Jonathan Guzman - Academia.edu (original) (raw)

Papers by Jonathan Guzman

Urologic Oncology: Seminars and Original Investigations

Research and Reports in Urology

Introduction: It is well documented in literature that most prostate carcinomas (PCa) arise in th... more Introduction: It is well documented in literature that most prostate carcinomas (PCa) arise in the peripheral zone (PZ). Additionally, an inverse relationship between prostate size and the incidence of PCa has been demonstrated in recent studies. However, little is known about gland distribution in the peripheral zone of larger prostates compared to smaller prostates. In this study, we examined the histo-anatomical gland distribution within the peripheral zone in small and large prostates and discuss possible clinical implications. Methods: A semi-quantitative analysis of gland density and capsule thickness was performed using light microscopy on 10 large (≥80 g) prostate specimens and 10 small (<30 g) prostate specimens from patients who underwent radical prostatectomy at Texas Tech University Health Sciences Center between the years 2010 and 2016. Samples from radical prostatectomies were used to ensure a whole, preserved prostate with an intact surgical capsule. Gland counts were performed on five random fields under 100 × magnification, while capsule thickness was measured on three random fields per case; thus, a total 50 fields and 30 fields were analyzed for each of the two groups for gland counts and capsule thickness measurements, respectively. Microscopy was standardized to the posterior aspect of the prostate, between 4 o'clock and 6 o'clock along the equatorial region between the apex and base. Results: Large prostates possessed a significantly lower mean gland count per field compared to small prostates (10.34±4.15, n=50 vs 18.00±5.41, n=50; t=8.16, df=49, P<0.001). Additionally, large prostates showed a significantly higher average capsule thickness in millimeters compared to small prostates (1.80 mm, ±1.12 mm, n=30 vs 0.90 mm, ±0.56, n=30; t=8.16, df=49, P<0.001). Conclusion: The results demonstrate that prostate hypertrophy leads to both decreased gland density in the peripheral zone and increased capsule thickness, suggesting that growth-induced expansion of the prostate against its capsule leads to compression-induced atrophy and fibrosis of glandular tissue within the peripheral zone (PZ). A decrease in gland density within the PZ may have clinical implications shedding light, for instance, on the reduction in PCa incidence in patients with large prostates as compared to smaller prostates, a phenomenon well documented in the literature.

Molecular Pharmaceutics

Bone marrow-derived dendritic cells (BMDCs) were harvested from the tibias of MHC-II-GFP mice unl... more Bone marrow-derived dendritic cells (BMDCs) were harvested from the tibias of MHC-II-GFP mice unless otherwise noted. The bone marrow was passed through a 40 µm cell strainer followed by the lysis of red blood cells using the red blood cell lysis buffer (Sigma-Aldrich). The cells after lysis were counted, pelleted by centrifugation, then seeded at 1~2 million/ml in RPMI (Invitrogen) supplemented with 10% fetal bovine serum (FBS, Invitrogen), 100 U/ml penicillin+streptomycin (Invitrogen). GM-CSF (Peprotech) was added to each well to a final concentration of 20 ng/ml. The culture was incubated for 3 days with occasional replenishment of fresh medium. B16-F10 cells were obtained from American Type Culture Collection (ATCC), and cultured in RPMI supplemented with 10% fetal bovine serum (FBS), 100 U/ml penicillin (Invitrogen), and 100 U/ml streptomycin. Human umbilical vein endothelial cells (HUVECs, Lonza) and human lymphatic dermal microvascular endothelial cells (Lym-HMVECs, Lonza) were cultured in EGM-2 MV media system (Lonza). For both HUVECs and Lym-HMVECs, only the cells between passage 5-7 were used. All cells were cultured in 37 °C and in a humidified incubator. Recombinant expression and purification of chemokines and their VHH fusions Target constructs were inserted into pET30 expressing vectors using standard cloning techniques. After sequence validation, the constructs were transformed into BL21 E. coli host for recombinant expression. Overnight starting culture was inoculated into fresh media at 1% (v/v) to grow at 37 o C until O.D.600 reaches between 0.4~0.8 followed by

Chem. Sci.

