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J Montoya

Publications and source records attributed to J Montoya.

At least 19 recordsLinked to original sources
PubMed2006

[Mitochondrial DNA deletions in Kearns-Sayre syndrome].

INTRODUCTION: Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by progressive external ophthalmoplegia, pigmentary retinopathy, onset before 20 years, and ragged-red fibers on muscle biopsy. KSS has been associated to mitochondrial DNA (mtDNA) mutations. We report neurological manifestations and mtDNA deletions in KSS. METHODS: Six KSS patients underwent neurological examination, biochemical analysis (muscle enzymes, lactate, cerebrospinal fluid analysis), electromicrography, muscle biopsy (Gomori stain, electronic microscopy), electrocardiogram, echocardiography, MRI/CT scan. MtDNA deletions were studied in blood and muscle samples using Southern blotting and long polymerase chain reaction. RESULTS: Four males and two females (mean age: 27.7 years; range: 17-42; mean age at onset: 8.2 years) were studied. Initial symptoms were ptosis and gaze restriction, fatigue, exercise intolerance and proximal limb weakness. Syncope and neurosensory hypoacusia were initial symptoms in two patients. All of them presented a unique deletion in the mitochondrial genome, in heteroplasmy, and their size was in the range of 4,420 and 9,437 basis pairs. Three of these deletions are reported for the first time in this article. Most of the deletions are flanked by small direct repeats elements. CONCLUSIONS: Proximal muscle weakness and fatigue appear frequently in KSS patients during follow up. The syndrome in these patients has been caused by mtDNA deletions.

Adolescent↗
PubMed2005

Evidence of biochemical and biomagnetic interactions in Alzheimer's disease: an MEG and MR spectroscopy study.

BACKGROUND: Several neuroimaging studies have shown reliable differences between Alzheimer's disease (AD) patients and age-matched controls. However, few studies have demonstrated the interactions between neuroimaging methods for the diagnoses of AD. OBJECTIVE: In this study, we try to elucidate the complementary nature of magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS) examinations in the assessmentof AD. METHODS: Ten patients fulfilling the NINCDS-ADRDA criteria of probable AD, and 10 elderly individuals with no history of neurological or psychiatric illness serving as age-matched controls participated in the study. All patients and controls received an MRS, MEG and neuropsychological assessment. MEG data were obtained in the context of a working memory task, previously utilized in a similar sample of patients. RESULTS: The AD group showed a reduced number of activity sources over left temporoparietal areas during the late portion of the evoked magnetic field (between 400-800 ms), as well as a bilateral temporoparietal increase in creatine and myoinositol concentrations, and in the myoinositol/N-acetyl-aspartate ratio. The combination of the variables 'number of dipoles during the late portion of the evoked magnetic field' and 'myoinositol/N-acetyl-aspartate ratio' accounted for 65% of the variance of the Mini Mental State Examination scores. CONCLUSIONS: These results highlight the importance of assessing the complex brain pathology underlying AD by utilizing multiple brain examination modalities in a coordinate approach.

Aged↗
PubMed2005

Muscle coenzyme Q10 concentrations in patients with probable and definite diagnosis of respiratory chain disorders.

Coenzyme Q(10) (CoQ) deficiency syndrome is a disorder of unknown ethiology that may cause different forms of mitochondrial encephalomyopathy. In the present study our aim was to analyse CoQ concentration and mitochondrial respiratory chain (MRC) enzyme activities in muscle biopsies of patients with clinical suspicion and/or biochemical-molecular diagnosis of a mitochondrial disorder. We studied 36 patients classified into 3 groups: 1) 14 patients without a definitive diagnosis of mitochondrial disease, 2) 13 patients with decreased CI + III and II + III activities of the MRC, and 3) 9 patients with definitive diagnosis of mitochondrial disease. Only 1 of the 14 patients of group 1 showed slightly reduced CoQ values in muscle. Six of the 13 patients from group 2 showed partial CoQ deficiency in muscle and 1 of the 9 cases from group 3 presented a slight CoQ deficiency. Significantly positive correlation was observed between CI + III and CII + III activities with CoQ concentrations in the 36 muscle homogenates from patients (r = 0.555; p = 0.001; and r = 0.460; p = 0.005, respectively). In conclusion, measurement of MRC enzyme activities is a useful tool for the detection of CoQ deficiency, which should be confirmed by CoQ quantification.

