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Biomedical subjects

S Gonzalez

Publications and source records attributed to S Gonzalez.

At least 37 records · Page 2Linked to original sources
PubMed2001

Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy.

BACKGROUND: Near-infrared confocal scanning laser microscopy (CSLM) represents a novel imaging technique for in vivo microscopic analysis of skin lesions, including pigmented lesions. OBJECTIVES: To investigate the feasibility of detecting a clinically amelanotic malignant cutaneous melanoma using CSLM and to explore the use of this technique for assessing its margins. PATIENTS AND METHODS: Two lesions from 2 patients were imaged and analyzed using CSLM. Sites suspected to represent melanoma or benign skin on CSLM were marked as such; then, biopsy specimens were obtained for diagnosis using conventional histological analysis. Both lesions were stained for melanin pigment and analyzed immunohistochemically for the expression of melanosomal markers. In 1 case, a biopsy specimen was also examined with electron microscopy. RESULTS: The images obtained using CSLM allowed recognition of an abnormal intraepidermal melanocytic proliferation that was distinctly different from normal skin. Comparison of the sites examined using CSLM and subsequently using conventional histological methods revealed that CSLM correctly identified intraepidermal melanoma and benign skin. Fontana-Masson stains and immunohistochemical and ultrastructural studies showed that clinically amelanotic melanoma cells contained melanosomes and rare melanin granules. CONCLUSIONS: We demonstrated, for the first time, the detection of clinically amelanotic melanoma using CSLM. This technique may aid in the early detection of clinically barely visible or nonpigmented melanomas and may facilitate preoperative noninvasive assessment of their margins.

Aged↗
PubMed2000

Usefulness of unipolar electrograms to detect isthmus block after radiofrequency ablation of typical atrial flutter.

BACKGROUND: RS morphology of the unipolar electrogram is associated with propagation of the wave front through the exploring electrode, whereas positive uniphasic (R) unipolar electrograms are characteristic of the end of activation. METHODS AND RESULTS: Unipolar electrograms were recorded in 45 consecutive patients with atrial flutter who were undergoing radiofrequency ablation (RFA). Bidirectional cavotricuspid isthmus (CTI) block was achieved in 44 patients. The unipolar electrogram obtained before RFA at the low anterolateral right atrium during coronary sinus pacing changed from RS, rS, or QS to R or Rs in all patients after clockwise CTI block was obtained. The morphology of unipolar electrograms recorded close to the coronary sinus during pacing from the low anterolateral right atrium changed from RS or rS to R or Rs in all but 4 patients after counterclockwise CTI block. In the patient in whom CTI block was not achieved, the RS morphology of the unipolar electrogram remained unchanged. In 18 patients, the results of the RFA were assessed with only the unipolar electrogram. The unipolar electrogram correctly predicted 100% and 89% of the cases of clockwise and counterclockwise CTI block, respectively. CONCLUSIONS: The creation of CTI block is associated with an easily detectable loss of negative components and development of an R or Rs pattern of the unipolar electrogram recorded close to the ablation line while pacing at the opposite side of the CTI.

Aged↗
PubMed2000

The ruv proteins of Thermotoga maritima: branch migration and resolution of Holliday junctions.

In homologous recombination in bacteria, the RuvAB Holliday junction-specific helicase catalyzes Holliday junction branch migration, and the RuvC Holliday junction resolvase catalyzes formation of spliced or patched structures. RuvAB and RuvC from the hyperthermophile Thermotoga maritima were expressed in Escherichia coli and purified to homogeneity. An inverted repeat sequence with unique termini was produced by PCR, restriction endonuclease cleavage, and head-to-tail ligation. A second inverted repeat sequence was derived by amplification of a second template containing a three-nucleotide insertion. Reassociation products from a mixture of these two sequences were homoduplex linear molecules and heteroduplex heat-stable Holliday junctions, which acted as substrates for both T. maritima RuvAB and RuvC. The T. maritima RuvAB helicase catalyzed energy-dependent Holliday junction branch migration at 70 degrees C, leading to heteroduplex linear duplex molecules with two three-nucleotide loops. Either ATP or ATP gamma S hydrolysis served as the energy source. T. maritima RuvC resolved Holliday junctions at 70 degrees C. Remarkably, the cleavage site was identical to the preferred cleavage site for E. coli RuvC [(A/T)TT(downward arrow)(G/C)]. The conservation of function and the ease of purification of wild-type and mutant thermophilic proteins argues for the use of T. maritima proteins for additional biochemical and structural studies.

