A survey of the Leishmania major Friedlin strain V1 genome by shotgun sequencing: a resource for DNA microarrays and expression profiling.
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Animals↗
Biomedical subjects
J Martin
Publications and source records attributed to J Martin.
Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases.
Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with members of the transforming growth factor-beta family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of TbetaRII. Of the type I receptors, SNX6 was found to interact only with inactivated TbetaRI. SNXs 1-4 also interacted with the transforming growth factor-beta receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases.
Amino Acid Sequence↗
An orchestrated gene expression component of neuronal programmed cell death revealed by cDNA array analysis.
Programmed cell death (PCD) during neuronal development and disease has been shown to require de novo RNA synthesis. However, the time course and regulation of target genes is poorly understood. By using a brain-biased array of over 7,500 cDNAs, we profiled this gene expression component of PCD in cerebellar granule neurons challenged separately by potassium withdrawal, combined potassium and serum withdrawal, and kainic acid administration. We found that hundreds of genes were significantly regulated in discreet waves including known genes whose protein products are involved in PCD. A restricted set of genes was regulated by all models, providing evidence that signals inducing PCD can regulate large assemblages of genes (of which a restricted subset may be shared in multiple pathways).
Algorithms↗
Actigraphic estimates of circadian rhythms and sleep/wake in older schizophrenia patients.
Twenty-four hour circadian activity rhythms and light-exposure levels of 28 older schizophrenia patients (mean age=58years) were examined using an Actillume recorder. Sleep and wake were scored using the algorithm of the ACTION3 software which revealed that the patients slept for 67% of the night and napped for 9% of the day. Patients with more disturbed sleep and less robust circadian rhythms performed more poorly on neuropsychological tests. Patients with higher cognitive functioning and fewer extrapyramidal symptoms were more alert during the day. Few patients were exposed to high levels of illumination during the day, and older age was associated with lower levels of light exposure. Duration of antipsychotic use and higher antipsychotic doses were associated with decreased daytime alertness and less robust circadian activity rhythms. Patients taking antipsychotics were more sleepy both during the day and night than patients not taking antipsychotics. The circadian rhythm disturbances found in these patients did not seem to be due solely to low levels of illumination exposure. Life-style factors, behavioral factors, psychiatric symptoms and medications were likely contributors to the disturbed rhythms. The effects of the sleep disturbances did not seem to be benign. There were strong relationships between sleep and circadian rhythms and functioning.
Age Factors↗
Phylogeny of the genus Chironomus (Diptera) inferred from DNA sequences of mitochondrial cytochrome b and cytochrome oxidase I.
Two mitochondrial genes, Cytochrome b (Cytb) and Cytochrome c oxidase subunit I (COI), have been used as phylogenetic markers in Chironomids. The nucleotide sequences of 685 bp from Cytb and 596 bp from COI have been determined for 36 Chironomus species from the Palearctic, or Holarctic, and Australasia. The concatenated sequence of 1281 bp from both genes was used to investigate the phylogenetic relationships among these species. The nucleotide sequence alignments were used for construction of phylogenetic trees based on maximum-parsimony and neighbor-joining methods. Both techniques produced similar phylogenies. Monophyly of the genus Chironomus is supported by a bootstrap value of 100% at the basal branch. Six clusters of species have been revealed with high bootstrap values supporting both monophyly of each cluster and the validity of the branching order within each cluster. Four species, C. circumdatus, C. nepeanensis, C. dorsalis, and C. crassiforceps, cannot be placed into any cluster. Cytological phylogenies were constructed using the same set of species, except for C. biwaprimus. These trees showed many similarities to that obtained from the mitochondrial (mt) sequence analysis, but also a number of significant differences. When compared with the tree constructed from the sequence of 23 species available for one of the globin genes, globin 2b (gb2b), there was better support for the mt tree than for the cytological trees. An intron, which varies in its occurrence and position in gb2b, was also investigated and the distribution of the introns supports the phylogenetic history of the genus Chironomus obtained with mt data. The differences observed in the cytological trees seem to be attributable more to the retention of the same chromosome banding sequence across several species, rather than convergent evolutionary events. An important question is the determination of the position of the subgenus Camptochironomus in relation to the representatives of the nominal subgenus Chironomus, since it has been suggested that this is a separate genus. The Camptochironomus species are internal to the trees and have arisen more recently than some of the species of the subgenus Chironomus, indicating that they are not sufficiently differentiated to be considered more than a subgenus.
Animals↗
Surgery for non-small cell lung cancer.
