Biomedical subjects

A Gruber

Publications and source records attributed to A Gruber.

At least 73 records · Page 4Linked to original sources

PubMed2000

Heterogeneity of isolated mononuclear cells from patients with acute myeloid leukemia affects cellular accumulation and efflux of daunorubicin.

BACKGROUND AND OBJECTIVE: Pharmacologic studies on blasts from patients with leukemia are generally performed on density gradient isolated blood or bone marrow cells. Thereby, cellular drug accumulation and efflux are determined as mean values of the entire cell population. The objective of the present study was to characterize the heterogeneity in the accumulation and efflux of daunorubicin in various subpopulations of mononuclear cells isolated from patients with acute myeloid leukemia (AML). DESIGN AND METHODS: Mononuclear cells from 33 patients with AML were isolated from peripheral blood by density gradient centrifugation on Lymphoprep (1. 077 g/mL). Cellular accumulation of fluorescent daunorubicin was determined by flow cytometry after incubation of the cells at +37C for 1 hour. Thereafter, the cells were washed and reincubated in drug-free medium. Kinetics of drug efflux were determined by frequent determination of cellular fluorescence during 30 min. Daunorubicin accumulation and efflux were compared in the total isolated mononuclear cell population and in the various blast cell populations gated on FSC/SSC according to the results of immunophenotyping. RESULTS: In 8 of these 33 (24%) patient samples, two distinct blast cell populations could be identified. In 7 out of 8 these cases the more immature blasts had a lower drug accumulation and in 6 out of the 8 cases also a higher efflux rate than the differentiating cell population. Cyclosporin A increased daunorubicin accumulation and reduced efflux in the immature blast population. In the differentiating cell population cyclosporin A increased both the accumulation and the efflux. In patients with a single blast cell population, the gated blast cells had a significantly lower drug accumulation but also a lower drug efflux rate than the total cell population. INTERPRETATION AND CONCLUSIONS: The results imply that drug transport studies on cells isolated from patients with AML give somewhat different results depending on the cell population studied. Some, but not all, of these differences in daunorubicin accumulation and efflux as well as in the effect of cyclo-sporin A can be explained by a heterogenous expression of the mdr1-gene. The observed heterogeneity may be of special relevance with regard to drug resistance. The presence of even a small resistant cell clone may jeopardize the effect of the chemotherapy due to expansion resulting in relapse of disease.

Acute Disease↗

PubMed2000

Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high-dose therapy and infectious complications.

BACKGROUND AND OBJECTIVES: Autologous peripheral stem cell transplantation (APSCT) is increasingly used for various hematologic malignancies and solid tumors. The objective of this study was to analyze the immune reconstitution after APSCT and see if there was any correlation with diagnosis, age, type of high-dose therapy, CD34(+) selection of the autograft and double vs single APSCT. DESIGN AND METHODS: Lymphocyte subset recovery was studied in 46 consecutive patients with hematologic malignancies and breast cancer, who underwent APSCT. Eleven patients with multiple myeloma received tandem autografts. Thirty-one patients were given total body irradiation (TBI) as part of the high-dose treatment. Eighteen patients received a CD34(+) selected graft. The percentage and absolute numbers of lymphocyte populations, T-cells (CD2(+), CD3(+)), B-cells (CD19(+)), NK cells (CD56(+ )CD3(-) and CD16(+)CD3(-)) and T-cell subpopulations (CD4(+), CD8(+), CD4(+)CD45RA(+), CD4(+ )CD45RO(+), CD4(+)DR(+), CD8(+ )CD45RO(+), CD8(+)DR(+)), were monitored with flow cytometry during the first year after APSCT. RESULTS: The total B-cell (CD19(+)) and T-cell (CD3(+)) counts were reconstituted to normal levels 2-4 months after APSCT. All patients had a low CD4/CD8 ratio during the observation period, related to both a low number of CD4(+) cells and elevated numbers of CD8(+) cells. The low number of CD4(+) cells was due to a persistently low level of naive CD4(+)CD45RA(+) cells. A high proportion of the CD8+ cells displayed a phenotype compatible with activated T-cells (CD8(+)DR(+)) up to 10 months after autografting. The number of NK cells (CD56(+)3(-) or CD16(+)3(-)) reached normal values within one month post-transplant. No single variable, such as diagnoses, age, TBI as part of the high-dose treatment, tandem autografting or CD34(+) selection of the graft, influenced the immune or hematopoietic reconstitution and no correlation with documented infectious complications was found. INTERPRETATION AND CONCLUSIONS: Despite heterogeneity of diseases, age, initial treatment and high-dose regimens, lymphocyte subset analysis did not reveal any differences in hematopoietic or immune reconstitution. All patients had a low CD4(+)/CD8(+) ratio during at least the first year post-transplant, caused by a persistent increase of CD8(+) lymphocytes and a constant reduction of CD4(+) lymphocytes, making the patients susceptible to infections for a prolonged period of time post-transplant.

