Biomedical subjects

B Andersson

Publications and source records attributed to B Andersson.

At least 73 records · Page 4Linked to original sources

PubMed2000

Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma.

BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS AND METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.

Adult↗

PubMed2000

The N-terminal domain of the light-harvesting chlorophyll a/b-binding protein complex (LHCII) is essential for its acclimative proteolysis.

Variations in the amount of the light-harvesting chlorophyll a/b-binding protein complex (LHCII) is essential for regulation of the uptake of light into photosystem II. An endogenous proteolytic system was found to be involved in the degradation of LHCII in response to elevated light intensities and the proteolysis was shown to be under tight regulation [Yang, D.-H. et al. (1998) Plant Physiol. 118, 827-834]. In this study, the substrate specificity and recognition site towards the protease were examined using reconstituted wild-type and mutant recombinant LHCII. The results show that the LHCII apoprotein and the monomeric form of the holoprotein are targeted for proteolysis while the trimeric form is not. The N-terminal domain of LHCII was found to be essential for recognition by the regulatory protease and the involvement of the N-end rule pathway is discussed.

Amino Acid Sequence↗

PubMed2000

Trypanosoma cruzi: a putative vacuolar ATP synthase subunit and a CAAX prenyl protease-encoding gene, as examples of gene identification in genome projects.

An international genome program has been initiated to increase the knowledge about the Trypanosoma cruzi genome and thereby find effective tools to treat Chagas' disease. We here report the molecular characterization of two novel genes found in the course of this project. Two of the open reading frames (ORF) identified in the sequencing of the third smallest chromosome of the CL Brener strain of T. cruzi were selected for further molecular characterization due to their similarity to genes with interesting functions in other organisms and their potential as targets to combat the parasite. The first ORF (402 bp) showed homology to a 14-kDa vacuolar ATP synthase subunit F from a variety of organisms, such as yeast, rat, bovine, human, and a number of prokaryotes. The second ORF (1188 bp) resembled a CAAX prenyl protease-encoding gene, identified in different organisms, including Homo sapiens, Saccharomyces cerevisiae, and Arabidopsis thaliana, as well as several prokaryotes. RT-PCR from T. cruzi total epimastigote RNA allowed us to isolate the complete transcripts of these genes. Furthermore, screening of an available normalized cDNA library derived from the same stage of the parasite confirmed that both genes are expressed at least in the epimastigote stage of T. cruzi. Comparison of the putative T. cruzi proteins to their counterparts in other organisms revealed significant protein sequence conservation over large evolutionary distances. Computer analysis revealed the presence of several motifs in both proteins, possibly related to the regulation and localization of these proteins in the parasite.

ATP Synthetase Complexes↗

PubMed2000

Fine mapping of the constitutional translocation t(11;22)(q23;q11).

Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal translocation in man. Balanced carriers are phenotypically normal, except for decreased fertility, an increased spontaneous abortion rate and a possible predisposition to breast cancer in some families. Here, we report the high resolution mapping of the t(11;22)(q23;q11) breakpoint. We have localised the breakpoint, by using fluorescence in situ hybidisation (FISH) walking, to a region between D11S1340 and WI-8564 on chromosome 11, and D22S134 and D22S264 on chromosome 22. We report the isolation of a bacterial artificial chromosome (BAC) clone spanning the breakpoint in 11q23. We have narrowed down the breakpoint to an 80-kb sequenced region on chromosome 11 and FISH analysis has revealed a variation of the breakpoint position between patients. In 22q11, we have sequenced two BACs (BAC2280L11 and BAC41C4) apparently mapping to the region; these contain low copy repeats (LCRs). Southern blot analysis with probes from BAC2280L11 has revealed different patterns between normal controls and translocation carriers, indicating that sequences similar/identical to these probes flank the translocation breakpoint. The occurrence of LCRs has previously been associated with genomic instability and "unclonable" regions. Hence, the presence of such repeats renders standard translocation breakpoint cloning techniques ineffective. Thus, we have used high resolution fiber-FISH to study this region in normal and translocation cases by using probes from 22q11, LCRs and 11q23. We demonstrate that the LCR containing the gap in 22q11 is probably substantially larger than the previous estimates of 100 kb. Using fiber-FISH, we have localised the breakpoint in 22q11 to approximately 20-40 kb from the centromeric border of the LCR (i.e. the telomeric end of AC006547) and have confirmed the breakpoint position on 11q23.

Base Sequence↗

PubMed2000

Functional characterization of the PS II-LHC II supercomplex isolated by a direct method from spinach thylakoid membranes.