Amino Acid Sequence↗
PubMed2000

The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle.

Loss of genomic integrity is a defining feature of many human malignancies, including human papillomavirus (HPV)-associated preinvasive and invasive genital squamous lesions. Here we show that aberrant mitotic spindle pole formation caused by abnormal centrosome numbers represents an important mechanism in accounting for numeric chromosomal alterations in HPV-associated carcinogenesis. Similar to what we found in histopathological specimens, HPV-16 E6 and E7 oncoproteins cooperate to induce abnormal centrosome numbers, aberrant mitotic spindle pole formation, and genomic instability. The low-risk HPV-6 E6 and E7 proteins did not induce such abnormalities. Whereas the HPV-16 E6 oncoprotein has no immediate effects on centrosome numbers, HPV-16 E7 rapidly induces abnormal centrosome duplication. Thus our results suggest a model whereby HPV-16 E7 induces centrosome-related mitotic disturbances that are potentiated by HPV-16 E6.

Carcinoma, Squamous Cell↗
PubMed2000

Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer.

Germ-line mutations in the tumor suppressor gene APC are associated with hereditary familial adenomatous polyposis (FAP), and somatic mutations are common in sporadic colorectal tumors. We now report that methylation in the promoter region of this gene constitutes an alternative mechanism for gene inactivation in colon and other tumors of the gastrointestinal tract. The APC promoter is hypermethylated in 18% of primary sporadic colorectal carcinomas (n = 108) and adenoma (n = 48), and neoplasia with APC methylation fails to express the APC transcript. Methylation affects only wild-type APC in 95% of cases and is not observed in tumors from FAP patients who have germ-line APC mutations. As with APC mutation, aberrant APC methylation occurs early in colorectal carcinogenesis. When other tumor types are analyzed (n = 208), methylation of the APC promoter is not restricted to the colon but is present in tumors originating elsewhere in the gastrointestinal tract but rarely in other tumors. Our data suggest that hypermethylation of APC provides an important mechanism for impairing APC function and further underscores the importance of the APC pathway in gastrointestinal tumorigenesis.

Alleles↗
PubMed2000

Immunocytochemical evidence for a progesterone receptor in neurons and glial cells of the rat spinal cord.

Using the KC 146 monoclonal antibody recognizing the B-form of the progesterone receptor (PR) and immunocytochemical techniques, we investigated if PR-immunoreactive cells are present in the rat spinal cord. Neurons from ventral horn Lamina IX, glial cells in gray and white matter and ependymal cells were PR-positive. Evidence for estrogen-inducibility of PR in ovariectomized rats was not observed. There were no significant gender differences in neuronal PR immunostaining intensity in the spinal cord, measured by computerized image analysis. In pituitary and uterus from estrogenized female rats, PR showed a strict nuclear localization, whereas in neurons and glial cells of the spinal cord, PR localized in cytoplasm and/or nucleus and in some cell processes. This receptor may be implicated in some of the biological effects of progesterone described in the spinal cord.

Animals↗
PubMed2000

Efficient charge separation in C60-based dyads: triazolino

Triazoline[4,5][60]fullerenes are strong electron acceptors that form with tetrathiafulvalene (TTF), a novel type of donor-acceptor dyad exhibiting efficient improved electron-transfer dynamics. In particular, a rapid photoinduced intramolecular electron transfer, forming a charge-separated state, is followed by a slow charge recombination to generate the fullerene triplet excited state in moderate quantum yields.