Adult↗

PubMed1999

Evolving ideals of male body image as seen through action toys.

OBJECTIVE: We hypothesized that the physiques of male action toys--small plastic figures used by children in play--would provide some index of evolving American cultural ideals of male body image. METHOD: We obtained examples of the most popular American action toys manufactured over the last 30 years. We then measured the waist, chest, and bicep circumference of each figure and scaled these measurements using classical allometry to the height of an actual man (1.78 m). RESULTS: We found that the figures have grown much more muscular over time, with many contemporary figures far exceeding the muscularity of even the largest human bodybuilders. DISCUSSION: Our observations appear to represent a "male analog" of earlier studies examining female dolls, such as Barbie. Together, these studies of children's toys suggest that cultural expectations may contribute to body image disorders in both sexes.

Adult↗

PubMed1999

Trypanosoma cruzi: conformational preferences of antigenic peptides bearing the immunodominant epitope of the B13 antigen.

The Trypanosoma cruzi recombinant protein B13 contains tandemly repeated domains and shows high sensitivity in the serological diagnosis of Chagas' disease. It has been shown that the immunodominant epitope of B13 is contained in the GDKPSLFGQAAAGDKPSLF-NH(2) sequence and that the hexapeptide AAAGDK seems to be the "core" of that epitope. Three peptides containing that "core" sequence, one corresponding to the entire repeat motif GDKPSLFGQAAAGDKPSLF-NH(2), pB13, and two smaller fragments, FGQAAAGDK-NH(2), S4, and QAAAGDKPS-NH(2), S5, have been tested in competitive ELISA with recombinant protein B13 in the solid phase against 40 chagasic sera from Brazilian patients. The median percentage inhibition for pB13, S4, and S5 were, respectively, 91, 86, and 68%. The possibility that the distinct antigenic activity of those peptides correlates with the existence of preferential conformational properties has been investigated by CD and NMR spectroscopy. Results indicate their propensity to adopt a helical configuration, centered in the AAAGDK sequence, and whose extent and stability directly correlates with the peptides' antigenicity. The data are discussed in the light of the existence of conformational preferences involving immunodominant epitopes in tandemly repeated antigens.

Amino Acid Sequence↗

PubMed1999

Topoisomerase II-mediated alterations of K562 drug resistant sublines.

