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Biomedical subjects

F Diaz

Publications and source records attributed to F Diaz.

At least 19 recordsLinked to original sources

Treatment with adefovir dipivoxil in a renal transplant patient with renal insufficiency and lamivudine-resistant hepatitis B infection.

Lamivudine is a safe, effective treatment for hepatitis B virus (HBV) reactivation after renal transplantation. However, prolonged lamivudine therapy can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated efficacy in patients with lamivudine resistance, but there is limited clinical experience in patients with either renal transplants or severe renal insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal transplantation in November 1995. In September 2000 lamivudine therapy was initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA levels. Two years later, significant viral replication developed again. At that time the patient already had advanced renal insufficiency due to chronic graft nephropathy. The transaminase levels were increased, and the HBV DNA reached greater than 200,000 copies/mL by polymerase chain reaction, with development of ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose adjusted to renal function). There was rapid normalization of hepatic enzymes and progressive decline of the viral load. HBV DNA became negative after 6 months of ADV treatment. The renal function has since remained stable. This case suggests that ADV can be safe and effective in the treatment of renal transplant patients with lamivudine-resistant hepatitis B, even in the presence of advanced renal insufficiency.

Adenine↗

Thirst changes in offspring of hyperreninemic rat dams.

The aim of this study was to investigate the changes in thirst dependence on the renin-angiotensin system (RAS), in offspring of hyperreninemic, hyperdipsic, and natriophilic rat dams. Female rats underwent a partial aortic ligature between the renal arteries (PAL) or were sham-operated (SHAM). At 6 days of age, offspring of PAL (O-PAL) and SHAM (O-SHAM) dams were injected with isoproterenol (subcutaneously, 500 microg/kg body weight) or vehicle. Pretreatment with captopril (intraperitoneally, 50 mg/kg) on isoproterenol-induced thirst was also studied. Plasma renin activity in dams and hematocrit and osmolality in pups were measured. O-PAL had a greater water intake than O-SHAM. However, they responded similarly to isoproterenol or isoproterenol with captopril pretreatment. Only minor differences in hematocrit and osmolality were found between O-SHAM and O-PAL rats after isoproterenol or vehicle treatment. Beta-adrenergic or angiotensinergic responsivity seems not to be altered in offspring of hyperrenimic, hyperdipsic, and natriophilic dams. Nevertheless, other thirst responses of offspring may be critically dependent upon uterine conditions.

Animals↗

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↗

[Neurocysticercosis and immigration].

Formerly an endemic disorder, the frequency of neurocysticercosis (NCC) in Spain has been declining during recent decades until reaching its near extinction. However, the strong migratory flow during recent years towards large cities from countries where NCC is highly prevalent, particularly the Andean area of South America, has been followed by a growing increase ot this infestation among immigrants. Since NCC is commonly acquired by direct contamination from carriers of the tapeworm Taenia solium, there may be an emergence of NCC among Spanish-born population unless preventive measures are taken.

Emigration and Immigration↗

Retroesophageal subclavian artery aneurysm arising from Kommerell's diverticulum.

This report describes a novel technique used for management of retroesophageal subclavian artery aneurysm arising from Kommerell's diverticulum. The procedure consists of endoaortic exclusion of the aneurysmal neck, using a prosthetic patch after sternotomy during circulatory arrest, and antegrade cold blood cerebroplegia. The advantages of this technique are avoidance of hemorrhagic complications during clamping of the aneurysmal neck, limiting of the extent of dissection of the aortic arch, and elimination of the risk of inadvertent left recurrent nerve paralysis. Antegrade cold blood cerebroplegia provides good cerebral protection and decreases the duration and consequences of extracorporeal circulation.

Aged↗

Nitric oxide synthase as a marker in colorectal carcinoma.

Elevated inducible nitric oxide synthase (iNOS) activity has been found in 60 per cent of colon adenomas and 20 to 50 per cent of adenocarcinomas. We postulated that high levels of iNOS may increase the invasive and metastatic potential of colon carcinoma and could be indicative of survival potential. Data were reviewed for 52 patients with colorectal carcinoma diagnosed in 1991 and 1992. Specimens were stained for iNOS and catalogued as low-activity staining (LAS) or high-activity staining (HAS) on the basis of visual evaluation by three pathologists. Thirty patients were LAS and 22 HAS. Age, sex, preoperative carcinoembryonic antigen, tumor and nodal status, and American Joint Committee on Cancer staging were not different between groups. Forty-six per cent of the HAS group remained alive after 5 years versus 71 per cent in the LAS group. Survival was significantly lower and metastatic status significantly higher in the HAS group. Results indicated that iNOS activity may be a prognostic indicator of long-term survival potential after treatment for colon cancer. In addition results suggested that metastasis was greater in colon carcinoma specimens that maintain an activated iNOS and that these cells clinically react more aggressively. Conclusions are tempered by the fact that results were based on a limited sample size.

