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Biomedical subjects

C F Gonzalez

Publications and source records attributed to C F Gonzalez.

At least 19 recordsLinked to original sources
PubMed2004

Mechanism of chromate reduction by the Escherichia coli protein, NfsA, and the role of different chromate reductases in minimizing oxidative stress during chromate reduction.

Chromate [Cr(VI)] is a serious environmental pollutant, which is amenable to bacterial bioremediation. NfsA, the major oxygen-insensitive nitroreductase of Escherichia coli, is a flavoprotein that is able to reduce chromate to less soluble and less toxic Cr(III). We show that this process involves single-electron transfer, giving rise to a flavin semiquinone form of NfsA and Cr(V) as intermediates, which redox cycle, generating more reactive oxygen species (ROS) than a divalent chromate reducer, YieF. However, NfsA generates less ROS than a known one-electron chromate reducer, lipoyl dehydrogenase (LpDH), suggesting that NfsA employs a mixture of uni- and di-valent electron transfer steps. The presence of YieF, ChrR (another chromate reductase we previously characterized), or NfsA in an LpDH-catalysed chromate reduction reaction decreased ROS generation by c. 65, 40, or 20%, respectively, suggesting that these enzymes can pre-empt ROS generation by LpDH. We previously showed that ChrR protects Pseudomonas putida against chromate toxicity; here we show that NfsA or YieF overproduction can also increase the tolerance of E. coli to this compound.

Amino Acid Sequence↗
PubMed2004

Chromate-reducing properties of soluble flavoproteins from Pseudomonas putida and Escherichia coli.

Cr(VI) (chromate) is a toxic, soluble environmental contaminant. Bacteria can reduce chromate to the insoluble and less toxic Cr(III), and thus chromate bioremediation is of interest. Genetic and protein engineering of suitable enzymes can improve bacterial bioremediation. Many bacterial enzymes catalyze one-electron reduction of chromate, generating Cr(V), which redox cycles, generating excessive reactive oxygen species (ROS). Such enzymes are not appropriate for bioremediation, as they harm the bacteria and their primary end product is not Cr(III). In this work, the chromate reductase activities of two electrophoretically pure soluble bacterial flavoproteins--ChrR (from Pseudomonas putida) and YieF (from Escherichia coli)-were examined. Both are dimers and reduce chromate efficiently to Cr(III) (kcat/Km = approximately 2 x 10(4) M(-1) x s(-1)). The ChrR dimer generated a flavin semiquinone during chromate reduction and transferred >25% of the NADH electrons to ROS. However, the semiquinone was formed transiently and ROS diminished with time. Thus, ChrR probably generates Cr(V), but only transiently. Studies with mutants showed that ChrR protects against chromate toxicity; this is possibly because it preempts chromate reduction by the cellular one-electron reducers, thereby minimizing ROS generation. ChrR is thus a suitable enzyme for further studies. During chromate reduction by YieF, no flavin semiquinone was generated and only 25% of the NADH electrons were transferred to ROS. The YieF dimer may therefore be an obligatory four-electron chromate reducer which in one step transfers three electrons to chromate and one to molecular oxygen. As a mutant lacking this enzyme could not be obtained, the role of YieF in chromate protection could not be directly explored. The results nevertheless suggest that YieF may be an even more suitable candidate for further studies than ChrR.

Amino Acid Sequence↗
PubMed2001

Increased differentiation of intracranial white matter lesions by multispectral 3D-tissue segmentation: preliminary results.