In order to further elucidate the roles of DNA topoisomerase II (topo II) subtypes, alpha and beta, as drug targets in chemotherapy, we have determined the enzyme levels in K562 cells selected for resistance to mitoxantrone (K562/Mxn), daunorubicin (K562/Dnr) and idarubicin (K562/Ida 20 and K562/Ida 60), as well as topo II-DNA complex formation, DNA damage and cytotoxicity, induced by topo II interactive agents, for example etoposide, teniposide, mitoxantrone and amsacrine. As compared to the parental cells, topo IIalpha/beta protein levels in K562/Mxn, K562/Dnr, K562/Ida 20 and 60 lines, measured with Western blot, were 17/67%, 85/88, 24/31% and 10/7% respectively. DNA damage, determined by DNA unwinding technique, induced by teniposide and amsacrine correlated with both topo IIalpha/beta protein levels (r2 = 0.8/0.9, P = 0.03/0.01 and r2 = 0.8/0.9, P = 0.04/0.01, respectively). Topo II-DNA complex formation induced by all studied drugs correlated with topo IIbeta protein levels (r2-range 0.8-0.9, P-range 0.01-0.04), while the correlation with topo IIalpha was weaker. Topo IIalpha/beta protein levels tended to show an inverse correlation with the cytotoxicity of etoposide (r2 = -0.9/-0.7, P = 0.01/0.06). The overall topo II-DNA complex formation correlated with drug-induced DNA damage (r2 = 0.9, P = 0.0001), whilst not with the cytotoxicity. Our findings indicate that both topo II isozymes are the targets of the antitumor agents studied, and of potential clinical relevance for prediction of treatment efficacy. They could play a role in tailored chemotherapy.

Antigens, Neoplasm↗

PubMed1999

Human immunodeficiency virus type 1 protease inhibitor attenuates Candida albicans virulence properties in vitro.

The putative virulence factor secreted aspartyl proteinase (SAP) of Candida albicans and the human immunodeficiency virus type 1 (HIV-1) protease both belong to the aspartyl proteinase family. The present study demonstrates that the HIV-1 protease inhibitor Indinavir is a weak but specific inhibitor of SAP. In addition, Indinavir reduces the amount of cell bound as well as released SAP antigen from C. albicans. Furthermore, viability and growth of C. albicans are markedly reduced by Indinavir. These findings indicate that HIV-1 protease inhibitors may possess antifungal activity and we speculate that in vivo SAP inhibition may add to the resolution of mucosal candidiasis in HIV-1 infected subjects.

Amino Acid Sequence↗

PubMed1999

Characterization of drug-resistant cell lines by comparative genomic hybridization.

The development of resistance to cytostatic agents is a serious obstacle to the success of cancer therapy and has been the focus of many research efforts. Traditionally, cell lines are selectively cultured in the presence of cytostatic agents and the biochemical and cytogenetic properties of the cell lines are then analyzed. In order to better understand the mechanisms by which drug resistance is mediated, we have analyzed three cell lines, each derived from the parent line K562, which are resistant to vincristine, mitoxantrone, or idarubicin, using comparative genomic hybridization (CGH). In each case, CGH successfully identified amplifications and/or deletions unique to the drug-resistant selected cell lines. Further characterization of the genetic regions identified in the CGH analysis could greatly contribute to our understanding of acquired drug resistance, and could potentially impact the clinical management of cancer.

Antineoplastic Agents↗

PubMed1999

Dissimilar attenuation of Candida albicans virulence properties by human immunodeficiency virus type 1 protease inhibitors.

The secreted aspartyl proteinase (Sap) of Candida albicans, which is believed to represent an important virulence factor of this opportunistic yeast, and the human immunodeficiency virus type 1 (HIV-1) protease, which is obligatory for the production of infectious virions, both belong to the same family of aspartyl proteinases. We have previously shown that the HIV-1 protease inhibitor Indinavir directly inhibits secretion and proteinase activity of Sap in a dose-dependent manner. Furthermore, at very high concentrations, viability of C. albicans is markedly reduced by Indinavir, indicating that HIV-1 protease inhibitors may possess antifungal activity. We thus proposed that these drugs may add to the resolution of mucosal candidiasis in HIV-1 infected subjects. We have now compared three different HIV-1 protease inhibitors. The rank order of Sap inhibition, already significant at 0.1 mg/ml for all protease inhibitors, was Ritonavir > Indinavir > Saquinavir. However, the cross-reactivity of Ritonavir to pepsin was also more pronounced compared with the other two. Indinavir did not affect Candida viability at concentrations up to 1 mg/ml, in line with our previous study. In contrast, at this concentration Saquinavir was even fungicidal as assessed by three different viability assays (colony formation assay, MTT assay, propidium iodide staining) whereas Ritonavir significantly affected the mitochondrial activity only (MTT assay). No influence on Candida viability was observed for any of the three at concentrations of 0.1 mg/ml or lower. It remains to be examined whether HIV-1 protease inhibitors or derivatives thereof may be suitable for in vivo therapy of subjects suffering from mucosal candidiasis resistant to current antimycotics.

