Biomedical subjects
Publications and source records attributed to S González.
A 12-year-old girl presented with three yellowish polypoid lesions in the lateral border of tongue since birth. Histological examination showed oral mucosa covered by squamous epithelium and an underlying vascularized fibrous stroma, containing small and short bundles of striated muscle, corresponding to a rhabdomyomatous hamartoma.
BACKGROUND: Near-infrared reflectance confocal microscopy (RCM) is a noninvasive tool that provides real-time images of thin virtual horizontal tissue sections. AIMS/METHODS: We have used a rhino mouse model in combination with topical application of all-trans-retinoic acid and all-trans-retinol to investigate the usefulness of RCM as a noninvasive imaging tool to evaluate comedolysis in vivo and over time. Optical images were correlated with routine histology. RESULTS: Our results demonstrate that RCM in vivo can visualize the process of transformation of utriculi (pseudocomedones) towards a normal-appearing follicular structure during retinoid treatment. The retinoic acid intervention group showed a dose-related response, while the vehicle-treated group did not show utricular changes. CONCLUSIONS: RCM represents a useful tool for in vivo morphological and quantitative evaluation of skin utriculi over time and could be used as an adjunct tool to histopathological techniques for comedolysis studies.
OBJECTIVES: Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. METHODS: A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene. RESULTS: A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found. CONCLUSIONS: MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.
In this report, we demonstrate a possible molecular mechanism by which a hydrophilic extract of the leaves of the fern Polypodium leucotomos (Fernblock, PL) blocks ultraviolet (UV)-induced skin photodamage. The extract inhibits UVA and UVB light induced photoisomerization of trans-urocanic acid (t-UCA), a common photoreceptor located in the stratum corneum, and also blocks its photodecomposition in the presence of oxidizing reagents such as H2O2, and titanium dioxide (TiO2). PL protects in vitro human fibroblasts from UV-induced death as well. These results suggest the potential of employing the PL extract as a component of sunscreen moistures in order to prevent photodecomposition of t-UCA, to inhibit UV-induced deleterious effects of TiO2 and to protect skin cells and endogenous molecules directly involved in skin immunosurveillance.
The NKG2D-DAP10 receptor complex activates natural killer (NK) cells and costimulates effector T cell subsets upon engagement of ligands that can be conditionally expressed under physiologically harmful conditions such as microbial infections and malignancies. These characteristics have given rise to the widely embraced concept of immunorecognition of "induced or damaged self," complementing the "missing self" paradigm that is represented by MHC class I allotypes and their interactions with inhibitory receptors on NK cells. However, this notion may only be partially sustainable, as various patterns of constitutive tissue distributions have become apparent among members of one NKG2D ligand family. This review summarizes the biological properties of NKG2D and its ligands and discusses the interactions and regulation of these molecules with emphasis of their significance in microbial infections, tumor immunology, and autoimmune disease.
It was recently proved that solitons embedded in the spectrum of linear waves may exist in discrete systems, and explicit solutions for isolated unstable embedded lattice solitons (ELS) of a differential-difference version of a higher-order nonlinear Schrodinger equation were found [Gonzalez-Perez-Sandi, Fujioka, and Malomed, Physica D 197, 86 (2004)]. The discovery of these ELS gives rise to relevant questions such as the following: (1) Are there continuous families of ELS? (2) Can ELS be stable? (3) Is it possible for ELS to move along the lattice? (4) How do ELS interact? The present work addresses these questions by showing that a novel equation (a discrete version of a complex modified Korteweg-de Vries equation that includes next-nearest-neighbor couplings) has a two-parameter continuous family of exact ELS. These solitons can move with arbitrary velocities across the lattice, and the numerical simulations demonstrate that these ELS are completely stable. Moreover, the numerical tests show that these ELS are robust enough to withstand collisions, and the result of a collision is only a shift in the positions of the solitons. The model may apply to the description of a Bose-Einstein condensate with dipole-dipole interactions between the atoms, trapped in a deep optical-lattice potential.