Journal Article↗
PubMed2000

Confirmation of onychomycosis by in vivo confocal microscopy.

Onychomycosis is common in adults and constitutes 20% of all nail disease. Widely used methods to confirm a clinical diagnosis of onychomycosis often yield negative results (ie, potassium hydroxide [KOH] preparation) or are slow (ie, dermatophyte cultures). We report a case of onychomycosis in which we used in vivo confocal microscopy to diagnose the disease; we also correlated our findings with results from routine KOH preparations. On the basis of our findings, we hypothesize that in vivo confocal microscopy may be faster and more accurate than the conventional microscope used in KOH preparations in the diagnosis of onychomycosis.

Adult↗
PubMed2000

HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility.

Characterization of non-B27 susceptibility genes will be required to know the pathogenesis of AS. The aim of this study was to examine whether ankylosing spondylitis (AS) susceptibility is controlled by B27 alone rather than B27 haplotypes and, whether other closely related class I loci, such as MICA and TNFA genes might play a role in AS. Three hundred eleven B27-positive samples from Caucasoid, Asian, and African populations were selected and genotypes were carried out by PCR/SSOP (HLA-B27 and HLA-C), PCR/SSP (MICA-TM polymorphism in the transmembrane region), PCR/SSCP (MICA alleles), and PCR-RFLP (TNF-alpha). Of these, 161 were AS patients, chosen in order to investigate the contribution of TNFA and MICA loci to AS in HLA-B27 positive individuals. Some findings can be concluded from the study: (a) No significant differences of TNF-alpha promoter alleles at position -308 and -238 (A/G) were found between AS patients and B27 matched alleles from healthy controls; (b) strong linkage disequilibrium was found between the B27 and the MICA alleles. The MICA-A4 was found to be in association with B*2705,02,03 and 08; MICA-A5 with B*2704 and B*2707 and MICA-A.5.1 with B*2706; (c) no significant differences of MICA alleles were found between AS and controls carrying the B27-associated alleles, and therefore no evidence is provided for an additional role of MICA gene in AS susceptibility; (d) there are a striking correlations between the structure of B27 extended haplotypes (from MICA region to HLA-C) and the ethnic distribution of these subtypes. The results of differential linkage disequilibrium with HLA-B27 subtypes suggest that B27 itself remains the primary gene for AS susceptibility, and TNFA and MICA are not involved in the pathogenesis of the disease.

Alleles↗
PubMed2000

Modulation of NADPH-diaphorase and glial fibrillary acidic protein by progesterone in astrocytes from normal and injured rat spinal cord.

Progesterone (P4) can be synthesized in both central and peripheral nervous system (PNS) and exerts trophic effects in the PNS. To study its potential effects in the spinal cord, we investigated P4 modulation (4 mg/kg/day for 3 days) of two proteins responding to injury: NADPH-diaphorase, an enzyme with nitric oxide synthase activity, and glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivity. The proteins were studied at three levels of the spinal cord from rats with total transection (TRX) at T10: above (T5 level), below (L1 level) and caudal to the lesion (L3 level). Equivalent regions were dissected in controls. The number and area of NADPH-diaphorase active or GFAP immunoreactive astrocytes/0.1 mm(2) in white matter (lateral funiculus) or gray matter (Lamina IX) was measured by computerized image analysis. In controls, P4 increased the number of GFAP-immunoreactive astrocytes in gray and white matter at all levels of the spinal cord, while astrocyte area also increased in white matter throughout and in gray matter at the T5 region. In control rats P4 did not change NADPH-diaphorase activity. In rats with TRX and not receiving hormone, a general up-regulation of the number and area of GFAP-positive astrocytes was found at all levels of the spinal cord. In rats with TRX, P4 did not change the already high GFAP-expression. In the TRX group, instead, P4 increased the number and area of NADPH-diaphorase active astrocytes in white and gray matter immediately above and below, but not caudal to the lesion. Thus, the response of the two proteins to P4 was conditioned by environmental factors, in that NADPH-diaphorase activity was hormonally modulated in astrocytes reacting to trauma, whereas up-regulation of GFAP by P4 was produced in resting astrocytes from non-injured animals.