Animals↗

PubMed1999

Suppression of telomerase reverse transcriptase (hTERT) expression in differentiated HL-60 cells: regulatory mechanisms.

Telomerase activity, associated with cellular immortalization and tumorigenesis, is suppressed during terminal differentiation of HL-60 promyelocytic leukaemic cells. However, it is poorly understood how telomerase activity is regulated in differentiated HL-60 cells. In the present study, we demonstrate that the down-regulation of telomerase reverse transcriptase (hTERT) expression, the catalytic subunit, occurs prior to the suppression of telomerase activity in differentiated HL-60 cells. In contrast, the expression of telomerase RNA template (hTR) and telomerase associated protein (TP1) is not reduced. This down-regulation of hTERT expression is achieved through inhibition of gene transcription, in which process new protein synthesis is required. Moreover, the rapid down-regulation of hTERT expression followed by the inhibition of telomerase activity is a specific component of the differentiation programme and not simply a consequence of cell cycle arrest. Serum-deprivation of HL-60 cells causes cell cycle arrest without differentiation and this does not result in a significant reduction in hTERT mRNA levels within the first 24 h. Our findings suggest that hTERT expression is stringently controlled at transcriptional level in HL-60 cells. The downregulation of hTERT expression in the HL-60 cell differentiation model may represent a general regulatory mechanism through which telomerase becomes repressed during development and differentiation of human somatic cells.

Cell Cycle↗

PubMed1999

Arterial blood oxygenation, maximum exercise capacity and oxygen transport in patients before and after autologous peripheral blood progenitor cell transplantation.

Several studies have reported a reduced pulmonary diffusion capacity for carbon monoxide after total body irradiation (TBI) and/or high-dose chemotherapy (HDCT) and autologous peripheral blood progenitor transplantation (APBPC). The present study describes the oxygenation of arterial plasma (paO2), the maximum exercise capacity (Wmax) and maximum oxygen transport (VO2max) before and after such treatment. Pulmonary gas exchange and paO2 were measured in 15 patients at maximum dynamic bicycle exercise, performed before and at 8+/-0.9 (s.e.m.) months after TBI/HDCT (n = 12) and HDCT (n = 3) followed by APBPC. Wmax was 169+/-14 and 157+/-15 watts (P>0.05) before and after therapy, respectively. VO2max, 1.8+/-0.1 l/min before treatment, fell to 1.6+/-0.1 l/min (P<0.05) after therapy. The maximum exercise paO2 was 13.2+/-0.4 kPa before and 13.6+/-0.4 kPa (P>0.05) after the treatment period. The findings indicate no significant reduction of Wmax or pulmonary diffusion capacity for O2 after TBI/HDCT and APBPC while VO2max fell modestly by approximately 11%. The study was restricted to patients who remained in remission.

Adult↗

PubMed1999

High levels of lung resistance related protein mRNA in leukaemic cells from patients with acute myelogenous leukaemia are associated with inferior response to chemotherapy and prior treatment with mitoxantrone.

Expression of the mdr1 (multidrug resistance), mrp (multidrug resistance associated protein), and lrp (lung resistance related protein) genes is associated with transport related MDR (multidrug resistance). We quantified mRNA levels of these genes using competitive reverse transcription polymerase chain reaction (RT-PCR) in 128 samples of leukaemic cells from 92 patients with acute myelogenous leukaemia (AML). There was a wide variation between the samples in mRNA levels of all three genes. The mean mdr1 mRNA level was 1.3 transcripts per cell (range undetectable to 15.8), the mean mrp level was 7.9 (range 0.1-36.2) and mean lrp 3.9 (range 0.1-29). Lrp mRNA levels were higher in samples drawn at diagnosis from the 15 patients with resistant disease than from the 37 with chemosensitive disease (4.9 SD 3.1 v 2.9 SD 2.3, P = 0.016). Neither mdr1 nor mrp mRNA levels were predictive for response to chemotherapy. In samples from patients who had received chemotherapy, those that had received mitoxantrone (n = 24) had higher lrp mRNA levels (mean 4.8, SD 2.5) than those that had not (n = 20, mean 2.8, SD 2.4, P = 0.012). In conclusion, the results indicate that lrp expression is associated with inferior response to chemotherapy in AML and that lrp expression increases after exposure to mitoxantrone.