MRI is a very sensitive imaging modality, however with relatively low specificity. The aim of this work was to determine the potential of image post-processing using 3D-tissue segmentation technique for identification and quantitative characterization of intracranial lesions primarily in the white matter. Forty subjects participated in this study: 28 patients with brain multiple sclerosis (MS), 6 patients with subcortical ischemic vascular dementia (SIVD), and 6 patients with lacunar white matter infarcts (LI). In routine MR imaging these pathologies may be almost indistinguishable. The 3D-tissue segmentation technique used in this study was based on three input MR images (T(1), T(2)-weighted, and proton density). A modified k-Nearest-Neighbor (k-NN) algorithm optimized for maximum computation speed and high quality segmentation was utilized. In MS lesions, two very distinct subsets were classified using this procedure. Based on the results of segmentation one subset probably represent gliosis, and the other edema and demyelination. In SIVD, the segmented images demonstrated homogeneity, which differentiates SIVD from the heterogeneity observed in MS. This homogeneity was in agreement with the general histological findings. The LI changes pathophysiologically from subacute to chronic. The segmented images closely correlated with these changes, showing a central area of necrosis with cyst formation surrounded by an area that appears like reactive gliosis. In the chronic state, the cyst intensity was similar to that of CSF, while in the subacute stage, the peripheral rim was more prominent. Regional brain lesion load were also obtained on one MS patient to demonstrate the potential use of this technique for lesion load measurements. The majority of lesions were identified in the parietal and occipital lobes. The follow-up study showed qualitatively and quantitatively that the calculated MS load increase was associated with brain atrophy represented by an increase in CSF volume as well as decrease in "normal" brain tissue volumes. Importantly, these results were consistent with the patient's clinical evolution of the disease after a six-month period. In conclusion, these results show there is a potential application for a 3D tissue segmentation technique to characterize white matter lesions with similar intensities on T(2)-weighted MR images. The proposed methodology warrants further clinical investigation and evaluation in a large patient population.

Adult↗
PubMed2001

A clinical comparison of the safety and efficacy of MultiHance (gadobenate dimeglumine) and Omniscan (Gadodiamide) in magnetic resonance imaging in patients with central nervous system pathology.

RATIONALE AND OBJECTIVES: The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial. METHODS: Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg. RESULTS: Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide. CONCLUSIONS: Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.

Brain Neoplasms↗
PubMed1999

Fast tissue segmentation based on a 4D feature map in characterization of intracranial lesions.

The aim of this work was to develop a fast and accurate method for tissue segmentation in magnetic resonance imaging (MRI) based on a four-dimensional (4D) feature map and compare it with that derived from a 3D feature map. High-resolution MRI was performed in 5 normal individuals, in 12 patients with brain multiple sclerosis (MS), and 9 patients with malignant brain tumors. Three inputs (proton-density, T2-weighted fast spin-echo, and T1-weighted spin-echo MR images) were routinely utilized. As a fourth input, either magnetization transfer MRT was used or T1-weighted post-contrast MRI (in patients only). A modified k-nearest neighbor segmentation algorithm was optimized for maximum computation speed and high-quality segmentation. In that regard, we a) discarded the redundant seed points; b) discarded the points within 0.5 standard deviation from the cluster center that were non-overlapping with other tissue; and c) removed outlying seed points outside 5 times the standard deviation from the cluster center of each tissue class. After segmentation, a stack of color-coded segmented images was created. Our new technique utilizing all four MRI inputs provided better segmentation than that based on three inputs (P < 0.001 for MS and P < 0.001 for tumors). The tissues were smoother due to the reduction of statistical noise, and the delineation of the tissues became sharper. Details that were previously blurred or invisible now became apparent. In normal persons a detailed depiction of deep gray matter nuclei was obtained. In malignant tumors, up to five abnormal tissue types were identified: 1) solid tumor core, 2) cyst, 3) edema in white matter 4) edema in gray matter, and 5) necrosis. Delineation of MS plaque in different stages of demyelination became much sharper. In conclusion, the proposed methodology warrants further development and clinical evaluation.

Brain↗
PubMed1999

Optimization of tissue segmentation of brain MR images based on multispectral 3D feature maps.

The purpose of this work was to optimize and increase the accuracy of tissue segmentation of the brain magnetic resonance (MR) images based on multispectral 3D feature maps. We used three sets of MR images as input to the in-house developed semi-automated 3D tissue segmentation algorithm: proton density (PD) and T2-weighted fast spin echo and, T1-weighted spin echo. First, to eliminate the random noise, non-linear anisotropic diffusion type filtering was applied to all the images. Second, to reduce the nonuniformity of the images, we devised and applied a correction algorithm based on uniform phantoms. Following these steps, the qualified observer "seeded" (identified training points) the tissue of interest. To reduce the operator dependent errors, cluster optimization was also used; this clustering algorithm identifies the densest clusters pertaining to the tissues. Finally, the images were segmented using k-NN (k-Nearest Neighborhood) algorithm and a stack of color-coded segmented images were created along with the connectivity algorithm to generate the entire surface of the brain. The application of pre-processing optimization steps substantially improved the 3D tissue segmentation methodology.