Recently, a novel procedure to isolate a highly pure and active Photosystem II preparation directly from thylakoid membranes, referred to as PS II-LHC II supercomplex, was reported [Eshaghi et al. (1999) FEBS Lett 446: 23-26]. In addition to the reaction center core proteins, the supercomplex contains all the extrinsic proteins of the oxygen evolving complex and a set of chlorophyll a/b binding proteins. In this paper, the functional properties of this isolated supercomplex are further characterized by using EPR spectroscopy, thermoluminescence, fluorescence relaxation kinetics and flash induced oxygen yield measurements. The PS II-LHC II supercomplex contains, in addition to Q(A) and Q(B), a small pool of plastoquinone (PQ). Although the isolated complex is no longer membrane bound, it has preserved functional characteristics of a well defined PS II preparation with the exception of some modification of Q(B) sites.

Journal Article↗

PubMed2000

Regulation of Photosystem II core protein phosphorylation at the substrate level: Light induces exposure of the CP43 chlorophyll a protein complex to thylakoid protein kinase(s).

Light induces conformational changes in the CP43 chl-a-protein antenna complex in isolated PS II core-complexes exposing phosphorylation site(s) to PS II core-associated protein kinase(s), to added solubilized thylakoid protein kinase(s), as well as to tryptic cleavage. The substrate-activation effect is demonstrated by exposure of the PS II cores to light during the kinase assay as well as by preillumination of the PS II cores in which the endogenous kinase(s) has been inactivated by treatment with N-ethylmaleimid. In the latter case, phosphorylation was performed in darkness following addition of the solubilized protein kinase(s). The solubilized protein kinase(s) does not require light activation. The apparent molecular masses of the main protein kinase(s) associated with the PS II cores (about 31-35 kDa and 45 kDa) differ from that of the major protein kinase present in solubilized preparations obtained from spinach thylakoids (64 kDa). The light-induced exposure of CP43 increases with the light intensity in the range of 20-100 mumol photons m(-2) s(-1) as demonstrated by preillumination of N-ethylmaleimid treated cores followed by addition of the solubilized protein kinase(s) and performing the phosphorylation assay in darkness.

Journal Article↗

PubMed2000

The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men.

OBJECTIVE: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. RESEARCH METHODS AND PROCEDURES: Fifty non-diabetic, middle-aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables. RESULTS: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin-releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites. DISCUSSION: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.

Adipose Tissue↗

PubMed2000

High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant.

Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis. We studied the use of melphalan 180 mg/m2 followed by allogeneic peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing after related (n = 7) or matched unrelated transplants (n = 3). Diagnoses were AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast crisis (n = 1). Eight patients were beyond first relapse and none were in remission. The median time from previous transplant to relapse was 146 days (range 66-206). The melphalan dose was 90 mg/m2 intravenously on days -4 and -3 with PBSC infusion on day 0. GVHD prophylaxis consisted of cyclosporine and methylprednisolone. The median time to an absolute neutrophil count >0.5 x 10(9)/l and to a platelet count >20 x 10(9)/l was 11 and 13 days, respectively. All engrafting patients (n = 8) had 100% donor cells. Two patients died before day 30, but no other grade 3 or 4 toxicity occurred. Acute GVHD grades II-III occurred in two subjects, and chronic GVHD in four. Seven patients achieved CR, but relapsed at a median of 116 days (range 56-614). Leukemia was the cause of death in eight patients. Median survival was 149 days (range 6-614). This treatment produced responses in the majority of this poor prognosis group. However, durable remissions were not observed, and new treatments to consolidate the responses achieved in this setting are needed. This regimen could be considered for short-term disease control to facilitate donor lymphocyte infusion-based immunotherapy or other measures to prevent disease recurrence.

Acute Disease↗

PubMed2000

Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin's disease.