Adult↗

PubMed1999

Coiling of recurrent and residual cerebral aneurysms after unsuccessful clipping.

We treated four patients with 3 recurrent and 1 residual aneurysm after surgical clipping by using Guglielmi detachable coils (GDCs). Three subjects presented after a second subarachnoid hemorrhage (SAH) occurring between 10 and 25 years after the first bleeding. Early postoperative angiography of the fourth patient showed an incompletely clipped aneurysm. In three poor grade patients we observed one good outcome, one fair result and one death due to the sequelae of SAH. One good grade patient remained in excellent condition postoperatively. Three aneurysms were totally occluded and in one a more than 90% occlusion was achieved with GDCs. We consider the treatment with GDC a viable alternative to reoperation in all patients with recurrent or residual aneurysms following failed attempt at surgical obliteration.

Adult↗

PubMed1999

Histopathological findings in experimental aneurysms embolized with conventional and thrombogenic/antithrombolytic Guglielmi coils.

We studied the short- and long-term histological responses induced by conventional and modified electronically detachable coils (GDCs) in experimental aneurysms. Eighteen carotid bifurcation aneurysms were produced microsurgically in rabbits. Six animals each were treated either with conventional or with GDCs coated with a mixture of tissue-thromboplastin to enhance intra-aneurysmal thrombus formation and of plasminogen activator inhibitor type-1 (PAI-1) in inhibit intra-aneurysmal clot fibrinolysis. Six served as untreated controls. Follow-up angiograms were obtained immediately and at 3, 6, 9, 12, 17, and 24 weeks after embolization prior to sacrifice of the animals. All aneurysms were studied macroscopically and histopathologically with the coils in situ. Five of six control aneurysms remained patent. Endovascular occlusion rates between > 90% and 100% were achieved in nine of twelve coiled aneurysms. Follow-up angiography demonstrated recanalization and coil compaction in 5 of them. Gross and microscopic histopathological examination revealed a membrane covering the orifice, intra-aneurysmal scar formation, and development of a neo-intima in both treatment groups at 17 and 24 weeks postembolization. The granulation tissue response appeared to be equally distributed in aneurysms treated with either uncoated or coated coils. Further quantitative morphometric studies are needed to prove if a thrombogenic/antithrombolytic coil-coating might be of value in providing a more enduring anatomic result after GDC-treatment of human brain aneurysms.

Aneurysm↗

PubMed1999

Molecular basis of congenital lp(a) deficiency: a frequent apo(a) 'null' mutation in caucasians.

High plasma concentrations of lipoprotein(a) [Lp(a)], a covalent low-density lipoprotein-apolipoprotein(a) [apo(a)] complex, are associated with coronary heart disease and stroke. Heritability of Lp(a) levels is high and the major locus determining Lp(a) concentrations is the apo(a) gene. We here demonstrate that a G-->A substitution at the +1 donor splice site of the apo(a) kringle (K) IV type 8 intron occurs with a high frequency ( approximately 6%) in Caucasians but not in Africans and is associated with congenital deficiency of Lp(a) in plasma. This mutation alone accounts for a quarter of all 'null' apo(a) alleles in Caucasians. RT-PCR analysis based on apo(a) illegitimate transcription in lympho- blastoid cells demonstrated that the donor splice site mutation results in an alternative splicing of the K IV type 8 intron and encodes a truncated form of apo(a). Expression of the alternatively spliced cDNA analogue in HepG2 cells showed that the truncated apo(a) form is secreted but is unable to form the covalent Lp(a) complex. Immunoprecipitated plasma apo(a) from homozygotes for the mutation was almost completely fragmented. Taken together, our data indicate that a failure in complex formation followed by fast degradation in plasma of the truncated free apo(a) is one mechanism which underlies the null Lp(a) type associated with the donor splice site mutation.

