Search PubMedSearch

Biomedical subjects

M Castillo

Publications and source records attributed to M Castillo.

At least 19 recordsLinked to original sources

Enhancement of paclitaxel activity against hormone-refractory prostate cancer cells in vitro and in vivo by quinacrine.

Cytoplasmic phospholipase A2 (PLA2) is known to be phosphorylated and activated by MAP kinase (Lin et al 1993, Cell 72: 269-278), an important downstream component of signal transduction, whereas paclitaxel has been shown to inhibit isoprenylation of ras proteins (Danesi et al 1995, Mol Pharmacol 47: 1106-1111). Given that quinacrine (Q), a PLA2 inhibitor, and paclitaxel (P) might act at different sites in the cell signalling pathway, our aim was to test whether they were synergistic in combination against prostate cancer cells. Cell viability of PC-3, PC-3M and DU145 cells in 96 - well plates was assessed 96 h after drugs were added concurrently. Using Chou analysis, we demonstrated synergy for the combination against all three cell lines. Further, synergy was present under both conservative (mutually non-exclusive) and non-conservative (mutually exclusive) models. Studies in the nude mouse xenograft model support the finding of synergy in vitro. In DU145-bearing mice, Q (50 mg kg(-1)) and P (0.5 mg kg(-1)) given daily for 12 consecutive days, either concurrently or sequentially, was more effective than either drug alone, at twice the dose intensity. In an enzyme-linked immunosorbent (ELISA) apoptosis assay, arachidonic acid was able to partially reverse Q- and P-induced apoptosis, suggesting PLA2 pathway involvement. Finally, the combination of lovastatin, another inhibitor of ras isoprenylation, and quinacrine had synergistic inhibitory effects on the growth of PC-3 cells in vitro, suggesting that the combination of these two classes of compounds might serve as an attractive therapeutic approach for prostate cancer.

Animals

Papillary endolymphatic sac tumors: CT, MR imaging, and angiographic findings in 20 patients.

PURPOSE: To determine the computed tomographic (CT), magnetic resonance (MR) imaging, and angiographic findings of papillary endolymphatic sac tumors. MATERIALS AND METHODS: Clinical and imaging studies in 20 patients (aged 17-65 years) with histopathologically proved papillary endolymphatic sac tumors were retrospectively reviewed. Patients underwent CT (n = 18), MR imaging (n = 15), or angiography (n = 12). CT scans were evaluated for bone erosion and calcification; MR images, for signal intensity, enhancement patterns, and flow voids; and angiograms, for tumoral blood supply. RESULTS: All tumors were destructive and contained calcifications centered in the retrolabyrinthine region at CT. The MR imaging appearance varied with lesion size; 12 of 15 tumors showed increased signal intensity at T1-weighted imaging. The high-signal-intensity area was circumferential in lesions 3 cm or smaller and was scattered throughout the lesion in advanced tumors. Only tumors larger than 2 cm had flow voids. The blood supply arose predominantly from the external carotid artery. Large tumors had additional supply from the internal carotid and posterior circulation. CONCLUSION: Papillary endolymphatic sac tumors are destructive, hypervascular lesions that arise from the temporal bone retrolabyrinthine region. Increased signal intensity at unenhanced T1-weighted MR imaging is common and may help distinguish these lesions from more common, aggressive temporal bone tumors.

Adenocarcinoma

Comparison of CT and MR features with clinical outcome in patients with Rocky Mountain spotted fever.

PURPOSE: To compare neuroimaging findings and clinical features in patients with Rocky Mountain spotted fever and to determine the impact of imaging studies in the treatment of these patients. MATERIALS: We reviewed the brain CT scans (n = 44), MR images (n = 6), or both (n = 4), and one MR spinal study in 34 patients with Rocky Mountain spotted fever, proved by definitive serologic criteria. Records were reviewed with attention to clinical symptoms and therapeutic modifications based on neuroimaging; outcomes were compared with imaging findings. RESULTS: Abnormalities, consisting of infarctions, cerebral edema, meningeal enhancement, and prominent perivascular spaces, were found on four of 44 CT scans and on four of six MR studies. The spinal MR study showed abnormal enhancement of the lower spinal cord and cauda equina. Nonspecific clinical symptoms were present in all patients in whom neuroimaging findings were abnormal and in 80% of patients whose CT and/or MR findings were normal. After treatment, return to baseline clinical status was documented in 67% of patients with abnormal imaging findings and in 93% with normal findings. Death occurred in 17% of patients with abnormal neuroimaging results and in none of those with normal results. CONCLUSIONS: Abnormalities on neuroimaging studies were not common in patients with Rocky Mountain spotted fever. When present, they were subtle. Symptoms at presentation and unfavorable outcomes were more prevalent when CT or MR findings were abnormal. Abnormalities identified on neuroimaging studies did not alter clinical treatment in any patient.