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Carcinoma, Non-Small-Cell Lung↗
Distribution of HERV-LTR elements in the 5'-flanking region of HLA-DQB1 and association with autoimmunity.
We established the detailed polymorphism of the 5'-flanking region and the first exon of the human leukocyte antigen (HLA)-DQB1 alleles. One hundred and forty-five Spanish rheumatoid arthritis (RA) patients and 200 healthy voluntary blood donors from southern Spain along with 42 B-cell lines were analyzed for the presence of the retrovirus-derived long terminal repeats (LTRs) LTR3, LTR5, and LTR13. LTR3 positivity was always associated with certain DQB1 alleles, i.e., *0302, *0402, *0601, *0202, and *0305. Sequencing analysis of the 5'-flanking region of DQB1*0301, *0303 and *0502 alleles in homozygous B-cell lines showed the absence of LTR3 and a massive deletion of 5635 base pairs. The undetected deletion in the flanking region of some DQB1 alleles and a lack of stratification for HLA typing explain previously reported associations of the LTR3 element with RA and type I diabetes (IDDM). LTR5 showed identical distribution to LTR3, consistent with a previously suggested LTR3-LTR5 tandem arrangement. LTR13 positivity was associated with DQB1*0302, *0303, and *0402 alleles. Distributions of the LTR elements in all B-cell lines, RA patients, and controls could be explained entirely by linkage disequilibrium with DQB1 alleles, independently of the haplotypes carrying them. LTR elements are known to regulate gene expression. Therefore, a possible involvement of LTR13 in the association of DQB1*0302, *0303, and *0402 with IDDM requires further investigation. The sequencing results of the DQB1 first exon demonstrated that DQB1*0601 was generated by a recombination event between a DR53 and a non-DR53 haplotype. Our results shed new light on the phylogeny of the HLA region and the possible contribution of DQB1 to susceptibility to autoimmunity.
Alleles↗
Influence of mild hypothermia on myocardial contractility and circulatory function.
Myocardial contractility depends on temperature. We investigated the influence of mild hypothermia (37-31 degrees C) on isometric twitch force, sarcoplasmic reticulum (SR) Ca2+-content and intracellular Ca2+-transients in ventricular muscle strips from human and porcine myocardium, and on in vivo hemodynamic parameters in pigs. In vitro experiments: muscle strips from 5 nonfailing human and 8 pig hearts. Electrical stimulation (1 Hz), simultaneous recording of isometric force and rapid cooling contractures (RCCs) as an indicator of SR Ca2+-content, or intracellular Ca2+-transients (aequorin method). In vivo experiments: 8 pigs were monitored with Millar-Tip (left ventricle) and Swan-Ganz catheter (pulmonary artery). Hemodynamic parameters were assessed at baseline conditions (37 degrees C), and after stepwise cooling on cardiopulmonary bypass to 35, 33 and 31 degrees C. Hypothermia increased isometric twitch force significantly by 91 +/- 16 % in human and by 50 +/- 9 % in pig myocardium (31 vs. 37 degrees C; p < 0.05, respectively). RCCs or aequorin light emission did not change significantly. In anesthetized pigs, mild hypothermia resulted in an increase in hemodynamic parameters of myocardial contractility. While heart rate decreased from 111 +/- 3 to 73 +/- 1 min(-1), cardiac output increased from 2.4 +/- 0.1 to 3.1 +/- 0.31/min, and stroke volume increased from 21 +/- 1 to 41 +/- 3 ml. +dP/dtmax increased by 25 +/- 8% (37 vs. 31 degrees C; p < 0.05 for all values). Systemic and pulmonary vascular resistance did not change significantly during cooling. Mild hypothermia exerts significant positive inotropic effects in human and porcine myocardium without increasing intracellular Ca2+-transients or SR Ca2+-content. These effects translate into improved hemodynamic parameters of left ventricular function.
Aequorin↗
Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy.
BACKGROUND: The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further. METHODS: All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events. RESULTS: Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate. CONCLUSIONS: Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.
Adult↗
Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo.