Alleles↗

PubMed1999

Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To analyze the influence of extracerebral organ system dysfunction after aneurysmal subarachnoid hemorrhage (SAH) on mortality and neurologic outcome. DESIGN: Observational study with retrospective data extraction. SETTING: Neurosurgical intensive care unit (NICU) at a primary level university hospital, supervised and staffed by both members of the Clinic of Neurosurgery and the Clinic of Anesthesiology and General Intensive Care. PATIENTS: Two hundred forty-two patients treated for intracranial aneurysm rupture within 7 days of the most recent SAH. INTERVENTIONS: Routine neurosurgical interventions for obliteration of the ruptured aneurysm (microsurgery, Guglielmi Detachable Coils embolization) and for treatment of posthemorrhagic hydrocephalus (ventriculostomy, cerebrospinal fluid shunt implantation). MEASUREMENTS AND MAIN RESULTS: Respiratory, renal, hepatic, cardiovascular, and hematologic organ system functions were evaluated both individually and in aggregate by using a modified version of the Multiple Organ Dysfunction (mMOD) score. Of 1,452 organ system functions assessed in 242 patients during their NICU stay, 714 organ system functions were intact (cerebral: 0, extracerebral: 714), 556 organ systems had mild-to-moderate dysfunctions (mMOD scoremax 1-2 for the affected organ system; cerebral: 153, extracerebral: 403), and 182 organ systems failed (mMOD scoremax 3 for the affected organ system; cerebral: 89, extracerebral: 93). Severity of extracerebral organ system dysfunctions correlated with the degree of neurologic impairment (Hunt and Hess [H&H] score) in a graded fashion. Similarly, the chance to develop systemic inflammatory response syndrome (SIRS) during the NICU stay increased with increasing admission H&H grade. The incidence of SIRS and septic shock was 29% and 10.3%, respectively. The mortality rate was 40.2% in patients with SIRS and 80% for patients suffering septic shock. Seventy-seven percent of extracerebral organ system failures (OSFs) occurred in conjunction with SIRS: 51% of respiratory OSFs, 97% of renal OSFs, 100% of hepatic OSFs, 96% of cardiovascular OSFs, and 73% of hematopoietic OSFs. Both CNS dysfunction and extracerebral organ system dysfunctions were significantly related to neurologic outcome. The probability of unfavorable neurologic outcome significantly increased with both decreasing cerebral perfusion pressure (CPP) and increasing severity of extracerebral organ dysfunction. CONCLUSION: Aneurysmal SAH and its neurologic sequelae accounted for the principal morbidity and mortality in the current series. Development of extracerebral organ system dysfunction was associated with a higher probability of unfavorable neurologic outcome. Systemic inflammation (SIRS) and secondary organ dysfunction were the principal non-neurologic causes of death.

Adult↗

PubMed1999

Chronic shunt-dependent hydrocephalus after early surgical and early endovascular treatment of ruptured intracranial aneurysms.