Adolescent

Imaging findings in patients with clinical anophthalmos.

PURPOSE: To review the intracranial and facial imaging features in children with congenital anophthalmos. METHODS: We retrospectively studied eight children with anophthalmos with respect to intraorbital, intracranial, and craniofacial anomalies (six had CT examinations, including the face, orbits, and brain, and four had MR imaging, including the orbits and brain). RESULTS: Three patients had primary bilateral anophthalmos on CT (n = 1) and MR (n = 3) studies. In these patients, MR images showed hypoplasia of the optic chiasm and posterior visual pathways (n = 3), agenesis (n = 1) or dysgenesis of the corpus callosum (n = 2), and a mass in the tuber cinereum region (n = 1). One patient had incontinentia pigmenti. Five patients had unilateral anophthalmos on CT (n = 5) and MR (n = 1) studies. One of these patients had a contralateral congenital cystic eye and one had contralateral severe microphthalmia and absent optic chiasm. All had craniofacial anomalies that consisted of midline facial clefts (n = 2) and concomitant hemifacial hypoplasia (n = 2). One had a craniosynostosis. All five had normal-appearing brains. CONCLUSION: Patients with bilateral anophthalmos represent a distinct group from those with unilateral anophthalmos. In our patients, bilateral anophthalmos was associated with absence of the optic chiasm, diminished size of the posterior optic pathways, and agenesis or dysgenesis of the corpus callosum. Patients with unilateral anophthalmos had severe craniofacial anomalies. Imaging of the face is helpful in patients with unilateral anophthalmos.

Agenesis of Corpus Callosum

Choristomas of the seventh and eighth cranial nerves.

Choristomas, masses of normal tissues in aberrant locations, contain smooth muscle fibers and fibrous tissues. We describe the MR imaging features of two choristomas located in the internal auditory canals and arising from the facial and vestibulocochlear nerves. Both lesions enhanced with contrast material. In one case, enhancement was seen in the geniculate ganglion and greater superficial petrosal nerve. In the other, a medial component enhanced less than the lateral component did.

Adult

Postmortem MR imaging of the brains of patients with AIDS.

Forty-two postmortem formalin-fixed brains of known patients with AIDS were examined with T2-weighted MR imaging before brain cutting. The gross and microscopic brain findings were correlated with the T2 signal changes in the postmortem MR imaging. The brains included examples of progressive multifocal leukoencephalopathy with involvement of the central brain and cerebellum. The authors also encountered the coexistence of progressive multifocal leukoencephalopathy and HIV encephalitis, and the T2 signal changes for each were compared. The T2 signal changes of leptomeningeal and perivascular space cryptococcal infection and CMV ependymitis are documented. Several expressions of primary cerebral lymphoma, including large nodules, choroid plexus infiltration, and diffuse microscopic sites of tumor also are assessed.

AIDS-Related Opportunistic Infections

Proton MR spectroscopy in Coats disease.

We describe a case of acute left-sided visual loss in a 4-year-old boy. CT showed hyperdense retinal detachment with a tiny calcification, and MR imaging showed subretinal hyperintensity on both T1- and T2-weighted images. Proton MR spectroscopy showed a large peak between 1 and 1.6 ppm that we believe corresponds mainly to lipids, which are characteristic of the exudate present in Coats disease.

Blood-Retinal Barrier

Binding site on pea chloroplast fructose-1,6-bisphosphatase involved in the interaction with thioredoxin.

When we compare the primary structures of the six chloroplast fructose-1,6-biophosphatases (FBPase) so far sequenced, the existence of a poorly conserved fragment in the region just preceeding the redox regulatory cysteines cluster can be observed. This region is a good candidate for binding of FBPase to its physiological modulator thioredoxin (Td), as this association shows clear differences between species. Using a cDNA clone for pea chloroplast FBPase as template, we have amplified by PCR a DNA insert coding for a 19 amino acid fragment (149Pro-167Gly), which was expressed in pGEMEX-1 as a fusion protein. This protein strongly interacts with pea Td m, as shown by ELISA and Superose 12 gel filtration, depending on pH of the medium. Preliminary assays have shown inhibition of FBPase activity in the presence of specific IgG against the 19 amino acid insert. Surprisingly the fusion protein enhances the FBPase activation in competitive inhibition experiments carried out with FBPase and Td. These results show the fundamental role played by this domain in FBPase-Td binding, not only as docking point for Td, but also by inducing some structural modification in the Td molecule. Taking as model the structural data recently published for spinach photosynthetic FBPase, this sequence from a tertiary and quaternary structural point of view appears available for rearrangement.

