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Biomedical subjects

C Delgado

Publications and source records attributed to C Delgado.

At least 19 recordsLinked to original sources

OAS1 gene haplotype confers susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is associated with genetic susceptibility and unknown environmental triggers, possible viral infections, but the specific etiological mechanism that subsequently develops into an inflammatory/autoimmune cascade of events is poorly understood. Recently, genetic variants of 2',5'- oligoadenylate synthetase 1 (OAS1) gene, a critical enzyme involved in innate antivirus response, have been associated with differential enzyme activity and type 1 diabetes in both case-control and family studies. We hypothesized that polymorphisms in the OAS1 gene could influence the susceptibility to MS. To test this hypothesis, we conducted a case-control study of 333 patients with MS and 424 healthy controls and genotyped two OAS1 single nucleotide polymorphisms (SNPs) by restriction fragment length polymorphism method: rs 10774671, A/G SNP altering the splicing site at the seventh exon, and rs 3741981, a nonsynonymous (Ser162Gly) A/G SNP in the third exon. Haplotype but not single-marker analysis revealed an association of the haplotype created by the G allele at rs 10774671 and the A allele at rs 3741981 with the susceptibility to MS (P value = 8.8 x 10(-5)). Subjects carrying this haplotype had an increased risk of MS comparing with those not carrying it (odds ratio = 4.7, 95% confidence interval 2.1-10.9). Our findings indicate that the OAS1 gene polymorphisms may confer susceptibility to MS or serve as markers of functional variants and suggest that OAS1 activity is involved in the etiology of the disease. Future studies in a larger sample and association analysis with functional variants will clarify the role of the OAS1 gene in the susceptibility to MS.

2',5'-Oligoadenylate Synthetase↗

[Pulsed radiofrequency treatment in idiopathic and secondary glossopharyngeal neuralgia: preliminary results in 2 cases].

OBJECTIVES: To describe the use of pulsed radiofrequency (PRF) to treat 2 cases of glossopharyngeal neuralgia, 1 idiopathic and 1 secondary. PATIENTS: The first case involved a man diagnosed with Hodgkin's lymphoma involving the tonsils and manifesting as glossopharyngeal neuralgia that was refractory to all treatment approaches tried, including opioids and neuromodulation. The second case involved a patient diagnosed with essential glossopharyngeal neuralgia that was also resistant to drug treatment. The PRF procedure was performed in the operating room on an outpatient basis, under fluoroscopic guidance and with conventional monitoring. No perioperative events were reported. RESULTS: The treatment was effective for both patients, leading to decreases in visual analog scale pain reports between 5 and 7 points that were maintained over 6 months, although improvement for the patient with essential neuralgia was less intense and of shorter duration. Overall self-reported improvement assessed subjectively 6 months after PRF was 75% for the patient with Hodgkin's lymphoma and 50% for the patient with essential neuralgia, for whom a second PRF procedure was scheduled. Neither patient suffered complications or side effects that were potentially attributable to the procedure. CONCLUSIONS: PRF seems to be a safe, effective approach to treating neuralgia of the glossopharyngeal nerve, whether the condition is essential or secondary to another process. It is possible that if the condition is secondary, the clinical response may be greater in intensity and last longer.

Electric Stimulation Therapy↗

[Oxidized cellulose (Surgicel) mimics an abscess after laparoscopic partial nephrectomy].

INTRODUCTION: Oxidized cellulose gauze (Surgicel) left into the surgical bed can mimic a gas-forming abscess in the close postoperative image studies, because of air trapped within the interstices of the gauze, before that being degraded. PATIENT AND METHOD: In the early postoperative CT scan of a laparoscopic partial nephrectomy due to renal cell carcinoma, two small collections of gas were found, at the sites where Surgicel was placed. Being aware of the surgical details, they were not confused with an abscess. COMMENT: Small collections of gas into a Surgicel gauze may be detected until more than a month after surgery, imitating a bacterial abscess, but the clinical context, operative reports and a good communication between the surgeon and the radiologist should avoid this mistake.

Abscess↗

[Low grade collecting duct carcinoma of the kidney. Presentation of one case and literature revision].

