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Biomedical subjects

A Gonzalez

Publications and source records attributed to A Gonzalez.

At least 37 records · Page 2Linked to original sources

Transvascular ethanol embolization: first option for the management of symptomatic nonfunctioning renal allografts left in situ.

BACKGROUND: Transplantectomy has been the conventional therapy for symptomatic failed grafts left in situ (FGLIS). Graft intolerance syndrome (GIS) is a common complication after withdrawal of immunosuppression. Our group first reported transvascular ethanol embolization (TVEE) as an alternative for the management of GIS. OBJECTIVE: Our goal was to evaluate the efficacy and safety of TVEE in a large series of patients with symptomatic FGLIS. PATIENTS AND METHODS: From January 1989 to December 2001, 944 patients received cadaveric renal transplants in our center. During this period, 59 patients with FGLIS underwent TVEE (50+/-7 years, 71% men, 15% diabetics). TVEE was performed using a transfemoral approach. A balloon occlusion catheter was inflated in the renal artery before ethanol injection (10-12 cc). The position of coils completed the procedure. No systematic prophylactic antibiotic or steroid treatment was administered. RESULTS: The main indication for TVEE was GIS (51 patients, 86%). TVEE was initially successful in 39 patients (66%). A second TVEE, which was performed in 9 of 20 unresolved cases, was successful in six. After a second TVEE, the efficacy increased to 76%. The most frequent complication was postembolization syndrome (62%), which was manifested by fever, local pain, and inflammation that generally resolved in 48-72 hours. No major complications or deaths were observed. One of four patients underwent transplantectomy. Histologic examination of the removed graft showed renal tissue necrosis (10 cases) and pyonephrosis (4 cases). CONCLUSIONS: TVEE, a safe and effective technique, may be considered as the treatment of choice for symptomatic FGLIS.

Balloon Occlusion↗

Antifungal activities of nine traditional Mexican medicinal plants.

Eighteen plant extracts from nine traditional Mexican medicinal plants were tested for antifungal activity against two dermatophyte fungal species (Trichophyton mentagrophytes and Trichophyton rubrum), one non-dermatophyte (Aspergillus niger), and one yeast (Candida albicans). The strongest effect was manifested by the hexane extracts from Eupatorium aschenbornianum and Sedum oxypetalum, as well as the methanol extracts from Lysiloma acapulcensis and Annona cherimolia.

Antifungal Agents↗

Spinal cord compression due to tumoral idiopatic calcinosis.

STUDY DESIGN: A case of thoracic spinal cord compression due to tumoral calcinosis (TC) is reported. SETTING: Galiza, Spain. CASE REPORT: A 59-year-old man was admitted to our hospital with a 2-month history of gradual leg weakness and sensory deficit. The neurological examination revealed paraparesis with T12 sensory level. Magnetic resonance imaging (MRI) showed an extradural right posterolateral mass at T11-T12 level, resulting in a marked spinal cord compression. He underwent T11-T12 laminectomy and mass excision. Histological examination finally led to the diagnosis of TC. CONCLUSION: TC is an uncommon cause of mass lesions of the spine. Since there is no typical spine TC MRI appearance, the final diagnosis is done by histological studies. TC should be considered in differential diagnosis of spinal cord compression and constitutes a treatable cause of paraparesis.

Calcinosis↗

Ca2+ sparks and embers of mammalian muscle. Properties of the sources.

Ca2+ sparks of membrane-permeabilized rat muscle cells were analyzed to derive properties of their sources. Most events identified in longitudinal confocal line scans looked like sparks, but 23% (1,000 out of 4,300) were followed by long-lasting embers. Some were preceded by embers, and 48 were "lone embers." Average spatial width was approximately 2 microm in the rat and 1.5 microm in frog events in analogous solutions. Amplitudes were 33% smaller and rise times 50% greater in the rat. Differences were highly significant. The greater spatial width was not a consequence of greater open time of the rat source, and was greatest at the shortest rise times, suggesting a wider Ca2+ source. In the rat, but not the frog, spark width was greater in scans transversal to the fiber axis. These features suggested that rat spark sources were elongated transversally. Ca2+ release was calculated in averages of sparks with long embers. Release current during the averaged ember started at 3 or 7 pA (depending on assumptions), whereas in lone embers it was 0.7 or 1.3 pA, which suggests that embers that trail sparks start with five open channels. Analysis of a spark with leading ember yielded a current ratio ranging from 37 to 160 in spark and ember, as if 37-160 channels opened in the spark. In simulations, 25-60 pA of Ca2+ current exiting a point source was required to reproduce frog sparks. 130 pA, exiting a cylindric source of 3 microm, qualitatively reproduced rat sparks. In conclusion, sparks of rat muscle require a greater current than frog sparks, exiting a source elongated transversally to the fiber axis, constituted by 35-260 channels. Not infrequently, a few of those remain open and produce the trailing ember.