Unusual patterns of glycosylation on the surface of transformed cells contribute to immune modula... more Unusual patterns of glycosylation on the surface of transformed cells contribute to immune modulation and metastasis of malignant tumors. Active immunization against them requires effective antigen presentation, which is complicated by a lack of access to tumor-specific posttranslational modifications through standard genetic approaches and by the low efficiency of passive antigen sampling. We found that antigen targeted to antigen presenting cells via class II MHC products can elicit a robust immune response against MUC1(Tn) bearing a defined tumor-associated glycoform, Tn. The two-component vaccine construct was prepared by sortase-mediated protein ligation of a synthetic MUC1(Tn) fragment to a class II MHC-binding singledomain antibody fragment (VHH7) as targeting moiety. We show that VHH7 targets antigen presenting cells in vivo, and when conjugated to MUC1(Tn) can elicit a strong aMUC1(Tn) immune response in mice. The resulting sera preferentially recognized the MUC1 epitope with the tumor-associated carbohydrate antigen Tn and were capable of killing cancer cells in a complement-mediated cytotoxicity assay. Immunoglobulin isotype analysis and cytokine release assays suggested a favorable Th1 response. A single boost 12 months after primary immunization triggered a recall response of the same quality, suggesting that long-term aMUC1(Tn) memory had been achieved.

Discrete Mathematics

We show that the cop number of every generalized Petersen graph is at most 4. The strategy is to ... more We show that the cop number of every generalized Petersen graph is at most 4. The strategy is to play a modified game of cops and robbers on an infinite cyclic covering space where the objective is to capture the robber or force the robber towards an end of the infinite graph. We prove that finite isometric subtrees are 1-guardable and apply this to determine the exact cop number of some families of generalized Petersen graphs. We also extend these ideas to prove that the cop number of any connected I-graph is at most 5.

Hidrobiologica, 2008

Desde 1979 se han reportado florecimientos de especies de microalgas nocivas (FAN) en la costa Pa... more Desde 1979 se han reportado florecimientos de especies de microalgas nocivas (FAN) en la costa Pacífica de Costa Rica, reconociéndose hasta el 2005 al menos 13 taxa de dinoflagelados. En años recientes estos fenómenos se han intensificado tanto espacial como temporalmente, produciéndose discoloraciones casi ininterrumpidas que se extienden por toda la costa produciendo mortalidad de peces y fetidez en el agua. Tales FAN masivos se iniciaron con Pyrodinium bahamense en el 2000, quien perduró por más de un año y en el cual se observaron morfotipos correspondientes a las dos variedades de la especie, coexistiendo junto a Gymnodinium catenatum y ocasionando serios casos de Intoxicación Paralizante por Consumo de Mariscos (IPM). Posteriormente, de septiembre del 2003 hasta junio del 2004, Cochlodinium cf. polykrikoides produjo discoloraciones en toda la costa Pacífica, seguidas por manchas extensas de Akasiwo sanguinea y Gymnodinium instriatum. El evento más reciente se observó en junio del 2005 cuando Alexandrium monilatum produjo extensas discoloraciones con cadenas formadas por más de 100 células. Los FAN de dinoflagelados ahora son comunes en las costas de Costa Rica, posiblemente como resultado de las condiciones ambientales actuales que favorecen la proliferación masiva de especies invasivas (agresivas), las cuales incluso pueden afectar otros sitios del Pacífico americano como es el caso de P. bahamense var. compressum que puede desplazarse hasta México, a lo largo de la costa del Pacífico centroamericano a través

Pediatric Anesthesia, 2016

Dexmedetomidine is increasingly used by various routes for pediatric sedation. However, there are... more Dexmedetomidine is increasingly used by various routes for pediatric sedation. However, there are few randomized controlled trials comparing the efficacy of dexmedetomidine to other commonly used sedatives. To compare the efficacy of sedation with intranasal dexmedetomidine to oral chloral hydrate for auditory brainstem response (ABR) testing. In this double-blind, double-dummy study, children undergoing ABR testing were randomized to receive intranasal dexmedetomidine 3 mcg·kg(-1) plus oral placebo (Group IN DEX) or oral chloral hydrate 50 mg·kg(-1) plus intranasal saline placebo (Group CH). We recorded demographic data, times from sedative administration to start and completion of testing, quality of sedation, occurrence of predefined adverse events, discharge times, and return to baseline activity on the day of testing. Testing completion rates with a single dose of medication were higher in the IN DEX group (89% vs 66% for CH, odds ratio with 95% confidence intervals 4.04 [1.3-12.6], P = 0.018). The median [95% CI)] time to successful testing start was shorter (25 [20-29] min vs 30 [20-49] min for IN DEX and CH, respectively, log rank test P = 0.02) and the proportion of children whose parents reported a return to baseline activity on the day of testing was greater for the IN DEX than the CH group (89% vs 64%, OR [95% CI] 4.71 [1.34-16.6], P = 0.02). There were no major adverse events in either group and no significant differences in the incidence of minor events. Intranasal dexmedetomidine is an effective alternative to oral chloral hydrate sedation for ABR testing, with the advantages of a higher incidence of testing completion with a single dose, shorter time to desired sedation level, and with significantly more patients reported to return to baseline activity on the same day.