Adolescent↗
PubMed2005

Acetophenones with selective antimycobacterial activity.

AIMS: Mycobacteria are a serious cause of infections in humans, with limited treatment options, as no new antibiotics have been developed against mycobacteria since the 1960s. In this study, the antimycobacterial activity of a small library of acetophenone (AP) compounds was analysed. METHODS AND RESULTS: Twenty-three AP derivatives were examined for activity against mycobacteria using a microbroth assay. The compounds were bacteriostatic, with the most effective (cyclohexylacetophenone and piperidinoacetophenone) having minimal inhibitory concentrations of 246 microM. Active compounds tended to be more hydrophobic, and may work by alkylation of as yet undetermined intracellular target protein(s). Cytotoxicity against eukaryotic cells was also determined and appears to be unrelated to the bacteriostatic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: AP may serve as a novel group of useful therapeutics against the mycobacteria.

Acetophenones↗
PubMed2001

Sea urchin mtDBP is a two-faced transcription termination factor with a biased polarity depending on the RNA polymerase.

The sea urchin mitochondrial displacement (D)-loop binding protein mtDBP has been previously identified and cloned. The polypeptide (348 amino acids) displays a significant homology with the human mitochondrial transcription termination factor mTERF. This similarity, and the observation that the 3' ends of mitochondrial RNAs coded by opposite strands mapped in correspondence of mtDBP-binding sites, suggested that mtDBP could function as transcription termination factor in sea urchin mitochondria. To investigate such a role we tested the capability of mtDBP bound to its target sequence in the main non-coding region to affect RNA elongation by mitochondrial and bacteriophage T3 and T7 RNA polymerases. We show that mtDBP was able to terminate transcription bidirectionally when initiated by human mitochondrial RNA polymerase but only unidirectionally when initiated by T3 or T7 RNA polymerases. Time-course experiments indicated that mtDBP promotes true transcription termination rather than transcription pausing. These results indicate that mtDBP is able to function as a bipolar transcription termination factor in sea urchin mitochondria. The functional significance of such an activity could be linked to the previously proposed dual role of the protein in modulating mitochondrial DNA transcription and replication.

Animals↗
PubMed2001

Mechanism of mammalian mitochondrial DNA replication: import of mitochondrial transcription factor A into isolated mitochondria stimulates 7S DNA synthesis.

The light strand promoter of mammalian mitochondrial DNA gives rise to a primary transcript, but also to the RNA primer necessary for initiation of replication and 7S DNA synthesis as well as 7S RNA. Here we have studied the turnover of 7S DNA in isolated rat liver mitochondria and whether import of mitochondrial transcription factor A (mtTFA), which is necessary for transcription initiation, increases its rate of synthesis. 7S DNA was present as two species, probably due to two different sites of RNA-DNA transition. Time course and pulse-chase experiments showed that the half-life of this DNA is approximately 45 min. Import of mtTFA, produced in vitro, into the mitochondrial matrix in stoichiometric amounts significantly increased the rate of 7S DNA formation. We conclude that isolated rat liver mitochondria faithfully synthesize and degrade 7S DNA and that increased matrix levels of mtTFA are sufficient to increase its rate of synthesis, strongly supporting the hypothesis that this process is transcription primed.

Animals↗
PubMed2001

A study on the human mitochondrial RNA polymerase activity points to existence of a transcription factor B-like protein.

In the present work, the RNA polymerase activity of the human mitochondrial RNA polymerase mature protein (h-mtRPOLm) is shown, and its molecular activity calculated (2.1+/-0.9 min(-1)). An activity analysis of h-mtRPOLm and deleted versions of it has demonstrated that the entire recombinant protein is required for this activity. In addition, h-mtRPOLm alone or in presence of the known mitochondrial transcription factors (human mitochondrial transcription factor A and/or human mitochondrial transcription termination factor) is not able to initiate transcription from the specific human mitochondrial promoters pointing to the existence of a human mitochondrial transcription factor B-like protein.