Animals↗

The three most common CARD15 mutations associated with Crohn's disease and the chromosome 16 susceptibility locus for systemic lupus erythematosus.

OBJECTIVE: To test if the three most common mutations contributing to Crohn's disease on the CARD15/NOD2 gene could contribute also to genetic susceptibility to systemic lupus erythematosus (SLE), which has been found to be linked to the region of chromosome 16q13 where the CARD15 gene is located. METHODS: We obtained DNA samples from the blood of 189 SLE patients (according to the American College of Rheumatology classification criteria) and 194 controls of Spanish ancestry. Genotypes for the three CARD15 mutations (3020insC, 2722G>C and 2104C>T) were determined by hybridization with fluorescence resonance energy transfer probes on a LightCycler real-time polymerase chain reaction system. RESULTS: CARD15 genotypes were similar in SLE patients and in controls from the general population (allelic frequencies for 3020insC 0.013 in SLE patients vs 0.013 in controls; for 2722G > C 0.011 vs 0.008; and for 2104C > T 0.032 vs 0.051). CONCLUSION: We did not find evidence that the Crohn's disease-associated mutations on CARD15 contributed to SLE susceptibility.

Carrier Proteins↗

Low-pathogenicity avian influenza virus in live bird markets--what about the livestock area?

Low-pathogenic avian influenza virus (AV) continues to be isolated from the live bird markets (LBMs) in the Northeasten United States. Recent years have seen increasing numbers of these markets opening and an expansion of the type of animals they sell in conjunction with traditional live poultry. Specific-pathogen-free chickens were released into the livestock area of 13 New York City LBMs and then tested for evidence of AIV. We were able to recover virus or demonstrate seroconversion among the chickens introduced to four of the markets.

Agriculture↗

A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma.

Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.

Adenocarcinoma↗

Sinus venosus syndrome: atrial septal defect or anomalous venous connection? A multiplane transoesophageal approach.

OBJECTIVE: To discuss the anatomical features of sinus venosus atrial defect on the basis of a comprehensive transoesophageal echocardiography (TOE) examination and its relation to surgical data. METHODS: 24 patients (13 men, 11 women, mean (SD) age 37 (17) years, range 17-73 years) with a posterior interatrial communication closely related to the entrance of the superior (SVC) or inferior vena cava (IVC) who underwent TOE before surgical repair. Records of these patients were retrospectively reviewed and compared with surgical assessments. RESULTS: In 13 patients, TOE showed a deficiency in the extraseptal wall that normally separates the left atrium and right upper pulmonary vein from the SVC and right atrium. This deficiency unroofed the right upper pulmonary vein, compelling it to drain into the SVC, which overrode the intact atrial septum. In three patients, TOE examination showed a defect in the wall of the IVC, which continued directly into the posterior border of the left atrium. Thus, the intact muscular border of the atrial septum was overridden by the mouth of the IVC, which presented a biatrial connection. In the remaining eight patients, the defect was located in the muscular posterior border of the fossa ovalis. A residuum of atrial septum was visualised in the superior margin of the defect. Neither caval vein overriding nor anomalous pulmonary vein drainage was present. CONCLUSIONS: Sinus venosus syndrome should be regarded as an anomalous venous connection with an interatrial communication outside the confines of the atrial septum, in the unfolding wall that normally separates the left atrium from either caval vein. It results in overriding of the caval veins across the intact atrial septum and partial pulmonary vein anomalous drainage. It should be differentiated from posterior atrial septal defect without overriding or anomalous venous connections.