Angewandte Chemie International Edition, 2016

Antibody-drug conjugates (ADCs) of defined structure hold great promise for cancer therapies, but... more Antibody-drug conjugates (ADCs) of defined structure hold great promise for cancer therapies, but further advances are constrained by the complex structures of full-sized antibodies. Camelid-derived single-domain antibody fragments (VHHs or nanobodies) offer a possible solution to this challenge by providing expedited target screening and validation through switching between imaging and therapeutic activities. We used a nanobody (VHH7) specific for murine MHC-II and rendered &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;sortase-ready&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; for the introduction of oligoglycine-modified cytotoxic payloads or NIR fluorophores. The VHH7 conjugates outcompeted commercial monoclonal antibodies (mAbs) for internalization and exhibited high specificity and cytotoxicity against A20 murine B-cell lymphoma. Non-invasive NIR imaging with a VHH7-fluorophore conjugate showed rapid tumor targeting on both localized and metastatic lymphoma models. Subsequent treatment with the nanobody-drug conjugate efficiently controlled tumor growth and metastasis without obvious systemic toxicity.

DESCRIPTION Descripción de la fauna que habita un ecosistema compuesto por una especie vegetal (t... more DESCRIPTION Descripción de la fauna que habita un ecosistema compuesto por una especie vegetal (tillandsia landbeckii) y algunas especies de líquenes en Tarapacá, (desierto de Atacama).

SSRN Electronic Journal, 2000

Taxes, bankruptcy costs, transactions costs, adverse selection, and agency conflicts have all bee... more Taxes, bankruptcy costs, transactions costs, adverse selection, and agency conflicts have all been advocated as major explanations for the corporate use of debt financing. These ideas have often been synthesized into the trade-off theory and the pecking order theory of leverage. These theories and the related evidence are reviewed in this survey. A number of important empirical stylized facts are identified. To understand the evidence, it is important to recognize the differences among private firms, small public firms and large public firms. Private firms seem to use retained earnings and bank debt heavily. Small public firms make active use of equity financing. Large public firms primarily use retained earnings and corporate bonds. The available evidence can be interpreted in several ways. Direct transaction costs and indirect bankruptcy costs appear to play important roles in a firm's choice of debt. The relative importance of the other factors remains open to debate. No currently available model appears capable of simultaneously accounting for all of the stylized facts.

Gayana (Concepción), 2009

Se estudió la dieta de Orestias agassii en tres lagunas asociadas al Salar del Huasco en el altip... more Se estudió la dieta de Orestias agassii en tres lagunas asociadas al Salar del Huasco en el altiplano de la I Región. El contenido estomacal presentó; ostracodos, anfípodos, copépodos, moluscos, coleópteros, ácaros y algas macrófitas. Los resultados permiten afirmar que O. agassii es un predador carnívoro, que consume una amplia variedad de microcrustaáeos que busca activamente entre la vegetación.

Mastozoología Neotropical, 2011

ABSTRACT: Abrocoma bennettii is a relatively robust abrocomid rodent endemic to Chile. It is dist... more ABSTRACT: Abrocoma bennettii is a relatively robust abrocomid rodent endemic to Chile. It is distributed from approximately 27 18'S–70 25'W in the north (Atacama) to 36 00'S–73 7'W in the south (BíoBío). We report the finding of a cranium in excellent conditions, which is ...

Mastozoología neotropical, 2011

... Other rodent species inhabiting the Paposo area are Thylamys elegans, Abrothix olivaceus andP... more ... Other rodent species inhabiting the Paposo area are Thylamys elegans, Abrothix olivaceus andPhyllotis darwini, all typically central ... e Instituto Miguel Lillo Miguel Lillo 205 - Piso 4 - Sección de mamíferos (T4000JFE) - San Miguel de Tucumán, Tucumán República Argentina ...

Gayana (Concepc.), 2009

... Jonathan A. Guzmán 1,2 & Walter Sielfeld 1. ... Marine Biology 50: 263-273. [ Links ]. Ca... more ... Jonathan A. Guzmán 1,2 & Walter Sielfeld 1. ... Marine Biology 50: 263-273. [ Links ]. Campos, CH, G. Dazarola, B. Dyer, L. Fuentes, JF Gavilán, L. HuaiquIn, G. Martínez, R. Meléndez, G. Pequeño, F. Ponce, VH Ruiz, W. Sielfeld, D. Soto, R. Vega & I. Vila. 1998. ...

Hidrobiológica, 2008