Anisotropy↗
PubMed1997

Moyamoya disease in the United States.

The epidemiology and radiological features of Moyamoya disease (MMD) in the US were investigated. This study encompassed 98 cases; 26 were newly collected from eight US institutions and 72 were previously reported in the US literature. The patients ranged in age from 6 months to 67 years with age peaks in the first, third and fourth decades. MMD was seen in various ethnic groups and females were more commonly involved (71%) than males. A specific etiology could not be determined in most cases but arteriosclerosis and use of oral contraceptives were occasional associations. On angiography and/or magnetic resonance angiography (MRA), carotid arterial stenosis or occlusion was seen bilaterally in 95 cases (97%) and unilaterally in three. On MR or MRA, internal carotid steno-occlusive lesions were well demonstrated in all cases but Moyamoya collateral vessels (MMVs) were visualized in only 65% of the patients. MMVs in the basal ganglia and thalami were best demonstrated on T1 weighted images. Parenchymal lesions were seen in all patients and were often bilateral. With advances in MR techniques and increasing awareness of diagnostic guidelines, MMD will be diagnosed more frequently than before in the US.

Adolescent↗
PubMed1997

Synthetic peptide combinatorial libraries: a method for the identification of bioactive peptides against phytopathogenic fungi.

Synthetic combinatorial libraries were evaluated with an iterative process to identify a hexapeptide with broadspectrum activity against selected phytopathogenic fungi. A D-amino acid hexapeptide (FRLKFH) and pentapeptide (FRLHF) exhibited activity against Fusarium oxysporum f. sp. lycopersici, Rhizoctonia solani (anastomosis group 1), Ceratocystis fagacearum, and Pythium ultimum. The peptides showed no hemolytic or mutagenic activity. Fluorescent microscopy studies with a membrane impermeant dye indicated that fungal cytoplasmic membranes were compromised rapidly and that the nuclear membrane was also affected.

Amino Acid Sequence↗
PubMed1997

Mobilization, cloning, and sequence determination of a plasmid-encoded polygalacturonase from a phytopathogenic Burkholderia (Pseudomonas) cepacia.

Phytopathogenic strains of Burkholderia cepacia (synonym Pseudomonas cepacia) produce endopolygalacturonase, whereas strains of clinical and soil origin do not. Growth of a phytopathogenic strain (ATCC25416) at elevated temperatures resulted in nonpectolytic derivatives that were either cured of a resident plasmid or contained a plasmid of reduced mass. The resident 200-kb plasmid (pPEC320) in strain ATCC25416 was tagged with Tn5-Mob. The pPEC320::Tn5-Mob (pPEC321) plasmid was mobilized in B. cepacia strains of soil and clinical origin. Transconjugants containing pPEC321 expressed the endopolygalacturonase and showed differential activity on plant tissue. No evidence for self-transfer of pPEC320 or the tagged derivative was observed. A 285-kb cloned fragment from pPEC320 containing the plasmid-borne pehA gene was sequenced and compared to the pehA gene from Erwinia carotovora subsp. carotovora and Ralstonia solanacearum and the polygalacturonase sequence from Lycopersicon esculentum.

Amino Acid Sequence↗
PubMed1996

Hemodynamic changes in recurrent intracranial terminal aneurysm after endovascular treatment.