Base Sequence↗
PubMed2001

Interexaminer reliability and validity of a three-dimensional model to assess prostate volume by digital rectal examination.

OBJECTIVES: To evaluate the interexaminer reliability and accuracy compared with transrectal ultrasound (TRUS) of a three-dimensional (3D) model and other scales to improve the estimation of prostate volume by digital rectal examination (DRE). METHODS: Volunteers from a urology clinic (n = 121) were examined independently by three examiners with different levels of experience in randomized order. During DRE, the examiners estimated the prostate size in increments of 5 g, using various rating scales and a 3D sizing model, without access to the findings of the other investigators. TRUS was then performed by each examiner. RESULTS: The 121 volunteers were 39 to 82 years old, with a mean +/- SD total TRUS prostate size of 35.9 +/- 27.2 g. The DRE size estimates ranged from 15 to 100 g across all examiners and patients. The interexaminer reliability across examiners for the best DRE prostate size estimates (in grams) was 0.78 (95% confidence interval 0.70 to 0.84), and the correlation coefficients (r(s)) with the TRUS volume ranged from 0.61 to 0.72 for the three examiners. A 3D model showed good reliability (intraclass correlation coefficient 0.86, 95% confidence interval 0.75 to 0.93), and correlated well with the TRUS volume (r(s) = 0.67 to 0.75). Other scales showed fair reliability (0.58 to 0.68) and correlated with the TRUS measurements (0.57 to 0.67). The area under the receiver operating characteristic curve to identify prostate volumes greater than 40 g ranged from 0.78 to 0.90 for DRE estimates (in grams) and 0.69 to 0.89 for the 3D model. CONCLUSIONS: DRE size estimates and TRUS volume were moderately to highly correlated in men without prostate cancer. A 3D sizing model showed comparable reliability and correlation with TRUS. Although the DRE estimates generally tend to underestimate the TRUS-measured prostate volume, these tools may be useful in identifying men with enlarged prostate glands.

Adult↗
PubMed2001

Exercise intolerance resulting from a muscle-restricted mutation in the mitochondrial tRNA(Leu (CUN)) gene.

BACKGROUND: Some patients presenting with isolated lifelong exercise intolerance and ragged-red fibres, harbour skeletal-muscle restricted mutations in their mitochondrial DNA. AIM: To identify the molecular defect in a patient presenting with lifelong exercise intolerance, ragged-red fibres and deficiencies of complexes III and IV in skeletal muscle. METHODS: The muscle biopsy was studied for activities of the respiratory chain, histochemical stains, and sequencing the tRNA genes of mitochondrial DNA. RESULTS: The patient had a heteroplasmic mutation in the tRNA(Leu (CUN)) gene of mitochondrial DNA (G12334A). Clinical and morphological data as well as restriction fragment length polymorphism (RFLP) and single-fibre polymerase chain reaction (PCR) analyses strongly indicate that this molecular defect is the primary cause of the myopathy. CONCLUSION: Mutations in any mitochondrial gene should be considered in the differential diagnosis of patients with lifelong exercise intolerance, even when the neurological examination is normal.

Adult↗
PubMed2001

Interexaminer reliability of transrectal ultrasound for estimating prostate volume.

PURPOSE: We investigated the interexaminer reliability of transrectal ultrasound measurement of total prostate and transition zone volume among 3 examiners with various levels of experience. MATERIALS AND METHODS: A total of 121 patients 39 to 82 years old (average plus or minus standard deviation 60.7 +/- 10.3) from a single urology clinic volunteered to participate. Patients with prostate cancer, previous prostate surgery or recent invasive prostatic examination were excluded from study. Each individual was examined independently by each of 3 examiners with various levels of experience, including an attending urologist, a PGY-2 resident in the second year of general surgery before urology training and a PGY-4 resident in the second year of urology training. Transrectal ultrasound was performed in each case by each examiner in pre-specified random order. RESULTS: Mean total prostate and transition zone volume was 35.9 +/- 27.2 and 15.6 +/- 18.8 ml., respectively. Interexaminer agreement or reliability of the ultrasound measurements was high for total prostate and transition zone volume (intraclass correlation 0.96, 95% confidence interval [CI] 0.95 to 0.97 and 0.93, 95% CI 0.90 to 0.95, respectively). For individual prostatic dimensions reliability estimates were 0.78 to 0.86, while for transition zone dimensions reliability was 0.85 to 0.90. Total prostate volume reliability was higher for prostate volume greater than 40 ml. versus smaller prostates (intraclass correlation 0.95, 95% CI 0.90 to 0.97 versus 0.77, 95% CI 0.67 to 0.84). Mean differences in transrectal ultrasound measurements by different examiners were highest for the resident with least experience. CONCLUSIONS: The reliability of transrectal ultrasound measured total prostate and transition zone volume is high for examiners with different levels of experience at this institution. Reliability in patients without prostate cancer appears to be better for larger volume prostates and for examiners with more experience.