Six patients with advanced Hodgkin's disease in which multiple conventional treatments (median prior chemotherapy regimens: seven), radiation therapy, and a prior autologous stem cell transplantation (SCT) had failed underwent allogeneic SCT following a fludarabine-based conditioning regimen. Median age was 29 years (22-30). Median time to progression after autologous SCT was 6 months (4-21). Disease status at transplant was refractory relapse (n = 3) and sensitive relapse (n = 3). Cell source was filgrastim-mobilized peripheral blood stem cells from an HLA-identical sibling (n = 4) or matched unrelated donor marrow (n = 2). Conditioning regimens were fludarabine-cyclophosphamide-antithymocyte globulin (n = 4), fludarabine-melphalan (n = 1) and fludarabine-cytarabine-idarubicin (n = 1). Myeloid recovery was prompt, with an absolute neutrophil count > or =500/microl on day 12 (11-15). Median platelet recovery to > or =20000/microl was on day 9 (0-60). Chimerism studies on day 30 indicated 100% donor-derived hematopoiesis in 4/5 evaluable patients (4/4 non-progressors). All responders (3/3) have ongoing 100% donor-derived chimerism. Acute graft-versus-host disease (GVHD) was diagnosed in 4/6 evaluable patients. Chronic GVHD was present in 2/4 evaluable patients. There were no regimen-related deaths. Overall day 100 transplant-related mortality was 2/6 (33%). Three patients have expired and three are alive and progression-free with a median follow-up of 9 months (6-26) post transplant. We conclude that allogeneic stem cell transplantation with fludarabine-based preparative regimens is feasible in these high-risk, heavily pretreated HD patients.

Adult↗

PubMed2000

A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure.

AIMS: The adrenergic nervous system is of major importance in congestive heart failure. No genetic polymorphism has previously been identified in the beta(1)-adrenergic receptor gene. The aim of this study was to find possible mutations in this gene and to relate such findings to morbidity and prognosis in heart failure. METHODS AND RESULTS: Genomic DNA was extracted from blood leukocytes from patients with congestive heart failure (n=184) and from age-matched controls (n=77). The part of the beta(1)-adrenergic receptor gene corresponding to nucleotide 1-255 was amplified by polymerase chain reaction and analysed by automated sequencing. The patients were investigated by echocardiography and followed regarding symptoms and survival for 5 years. A missense mutation was identified at nucleotide position 145 in the beta(1)-adrenergic receptor gene, which predicted an amino acid substitution at position 49 (Ser49Gly). The allele frequency of the Gly49 variant was 0.13 in controls and 0.18 in patients (P=0.19). At the time of the 5-years follow-up, 62% of the patients with the wild type gene and 39% of the patients with the Ser49Gly variant had died or had experienced hospitalization (P=0.005). Patients without the mutation had significantly poorer survival compared to those with the mutation, risk ratio 2.34 (95% CI 1.30-4.20), P=0.003. In a mulivariate analysis, the risk ratio was 2.03 (95% CI 0.99-4.16) P=0.05. CONCLUSION: A novel missense mution in the beta(1)-adrenergic receptor gene was associated with a decreased mortality risk in patients with congestive heart failure. These data suggest that the beta(1)-receptor Ser49Gly variant might be associated with altered receptor function, resulting in myocardial protection in patients with heart failure.

Adolescent↗

PubMed2000

Simultaneous changes in bone mineral density and articular cartilage in a rabbit meniscectomy model of knee osteoarthrosis.

OBJECTIVE: It was hypothesized that increased bone mineral density of the medial proximal tibia would precede or coincide with the development of more severe cartilage changes after meniscectomy. METHODS: In a rabbit knee model, mineral density of subchondral bone and changes of articular cartilage were monitored 13 to 40 weeks after medial meniscectomy or a sham operation. RESULTS: Both procedures resulted in a decrease of bone mineral density, especially of the medial proximal tibia, which persisted up to 40 weeks (P< 0.02-0.0007). Meniscectomy induced cartilage changes typical for osteoarthrosis (P< 0.009), which progressed over time on the posterior aspect of the medial tibial plateau (P< 0.009), which is physiologically covered by the meniscus, but the procedure also induced iatrogenic changes which were located mainly on the anterior aspect of the concerned compartment, and which did not progress or develop to osteoarthrosis. CONCLUSIONS: The data suggest that the cartilage changes after meniscectomy in this animal model are caused by the surgical trauma, subsequent limb misuse, and altered load distribution, and initially associated by a decrease not an increase in bone mineral density of the proximal tibia. Moreover, the cartilage changes progressed without a simultaneous increase of the bone mineral density at corresponding sites.

Animals↗

PubMed2000

The expression of lymphocyte surface antigens in bronchial biopsies, bronchoalveolar lavage cells and blood cells in healthy smoking and never-smoking men, 60 years old.