OBJECTIVE: The goal of this study was to document the influence of the treatment method (early surgery versus early endovascular treatment) on the development of chronic shunt-dependent hydrocephalus in a series of 242 patients treated within 7 days after aneurysmal subarachnoid hemorrhage (SAH). METHODS: The following parameters were prospectively recorded in a computerized database and retrospectively analyzed for association with chronic shunt-dependent hydrocephalus: 1) Hunt and Hess grade, 2) Fisher computed tomographic grade, 3) incidence of repeat SAH, 4) aneurysm location, and 5) treatment method (early surgery versus early endovascular treatment). RESULTS: Forty of 187 patients (21.4%) who survived the SAH and its neurological and/or medical sequelae underwent definitive shunting for treatment of chronic hydrocephalus. The rate of shunt dependency was positively correlated with a higher Hunt and Hess grade (P < 0.001), a higher Fisher computed tomographic grade (P = 0.003), the occurrence of intraventricular hemorrhage (P < 0.001), repeat SAH (P = 0.003), and aneurysms arising at the anterior communicating artery (P < 0.001). CONCLUSION: The results of the present study indicate that the treatment method used does not affect the risk of the later development of chronic shunt-dependent hydrocephalus (early surgery, 23.2% [29 of 125]; early endovascular treatment, 17.7% [11 of 62]; P = 0.45).

Adult↗

PubMed1999

Clinical and angiographic results of endosaccular coiling treatment of giant and very large intracranial aneurysms: a 7-year, single-center experience.

OBJECTIVE: To evaluate whether the objectives of surgical treatment, i.e., prevention of aneurysmal rebleeding, relief of aneurysmal mass effect, and prevention of embolic complications, are met by endosaccular coiling treatment applied to giant and very large wide-necked aneurysms. METHODS: Thirty patients with 31 giant or very large aneurysms were considered to show unacceptable risk/benefit ratios for open surgery and were treated using the Guglielmi detachable coil (GDC) method between 1992 and 1998. RESULTS: With endosaccular GDC treatment, 73.3% of the population experienced excellent to good recoveries (Glasgow Outcome Scale scores of 4 or 5), with a 13.3% procedure-related morbidity rate and a 6.7% procedure-related mortality rate. Two hemorrhaging episodes occurred after GDC treatment (annual bleeding rate, 2.5%; 2 hemorrhaging episodes/79.2 patient-yr). Symptoms related to aneurysmal mass effect were improved for 45.5% of the patients presenting with signs of neural compression. Among 23 patients with 24 aneurysms who were available for angiographic follow-up assessment, complete or nearly complete occlusion was observed for 17 aneurysms (71%; angiographic follow-up period, 24.3 +/- 19.6 mo, mean +/- standard deviation). A single total embolization served as definitive treatment for only 12.5% of the giant aneurysms and 31% of the very large aneurysms. CONCLUSION: Endosaccular GDC treatment of giant and very large aneurysms was accomplished with procedure-related morbidity and mortality rates comparable to those for open surgery performed by experts. However, because coil stability was unsatisfactory, we suggest that the GDC method should currently be reserved for individuals who are considered poor candidates for open surgery.

Adult↗

PubMed1999

Presence of polydnavirus transcripts in an egg-larval parasitoid and its lepidopterous host.

The parasitoid Chelonus inanitus (Braconidae, Hymenoptera) oviposits into eggs of Spodoptera littoralis (Noctuidae, Lepidoptera) and, along with the egg, also injects polydnaviruses and venom, which are prerequisites for successful parasitoid development. The parasitoid larva develops within the embryonic and larval stages of the host, which enters metamorphosis precociously and arrests development in the prepupal stage. Polydnaviruses are responsible for the developmental arrest and interfere with the host's endocrine system in the last larval instar. Polydnaviruses have a segmented genome and are transmitted as a provirus integrated in the wasp's genome. Virions are only formed in female wasps and no virus replication is seen in the parasitized host. Here it is shown that very small amounts of viral transcripts were found in parasitized eggs and early larval instars of S. littoralis. Later on, transcript quantities increased and were highest in the late last larval instar for two of the three viral segments tested and in the penultimate to early last larval instar for the third segment. These are the first data on the occurrence of viral transcripts in the host of an egg-larval parasitoid and they are different from data reported for hosts of larval parasitoids, where transcript levels are already high shortly after parasitization. The analysis of three open reading frames by RT-PCR revealed viral transcripts in parasitized S. littoralis and in female pupae of C. inanitus, indicating the absence of host specificity. For one open reading frame, transcripts were also seen in male pupae, suggesting transcription from integrated viral DNA.

Animals↗