RATIONALE AND OBJECTIVES: Multiple cases of recurrence of aneurysms after endovascular treatment have been reported. The purpose of the current hemodynamic study was to identify changes in shear stress and pressure associated with the recurrence of terminal intracranial aneurysms after endovascular occlusion. METHODS: Using a finite element method, a pulsed flow with a non-Newtonian viscosity of blood was simulated within the aneurysm cavity. A recurrent terminal intracranial aneurysm of a patient originally treated with balloon occlusion was then studied. This was based on a physiologic pulsatile flow, which was observed in the middle cerebral artery. Before and after the balloon occlusion, local maximum wall shear stress and pressure drop at the neck of the aneurysm were calculated and compared with the normal shear stress. RESULTS: Although the maximum shear stress at the right neck of the aneurysm was significantly reduced after balloon insertion, it was still 2.5 times greater than the normal maximum shear stress. This was attributable to the presence of a portion of the aneurysmal neck (residual neck), which was not obliterated by the balloon. The balloon also helped to reduce the maximum pressure inside the aneurysm by approximately 15%. Hemodynamic changes in the residual aneurysm neck, where the shear stress and the pressure are high, and other factors may be responsible for the recurrence of aneurysms after balloon or coil occlusion. CONCLUSION: Residual necks after balloon occlusion, coil occlusion, or both are attributable to the geometric orientation of the aneurysm with respect to parent and daughter vessels and the variety of configurations of the balloon and coils used to occlude the aneurysms. Inadequate reduction in local shear stress found in these residual necks is an important factor in the recurrence and rupture of the aneurysm after endovascular occlusion.

Blood Flow Velocity↗
PubMed1995

MR imaging: quality assessment method and ratings at 33 centers.

PURPOSE: To outline a quality assessment method with peer review for magnetic resonance (MR) imaging. MATERIALS AND METHODS: Thirty-three providers in the Philadelphia area were rated on a random sample of 132 brain, 124 cervical spine, and 113 lower extremity MR imaging examinations performed during 1990. Blinded peer review was performed by panels of three subspecialty-trained academic radiologists. Technical performance, completeness, and report appropriateness of each MR imaging examination were evaluated. Aggregated scores were calculated to rate provider performance for each of the three parameters of quality. RESULTS: Two or three panelists assessed technical performance as inadequate in 15 cases, completeness as incomplete in 58 cases, and the interpretative report as inappropriate and affecting treatment in 72 cases. Eleven providers received an unsatisfactory rating on one or more parameters of quality. The association between unsatisfactory ratings and the use of low-field-strength (< or = 0.6-T) imagers was statistically significant (P < .008). CONCLUSION: Substantial deficiencies were identified in the performance of examinations and interpretation of MR images in the Philadelphia area in 1990. These findings indicate the need for a program to monitor quality of MR imaging.

Brain↗
PubMed1994

Distributional patterns of multiple sclerosis brain lesions. Magnetic resonance imaging--clinical correlation.

Forty-one patients with multiple sclerosis were studied with magnetic resonance imaging (MRI) and a battery of neuropsychological tests to determine the pattern of lobar distribution of lesions in the relapsing-progressive and relapsing-remitting forms of the disease. Correlation of lesions with the patient's cognitive and emotional dysfunction was also obtained. The results of this study indicate that patients with relapsing-progressive multiple sclerosis are characterized by the large or coalescent lesions located predominantly in the periventricular area. These lesions were more frequently found in the parietooccipital areas and were accompanied by significant cognitive dysfunction and severe personality changes. The patients with relapsing-remitting disease, however, were characterized by punctiform or small discrete lesions predominantly located in the intermediate and subcortical areas. These lesions were more frequently seen in the parietooccipital regions and the patients had significantly less severe cognitive and emotional involvement than did the patients with relapsing-progressive disease. Recognition of these patterns was easily accomplished by MRI. In this investigation MRI studies were utilized as an index of the pathological changes occurring at one point in time in the evaluation of the disease. Only repeated MRI studies and continuous clinical observation can establish the final diagnosis.

Adult↗
PubMed1992

The sensitivity of the Mini-Mental State Exam in the white matter dementia of multiple sclerosis.

Fifty-six patients diagnosed with definite multiple sclerosis (MS) according to Poser criteria were administered the Mini-Mental State Examination (MMSE) and a comprehensive battery of neuropsychological tests. Extent of cerebral lesion involvement was determined by quantitative magnetic resonance imaging (MRI) ratings. The MMSE correlated with overall levels of physical disability, but did not correlate with total lesion area on MRI. Sensitivity of the MMSE to the subcortical dementia of MS was low (28%) when performance on the neuropsychological testing battery was used as the criterion. Impairment on tests of memory, speed of information processing, abstract reasoning, naming/verbal fluency, as well as visuoperceptual organization, were correlated highly with total lesion area on MRI. The low sensitivity of the MMSE to cognitive impairment in MS is discussed in terms of its item composition and the characteristic pattern of deficits found in MS.