Collecting duct renal cell carcinoma is an uncommon variant of renal carcinoma. Typically its behaviour is more aggressive than other forms of renal carcinoma and usually it is diagnosed at advanced stages. A 57-year-old man visited our hospital by right lumbar pain. Abdominal CT showed a enhanced mass on the right kidney. A right partial nephrectomy was done. Histological examination of the surgical specimen showed a low grade collecting duct carcinoma of the kidney. This is a new entity, with unknown behaviour but seems to be less aggressive than classical collecting duct carcinoma of the kidney. The clinical, radiological, pathological and immunohistochemical characteristics of this tumor are reported, and the literature is reviewed.

Humans↗

Pulmonary hyalohyphomycosis caused by Fusarium spp in a Kemp's ridley sea turtle (Lepidochelys kempi): an immunohistochemical study.

AIM: To describe the microscopic and immunohistochemical findings in a case of pulmonary hyalohyphomycosis in a Kemp's ridley sea turtle (Lepidochelys kempi). METHODS: Samples of lung, liver and kidney from a stranded, dead Kemp's ridley sea turtle were routinely processed for histopathological studies. Two monoclonal antibodies that reacted specifically with antigens of Aspergillus spp and the Mucorales (Zygomycetes) group, and a panel of polyclonal antibodies raised against Aspergillus fumigatus, Candida albicans, Geotrichum candidum, Fusarium solani, and Scedosporium apiospermum were used for immunohistochemical or immunofluorescence staining. RESULTS: Histologically, a severe multifocal granulomatous pneumonia associated with fungal infection was diagnosed. All hyphae were identified as Fusarium spp because a strong and uniform reactivity was obtained only with a heterologously-absorbed polyclonal antibody raised against somatic antigens of Fusarium solani. CONCLUSIONS: Fusarium spp should be included in the differential diagnosis of mycotic pneumonia in Kemp's ridley sea turtles. CLINICAL RELEVANCE: This is the first report of a pulmonary mycotic infection in a sea turtle diagnosed using immunohistochemistry. Wildlife rehabilitators and pathologists should be aware of the availability of immunohistochemical techniques for identifying fungi in sea turtles.

Journal Article↗

Neuropeptide Y increases 4-aminopyridine-sensitive transient outward potassium current in rat ventricular myocytes.

1. The modulation of 4-aminopyridine sensitive transient outward potassium current (4-AP I(to)) by neuropeptide Y (NPY) (100 nM) in rat ventricular myocytes was examined using the whole cell voltage-clamp technique. 2. Continuous exposure to NPY (100 nM) for 3 - 6 h significantly increased 4-AP I(to) density. The stimulation of 4-AP I(to) density by NPY was concentration-dependent (EC(50)=10 nM). 3. In the presence of BIBP 3226, an NPY receptor antagonist that binds selectively to NPY Y1-receptors, the effect of NPY on 4-AP I(to) density was maintained. However, in the presence of BIIE 0246, a highly selective non-peptide NPY Y2-receptor antagonist, NPY was unable to increase 4-AP I(to) density. 4. The effect of NPY on 4-AP I(to) density was prevented by pretreatment with 500 ng ml(-1) pertussis toxin (PTX) and by the specific protein kinase C (PKC) inhibitor, calphostin C (100 nM). 5. Thus, short term exposure to NPY induces an increase of 4-AP I(to) density in rat ventricular myocytes mediated by Y2-receptors and involving the action of PKC via a PTX-sensitive signalling cascade.

4-Aminopyridine↗

Analysis of -631 and -475 interleukin-2 promoter single nucleotide polymorphisms in multiple sclerosis.

We have analysed the interleukin-2 (IL-2) promoter single nucleotide polymorphisms -475 A/T and -631 G/A, relative to the initiation codon, in patients with multiple sclerosis (MS) and in healthy controls. Both groups showed a very low frequency of T at -475 and A at -631. Our results suggest that these polymorphisms do not contribute to MS susceptibility.

Genetic Predisposition to Disease↗

Allelic expression and interleukin-2 polymorphisms in multiple sclerosis.