Four strains of Enterobacter sakazakii were inoculated into tryptic soy broth and reconstituted powdered infant formula and exposed to high-pressure processing. Pressures of 200, 400, and 600 MPa were used for each medium for 1 min. E. sakazakii was reduced by more than 6 log (strains A and B) in both media at 600 MPa. Strain B was significantly (P < or = 0.05) more pressure resistant than the other strains, with just more than a 3-log reduction at 600 MPa in both media. The reconstituted infant formula has a significant (P < or = 0.05) protective effect for certain strains and pressures (strain B at 400 MPa and strain D at 400 and 600 MPa). Differences in log reductions between media (milk and broth) were also observed for certain strains and specific pressures (strain B at 400 MPa and strain D at 400 and 600 MPa; P < or = 0.05). This research showed that E. sakazakii, when present in reconstituted powdered infant formula, can be submitted to high-pressure processing (600 MPa for 1 min) and achieve log reductions ranging from 3 to 6.84, depending on the strain.
The extract of the fern Polypodium leucotomos (PL, Fernblock) is an oral photoprotectant with strong antioxidative properties. Recent studies to determine its chemical composition have shown 4-hydroxycinnamic acid (p-coumaric), 3 methoxy-4-hydroxycinnamic acid (ferulic), 3,4-dihydroxycinnamic acid (caffeic), 3-methoxy-4-hydroxybenzoic acid (vanillic) and 3-caffeoilquinic acid (chlorogenic) to be among its major phenolic components. No conclusive data are available, however, on the H2O2-scavenging capacity of these compounds, or on their absorption and metabolism following their oral intake. In the present work, their antioxidative capacity was assessed by the luminol/H2O2 assay, their absorption studied using Caco-2 cells to resemble the intestinal barrier, and their metabolism investigated using cultured primary rat hepatocytes. The antioxidant capacity of PL components increased in a concentration-dependent manner, with ferulic and caffeic acids the most powerful antioxidants. The apparent permeability results correspond to a human post-oral administration absorption of 70-100% for all tested substances. Coumaric, ferulic and vanillic acids were metabolized by CYP450-dependent mono-oxygenases and partially conjugated to glucuronic acid and sulfate. These phenolic compounds may contribute to the health benefits afforded by this oral photoprotectant.
BACKGROUND: Spontaneous supratentorial intracerebral haemorrhages (SSIH) carry high morbidity and mortality rates. At present, the proper role of surgery is not clear and data from the International STICH trial have not clarified this challenging question. On the other hand, few prospective studies have measured long term survival regardless of the treatment and clinical condition of the patient. PATIENTS AND METHODS: We prospectively collected data from all SSIH patients (n = 356) admitted at a tertiary reference hospital over a 40-month time period regardless of their clinical condition and treatment received. Among data investigated were preclinical neurological state, GCS on admission, history of systemic hypertension and treatment (surgical or conservative). Clinical factors influencing mortality at 1-year follow-up were analysed statistically by univariable and multivariable methods. FINDINGS: We found that patients in the eighth decade were the most frequent. Hypertension was present in 47% of patients. Based on the prehospitalisation modified Rankin Scale, 305 (86%) patients were independent for activities of daily living (ADL). At 12-months follow-up, 91 (46% of alive patients) remained independent for ADL. The surgical rate was 22%. Although it was not a randomised study, we did not find a significantly different mortality rate according to whether the patient was treated surgically or conservatively. Overall, the mortality rate was 44% (157 patients) with a 79% of deaths taking place in the first 30 days after admission. CONCLUSIONS: This study underscores the high mortality rate of SSIH, especially so in the first month after admission. Among the subgroup of patients clinically independent before the haemorrhagic stroke, only 29.8% remained independent one year after the event. We did not find any statistically significant difference in mortality according to treatment modality received (surgical vs conservative) although treatment assignment was not randomised. Among other clinical factors, pre-ictal functional status, age, level of consciousness on admission and volume of haemorrhage strongly influence mortality as determined at the 1-year follow-up.
