Computational Model Based on Optical Coherence Tomography (OCT) Skin Scanning to Identify and Quantify Acute Radiation Dermatitis (ARD): A Prospective Diagnostic Study. / Modelo computacional basado en la tomografía de coherencia óptica (TCO) para identificar y cuantificar la radiodermatitis aguda (RA): estudio observacional prospectivo.

BACKGROUND: Acute radiation dermatitis (ARD) is the most widely reported radiotherapy-induced adverse event. Currently, there is no objective or reliable method to measure ARD. OBJECTIVE: Our main objective was to identify and quantify the effects of radiotherapy with a computational model using optical coherence tomography (OCT) skin scanning. Secondary objectives included determining the ARD impact of different radiotherapeutic schemes and adjuvant topical therapies. METHODS: We conducted a prospective, single-center case series study in a tertiary referral center of patients with breast cancer who were eligible for whole breast radiotherapy (WBRT). RESULTS: A total of 39 women were included and distributed according to the radiotherapeutic schemes (15, 20, and 25 fractions). A computational model was designed to quantitatively analyze OCT findings. After radiotherapy, OCT scanning was more sensitive revealing vascularization changes in 84.6% of the patients (vs 69.2% of the patients with ARD by clinical examination). OCT quantified an increased vascularization at the end of WBRT (P<.05) and a decrease after 3 months (P=.032). Erythematous skin changes by OCT were more pronounced in the 25-fraction regime. CONCLUSION: An OCT computational model allowed for the identification and quantification of vascularization changes on irradiated skin, even in the absence of clinical ARD. This may allow the design of standardized protocols for ARD beyond the skin color of the patients involved.

Computational Model Based on Optical Coherence Tomography (OCT) Skin Scanning to Identify and Quantify Acute Radiation Dermatitis (ARD): A Prospective Diagnostic Study.

BACKGROUND: Acute radiation dermatitis (ARD) is the most widely reported radiotherapy-induced adverse event. Currently, there is no objective or reliable method to measure ARD. OBJECTIVE: Our main objective was to identify and quantify the effects of radiotherapy with a computational model using optical coherence tomography (OCT) skin scanning. Secondary objectives included determining the ARD impact of different radiotherapeutic schemes and adjuvant topical therapies. METHODS: We conducted a prospective, single-center case series study in a tertiary referral center of patients with breast cancer who were eligible for whole breast radiotherapy (WBRT). RESULTS: A total of 39 women were included and distributed according to the radiotherapeutic schemes (15, 20, and 25 fractions). A computational model was designed to quantitatively analyze OCT findings. After radiotherapy, OCT scanning was more sensitive revealing vascularization changes in 84.6% of the patients (vs 69.2% of the patients with ARD by clinical examination). OCT quantified an increased vascularization at the end of WBRT (P<.05) and a decrease after 3 months (P=.032). Erythematous skin changes by OCT were more pronounced in the 25-fraction regime. CONCLUSION: An OCT computational model allowed for the identification and quantification of vascularization changes on irradiated skin, even in the absence of clinical ARD. This may allow the design of standardized protocols for ARD beyond the skin color of the patients involved.

Plant mitogen-activated protein kinase signaling cascades.

Mitogen-activated protein kinase (MAPK) cascades have emerged as a universal signal transduction mechanism that connects diverse receptors/sensors to cellular and nuclear responses in eukaryotes. Recent studies in plants indicate that MAPK cascades are vital to fundamental physiological functions involved in hormonal responses, cell cycle regulation, abiotic stress signaling, and defense mechanisms. New findings have revealed the complexity and redundancy of the signaling components, the antagonistic nature of distinct pathways, and the use of both positive and negative regulatory mechanisms.

Functional analysis of oxidative stress-activated mitogen-activated protein kinase cascade in plants.

Despite the recognition of H(2)O(2) as a central signaling molecule in stress and wounding responses, pathogen defense, and regulation of cell cycle and cell death, little is known about how the H(2)O(2) signal is perceived and transduced in plant cells. We report here that H(2)O(2) is a potent activator of mitogen-activated protein kinases (MAPKs) in Arabidopsis leaf cells. Using epitope tagging and a protoplast transient expression assay, we show that H(2)O(2) can activate a specific Arabidopsis mitogen-activated protein kinase kinase kinase, ANP1, which initiates a phosphorylation cascade involving two stress MAPKs, AtMPK3 and AtMPK6. Constitutively active ANP1 mimics the H(2)O(2) effect and initiates the MAPK cascade that induces specific stress-responsive genes, but it blocks the action of auxin, a plant mitogen and growth hormone. The latter observation provides a molecular link between oxidative stress and auxin signal transduction. Finally, we show that transgenic tobacco plants that express a constitutively active tobacco ANP1 orthologue, NPK1, display enhanced tolerance to multiple environmental stress conditions without activating previously described drought, cold, and abscisic acid signaling pathways. Thus, manipulation of key regulators of an oxidative stress signaling pathway, such as ANP1/NPK1, provides a strategy for engineering multiple stress tolerance that may greatly benefit agriculture.

Cytosolic acidification but not auxin at physiological concentration is an activator of MAP kinases in tobacco cells.