We have investigated the association of two single nucleotide polymorphisms (SNPs) at positions -384 and 114 in the human interleukin-2 (hIL-2) with multiple sclerosis (MS). For two of the -384 genotypes (G/T, T/T), we observed an association with the susceptibility to secondary progressive (SP) course of MS (P=0.005 and P=0.013, respectively). Expression level differences of the IL-2 alleles (between one- and three-fold) were not attributable to the -384 promoter polymorphism. These data indicate for the first time the relevance of the il-2 gene locus in human MS and its possible involvement in other autoimmune diseases.

Age of Onset↗

Urea equilibrium unfolding of the major core protein of the retrovirus feline immunodeficiency virus and its tryptophan mutants.

Circular dichroism and fluorescence spectroscopy have been employed to study the urea unfolding mechanism of a recombinant form of the major core protein of feline immunodeficiency virus (FIV-rp24) and its native tryptophan mutants. The equilibrium denaturation curves indicate the existence of two transitions. The first unfolding transition most likely reflects the denaturation of the carboxy-terminal region of FIV-rp24. Consequently, the second transition, where the changes in fluorescence are produced, should reflect the denaturation of the amino-terminal region. If the intermediate observed upon urea denaturation is an on-pathway species, the data described herein can reflect the sequential and independent loss of structure of the two domains that this type of proteins possesses.

Circular Dichroism↗

Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer.

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.

Animals↗

Non-immunogenic murine hepatocellular carcinoma Hepa1-6 cells expressing the membrane form of macrophage colony stimulating factor are rejected in vivo and lead to CD8+ T-cell immunity against the parental tumor.

Hepatocellular carcinoma is a lethal disease and methods that develop effective cellular-based immunotherapy are needed. We retrovirally transduced non-immunogenic mouse Hepa1-6 hepatoma cells with the gene encoding the membrane form of macrophage colony stimulating factor (mM-CSF). Excess recombinant M-CSF and phagocytosis-inhibiting chemicals blocked macrophage-mediated killing of cloned mM-CSF transfected Hepa1-6 hepatoma cells. Macrophages derived from Hck(-/-)Fgr(-/-) and Lyn(-/-) triple knockout mice, which are incapable of performing phagocytosis, failed to kill the mM-CSF transduced cells. The mM-CSF transfected tumor clones failed to grow when injected into C57BL/6 or C57L/J mice. Splenocytes from these vaccinated mice displayed cytotoxicity against parental Hepa1-6 cells, but not against B16 and CT-26 tumor cells in vitro. Mice that rejected the mM-CSF transfected Hepa1-6 tumor subsequently rejected parental Hepa1-6 cells but not the B16 melanoma cells when rechallenged. Elimination of the CD8+ effector cells by an anti-CD8 antibody and complement treatment prevented the adoptive transfer of anti-Hepa1-6-specific immunity into naive animals. Thus, mM-CSF provides a method of generating effective anti-tumor immune responses by macrophages and cytotoxic T cells against the parental Hepa1-6 cells. Our work suggests that mM-CSF transduced hepatoma cells could be used as a tumor vaccine to stimulate immune responses against hepatocellular carcinoma.

Animals↗

Cloning, expression, and purification of histidine-tagged preS domains of hepatitis B virus.

The preS domains of the hepatitis B virus are hydrophilic polypeptides that have been implicated, among other functions, in the binding of the virus to hepatocytes and in the induction of virus-neutralizing antibodies. A method of overproducing the preS domains of two different subtypes, adw and ayw, has been developed by adding a 6x His tag at the carboxy-terminal end of the polypeptides. Codons for the 6x His were added in reverse primers used to amplify the corresponding cDNAs. The polymerase chain reaction products were cloned into the expression vectors pET-3d (subtype ayw) and pT7-7 (subtype adw), under the control of the inducible bacteriophage T7 RNA polymerase promoter. Upon induction with isopropyl-beta-d-thiogalactopyranoside, proteins were overexpressed and purified by affinity chromatography on a Ni-nitrilotriacetic acid agarose column. This method yielded 20-40 mg of highly pure and very stable proteins per liter of cell culture. Circular dichroism and fluorescence spectroscopy of isolated preS-his-ayw and preS-his-adw, as well as their ability to bind polymerized human serum albumin, indicate that the 6x His tag does not modify the native-like conformation and, therefore, they may be considered as useful tools to study the function of these viral polypeptide regions.

Amino Acid Sequence↗

Antipsychotic drugs and obesity: is prolactin involved?