Animals↗
PubMed2000

The OTF3 gene polymorphism confers susceptibility to psoriasis independent of the association of HLA-Cw*0602.

Psoriasis has been strongly associated to HLA-Cw6, but it remains unclear whether Cw6 itself or a closely linked gene is associated with the disease. The aim of this study was to clarify whether the HLA-C itself determines disease susceptibility or whether it acts only as a marker for the susceptibility allele. We examined a sample of 95 type I psoriasis patients and 104 Spanish matched controls to investigate whether HLA-Cw*0602 or other closely related class I loci, such as HLA-B and MICA (which are centromeric to HLA-C), or corneodesmosin gene and octamer transcription factor-3 genes (which are telomeric to HLA-C), might play a part in disease development. DNA samples were genotyped by polymerase chain reaction/sequence-specific primers (HLA-C), polymerase chain reaction/sequence-specific primers (HLA-B), radioactive polymerase chain reaction (MICA-TM polymorphism in the transmembrane region), and polymerase chain reaction/restriction fragment length polymorphism (protein S and octamer transcription factor-3). Our results show a significant increase of Cw*0602 in psoriasis patients (odds ratio = 3.64; pc < 0.0006). A significant association between the beta allele of octamer transcription factor-3 (HindIII) and psoriasis was also detected (odds ratio = 3.76; pc < 0.0003). The allele octamer transcription factor-3B (etiologic fraction = 0.62) was found to be more strongly associated to psoriasis vulgaris than Cw*0602 (etiologic fraction = 0.35) and the increase of octamer transcription factor-3 B allele is independent of the linkage disequilibrium with Cw*0602 as this was also found in Cw*0602 negative patients (odds ratio = 3.63; pc < 0.015, etiologic fraction = 0.55). We did not detect an association between the corneodesmosin gene and psoriasis. This fact suggests that the psoriasis susceptibility gene is located within a critical region of 147 kb, telomeric to HLA-C and centromeric to the corneodesmosin gene, and the association of Cw6 to psoriasis may be secondary to linkage disequilibrium.

Adolescent↗
PubMed2000

Molecular analysis of the Saccharomyces cerevisiae YHR076w gene.

Our results demonstrate that open reading frame (ORF) YHR076w on chromosome VIII of Saccharomyces cerevisiae that was previously described as a hypothetical gene is expressed. This ORF is transcribed as an mRNA of approximately 1,100 nucleotides. A 41.2-kDa polypeptide and three others predicted to be modified forms of Yhr076wp are detected by Western blot with a Yhr076wp-specific antibody. Promoter activity assays indicate that YHR076w transcription is regulated by carbon source and primarily by ethanol. Consistent with this observation, we have identified two potential ADR1 regulatory elements in the YHR076w upstream DNA region. Potential YAP1 and HSP elements are also identified in this region, suggesting other forms of regulation. YHR076w knockout strains do not exhibit any measurable growth or morphological phenotype under any conditions tested. However, increased YHR076w gene dosage confers a growth advantage to both wild-type and YHR076w knockout strains on 2% ethanol or 2% galactose medium in a low O2 growth environment. The fluorescence emitted by a Yhr076wp protein fusion to A. aquorin GFP colocalizes with the mitochondria in vivo.

Calmodulin-Binding Proteins↗
PubMed1999

Rate-dependent conduction block of the crista terminalis in patients with typical atrial flutter: influence on evaluation of cavotricuspid isthmus conduction block.