OBJECTIVE: To investigate whether the deleterious effect of E(2) on embryonic implantation is due to a direct effect on the endometrium, on the embryo, or both. DESIGN: Prospective, controlled in vitro study. SETTING: Tertiary infertility center. PATIENT(S): Fertile patients in the luteal phase with histologically normal endometrium who were attending the infertility clinic as oocyte donors (n = 14). INTERVENTION(S): E(2) dose-response (0, 10(-8), 10(-7), 10(-6), 10(-5), and 10(-4) M) and time course (day 2 vs. day 5) experiments were performed in an in vitro embryo adhesion assay composed of human polarized endometrial epithelial cells obtained from fertile patients and mouse embryos. MAIN OUTCOME MEASURE(S): Blastocyst formation rate and embryo adhesion rate. RESULTS: Monolayers of polarized endometrial epithelial cells expressed ERalpha at the mRNA level. The E(2) dose response of blastocysts with polarized endometrial epithelial cells (n = 235) demonstrated a progressive reduction in embryonic adhesion that was statistically significant at 10(-6) M. When polarized endometrial epithelial cells were treated alone with increasing doses of E(2) for 3 days and E(2) was then removed and blastocysts added (n = 410), embryonic adhesion was not significantly reduced, except at 10(-4) M. When 2-day mouse embryos (n = 609) were treated with increasing E(2) concentrations until day 5, the rate of blastocyst formation significantly decreased at a concentration >or= 10(-6) M, and embryonic adhesion decreased when blastocysts (n = 400) were obtained at a concentration >or= 10(-7) M. Time course experiments of embryos cultured for 2 days with polarized endometrial epithelial cells (n = 426) showed that the adhesion rate was higher at E(2) levels of 10(-7), 10(-6) and 10(-5) M compared with embryos cultured for 5 days (n = 495). CONCLUSION(S): High E(2) levels are deleterious to embryo adhesion in vitro, mainly because they have a direct toxic effect on the embryo that may occur at the cleavage stage.
Animals↗
Radical vaginal hysterectomy: classic and modified.
RVH offers significant advantages to the corresponding abdominal procedure, including: the possibility for regional anesthesia, particularly in patients with poor medical conditions; reduced surgical trauma because of the absence of an abdominal incision; applicability in obese patients; shorter surgical time when performed by an experienced surgeon; decreased need for blood transfusions; lower risk for complications; faster postoperative recovery period; shorter hospitalization. The primary drawback to the use of RVH for early stage cervical cancer has always been the lack of lymph node dissection. This has now been modified by the widespread use of laparoscopic lymphadenectomy. The increasing reliability of noninvasive radiologic techniques has provided and will continue to provide greater possibilities for preoperative staging to best determine the needs of the patient. The authors believe that an oncologic surgeon familiar with advanced laparoscopic techniques and RVH is able to take advantage of the benefits of both routes. Furthermore, a surgeon skilled in these techniques and RAH has the tools to ideally care for the specific needs, of each patient. The authors encourage individualization of surgical management, with special emphasis on the revision of the role of RVH in gynecologic oncology.
Female↗
The telomeric part of the HLA region predisposes to rheumatoid arthritis independently of the class II loci.
We have evaluated the possible contribution of genes besides DQ and DR to the association of HLA with rheumatoid arthritis (RA). To this end, we have looked at the allele distributions of six microsatellites, D6S1014, D6S2673, TNFalpha, MIB, C1-2-5, and C1-3-2 among 132 RA patients and 254 controls. We have defined 19 microsatellite clusters corresponding to previously described ancestral haplotypes. One of them was D6S1014*143-D6S273*139-TNFalpha*99-MIB*350-C1-2-5*196-C1-3-2*354, often found associated with DQB1*0201-DRB1*0301. As part of this microsatellite cluster, the allele MIB*350 was found to be a RA-predisposing factor, independent of DRB1*0301 and RA-predisposing haplotypes DQB1*03-DRB1*04 and DQB1*0501-DRB1*01. We conclude that the telomeric part of the HLA region contains a locus conferring predisposition to RA independently of HLA class II.
Arthritis, Rheumatoid↗
[Hodgkin's disease and acute nephrotic syndrome association].
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Acute Disease↗
Team performance in the emergency room: assessment of inter-disciplinary attitudes.
In-hospital emergency medicine in central Europe relies on inter-disciplinary co-operation. To improve team performance in the emergency room (ER), a questionnaire for assessment of attitudes and judgements in resuscitation procedures was developed. A total of 43 items were evaluated according to a five-point Likert scale. With a response rate of 81%, 143 questionnaires were evaluated. Assessment of data was performed with regard to professional speciality and level in the medical hierarchy. Factorial analysis identified four main factors: Assessment of 'quality of performance' (F1), 'importance of structure' (F2), 'quality of team culture' (F3), and 'importance of hierarchy' (F4). Influences from the categories 'speciality' and 'hierarchy' and from the covariate 'gender' on these main factors were evaluated by two-factorial analysis of variance. For all four factors, 'speciality' produced significant differences. Surgeons accorded high values to F1 and low values to F2, whereas anaesthesiologists accorded low values to F1 and high values to F2. F3 showed a low ranking from within the ER nursing staff and the residents in internal medicine, whereas F4 received high scores by medical residents and staff members. For F1 and F3, there was a tendency towards hierarchy dependency, whereas no factor was influenced by gender. In conclusion, team performance in the ER is mainly influenced by different perceptions and attitudes of the different disciplines involved in the resuscitation process.