OBJECTIVES: To correlate the anthropometric indexes (Body Mass Index [BMI] and Waist-Hip ratio [WHR]) with the serum prolactin levels in a heterogeneous population of patients treated with typical antipsychotic (AP) drugs. METHODS: We evaluated BMI, WHR, and fasting serum prolactin of inpatients (n = 105) and outpatients (n = 122) treated with APs, in outpatients receiving other psychotropic drugs (OPDs) (n = 77), and in drug-free subjects (n = 33). Outpatients had free access to food, whereas the inpatient sample comprised people with a monotonous diet of approximately 2000 Kcal daily. RESULTS: Prolactin correlated positively with the BMI in the whole group of AP-treated outpatient men (P = 0.03) and with the WHR in AP-treated inpatient men (P = 0.053). Regarding treatment duration, prolactin and BMI correlated positively in men consecutively treated for more than 1 year (P = 0.023). By contrast, a trend toward a negative correlation between prolactin and BMI was observed in AP-treated outpatient women (P = 0.08). No significant correlation, or even a trend, was observed in the other groups. CONCLUSIONS: Prolactin may be involved in AP-induced weight gain, particularly in men. Future studies should characterize the period of maximal prolactin impact on body weight during AP treatment. Specific populations particularly sensitive to hyperprolactinemia might be identified as well. The negative correlation between prolactin and BMI detected in AP-treated women resembles the dampened prolactin response observed in severe primary obesity.

Adult↗

Therapeutic embolisation for postoperative haemorrhage after total arthroplasty of the hip and knee.

We describe three cases of postoperative haemorrhage, two after total hip and one after total knee replacement, treated by percutaneous embolisation. After diagnostic angiography, this is the preferred method for the treatment of postoperative haemorrhage due to the formation of a false aneurysm, after hip or knee arthroplasty. This procedure, carried out under local anaesthesia, has a low rate of complications and avoids the uncertainty of further surgical exploration.

Aged↗

Allelic selection of human IL-2 gene.

The allelic expression of mouse IL-2 cannot be definitely extrapolated to what might happen in humans. Therefore, we investigated the regulation of allelic expression of the IL-2 gene in non-genetically manipulated human T lymphocytes by following natural allelic polymorphisms. We found a phenotypically silent punctual change in the human IL-2 at position 114 after the first nucleotide of the initiation codon, which represents a dimorphic polymorphism at the first exon of the IL-2 gene. This allowed the study by single-cell PCR of the regulation of the human IL-2 allelic expression in heterozygous CD4(+) T cells, which was found to be tightly controlled monoallelically. These findings may be used as a suitable marker for monitoring the IL-2 allelic contribution to effector activities and in immune responses against different infections or in pathological situations.

Alleles↗

Central venous catheter placement in the inferior vena cava via the direct translumbar approach.

The aim of this study was to evaluate the technical aspects and efficacy of placing tunneled central venous access catheters (CVA) in the inferior vena cava (IVC) via a direct translumbar approach. Between August 1994 and July 1998, 50 CVA (Hickman 13.5 F) were placed in the IVC via a direct translumbar approach in 46 patients (10 males, 36 females) with a mean age of 39.9 years (age range 10-87 years). The indications were chemotherapy administration plus leukoaphoresis (n = 39), bone marrow transplantation (n = 2) and hemodialysis (n = 5). The reasons for placing the CVA in the IVC were cosmetic (n = 34), supradiaphragmatic venous thrombosis (n = 8), previous catheter infection (n = 2), and non-functioning arteriovenous fistula (n = 2). There were no immediate complications. The mean period of time the CVA was in place was 3 months (15 days to 15 months), during which the function was excellent. The commonest late complication was infection (4 local, 6 bacteremia). Others included: pain (n = 2), ureteric fistula (n = 1), pericatheter fibrin sheath formation (n = 6) and catheter-tip impaction (n = 2). Two catheters were damaged due to postprocedural inappropriate manipulations and two others fell off due to incorrect fixation. Due to these complications, it was necessary to remove ten catheters, replace an additional four and reposition two. Direct translumbar catheterization of the IVC is a safe and effective way of placing a long-term CVA with a moderate complication rate.

Adolescent↗