BACKGROUND: The crista terminalis (CT) has been identified as the posterior boundary of typical atrial flutter (AFL) in the lateral wall (LW) of the right atrium (RA). To study conduction properties across the CT, rapid pacing was performed at both sides of the CT after bidirectional conduction block was achieved in the cavotricuspid isthmus by radiofrequency catheter ablation. METHODS AND RESULTS: In 22 patients (aged 61+/-7 years) with AFL (cycle length, 234+/-23 ms), CT was identified during AFL by double electrograms recorded between the LW and posterior wall (PW). After the ablation procedure, decremental pacing trains were delivered from 600 ms to 2-to-1 local capture at the LW and PW or coronary sinus ostium (CSO). At least 5 bipolar electrograms were recorded along the CT from the high to the low atrium next to the inferior vena cava. No double electrograms were recorded during sinus rhythm in that area. Complete transversal conduction block all along the CT (detected by the appearance of double electrograms at all recording sites and craniocaudal activation sequence on the side opposite to the pacing site) was observed in all patients during pacing from the PW or CSO (cycle length, 334+/-136 ms), but it was fixed in only 4 patients. During pacing from the LW, complete block appeared at a shorter pacing cycle length (281+/-125 ms; P<0.01) and was fixed in 2 patients. In 3 patients, complete block was not achieved. CONCLUSIONS: These data suggest the presence of rate-dependent transversal conduction block at the crista terminalis in patients with typical AFL. Block is usually observed at longer pacing cycle lengths with PW pacing than with LW pacing. This difference may be a critical determinant of the counterclockwise rotation of typical AFL.

Aged↗
PubMed1999

The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis.

OBJECTIVE: To investigate the relative contribution of HLA antigens in the susceptibility to psoriasis and to localize additional genetic factors involved in psoriatic arthritis (PsA). METHODS: DNA from 45 patients with psoriasis, 65 with PsA, and 177 healthy control subjects was examined by polymerase chain reaction (PCR) using sequence-specific oligonucleotide probes to determine HLA-C. To examine whether MICA (class I major histocompatibility complex chain-related gene A) confers additional susceptibility, trinucleotide repeat polymorphism in the transmembrane region of the MICA gene was investigated by radioactive PCR. Further analysis of MICA was made by PCR-single-strand conformational polymorphism to determine the allelic variant corresponding to MICA transmembrane polymorphism. RESULTS: Our results reveal new findings: 1) the frequency of the Cw*0602 allele was significantly increased in both patient groups: psoriasis (corrected P [Pcorr] < 10(-5), relative risk [RR] 6.2), PsA (Pcorr < 10(-6), RR 6.3), 2) the trinucleotide repeat polymorphism MICA-A9 was present at a significantly higher frequency in PsA patients (Pcorr < 0.00035, RR 3.2), whereas a similar distribution was found in both the control and psoriasis population, 3) this polymorphism corresponds to the MICA-002 allele and was found to be overrepresented in patients with the polyarticular form (Pcorr < 0.0008, RR 9.35), 4) the increase in MICA-A9 in PsA patients is independent of linkage disequilibrium with Cw*0602, 5) this allele confers additional relative risk (RR 3.27, etiologic fraction 0.44; etiologic fraction is the proportion of disease cases among the total population that are attributable to 1 allele when the relative risk is > 1) in PsA patients who carry Cw*0602. CONCLUSION: The data obtained in this study are consistent with the polygenic inheritance of psoriasis. Cw*0602 appears to be the stronger genetic susceptibility factor for psoriasis. Independent of the HLA-C association, MICA-A9 polymorphism corresponding to the MICA-002 allele is a possible candidate gene for the development of PsA.

Adult↗
PubMed1999

Hydroxyurea-induced acute interstitial pneumonitis in a patient with essential thrombocythemia.

Hydroxyurea is a drug widely used to control myeloproliferative disorders, due in part to its relative lack of severe side effects. We present a case of acute interstitial pneumonitis in a patient who was treated with hydroxyurea for essential thrombocythemia. The clinical course suggests that the interstitial pneumonitis was induced by hydroxyurea. This is the first case of hydroxyurea-induced acute interstitial pneumonitis reported in the literature.

Humans↗