In higher plants, MAP kinase cascades are involved in the transduction of numerous stress-related signals but much less is known about the effect of mitogenic signals. We have analysed MAP kinase activation in tobacco cells after treatment by auxin, a growth factor required at physiological concentrations for mitosis in plant cell cultures. From in-gel assay of myelin basic protein kinase and from immunochemical detection of ERK related kinases, we show that the mitogenic effect of auxin, which was confirmed by the specific increase of several mRNAs species, did not rely on MAP kinase activation within the first 2 hours. These data contest previous results which could be due to the activation of MAP kinase by a signal other than auxin. In the second part of this study, we show that the treatment of the cells with high concentrations of various weak lipophilic acids such as auxin, in a nonphysiological concentration range, butyric or acetic acid is sufficient to activate transiently a MAP kinase. The data show that MAP kinase activation is the consequence of cytosolic acidification. Moreover, it is not sensitive to the protein kinase inhibitor staurosporine. These results suggest a functional role for cytosolic acidification as a second messenger mediating MAP kinase activation in the response of plant cells to various stresses.

Identification of 14 kDa auxin-binding proteins in a tobacco plasma membrane subfraction responsive to auxin.

Auxin binding by tobacco plasma membrane proteins was investigated. After photolabeling with [3H]IAA, 350 polypeptides were resolved on 2D gels and analyzed. Thirteen polypeptides were selected according to physico-chemical criteria. The labeling of three of them was further shown to increase, after treatment of cells with auxin, specifically in that plasma membrane subfraction where the sensitivity to the hormone of the H(+)-ATPase is enhanced by the treatment of cells. These polypeptides were those that exhibited the more specific labeling features according to physico-chemical criteria. They had similar apparent molecular weight (ca 14 kDa) that distinguished them from other auxin-binding proteins described up to now, and exhibited similar amino acid compositions. These 14 kDa polypeptides are proposed to constitute a group of new auxin-binding proteins, potentially involved, within specialized plasma membrane domains, in the stimulation of the proton pump by the hormone.

Heterogeneity of late-onset adrenal 3 beta-ol-hydroxysteroid dehydrogenase deficiency in patients with hirsutism and polycystic ovaries.

Nine women with clinical features of polycystic ovarian syndrome (PCOS) were studied in order to establish the differential diagnosis with late-onset adrenal hyperplasia (LOAH). Their hirsutism was classified as moderate in five patients and severe in the remaining four cases. All patients had bilateral polycystic ovarian enlargement by ultrasound examination. As a control group five women with normal ovarian function without hirsutism were submitted to the same protocol of study. The patients studied as well as the women of the control group had basal serum determinations of pregnenolone (P5),17-hydroxypregnenolone (17-OHP5),dehydroepiandrosterone (DHEA), pregesterone (P), 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone and cortisol by radioimmunoassay techniques. The basal serum levels of androgens showed no correlation with the severity of hirsutism or with the ultrasound findings. An adrenal stimulation with synthetic adrenocorticotropic hormone (ACTH) to all women was performed in order to assess their adrenal responsiveness. The analysis of the ratios between delta 5 and delta 4 steroids demonstrated a partial enzymatic blockade at the level of 3 beta-o1-hydroxysteroid dehydrogenase (3-HSD) in three patients. The blockade was particularly in the conversion of P5 to P and 17-OHP5 to 17-OHP. The lack of delta 4 steroid secretion in the presence of normal increase of delta 5 precursors following ACTH was noted. These findings confirm the clinical use of the ACTH stimulation test to reveal the presence of enzymatic alterations in adrenal steroidogenesis in some patients previously considered to have PCOS. Since it wa demonstrated that the conversion steps were affected in variable degrees, the presence of different isoenzymes of 3-HD is suggested.

Changes in the prolactin serum isoforms secreted by a pituitary adenoma associated with therapy.

Variations in serum molecular forms of prolactin (PRL) from an adolescent woman presenting amenorrhea-galactorrhea are reported. Persistent hyperprolactinemia and hypoestrogenism were demonstrated as well as the presence of a pituitary tumor with suprasellar extension. Bromocriptine was given at progressive doses up to 37 mg daily, decreasing the hyperprolactinemia and galactorrhea. After 2 years of treatment the patient noticed symptoms of gastric intolerance, bromocriptine was discontinued and a rebound of hyperprolactinemia was observed. Lisuride was administered instead resulting in a new decrease in PRL serum levels, disappearance of galactorrhea and beginning of regular menses. Serum gel chromatographic analysis was carried out before and during lisuride treatment. The first chromatographic analysis showed a predominance of high molecular weight (approximately 66 KD) PRL, accounting for more than 90% of the immunoreactive PRL. The second chromatography showed the major peak of immunoreactive PRL displaced to the right (molecular weight of 22 KD), which was eluted near the PRL standard. With these chromatographic patterns it is concluded that the pituitary macroprolactinoma secreted different molecular forms of PRL and treatment with lisuride appeared to exert some effect on the PRL molecular size secreted by the pituitary.

GC subtyping and HIV infection in a Spanish population: no evidence of an association between GC subtypes and AIDS.

Group-specific component (GC) subtyping was performed by isoelectric focusing in 318 Spanish drug users at risk for infection or infected by HIV (85 HIV seronegatives, 111 HIV seropositives without symptoms, 89 seropositives with symptoms, 33 AIDS patients) and 187 healthy individuals. There was no significant association between GC subtypes and susceptibility to HIV infection and/or progression to AIDS.

Chronic intoxication by heroin; histopathological effects on seminiferous tubules.

Seminiferous tubules from heroin abusers and from rats chronically intoxicated by heroin samples presented a striking reduction in the thickness of the germinal epithelium. Light and electron microscopical studies showed a considerable increase of lipids and phagosomes in Sertoli cells, disorganization of their junction complexes, detachment of immature germ cells which appeared free in the tubular lumen, and formation of giant multinucleate spermatids. These alterations point out that Sertoli cells could be the target element for the toxic effect of heroin samples on the seminiferous epithelium.