Adolescent↗

Tumoral calcinosis presenting as an extradural mass: MR findings and pathological correlation.

Two cases of idiopathic tumoral calcinosis presenting as an extradural mass are reported. There are few reports in the literature of this pathological process presenting as extradural masses, so both cases represent very unusual locations for tumoral calcinosis. Magnetic resonance imaging features and pathological correlation of these two cases are presented. Tumoral calcinosis might be considered as a rare but possible cause of extradural mass.

Calcinosis↗

NADP-glutamate dehydrogenase isoenzymes of Saccharomyces cerevisiae. Purification, kinetic properties, and physiological roles.

In the yeast Saccharomyces cerevisiae, two NADP(+)-dependent glutamate dehydrogenases (NADP-GDHs) encoded by GDH1 and GDH3 catalyze the synthesis of glutamate from ammonium and alpha-ketoglutarate. The GDH2-encoded NAD(+)-dependent glutamate dehydrogenase degrades glutamate producing ammonium and alpha-ketoglutarate. Until very recently, it was considered that only one biosynthetic NADP-GDH was present in S. cerevisiae. This fact hindered understanding the physiological role of each isoenzyme and the mechanisms involved in alpha-ketoglutarate channeling for glutamate biosynthesis. In this study, we purified and characterized the GDH1- and GDH3-encoded NADP-GDHs; they showed different allosteric properties and rates of alpha-ketoglutarate utilization. Analysis of the relative levels of these proteins revealed that the expression of GDH1 and GDH3 is differentially regulated and depends on the nature of the carbon source. Moreover, the physiological study of mutants lacking or overexpressing GDH1 or GDH3 suggested that these genes play nonredundant physiological roles. Our results indicate that the coordinated regulation of GDH1-, GDH3-, and GDH2-encoded enzymes results in glutamate biosynthesis and balanced utilization of alpha-ketoglutarate under fermentative and respiratory conditions. The possible relevance of the duplicated NADP-GDH pathway in the adaptation to facultative metabolism is discussed.

Base Sequence↗

Genetic influences on the end-stage effector phase of arthritis.

K/BxN T cell receptor transgenic mice are a model of inflammatory arthritis, most similar to rheumatoid arthritis, that is critically dependent on both T and B lymphocytes. Transfer of serum, or just immunoglobulins, from arthritic K/BxN animals into healthy recipients provokes arthritis efficiently, rapidly, and with high penetrance. We have explored the genetic heterogeneity in the response to serum transfer, thereby focussing on the end-stage effector phase of arthritis, leap-frogging the initiating events. Inbred mouse strains showed clear variability in their responses. A few were entirely refractory to disease induction, and those which did develop disease exhibited a range of severities. F1 analyses suggested that in most cases susceptibility was controlled in a polygenic additive fashion. One responder/nonresponder pair (C57Bl/6 x NOD) was studied in detail via a genome scan of F2 mice; supplementary information was provided by the examination of knock-out and congenic strains. Two genomic regions that are major, additive determinants of the rapidity and severity of K/BxN serum-transferred arthritis were highlighted. Concerning the first region, on proximal chromosome (chr)2, candidate assignment to the complement gene C5 was confirmed by both strain segregation analysis and functional data. Concerning the second, on distal chr1, coinciding with the Sle1 locus implicated in susceptibility to lupus-like autoimmune disease, a contribution by the fcgr2 candidate gene was excluded. Two other regions, on chr12 and chr18 may also contribute to susceptibility to serum-transferred arthritis, albeit to a more limited degree. The contributions of these loci are additive, but gene dosage effects at the C5 locus are such that it largely dominates. The clarity of these results argues that our focus on the terminal effector phase of arthritis in the K/BxN model will bear fruit.

Animals↗

Targeting drug delivery to radiation-induced neoantigens in tumor microvasculature.

