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1.
Nat Commun ; 12(1): 6496, 2021 11 11.
Article in English | MEDLINE | ID: mdl-34764250

ABSTRACT

The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2-/- hiPSCs but not from isogenic TSC2+/- or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2-/- renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.


Subject(s)
Phosphopyruvate Hydratase/metabolism , Tuberous Sclerosis Complex 2 Protein/metabolism , Animals , Computational Biology , Cytochromes c/metabolism , Disease Models, Animal , Engineering , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Immunoprecipitation , In Situ Nick-End Labeling , Induced Pluripotent Stem Cells/metabolism , Male , Mice, Transgenic , Organoids/metabolism , Phosphopyruvate Hydratase/genetics , Rats , Rats, Nude , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, RNA , Tuberous Sclerosis Complex 2 Protein/genetics
2.
Arch Soc Esp Oftalmol ; 85(3): 97-102, 2010 Mar.
Article in Spanish | MEDLINE | ID: mdl-20619120

ABSTRACT

PURPOSE: To evaluate intraocular pressure (IOP) and visual acuity (VA) results after glaucoma drainage device (GDD) implantation combined with simultaneous pars plana vitrectomy (PPV). MATERIAL AND METHODS: Retrospective review of 8 eyes (7 patients). The diagnosis was neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy in 4 eyes, in a which a double plate Molteno implant was placed, and glaucoma secondary (GS) to complicated cataract surgery in 3 eyes and penetrating trauma in one eye, in which a glaucoma Ahmed valve was implanted. RESULTS: Mean preoperative IOP was 35.77 mmHg (20-50) and 11.5 mmHg (2-20) postoperatively, and mean number hypotensive drugs was decreased from 2.33 (0-3) before surgery to 0.62 (0-3) after it. Preoperative VA in NVG was light perception or counting fingers, and it was lost in three eyes. In GS, VA before surgery was below 0.1 in all eyes, and three months after surgery mean VA was 0.42 (0.1-0.8). Mean follow-up was 10.12 months (5-27). The complications were tube obstruction in two cases, one of these presenting also a suprachoroidal hemorrage and ptisis bulbi, plate exposure in one case, and bullous keratopathy as a late complication in another eye. CONCLUSIONS: The VA and IOP were well controlled with this procedure in GS. In NVG, IOP was controlled, but visual results were poor due to complications and the underlying pathology.


Subject(s)
Glaucoma Drainage Implants , Glaucoma/surgery , Vitrectomy , Aged , Aged, 80 and over , Cataract Extraction , Choroid Hemorrhage/etiology , Corneal Diseases/etiology , Diabetic Retinopathy/complications , Equipment Failure , Eye Injuries, Penetrating/complications , Female , Glaucoma/etiology , Glaucoma, Neovascular/etiology , Glaucoma, Neovascular/surgery , Humans , Intraocular Pressure , Male , Middle Aged , Molteno Implants , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Treatment Outcome
3.
Arch. Soc. Esp. Oftalmol ; 85(3): 97-102, mar. 2010. tab, ilus
Article in Spanish | IBECS | ID: ibc-85861

ABSTRACT

Objetivo: Evaluar los resultados en cuanto a control de presión intraocular (PIO) y agudezavisual (AV) tras cirugía de implante de drenaje para glaucoma (DDG) combinada con vitrectomíapars plana (VPP) simultánea.Material y métodos: Revisión retrospectiva de 8 ojos (7 pacientes). El diagnóstico era glaucomaneovascular (GNV) secundario a retinopatía diabética proliferativa en 4 ojos, en los quese colocó un implante de Molteno de doble plato, y glaucoma secundario (GS) a cirugía decatarata complicada en 3 ojos y a traumatismo penetrante en otro, en los que se usó unaválvula de Ahmed.Resultados: La PIO media pasó de 35,77 mmHg (20-50) preoperatoria a 11,5 mmHg (2-20)postoperatoria, y el número de fármacos hipotensores medio de 2,33 (0-3) preoperatorio a0,62 (0-3) postoperatorio. En los GNV, la AV preoperatoria era percepción de luz o contardedos, y se perdió en 3 ojos. En los GS era inferior a 0,1, aumentando hasta una AV mediade 0,42 (0,1-0,8) a los 3 meses. El seguimiento medio fue de 10,12 meses (5-27). Las complicacionesfueron obstrucción del tubo por fibrina en 2 casos, uno de los cuales (GNV) presentóuna hemorragia supracoroidea tras la desobstrucción y evolución a ptisis bulbi, extrusióndel reservorio en un caso, y descompensación corneal tardía en un caso.Conclusiones: En los GS los resultados han sido buenos, con mejoría de la AV y PIO controlada.En los GNV se consiguió controlar la PIO y evitar dolor, pero los resultados visualesfueron malos por la enfermedad de base(AU)