The chemical conjugation of bacterial polysaccharide to carrier proteins has proved to be an efficient tool to improve the immunological response against these bacterial antigens. In this study, we characterized the antibody response generated in a non-human primate model against the meningococcal capsular polysaccharide serogroup C (CCPS) conjugated to the P64k protein. Similar to licensed vaccines the CCPS conjugate is able to generate a good memory immune response with antibody titers threefold higher than the free CCPS. Three different ELISA protocols were used to measure the antibody response and the importance of the coating antigen was demonstrated. The ELISA using the derivatized CCPS showed the best results and had a high correlation with the bactericidal activity. The antibodies elicited showed a high protective capacity when assayed in the infant rat protection model.
OBJECTIVE: To analyze the HLA distribution in a population of individuals from Zambia in order to establish a possible relationship between the progression of human immunodeficiency virus (HIV) infection and the development of spondylarthropathy (SpA). METHODS: A large epidemiologic analysis of rheumatology patients living in Zambia was performed in order to identify those who had SpA. We selected 64 patients with SpA and found that 54 also had HIV type 1 (HIV-1) infection; only 10 were HIV negative. Additionally, we selected 57 HIV-infected individuals without SpA and 43 healthy controls. Among all of the HIV-1-infected patients, 25 SpA-positive and 24 SpA-negative patients were classified as slow progressors to acquired immunodeficiency syndrome (AIDS), and 8 SpA-positive and 26 SpA-negative patients were classified as rapid progressors. All patients were typed for HLA-B alleles. RESULTS: Of the 64 patients with SpA, HIV infection was observed in 54 (84%). The frequency of B*5703 was increased in patients who were SpA positive and HIV positive compared with patients who were SpA negative and HIV positive (P = 0.0002, odds ratio [OR] 8.28). Among patients who were slow progressors to AIDS, this allele was overrepresented in those with SpA compared with those without SpA (corrected P = 0.001, OR 26.25). CONCLUSION: HLA-B*5703 seems to be a protective allele against the progression of HIV infection but could influence the increased incidence of SpA observed in this population.
KIR and HLA loci are both highly polymorphic, and some HLA class 1 products bind and trigger cell-surface receptors specified by KIR genes. We examined whether KIR genes act in concert with HLA-B locus to control HIV-1 infection in a sample of Zambian patients. DNA samples from 88 Zambian patients with HIV-1 were examined. Patients were classified as either slow progressors (SP; n = 54) or rapid progressors (RP; n = 34) to AIDS. All were typed for HLA-B and KIR genes. Our results reveal an association between B*57 supertype (B*57s, which includes B*57 and B*58 alleles) and delayed progression to AIDS (p = 0.0007 by pc = 0.015; OR = 5.25). We also observed an increase incidence of Bw4-I80 in patients with slow progression (p = 0.001 by pc = 0.003, OR = 5). This increase was found to be secondary to B*57s. The presence of both KIR3DL1 and B*57S has a significant effect on progression to AIDS (p = 0.0008; OR = 5.61). B*57s genotypes with another HLA-B allele different from those in the trans position, which also had a specificity different to Bw4-I80 (Bw4-T80 or Bw6), was also greater in the SP than in the RP group (p = 0.00003; OR = 10.11). The presence of the inhibitory allele KIR3DL1 in combination with the HLA-B*57s alleles that contain the Bw4-I80 epitope, has a highly protective effect against progression to AIDS in Zambian patients.
Catheter removal is now the standard recommendation of catheter-related fungemia even when tunneled devices are used. However, in the clinical practice, this procedure is not always without risks. Antibiotic-lock technique can resolve many cases of catheter-related bacteraemia, but cure of catheter-related candidemia by this method has been attempted in very few instances, reviewed in this article. Herein, we report a case of non-complicated Candida glabrata fungemia related to a Hickman catheter used for parenteral nutrition, cured with intraluminal amphotericin B in addition to systemic therapy. This case demonstrates that 'antifungal-lock therapy' can be effectively used in selected cases of catheter-related candidemia.