Adult↗

Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes.

OBJECT: This trial was designed to determine the ability of autologous whole-tumor cell vaccines to induce cell mediated immune responses in patients with recurrent malignant glioma, as well as to determine whether combining such vaccination with adoptive transfer of in vitro activated T lymphocytes prolongs patient survival. METHODS: Nineteen patients with recurrent malignant glioma, in whom previous external beam radiotherapy and at least one course of chemotherapy had failed were vaccinated twice with irradiated autologous whole tumor cells by using granulocyte-marcrophage colony-stimulating factor as an adjuvant. Patients then underwent leukapheresis followed by adoptive transfer of peripheral blood lymphocytes activated in vitro with anti-CD3 and interleukin-2. In vivo immune response, radiological response, clinical outcome, and survival were monitored. Seventeen patients developed a delayed-type hypersensitivity (DTH) response to vaccination that appeared to be directed against the autologous tumor. In eight patients there was radiological evidence of a response and in five there was evidence of clinical improvement. Median survival was 12 months (range 6-28 months), and both the presence of a DTH response and the radiological response correlated with survival (p < 0.02 and p < 0.04, respectively). CONCLUSIONS: These preliminary results suggest that autologous whole-tumor cell vaccines induce a cell-mediated immune response, which appears to be tumor specific in most patients. Furthermore, vaccination combined with adoptive immunotherapy with in vitro activated cells may induce a radiologically demonstrated tumor response and improved survival despite a condition of advanced disease and immunosuppression resulting from previous treatment or tumor burden. Further studies of immunotherapy are warranted.

Adjuvants, Immunologic↗

Colonoscopy in octogenarians and older patients.

INTRODUCTION: Colonoscopy in the elderly has been considered by many to be risky because of mechanical bowel preparation and dehydration, electrolyte disturbances, conscious sedation, and hypoxic complications. We hypothesized that colonoscopy in octogenarians and older patients is a safe procedure. MATERIALS AND METHODS: A retrospective review of 803 patients who underwent colonoscopy from January 1997 to October 1997 was performed. The patients were grouped by age: group A (17-49 years) had 166 patients (20%); group B (50-79 years) had 534 patients (67%); and group C (80 years and older) had 103 patients (13%). Results were considered significant at p value less than 0.05 unless otherwise noted. RESULTS: Blood in the stool (84%) and history of colonic vascular disease (5.8%) were the most common indication in group C (84%). Colonoscopy was used in group A (18%) more often than in the other groups to rule out inflammatory bowel disease. History of colon polyps was a more common indication in group B (20%) than in the other groups. Group A had a significantly higher incidence of normal examinations (84%) and diagnosis of inflammatory bowel disease (14%). Group B had a higher incidence of polyps than the other groups. Group C had the highest incidence of vascular disease (15%). Diverticular disease and carcinoma were more common in groups B (37%) and C (52%). The amount of sedation in the groups did not significantly differ. Completion of the colonoscopy to the cecum or anastomotic sites did not differ among the groups (p > 0.05), nor did complication rates among groups (p > 0.05). CONCLUSIONS: Colonoscopy is safe in octogenarians and older patients. Age does not, by itself, confer an increased risk to the procedure.

Adolescent↗

Selective down-regulation of IP(3)receptor subtypes by caspases and calpain during TNF alpha -induced apoptosis of human T-lymphoma cells.