Adult↗
PubMed1992

Cloning, expression, and nucleotide sequence of genes involved in production of pediocin PA-1, and bacteriocin from Pediococcus acidilactici PAC1.0.

The production of pediocin PA-1, a small heat-stable bacteriocin, is associated with the presence of the 9.4-kbp plasmid pSRQ11 in Pediococcus acidilactici PAC1.0. It was shown by subcloning of pSRQ11 in Escherichia coli cloning vectors that pediocin PA-1 is produced and, most probably, secreted by E. coli cells. Deletion analysis showed that a 5.6-kbp SalI-EcoRI fragment derived from pSRQ11 is required for pediocin PA-1 production. Nucleotide sequence analysis of this 5.6-kbp fragment indicated the presence of four clustered open reading frames (pedA, pedB, pedC, and pedD). The pedA gene encodes a 62-amino-acid precursor of pediocin PA-1, as the predicted amino acid residues 19 to 62 correspond entirely to the amino acid sequence of the purified pediocin PA-1. Introduction of a mutation in pedA resulted in a complete loss of pediocin production. The pedB and pedC genes, encoding proteins of 112 and 174 amino acid residues, respectively, are located directly downstream of the pediocin structural gene. Functions could not be assigned to their gene products; mutation analysis showed that the PedB protein is not involved in pediocin PA-1 production. The mutation analysis further revealed that the fourth gene, pedD, specifying a relatively large protein of 724 amino acids, is required for pediocin PA-1 production in E. coli. The predicted pedD protein shows strong similarities to several ATP-dependent transport proteins, including the E. coli hemolysin secretion protein HlyB and the ComA protein, which is required for competence induction for genetic transformation in Streptococcus pneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Acute cervical spine trauma: correlation of MR imaging findings with degree of neurologic deficit.

A retrospective analysis of magnetic resonance (MR) imaging studies of 78 patients with acute cervical spinal cord injuries was undertaken to determine which observations related directly to the neurologic injury. All MR imaging studies were performed on a 1.5-T unit and assessed with respect to 14 parameters related to the bony spine, ligaments, prevertebral soft tissues, intervertebral disks, and spinal cord. Forty-eight patients also underwent non-contrast material-enhanced thin-section computed tomography (CT) of the cervical spine. MR imaging was the definitive modality in the assessment of soft-tissue injury, especially in the evaluation of the spinal cord and intervertebral disks. All patients with a neurologic deficit had abnormal spinal cords at MR imaging. Intramedullary hemorrhage was predictive of a complete lesion. The degree of associated bone and soft-tissue injury had no bearing on the extent of spinal cord injury or neurologic deficit. Patients with residual cord compression following reduction demonstrated greater neurologic compromise than those without compression.

Acute Disease↗
PubMed1987

Plasmid-Associated Bacteriocin Production and Sucrose Fermentation in Pediococcus acidilactici.

Production of bacteriocin activity designated pediocin PA-1 was associated with the presence of a 6.2-megadalton plasmid in Pediococcus acidilactici PAC1.0. The bacteriocin exhibited activity against P. acidilactici, P. pentosaceus, Lactobacillus plantarum, L. casei, L. bifermentans, and Leuconostoc mesenteroides subsp. dextranicum. Partial characterization of pediocin PA-1 is described. The molecular weight of pediocin PA-1 was ca. 16,500. Additionally, strain PAC1.0 was found to contain a 23-megadalton plasmid associated with sucrose-fermenting ability.

Journal Article↗
PubMed1986

Evidence for Plasmid Linkage of Raffinose Utilization and Associated alpha-Galactosidase and Sucrose Hydrolase Activity in Pediococcus pentosaceus.

The ability to ferment the trisaccharide raffinose was linked with the presence of plasmid DNA in three strains of Pediococcus pentosaceus. Parental strains showed associated inducible alpha-galactosidase and sucrose hydrolase activities when grown in alpha-galactosides and sucrose, respectively. Derivative strains of PPE1.0, PPE2.0, and PPE5.0, which had lost 30-, 28-, and 23-megadalton plasmids, respectively, had no alpha-galactosidase or sucrose hydrolase activity.

Journal Article↗