Adult↗
PubMed2000

Uncoupling protein-1 mRNA expression in lipomas from patients bearing pathogenic mitochondrial DNA mutations.

Multiple symmetric lipomatosis (MSL) is a rare disorder characterised by large subcutaneous fat masses in some parts of the trunk. Mitochondrial disfunction is common in MSL, but the identity of the adipose cells developing in multiple lipomas is not well known. We determined that brown adipose tissue-specific uncoupling protein-1 (UCP-1) mRNA is expressed in the lipoma of a multiple symmetric lipomatosis patient bearing the 8344 mutation in the tRNALys gene of mitochondrial DNA. UCP1 mRNA was not detected in normal subcutaneous fat from the same patient or in the lipoma of another patient bearing a different mutation in the same tRNALys gene. These findings implicate brown adipose cells as the origin of lipomas in a subset of patients bearing tRNALys mutations in mitochondrial DNA.

Adipose Tissue, Brown↗
PubMed2000

Highly active antiretroviral therapy results in HIV type 1 suppression in lymph nodes, increased pools of naive T cells, decreased pools of activated T cells, and diminished frequencies of peripheral activated HIV type 1-specific CD8+ T cells.

This study examines sequential lymph nodes from 13 drug-naive patients before and after 24 weeks of highly active antiretroviral therapy (HAART). A multipronged approach was used to study changes in HIV-1 RNA in each paired lymph node in relation to tissue architecture and frequency of naive T cells. After 24 weeks, all patients showed significant suppression of plasma viral load and 12 of 13 showed concordant viral suppression in the lymph node (p = 0.001). Using in situ hybridization and quantitative image analysis, we showed that HIV-1 RNA was reduced to below detectable levels (two copies per cell) in follicular dendritic cell (FDC) and mononuclear cell pools. Independent immunohistochemical analysis of lymph node sections revealed that 5 of 13 patients displayed increased FDC networks and 6 of 13 showed no change and all patients showed increases in tissue-resident CD4+ cells. All lymph node biopsies at 24 weeks showed increased proportions of CD4+ and CD8+ cells coexpressing the naive markers CD45RA and CD62L when compared with baseline values. Significant correlations existed between viral load suppression and loss of activated CD8+ T cells after 24 weeks in both lymph node and blood, which was mirrored by significantly lowered frequencies of activated peripheral Gag peptide/MHC tetramer+ CD8+ cells. Overall, these data show that a potent and successful treatment strategy that significantly suppresses and removes FDC-resident HIV-1 results in improvements in lymphoid architecture and by so doing provides the structures available for increased numbers of naive cells to interact with cognate antigen. In addition, our article shows that suppression of HIV-1 replication results in diminished frequencies of peripherally activated antigen-specific CD8+ cells.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Iron(II) induces changes in the conformation of mammalian mitochondrial DNA resulting in a reduction of its transcriptional rate.

Living isolated mitochondria incubated with iron(II) show a major alteration in mitochondrial DNA (mtDNA) conformational forms as assessed by Southern blot analysis of undigested mtDNA. In the presence of iron(II), form I is transformed into form III in a dose-dependent manner. This alteration in mtDNA conformation shows a strong correlation with a decrease in the mtDNA transcription rate (r=0.965, P < 0.002), suggesting that iron(II) load results in double-strand breaks and unwinding of mtDNA, which, in turn, is unable to maintain its normal transcriptional rate.

Animals↗