There are at least three types of inositol 1,4,5-trisphosphate receptor (IP(3)R) [IP(3)-gated Ca(2+)channels], which are expressed in different cell types and mammalian tissues. In this study, we have identified three IP(3)R subtypes in human Jurkat T-lymphoma cells. All three subtypes have a molecular mass of about 260 kDa, and display Ca(2+)channel properties in an IP(3)-dependent manner. We have also demonstrated that TNFalpha promotes the activity of different proteases (e.g. caspase-8, caspase-3 and calpain), alters the TCR-mediated Ca(2+)response and subsequently induces apoptosis in Jurkat cells. During the first 6 h of incubation with TNFalpha, several IP(3)R subtype-related changes occur (e.g. proteolysis of IP(3)R subtypes, inhibition of IP(3)binding and impairment of IP(3)-mediated Ca(2+)flux) concomitantly with an elevation of protease (caspase-8, caspase-3 and calpain) activity. Furthermore, the caspase inhibitor, Z-VAD-fmk, significantly reduces TNFalpha-mediated perturbation of IP(3)R1 and IP(3)R2 (but not IP(3)R3) function; whereas the calpain inhibitor I, ALLN, is capable of blocking the inhibitory effect of TNFalpha on IP(3)R3 function. These findings suggest that IP(3)R1 and IP(3)R2 serve as cellular substrates for caspases, and IP(3)R3 is a substrate for calpain. We propose that the selective down-regulation of IP(3)R subtype-mediated Ca(2+)function by caspase-dependent and calpain-sensitive mechanisms may be responsible for the early onset of the apoptotic signal by TNFalpha in human T-cells.

Amino Acid Chloromethyl Ketones↗

Cloning of an endangered species (Bos gaurus) using interspecies nuclear transfer.

Approximately 100 species become extinct a day. Despite increasing interest in using cloning to rescue endangered species, successful interspecies nuclear transfer has not been previously described, and only a few reports of in vitro embryo formation exist. Here we show that interspecies nuclear transfer can be used to clone an endangered species with normal karyotypic and phenotypic development through implantation and the late stages of fetal growth. Somatic cells from a gaur bull (Bos gaurus), a large wild ox on the verge of extinction, (Species Survival Plan < 100 animals) were electrofused with enucleated oocytes from domestic cows. Twelve percent of the reconstructed oocytes developed to the blastocyst stage, and 18% of these embryos developed to the fetal stage when transferred to surrogate mothers. Three of the fetuses were electively removed at days 46 to 54 of gestation, and two continued gestation longer than 180 (ongoing) and 200 days, respectively. Microsatellite marker and cytogenetic analyses confirmed that the nuclear genome of the cloned animals was gaurus in origin. The gaur nuclei were shown to direct normal fetal development, with differentiation into complex tissue and organs, even though the mitochondrial DNA (mtDNA) within all the tissue types evaluated was derived exclusively from the recipient bovine oocytes. These results suggest that somatic cell cloning methods could be used to restore endangered, or even extinct, species and populations.

Alleles↗

Treatments for snoring: a comparison of somnoplasty and an oral appliance.

OBJECTIVES: Objectives of the study are 1) to test the effectiveness of somnoplasty (radiofrequency volumetric tissue reduction of the soft palate) for the control of loud, socially disruptive, snoring; 2) to test the long-term efficacy of this treatment by spouse report; and 3) to compare the effectiveness of somnoplasty with another treatment. STUDY DESIGN: Twenty patients with complaints of loud snoring and a respiratory disturbance index no greater than 15 respiratory events per hour with sleep-related episodes of oxygen desaturation no lower than 80% were offered an experimental treatment. Ten were treated with somnoplasty, and a comparison group of 10 matched patients used an oral appliance. All were restudied in the laboratory wearing a device programmed to count minutes of sleep during which snoring was loud, soft, or absent. METHODS: For the 10 somnoplasty patients, a spouse rating of snoring determined whether the patient received one or more treatments. Five patients had a single treatment to three sites, and five others had two such treatments. Ten patients wore an oral appliance of the tongue-retaining type (Snore X, Fremont, CA). RESULTS: Seven of the 10 somnoplasty patients met the improvement criteria set for reduced loud snoring (a spouse rating of 3 or less on a 10-point scale, and 10% or less of sleep time in loud snoring in the laboratory). The comparison group also had a significant improvement in the percentage of sleep time in loud snoring while wearing the Snore X appliance. CONCLUSION: Since there was no significant difference between the two groups in percentage of sleep time spent in loud snoring while treated, the choice of method to control snoring must be based on factors other than efficacy.

Humans↗

Axillary lymph node dissection in breast cancer: an evolving question?