In this study we investigated if smoking subjects with a normal or slightly decreased lung function differ in the lymphocyte pattern compared to never-smokers. In a group of 'healthy' smokers (n = 58) and never-smokers (n = 34) 60 years old, we investigated the lymphocyte pattern in both BAL (n = 30 and n = 18 respectively), bronchial epithelium and lamina propria (n = 14 and n = 10 respectively) and blood. We found that all subjects, despite smoking history, had a higher number of CD8+ cells per mm2 in the epithelium compared to the lamina propria in the bronchial biopsies. In smokers, these CD8+ cells were significantly negatively correlated to FEV1 (r = -0.56, P = 0.04). In smokers, the number of CD8+ lymphocytes was higher and the T cell activation markers (CD57+ and CD28+) were lower in BAL, than in never-smokers. This last finding was also seen in blood for CD3+ 57+. We conclude, that in 'healthy' smokers the lymphocyte patterns are different compared to never-smokers, to some extent in BAL. There is also a relation between lymphocytes in the bronchial mucosa and lung function. This has previously been shown in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis but not in asymptomatic smokers.

Antigens, Surface↗

PubMed2000

N-terminal proatrial natriuretic peptide and prognosis in patients with heart failure and preserved systolic function.

BACKGROUND: Congestive heart failure and preserved left ventricular systolic function is a common clinical condition. Although the prognosis in this type of heart failure is better in comparison to systolic dysfunction, prognostic markers to evaluate long-term outcome are lacking. The atrial peptide, N-terminal proatrial natriuretic peptide (proANP), has been shown to predict survival in patients with systolic dysfunction. We intended to evaluate the predictive capability of N-terminal proANP in patients with preserved systolic function (ejection fraction [EF] > or = 0.40). METHODS AND RESULTS: A clinical and echocardiographic examination was performed in 149 patients with idiopathic heart failure from a population-based cohort, and 84 patients were identified to have preserved systolic function, with an EF of 0.40 or greater. The patients were followed up during 7 years with regard to symptoms, treatment, hospitalization, and survival. The patients with normal EFs had greater plasma concentrations of N-terminal proANP compared with a control group, and N-terminal proANP level was an independent predictor of mortality (risk ratio, 2.44; 95% confidence interval, 1.28 to 4.67; P = .007). In addition, a high concentration of N-terminal proANP predicted an increased rate of hospitalization (50% for a level > 1,200 pmol/L versus 19% for a level < or = 1,200 pmol/L; P = .046) and a greater future dosage of diuretic (127+/-102 vs 51+/-39 mg; P = .007). CONCLUSION: N-terminal proANP level was an independent marker of increased mortality and morbidity in patients with preserved systolic function, whereas EF was not usable in this regard. It is suggested that this peptide could be used to identify clinically relevant left ventricular dysfunction in patients with EFs within the normal range.

Aged↗

PubMed2000

Prospective clinical 5-year study of ceramic-veneered titanium restorations with the Procera system.

STATEMENT OF PROBLEM: The biocompatibility of titanium has been well documented, but clinical outcomes of ceramic-veneered titanium restorations were not conclusive. PURPOSE: The study presents the results of a 5-year clinical study of individual crowns and fixed partial dentures (FPDs) veneered with a low-fusing ceramic of the Procera system. MATERIAL AND METHODS: All patients at one clinic who required crowns or FPDs during a 2-year period were invited to participate. A total of 260 patients received 333 ceramic-veneered Procera restorations (242 single crowns and 91 FPDs). Clinical registrations were performed annually, and the restorations were evaluated according to the California Dental Association rating system. At the 5-year follow-up, 198 (76%) patients were examined. Most of the loss of patients could be explained. RESULTS: Practically all Procera restorations were judged as satisfactory both at baseline and follow-up examinations. One artificial crown and 1 FPD were remade because of extensive fractures of ceramic veneers. Two FPDs had fractures of a soldered joint, but only 1 FPD was replaced. Some minor complications occurred, such as small porcelain fractures that could be polished (6% of single crowns, 13% of FPDs) and or loosened restorations that were recemented. Other recorded complications were not related to the Procera system but to dental caries, loosened posts and cores, and root fractures. CONCLUSION: Clinical outcomes over a 5-year period for ceramic-veneered titanium restorations with the Procera system were favorable.

Adult↗

PubMed2000

The disabilities of the arm, shoulder and hand (DASH) outcome questionnaire: reliability and validity of the Swedish version evaluated in 176 patients.