Radiation can be used to guide drugs to specific sites such as neoplasms or aberrant blood vessels. When blood vessels are treated with ionizing radiation, they respond by expressing a number of cell adhesion molecules and receptors that participate in homeostasis. Examples of radiation-induced molecules in blood vessels include ICAM-1, E-selectin, P-selectin and the beta(3) integrin. We have observed that the endothelium and blood components respond to oxidative stress in a similar, if not identical manner in all tumor models. Although we have identified several other radiation-induced molecules within tumor blood vessels, the beta(3) target for drug delivery achieves the greatest site-specific peptide binding within irradiated tumor blood vessels. We have focused on peptides and antibodies that bind to integrin beta(3). beta(3)-binding proteins have been conjugated to fluorochromes and radionuclides to study the site specificity and microscopic distribution. We have found immunofluorescent and immunohistochemical staining of beta(3) within the lumen of blood vessels immediately following irradiation. To determine whether it is feasible to guide drug delivery to irradiated tumors, we studied ligands to alpha(2b)beta(3) (fibrinogen). Peptides within fibrinogen that bind to alpha(2b)beta(3) includes the dodecapeptide, HHLGGAKQAGDV and the RGD peptide. We utilized 131I conjugation to these ligands to study the biodistribution in tumor bearing mice. Our clinical trial consists of the RGD peptidomimetic, biapcitide, labeled with 99mTc. This study shows that it is feasible to guide drugs to human neoplasms by use of radiation-guided peptides. These studies have shown that peptides that bind to these integrins bind to tumors following exposure to ionizing radiation.

Amino Acid Sequence↗

Arachidonic acid modulates the spatiotemporal characteristics of agonist-evoked Ca2+ waves in mouse pancreatic acinar cells.

In pancreatic acinar cells analysis of the propagation speed of secretagogue-evoked Ca2+ waves can be used to examine coupling of hormone receptors to intracellular signal cascades that cause activation of protein kinase C or production of arachidonic acid (AA). In the present study we have investigated the role of cytosolic phospholipase A2 (cPLA2) and AA in acetylcholine (ACh)- and bombesin-induced Ca2+ signaling. Inhibition of cPLA2 caused acceleration of ACh-induced Ca2+ waves, whereas bombesin-evoked Ca2+ waves were unaffected. When enzymatic metabolization of AA was prevented with the cyclooxygenase inhibitor indomethacin or the lipoxygenase inhibitor nordihydroguaiaretic acid, ACh-induced Ca2+ waves were slowed down. Agonist-induced activation of cPLA2 involves mitogen-activated protein kinase (MAPK) activation. An increase in phosphorylation of p38(MAPK) and p42/44(MAPK) within 10 s after stimulation could be demonstrated for ACh but was absent for bombesin. Rapid phosphorylation of p38(MAPK) and p42/44(MAPK) could also be observed in the presence of cholecystokinin (CCK), which also causes activation of cPLA2. ACh-and CCK-induced Ca2+ waves were slowed down when p38(MAPK) was inhibited with SB 203580, whereas inhibition of p42/44(MAPK) with PD 98059 caused acceleration of ACh- and CCK-induced Ca2+ waves. The spreading of bombesin-evoked Ca2+ waves was affected neither by PD 98059 nor by SB 203580. Our data indicate that in mouse pancreatic acinar cells both ACh and CCK receptors couple to the cPLA2 pathway. cPLA2 activation occurs within 1-2 s after hormone application and is promoted by p42/44(MAPK) and inhibited by p38(MAPK). Furthermore, the data demonstrate that secondary (Ca2+-induced) Ca2+ release, which supports Ca2+ wave spreading, is inhibited by AA itself and not by a metabolite of AA.

Acetylcholine↗

Role of Doppler echocardiography in the assessment of portopulmonary hypertension in liver transplantation candidates.

BACKGROUND: Portopulmonary hypertension is a severe complication of liver cirrhosis that carries a high risk for posttransplantation mortality. We aimed at evaluating the utility of Doppler echocardiography in screening for portopulmonary hypertension in liver transplantation candidates. METHODS: One hundred seven cirrhotic patients candidates for liver transplantation were studied by Doppler echocardiography and subsequently, by cardiac catheterization at transplantation. Two parameters were estimated by Doppler: systolic pulmonary arterial pressure (SPAP) derived from tricuspid regurgitation and the pulmonary acceleration time. Portpulmonary hypertension was suspected when SPAP was > or = 40 mm Hg and/or pulmonary acceleration time < 100 ms. RESULTS: Portpulmonary hypertension was suspected by Doppler study in 17 patients (15%). However, portopulmonary hypertension (mean pulmonary arterial pressure > or = 25 mm Hg and pulmonary vascular resistance > 120 dynes.s/cm5) was confirmed by the hemodynamic study in five patients (4.7%). Sensitivity and specificity of Doppler echocardiography for detecting portopulmonary hypertension was 100 and 88%, respectively, with a positive predictive value of 30%. The diagnostic accuracy of pulmonary acceleration time alone (96%) was better than pulmonary arterial pressure alone (90%). CONCLUSIONS: Doppler echocardiography, and especially the determination of pulmonary acceleration time, is a useful screening method for portopulmonary hypertension in patients with liver cirrhosis who are candidates for liver transplantation.