Axillary lymph node dissection (ALND) is performed for staging purposes. Sentinel lymph node biopsy may decrease the cost and morbidity of ALND. Are there patients that the procedure is not indicated avoiding cost and morbidity? We retrospectively studied the incidence of lymph node metastasis in 423 patients with T1 breast cancer. Thirty-one T1a, 146 T1b, and 246 T1c tumors were seen. The mean age was 61 years. Ten per cent were premenopausal, and 84 per cent were postmenopausal. Tumor size averaged 1.29 cm. Eighty-one per cent of the tumors were node negative and 19 per cent were node positive. One T1a patient (3 per cent) had an axillary metastasis, 19 T1b patients (13%), and 61 T1c patients (25%) were node positive, respectively. Seventy-three per cent were ER positive. Thirty-three patients (8%) died from cancer. Eighty-seven per cent received surgery with axillary lymph node dissection (ALND), and three per cent had surgery without ALND. Younger age, increased tumor size, premenopausal status, and ER negativity affected node positivity rates (P < 0.05). Death from breast cancer was more common among node-positive patients (P < 0.05). No difference was found regarding the performance of ALND and survival (P > 0.05). We feel that ALND can be safely omitted in T1a to reduce the morbidity and the expense of breast cancer treatment. In T1b and T1c tumors, the use of ALND is necessary, but morbidity and cost can be reduced by the use of sentinel lymph node biopsy.

Adult↗

An out-of-frame cytochrome b gene deletion from a patient with parkinsonism is associated with impaired complex III assembly and an increase in free radical production.

We have isolated transmitochondrial cybrids containing a mitochondrial DNA cytochrome b 4-base pair deletion previously identified in a patient with parkinsonism. This presentation is in contrast to that of most patients with cytochrome b mutations, who present with exercise intolerance. Clones containing different levels of the cytochrome b 4-base pair deletion showed that high levels of the mutation were associated with a respiratory deficiency and a specific complex III defect. Newly synthesized full-length cytochrome b was undetectable by metabolic labeling of mutant cells, and these cells were unable to grow in media that restricts proliferation of cells with defective oxidative phosphorylation. Steady state levels of some subunits previously found to be in close association with cytochrome b by crystallography and biochemical analysis (ie, Rieske [2Fe-2S] protein and subunit VI) were drastically reduced in clones containing high levels of the mutation, whereas the reduction in the core-1 subunit was milder. The absence of cytochrome b and complex III activity was also associated with increased hydrogen peroxide production. These findings, together with the variable tissue distribution of pathogenic mitochondrial DNA molecules, provide clues to the heterogeneous phenotypes associated with mitochondrial DNA mutations and establish a link between different forms of parkinsonism and oxidative phosphorylation defects.

Cytochrome b Group↗

Poly(ADP-ribosylation) protects maternally derived histones from proteolysis after fertilization.

Fertilization in sea urchins is followed by the replacement of sperm-specific histones by cleavage-stage histone variants recruited from maternal stores. Such remodelling of zygote chromatin involves a cysteine proteinase that degrades the sperm-specific histones in a selective manner, leaving the maternal cleavage-stage histone variants intact. The mechanism that determines the selectivity of the sperm-histone-selective proteinase (SpH-proteinase) was analysed by focusing on the post-translational modification status of both sets of histones. It has previously been reported that only native cleavage-stage histones are poly(ADP-ribosylated), whereas the sperm-specific histones are not modified. To determine whether the poly(ADP-ribose) moiety afforded protection from degradation, the ADP-ribose polymers were removed from the cleavage-stage histones in vitro; these proteins were then assayed as potential substrates of the SpH-proteinase. Strikingly, the cleavage-stage histone variants were extensively degraded after the enzymic removal of their ADP-ribose moieties. In addition, the SpH cysteine proteinase was not inhibited by isolated poly(ADP-ribose) polymers. Consequently, only poly(ADP-ribosylated) cleavage-stage histone variants are protected from proteolysis. These results demonstrate a novel role for this type of post-translational modification, namely the protection of nuclear proteins against nuclear proteinases after fertilization.

Animals↗

Stereological age-related changes in neurons of the rat dorsal lateral geniculate nucleus.