Amino Acid Sequence

Adenocarcinoma of the endolymphatic sac: imaging features and preoperative embolization.

Adenocarcinoma arising from the endolymphatic sac is very rare. Its imaging features are nonspecific and the differential diagnosis involves mainly paraganglioma or aggressive meningioma. In our case, the blood supply to the tumor was identical to that found in glomus jugulotympanicum tumors and the patient benefitted from preoperative embolization.

Adenocarcinoma

MRI of enlarged dorsal ganglia, lumbar nerve roots, and cranial nerves in polyradiculoneuropathies.

This paper describes the MRI findings in four patients with a clinical diagnosis of hypertrophic polyradiculoneuropathies. In two examination of the lumbar spine showed enlarged nerve roots and dorsal ganglia, and similar findings were present in the cervical spine in a third. The cisternal portions of the cranial nerves were enlarged in another patient. MRI allows identification of enlarged nerves in hypertrophic polyradiculopathies.

Adult

The brachial plexus.

The brachial plexus arises from the lower cervical and upper thoracic spinal nerve roots. It courses between the anterior and middle scalene muscles and adjacent to the subclavian artery. The brachial plexus may be visualized by both MRI and CT. Symptoms of a brachial plexopathy commonly are nonlocalizing. Traumatic injuries and involvement by tumors probably account for the majority of etiologies responsible for these plexopathies. Inflammatory processes also involve the brachial plexus. This article reviews the anatomy of the brachial plexus from both surgical and radiographic approaches and also addresses the symptomatology of brachial plexopathy underlying it.

Brachial Plexus

Predictive value of flow cytometric analysis in DNA contents in patients with locally advanced head and neck carcinoma.

A retrospective study was performed on 61 eligible patients with stage III and IV (AJC/UICC Staging System) squamous carcinomas of the head and neck region who were treated with definitive radiotherapy with, or without, surgery. DNA contents were measured by flow cytometric analysis of archival paraffin blocks and were correlated with clinicopathological findings, tumour response and patient survival. Comparison of variables including treatment modality was performed for identification of significant prognostic factors. There were 28 diploid, 27 aneuploid tumours and the remaining six were questionable. All patients were followed-up for at least two years or until death. Aneuploid tumours had a significantly higher S-phase fraction (percentage S-phase) (p < 0.001). Neither ploidy nor percentage S-phase were found to have predictive value in tumour response or patient survival within the power of a sample size of 61. Twenty of the 27 (74 per cent) aneuploid tumours had a complete response (CR) whereas 19 out of 28 (68 per cent) diploid tumours achieved CR. Five-year survival by the Kaplan-Meier method was 33 per cent for both aneuploid and diploid tumours. However, nodal stage (N stage) was found to have significant predictive value in both tumour response and patient survival. The complete response for stage N0 patients was 96 per cent, N1 patients 61 per cent, N2 patients 60 per cent and 43 per cent for N3 patients (p < 0.002). Similarly, the five year survival for the N0 and N3 groups of patients was 53 per cent and 29 per cent respectively (p < 0.05).

Adult

Coconut oil affects lipoprotein composition and structure of neonatal chicks.

Supplementation of 10 or 20% coconut oil in the diet for 1-2 weeks produced a significant hypercholesterolemia in neonatal chicks. Plasma triacylglycerol concentration significantly increased after the addition of 20% coconut oil for 2 weeks. These results show that newborn chicks are more sensitive to saturated fatty acids from coconut oil than adult animals. The effects of this saturated fat on lipoprotein composition were studied for the first 1-2 weeks of neonatal chick life. Coconut oil supplementation in the diet (20%) for 2 weeks increased cholesterol concentration in all the lipoprotein fractions, while 10% coconut oil only increased cholesterol in low-density and very-low-density lipoproteins, an increase that was significant after 1 week of treatment. Similar results were obtained for triacylglycerol concentration after 2 weeks of treatment. Changes in phospholipid and total protein levels were less profound. Coconut oil decreased low-density and very-low-density lipoprotein fluidity, measured as total cholesterol/phospholipid ratio. Changes in esterified cholesterol/phospholipid and triacylglycerol/phospholipid ratios suggest that coconut oil affects the distribution of lipid components in the core of very-low-density particles. Likewise, the esterified cholesterol/triacylglycerol ratio was clearly increased in the low-density, and especially in the very-low-density, fraction after the first week of coconut oil feeding. Our results show that neonatal chick provides a suitable model in which to study the role of very-low-density lipoproteins in atherogenesis and the rapid response to saturated fatty acids with 12-14 carbons.

Age Factors