Purpose: To evaluate intraocular pressure (IOP) and visual acuity (VA) results after glaucomadrainage device (GDD) implantation combined with simultaneous pars plana vitrectomy(PPV).Material and methods: Retrospective review of 8 eyes (7 patients). The diagnosis wasneovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy in 4 eyes, in awhich a double plate Molteno implant was placed, and glaucoma secondary (GS) tocomplicated cataract surgery in 3 eyes and penetrating trauma in one eye, in which aglaucoma Ahmed valve was implanted.Results: Mean preoperative IOP was 35.77 mmHg (20-50) and 11.5 mmHg (2-20) postoperatively,and mean number hypotensive drugs was decreased from 2.33 (0-3) before surgery to 0.62(0-3) after it. Preoperative VA in NVG was light perception or counting fingers, and it waslost in three eyes. In GS, VA before surgery was below 0.1 in all eyes, and three months aftersurgery mean VA was 0.42 (0.1-0.8). Mean follow-up was 10.12 months (5-27). Thecomplications were tube obstruction in two cases, one of these presenting also asuprachoroidal hemorrage and ptisis bulbi, plate exposure in one case, and bullouskeratopathy as a late complication in another eye.Conclusions: The VA and IOP were well controlled with this procedure in GS. In NVG, IOP wascontrolled, but visual results were poor due to complications and the underlyingpathology(AU)


Subject(s)
Humans , Male , Female , Aged , Glaucoma Drainage Implants , Vitrectomy , Glaucoma, Neovascular/diagnosis , Intraocular Pressure , Visual Acuity , Microscopy , Carbonic Anhydrase Inhibitors/therapeutic use
4.
Water Res ; 35(14): 3325-36, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11547853

ABSTRACT

Quantitative oligonucleotide probe hybridizations, immunostaining, and a simple foaming potential test were used to follow an incident of seasonal filamentous foaming at the Urbana-Champaign Sanitary District, Northeast Wastewater Treatment Plant. A positive correlation was observed between an increase in foaming potential and the appearance of foam on the surfaces of aeration basins and secondary clarifiers. In addition, during the occurrence of foaming, the mass and activity of Gordonia spp. increased as measured by fluorescence in situ hybridization, antibody staining, and quantitative membrane hybridization of RNA extracts. An increase in Gordonia spp. rRNA levels from 0.25 to 1.4% of total rRNA was observed using quantitative membrane hybridizations, whereas during the same period, the fraction of mixed liquor volatile suspended solids attributed to Gordonia spp. increased from 4% to more than 32% of the total mixed liquor volatile suspended solids. These results indicate that both the activity and biomass level of Gordonia spp. in activated sludge increased relative to the activity aid the biomass level of the complete microbial community during a seasonal occurrence of filamentous foaming. Thus, Gordonia spp. may represent a numerically dominant but metabolically limited fraction of the total biomass, and the role of Gordonia spp. in filamentous foaming may be linked more tightly to the physical presence of filamentous microorganisms than to the metabolic activity of the cells.


Subject(s)
Actinomycetales/isolation & purification , Immunoblotting , In Situ Hybridization, Fluorescence , Sewage/microbiology , Water Purification , Actinomycetales/genetics , Antibodies , Biomass , Oligonucleotide Probes , RNA, Ribosomal/genetics , Seasons
5.
Appl Environ Microbiol ; 64(7): 2503-12, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9647822

ABSTRACT

Previous studies have shown the predominance of mycolic acid-containing filamentous actinomycetes (mycolata) in foam layers in activated sludge systems. Gordona (formerly Nocardia) amarae often is considered the major representative of this group in activated sludge foam. In this study, small-subunit rRNA genes of four G. amarae strains were sequenced, and the resulting sequences were compared to the sequence of G. amarae type strain SE-6. Comparative sequence analysis showed that the five strains used represent two lines of evolutionary descent; group 1 consists of strains NM23 and ASAC1, and group 2 contains strains SE-6, SE-102, and ASF3. The following three oligonucleotide probes were designed: a species-specific probe for G. amarae, a probe specific for group 1, and a probe targeting group 2. The probes were characterized by dissociation temperature and specificity studies, and the species-specific probe was evaluated for use in fluorescent in situ hybridizations. By using the group-specific probes, it was possible to place additional G. amarae isolates in their respective groups. The probes were used along with previously designed probes in membrane hybridizations to determine the abundance of G. amarae, group 1, group 2, bacterial, mycolata, and Gordona rRNAs in samples obtained from foaming activated sludge systems in California, Illinois, and Wisconsin. The target groups were present in significantly greater concentrations in activated sludge foam than in mixed liquor and persisted in anaerobic digesters. Hybridization results indicated that the presence of certain G. amarae strains may be regional or treatment plant specific and that previously uncharacterized G. amarae strains may be present in some systems.


Subject(s)
DNA, Bacterial/genetics , Nocardia/genetics , RNA, Ribosomal/genetics , Sewage/microbiology , Anaerobiosis , Nocardia/classification , Nocardia/isolation & purification , Nucleic Acid Hybridization , Oligonucleotide Probes , Phylogeny , Sequence Analysis, DNA
6.
Aesthetic Plast Surg ; 7(2): 101-8, 1983.
Article in English | MEDLINE | ID: mdl-6613735

ABSTRACT

After the follow-up of breasts operated on using several breast reduction techniques that resect the glands removing its central section, we noted in the last postoperative period that with the passage of time, these breasts developed a depression on the upper pole causing a somewhat ungraceful profile and the visual impression that the breast was ptotic. It was noted that the techniques used were most concerned with mammary gland removal, without specific regard to the upper pole of the breast. Searching for an aesthetic solution for the construction and maintenance of the upper pole of the breast, we have developed two techniques in which fixation of mammary tissue flaps to the third costal arch assures both a graceful breast and pexis of the breasts. This report presents an analysis of the results of the author's experience.


Subject(s)
Breast/surgery , Surgical Flaps , Adolescent , Female , Humans , Methods , Middle Aged
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