Quantitative methods were used to compare the changes taking place in the volume of the dorsal lateral geniculate nucleus (dLGN) and corresponding neurons of young, adult and old rats. The study was carried out on male albino rats aged 3, 18, 24 and 28 months. In order to estimate the volume of the dLGN, neuronal volume density, numerical density and total number of neurons, we used serial sections stained according to the Klüver-Barrera technique and stereological methods. We found that dorsal lateral geniculate nucleus volume increases between 3 and 28 months, with a larger increase between 24 and 28 months. Neuronal volume density and numerical density of neurons are greater at 3 months and undergo a significant decrease between 24 and 28 months. Finally, the total number of neurons is shown to be smaller in adult and old animals than in younger ones, even though no significant variations are found between 18 and 28 months. Furthermore, this study confirms the need to analyze the total number of neurons and not just neuronal density if we want to correctly evaluate some of the microscopic changes occurring during senescence.

Aging↗

Alternative-splicing of serotonin receptor isoforms in the pharynx and muscle of the parasitic nematode, Ascaris suum.

Pharyngeal pumping is essential for nematode feeding and survival and is dramatically stimulated by serotonin (5-HT). In the present study, a cDNA pool was prepared from poly A + RNA isolated from pharynxes dissected from the parasitic nematode, Ascaris suum, and was used as a template for RT-PCR with degenerate primers designed from sequences conserved in 5-HT receptors from a variety of sources. A putative 5-HT receptor cDNA (AS1) was identified which exhibited most identity to the 5-HT2 family of receptors. AS1 was 1925 nucleotides, did not appear to be trans-spliced and contained a 3' untranslated region of 127 nucleotides with a polyadenylation signal (ATTAAA) and a short poly A+ tail. The coding region predicted a protein of 532 amino acids with a molecular weight of 60 176. When AS1 was transiently expressed in COS-7 cells, isolated membranes exhibited the high affinity, saturable binding of [125I]LSD. More importantly, [125I]LSD binding was inhibited by 5-HT, but not other biogenic amines, supporting the identification of AS1 as a 5-HT receptor. Additional cDNAs identical, in part, to AS1 were also identified. AS1deltaIV lacked a predicted 42 amino acids at the carboxy terminus of the third intracellular loop, while AS2 and AS3 contained different COOH-termini, regions implicated in G-protein coupling in other heptahelical receptors. A portion of the gene (5htn) encoding AS1 also was cloned and sequenced. This genomic fragment was about 10 kb, contained the entire AS1 open reading frame and included eight exons and seven introns. From this analysis, it appears that these different AS cDNAs were generated by alternative-splicing, AS1deltaIV from the deletion of exon IV, and AS2 and AS3 from the use of alternative sites within exon VII as 5' splice acceptor sites for exon VIII. Using RT-PCR and primers specific for each of the isoforms, AS1 -3 appeared to be expressed in pharynx, while only AS1 and AS2 were present in body wall muscle. More importantly, the deletion of exon IV appeared to be associated exclusively with AS1 in pharynx and AS2 in muscle.

Alternative Splicing↗

Effect of optical digitizer selection on the application accuracy of a surgical localization system-a quantitative comparison between the OPTOTRAK and flashpoint tracking systems.

Application accuracy is a crucial factor for stereotactic surgical localization systems, in which space digitization camera systems are one of the most critical components. In this study we compared the effect of the OPTOTRAK 3020 space digitization system and the FlashPoint Model 3000 and 5000 3D digitizer systems on the application accuracy for interactive localization of intracranial lesions. A phantom was mounted with several implantable frameless markers which were randomly distributed on its surface. The target point was digitized and the coordinates were recorded and compared with reference points. The differences from the reference points represented the deviation from the "true point." The root mean square (RMS) was calculated to show the differences, and a paired t-test was used to analyze the results. The results with the phantom showed that, for 1-mm sections of CT scans, the RMS was 0.76 +/- 0. 54 mm for the OPTOTRAK system, 1.23 +/- 0.53 mm for the FlashPoint Model 3000 3D digitizer system, and 1.00 +/- 0.42 mm for the FlashPoint Model 5000 system. These preliminary results showed that there is no significant difference between the three tracking systems, and, from the quality point of view, they can all be used for image-guided surgery procedures.

Equipment Design↗

Potential involvement of post-translational modifications as a mechanism modulating selective proteolysis after fertilization.

The role of proteolysis during fertilization has been investigated only to a very limited extent as compared with its role on the control of cell cycle progression. In this report, we discuss briefly the proteases involved in fertilization, their relevance in the egg-sperm interaction and in the chromatin remodeling that occurs before the reestablishment of the diploid condition of the zygote. We further emphasize how the post-translational modifications of target proteins modulate these proteolytic events. J. Cell. Biochem. Suppls. 32/33:149-157, 1999.

Animals↗