/metabolism , DNA/biosynthesis , Dehydroepiandrosterone/administration & dosage , Diethylnitrosamine/toxicity , Liver Neoplasms, Experimental/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , DNA Replication/drug effects , Dehydroepiandrosterone/analogs & derivatives , Diet , Drug Resistance , Glucosephosphate Dehydrogenase/metabolism , Glutathione Transferase/metabolism , Hepatocytes/drug effects , Immunoenzyme Techniques , Liver Neoplasms, Experimental/genetics , Liver Neoplasms, Experimental/pathology , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Rats , Rats, Inbred F344
17.
J Fr Ophtalmol ; 24(8): 851-3, 2001 Oct.
Article in French | MEDLINE | ID: mdl-11894537

ABSTRACT

We report a case of cloudiness occurring on the anterior surface of a hydrophilic acrylic foldable intraocular lens 1 year following implantation. This was not a case of phimosis of the capsulorhexis; the dondiness seemed secondary to fibroepithelial proliferation. Successful reopening was obtained with YAG laser. No recurrence was observed during the six months of follow-up.


Subject(s)
Lenses, Intraocular , Postoperative Complications/etiology , Acrylic Resins , Aged , Female , Humans , Postoperative Complications/pathology
18.
J Fr Ophtalmol ; 23(3): 217-20, 2000 Mar.
Article in French | MEDLINE | ID: mdl-10740045

ABSTRACT

PURPOSE: We report 3 cases of familial amyloid polyneuropathy type I (FAP) with amyloid infiltration of the vitreum and glaucoma. PATIENTS AND METHODS: We reviewed the records of three patients, 2 females and one male, aged 41, 47 and 83 years respectively. The 3 patients had familial amyloid polyneuropathy type I with vitreous infiltration and open angle glaucoma. The two women underwent a liver graft four years earlier. Vitrectomy allowed confirmation of the diagnosis in the 83-year-old patient. Two patients underwent trabeculectomy, histological analysis of the iris and the trabeculum was obtained for one patient. RESULTS: The tree patients presented a polyneuropathy, vitreous infiltration and open angle glaucoma. Results of light microscopy of the iris and the trabeculum showed amyloid deposits in the iris and the trabecular meshworks. CONCLUSION: Familial amyloid polyneuropathy is a hereditary disease which may have a wide range of ocular manifestations. Glaucoma is among the most serious complications of familial amyloid polyneuropathy.


Subject(s)
Amyloid Neuropathies/complications , Glaucoma/complications , Adult , Aged , Aged, 80 and over , Amyloid Neuropathies/diagnosis , Chronic Disease , Congo Red , Female , Glaucoma/diagnosis , Glaucoma/surgery , Humans , Male , Middle Aged , Trabeculectomy , Visual Acuity
19.
J Fr Ophtalmol ; 23(10): 1031-4, 2000 Dec.
Article in French | MEDLINE | ID: mdl-11139700

ABSTRACT

Cytomegalovirus retinitis is the most common opportunistic ocular infection in patients with AIDS affecting 30 to 40% of the patients. It usually occurs in patients in the terminal stage of the disease presenting with low CD4+ count (<50/mm(3)). Retinal detachment (RD) is a frequent complication of this disease, with an incidence varying from 18% to 29%. Risk factors for development of rhegmatogenous RD in patients with CMV retinitis were peripheral involvement greater than 25%, the presence of active retinitis, greater patient age and lower CD4+ cell counts. Multiple or single holes, as well as micro holes, were observed in areas of retinal necrosis leading to complex retinal detachments. Strong vitreoretinal adherences in these young patients, associated with chronic inflammation, were important elements in the pathophysiology of retinal detachment in AIDS patients. For localized RD, demarcating laser photocoagulation may delayed or avoided vitreoretinal surgery. For RD with macula off, good anatomical results have been obtained by repairing CMV retinitis-related retinal detachments using primary vitrectomy and instillation of silicone oil. Despite good anatomical results, poor long term functional results are related to optic atrophy. Since the introduction of highly active antiretroviral therapy (HAART), retinal detachment incidence has nevertheless dramatically decreased. Under HAART, CMV retinitis remains quiescent for long periods of time with a reduction of retinal detachment incidence of approximately 77%. For some patients on HAART, retinal reattachment can be obtained using vitrectomy, posterior hyaloid removal, and intraocular tamponade with SF-6 gas.


Subject(s)
AIDS-Related Opportunistic Infections/complications , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/drug therapy , Retinal Detachment/etiology , AIDS-Related Opportunistic Infections/physiopathology , Antiretroviral Therapy, Highly Active , Antiviral Agents/therapeutic use , Humans , Retinal Detachment/physiopathology , Retinal Detachment/surgery , Vitrectomy
20.
J Fr Ophtalmol ; 22(8): 872-5, 1999 Oct.
Article in French | MEDLINE | ID: mdl-10572800

ABSTRACT

We report a case of atypical circumscribed choroidal hemangioma with retinal detachment in a 41-year-old man referred with the diagnosis of Harada disease. B. Scan ultrasonography showed an hyperechogenic area extended through the sclera. Careful examination of the fundus showed a small peripapillary orange mass and an inferior retinal detachment. Surgical exploration revealed an extrascleral hemangioma. Proton beam irradiation was followed by retinal reattachment within three months. No recurrence has been observed 18 months after treatment.


Subject(s)
Choroid Neoplasms/diagnosis , Hemangioma/diagnosis , Sclera , Adult , Choroid Neoplasms/radiotherapy , Choroid Neoplasms/surgery , Combined Modality Therapy , Hemangioma/radiotherapy , Hemangioma/surgery , Humans , Male , Neoplasm Invasiveness , Radiotherapy, Adjuvant , Retinal Detachment/diagnosis , Retinal Detachment/radiotherapy , Retinal Detachment/surgery , Sclera/pathology , Scleral Buckling
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