The disabilities of the arm, shoulder and hand (DASH) questionnaire is a self-administered region-specific outcome instrument developed to measure upper-extremity disability and symptoms. The DASH consists mainly of a 30-item disability/symptom scale. We performed cross-cultural adaptation of the DASH to Swedish, using a process that included double forward and backward translations, expert and lay review, as well as field-testing to achieve linguistic and conceptual equivalence. The Swedish version's reliability and validity were then evaluated in 176 patients with upper-extremity conditions. The patients completed the DASH and SF-12 generic health questionnaire before elective surgery or physical therapy. Internal consistency of the DASH was high (Cronbach alpha 0.96). Test-retest reliability, evaluated in a subgroup of 67 patients who completed the DASH on two occasions, with a median interval of 7 days, was excellent (intraclass correlation coefficient 0.92). Construct validity was shown by a positive correlation of DASH scores with the SF-12 scores (worse upper-extremity disability correlating with worse general health), stronger correlation with the SF-12 physical than with the mental health component, correlation of worse DASH scores with worse self-rated global health, and ability to discriminate among conditions known to differ in severity. The Swedish version of the DASH is a reliable and valid instrument that can provide a standardized measure of patient-centered outcomes in upper-extremity musculoskeletal conditions.

Cross-Cultural Comparison↗

PubMed2000

Cervical lymph node infections with non-tuberculous mycobacteria in preschool children: interferon gamma deficiency as a possible cause of clinical infection.

UNLABELLED: Epidemiological studies have demonstrated a prevalence of positive PPD reactions to non-tuberculous mycobacteria (NTM) in 9% of 4-5-y-old children in the Göteborg area. Very few children of this age develop suppurative infections in lymph nodes that require surgical procedures. The hypothesis was that these children might have T cell deficiencies with abnormalities of macrophage functions, particularly with type 1 cytokines. Twenty-four children who needed operations were investigated immunologically and compared to 10 children of the same age operated on for non-infectious reasons. The methods used were flow cytometry analysis of lymphocytes in blood, blood lymphocyte stimulation assays and interferon gamma analyses. The patients had significantly lower levels of interferon gamma than the controls after stimulation with Candida antigens or Con A. The numbers of T and B lymphocytes were higher in patients than in controls. CONCLUSION: Children with necrotic lymph node infections in the cervical region due to NTM had lower interferon gamma production after stimulation than healthy age-matched controls.

Age Factors↗

PubMed2000

Provocation with stress and electricity of patients with "sensitivity to electricity".

Twenty-four patients with self-reported "sensitivity to electricity" were divided into two groups and tested in a double-blind provocation study. These patients, who reported increased skin symptoms when exposed to electromagnetic fields, were compared with 12 age- and sex-matched controls. Both groups were exposed to 30-minute periods of high or low stress situations, with and without simultaneous exposure to electromagnetic fields from a visual display unit. The matched controls were tested twice and given the same exposure as the patients but had the fields turned on every time. Stress was induced by requiring the participants to act in accordance with a random sequence of flashing lights while simultaneously solving complicated mathematical problems. Blood samples were analyzed for levels of the stress-related hormones melatonin, prolactin, adrenocorticotrophic hormone, neuropeptide Y, and growth hormone, and the expression of different peptides, cellular markers, and cytokines (somatostatin, CD1, factor XIIIa, and tumor necrosis factor-alpha). Skin biopsies were also analyzed for the occurrence of mast cells. Stress provocation resulted in feelings of more intense mental stress and elevated heart rate. The patients reported increased skin symptoms when they knew or believed that the electromagnetic field was turned on. With the blind conditions there were no differences between "on" or "off." Inflammatory mediators and mast cells in the skin were not affected by the stress exposure or by exposure to electromagnetic fields. The main conclusion was that the patients did not react to the fields.

Antibodies↗

PubMed2000

Gene survey of the pathogenic protozoan Trypanosoma cruzi.

We have performed a survey of the active genes in the important human pathogen Trypanosoma cruzi by analyzing 5013 expressed sequence tags (ESTs) generated from a normalized epimastigote cDNA library. Clustering of all sequences resulted in 771 clusters, comprising 54% of the ESTs. In total, the ESTs corresponded to 3054 transcripts that might represent one-fourth of the total gene repertoire in T. cruzi. About 33% of the T. cruzi transcripts showed similarity to sequences in the public databases, and a large number of hitherto undiscovered genes predicted to be involved in transcription, cell cycle control, cell division, signal transduction, secretion, and metabolism were identified. More than 140 full-length gene sequences were derived from the ESTs. Comparisons with all open reading frames in yeast and in Caenorhabditis elegans showed that only 12% of the T. cruzi transcripts were shared among diverse eukaryotic organisms. Comparison with other kinetoplastid sequences identified 237 orthologous genes that are shared between these evolutionarily divergent organisms. The generated data are a useful resource for further studies of the biology of the parasite and for development of new means to combat Chagas' disease.

Animals↗