Adult↗

Abrupt rise of the longitudinal recoil ion momentum distribution for ionizing collisions.

We report on the experimental observation of an abrupt rise in the longitudinal momentum distribution of recoil ions created in proton helium collision. The details of this structure can be related to electrons traveling with the velocity of the projectile [electron capture to the continuum (ECC)]. The longitudinal as well as the transverse distribution of the recoil ions can be explained as a continuation of the momentum distribution from ions resulting from electron capture illustrating the smooth transition from the capture to bound states of the projectile to the ECC.

Journal Article↗

Intergenerational effects of complete maternal deprivation and replacement stimulation on maternal behavior and emotionality in female rats.

The present study investigated the effects of early rearing experiences on the development of maternal behavior in Sprague-Dawley female rats. Pups from individual litters were assigned to four different groups on Day 3 of life. From days 4 to 20 of life, these were reared artificially, without mother and receiving minimal "licking-like" tactile stimulation (AR-MIN), or maximal stimulation (AR-MAX) or were reared with their mothers (MR-CONTROL and MR-SHAM). At 70-100 days all AR and MR animals were mated and then observed with their own offspring, culled to eight pups. After maternal testing open-field tests were conducted. The female offspring in these litters (all raised by their MR and AR mothers) were reared to adulthood and then observed interacting with their offspring. Results show that in adulthood AR mothers engaged in significantly fewer pup-retrievals and less pup-licking (genital and body), and crouching, but significantly more non-maternal tail-chasing, digging, and hanging/climbing. As well, they were more active in the open field. Comparisons between the two AR groups and the MR groups, showed that most of the differences were between the AR-MIN and MR groups, with the AR-MAX animals showing levels of behavior between the two, and differing from neither. Analyses of covariance indicated that early experience and adult emotional behavior both influence adult maternal behavior, but their effects are independent of one another. A cross-generational effect of artificial rearing was also found. Daughters of AR and MR mothers that were observed after the birth of their own litters in adulthood showed a pattern of behavior that mimicked the pattern shown by their mothers. These results are discussed in terms of the variety of possible behavioral, endocrine, and neurochemical mechanisms that mediate the effects of early experiences on adult maternal behavior.

Analysis of Variance↗

Maternally separated rats show deficits in maternal care in adulthood.

Although there is considerable research on the phenomenology, neuroendocrinology, neuroanatomy, and sensory control of maternal behavior, little is known about the influences of early postnatal and postweaning experiences on the development of maternal behavior. The purpose of this study was to assess how early life separation from the mother rat affects development of the offspring's juvenile and adult maternal behavior. From postnatal Days 1 to 17, 3 female rats within each litter were separated (SEP) from the mother and the rest of the litter for 5 hr daily while 3 of their sisters were not maternally separated (NSEP). On postnatal Day 21, all subjects were weaned and randomly assigned to one of three juvenile conditions. One female from both SEP and NSEP groups was either isolated (I), given a social conspecific (S), or given 1- to 4-day-old pups (P) for 5 consecutive days. Maternal behavior of SEP and NSEP animals was assessed and recorded on each of the 5 days. Once all animals reached adulthood, they were mated, gave birth, and were assessed for their maternal behavior. We found that the effects of maternal separation on juvenile maternal-like behaviors were minimal. On the other hand, maternal separation reduced adult maternal licking and crouching over pups. In addition, there was a significant interaction between postnatal and juvenile experience on maternal crouching in maternal animals. These results are discussed in terms of the variety of possible behavioral, endocrine, and neurochemical mechanisms that mediate the effects of early life experiences on adult maternal behavior.

Affect↗