A 57-year-old Caucasian woman with Type 2 diabetes treated for seven years with diet and oral combination hypoglycaemic therapy was referred because of the progressive deterioration of glycaemic control. She was obese (77 kg, BMI = 39.9), hypertensive, hypercholesterolaemic with marked osmotic symptoms (HbA(1c) 12.2%), therefore she was started on insulin (Human Mixtard 30 b.d.) with metformin therapy. Dietary counselling, recommendations to increase physical activity, and supervised self-injection technique with titration of her insulin were also provided. She was routinely followed-up to assess her progress. Two years later, her glycaemic control remained suboptimal. Average HbA(1c) was 10.4% despite an increasingly high dose of insulin (94 units/day) although it improved when metformin was increased to 1 g t.d.s. (HbA(1c) = 9.3%). Her BMI progressively rose from 39.9 to 42.1 (77 to 82.5 kg) despite dietary advice. A trial of orlistat (three months) was commenced, after intensive dietary counselling, that reduced her body weight by 1.5 kg (2% reduction, BMI 41.3). However, her HbA(1c) improved by 0.5% (from 9.3 to 8.8%). Six months after orlistat was stopped her HbA(1c) rose to 10.5% and weight increased to 81.8 kg (BMI 41.8). Despite the orlistat treatment broaching NICE guidelines should it have been continued?
Circumscribed palmar hypokeratosis is a recently described condition that consists of a solitary area of depressed skin affecting the palm (or sole). Its histopathological features include a thinned horny layer, a slightly diminished granular cell layer, and intraepidermal vacuolated cells. Prolonged treatment with topical calcipotriol resulted in complete recovery of the affected zone in the case reported here. A second biopsy of the lesion taken at around the fourth year of therapy showed a normalization of the granular layer, a reduction in the intraepidermal vacuolated cells, and a somewhat thicker horny layer. An ultrastructural study carried out at the same time showed a reduction in keratin bundles and keratohyalin granules, and an increase in lipid droplets up to the horny layer. These findings and the therapeutic response to topical calcipotriol support the concept that circumscribed palmar hypokeratosis is a focalized abnormal keratinization defect morphologically expressed at the granular and horny layers.
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We performed a family study to evaluate a total of 34 extended family members (8 siblings, 23 children and nephews, and 3 grandchildren) of an adult patient with celiac disease (CD), a 58- year-old male with severe neurologic involvement manifested as myoclonias. We found 3 other members affected with CD (a 44-year old sister, a 39-year old niece, and a 26-year old nephew). Two of them were completely asymptomatic and all had hypertransaminasemia. All exhibited a villous atrophy pattern of the duodenal mucosa (1 mild, 1 moderate, 1 severe). Overall family involvement was 11.8% (4/14). We wish to emphasize the need to perform extended family studies when diagnosing a case of CD, since risk is not restricted to only first-degree relatives.
OBJECTIVE: To map the locus for susceptibility to psoriasis in patients with psoriatic arthritis. METHODS: Seventy-four patients with psoriatic arthritis and 95 patients with psoriasis vulgaris were included in this study. Polymorphic genes and microsatellite markers centromeric (C1_2_5) and telomeric (C1_4_4, OTF3, HCR and the corneodesmosin gene) to HLA-C were studied in an association analysis. Typing was also performed on a control population of 104 matched donors. RESULTS: The allele Cw*0602 was associated both with psoriasis [49 vs 21%, Pc<0.0003; odds ratio (OR)=3.6, aetiological factor (AF)=0.72] and with psoriatic arthritis (62 vs 21%, Pc<0.000001; OR=6.1, AF=0.83). In psoriatic patients a susceptibility region telomeric to HLA-C that includes C1_4_4 (56 vs 22%, Pc<0.0002; OR=4.39, AF=0.77), OTF3 (85 vs 60%, Pc<0.0002; OR=3.7, AF=0.73) and HCR (63 vs 26%, Pc<0.00001; OR=3.8, AF=0.74) was observed. In psoriatic arthritis patients the susceptibility region was delimited by HLA-C and C1_4_4 (384 allele, 56 vs 22%, Pc<0.0002; OR=4.37, AF=0.77). CONCLUSIONS: Comparing the susceptibility regions associated with the two diseases, an overlapping interval of 100 kb between HLA-C and OTF3, which might contain the psoriasis gene, can be defined.