Analysis of Variance↗
Microperfusion enhancement after TMLR in chronically ischemic porcine hearts.
OBJECTIVE: The purpose of this study was to determine the effect of transmyocardial laser revascularization (TMLR) on myocardial perfusion and function in chronically ischemic myocardium. METHODS: In the first operation a stenosis of the left anterior descending artery was created in 20 open-chest anesthetized pigs to implement this ischemic model. In contrast, four pigs served as controls (thoracotomy only). Seven days later (2nd operation), all animals were studied at baseline by analyzing different parameters of perfusion (radioactive microspheres), function, and intramyocardial pressure. Afterwards, pigs who received a left anterior descending artery stenosis were randomized into one of three groups: animals in laser group 1 (n=7) received one and in laser group 2 (n=7) two laser channels per cm(2) in the left anterior descending artery territory. Animals of the ischemic group (n=6) underwent the same procedures without transmyocardial laser revascularization. Three months later, the animals were re-studied (3rd operation) and additional analysis of histochemistry and myocardial water content was performed. RESULTS: Regional myocardial blood flow (RMBF) in laser group 2 revealed statistically higher RMBF values compared to the ischemic group (0.39+/-0.13 versus 0.14+/-0.12 ml/min/g; P=0.043), after 3 months, whereas the absolute RMBF had not increased compared to the 1-week baseline values. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared to the initial values in all study groups (P=ns). Nevertheless, laser group 1 demonstrated relatively higher LVSWI(max) values compared to the ischemic (1.33+/-0.19 versus 0.93+/-0.16 mJ/kg; P=0.03) and laser group 2 (1.33+/-0.19 versus 1.02+/-0.15; P=0.024). Regional contractility of laser groups 1 and 2 recovered after 3 months (which had deteriorated shortly after transmyocardial laser revascularization) and increased under stress (100% versus 144.33+/-46.42, P=0.029 and 100% versus 116.26+/-21.06, P=0.034; respectively). In contrast, the corresponding ischemic group values were not different from initial values (P=ns). CONCLUSIONS: This model of chronic regional ischemia demonstrates that CO(2)-laser revascularization significantly improves microperfusion and regional function, whereas the overall perfusion and global LV function is unchanged.
Angioplasty, Laser↗
Investigations on the new free radical scavenger polynitroxyl-albumin to prevent ischemia and reperfusion injury after orthotopic heart transplantation in the pig model.
OBJECTIVE: Nitroxides have strong antioxidant capacity but their effectiveness is limited by their rapid intracellular inactivation. Polynitroxyl-Albumin (PNA) is capable of regenerating inactivated nitroxide. We tested the effect of PNA against reperfusion injury in heart transplantation. METHODS: Pig hearts were transplanted orthotopically. In the control group (n=9) reperfusion was performed without reperfusion modifications. In the experimental group (n=10) 1 ml/kg PNA was given before cross-clamp release. RESULTS: Hemodynamic performance was impaired after transplantation in both groups without significant intergroup differences. Plasma malonedialdehyde levels were significantly diminished in the PNA group as compared to the controls. CK-MB levels in both groups were increased within the first 2 h of reperfusion without significant intergroup differences. In contrast, there were found significant higher values of myocardial specific lactate dehydrogenase (LD1) in the controls versus PNA group. CONCLUSIONS: PNA was able to reduce lipid peroxidation and attenuate free radical activity. Contractile dysfunction could no be improved, indicating that (a) the radical scavenging effect was to weak or (b) other mechanisms than free oxygen radicals are responsible for myocardial damage in this experimental model.
Albumins↗
Aortic side branch embolization before endovascular aneurysm repair: incidence of type II endoleak.
PURPOSE: To assess the feasibility of embolization of aortic side branches and its impact on the incidence of type II endoleak after endovascular aneurysm repair. MATERIALS AND METHODS: Endovascular aneurysm repair was performed in 74 patients. Aortic side branch vessels were evaluated on the preoperative angiogram and computed tomography (CT) and, where embolization of lumbar and inferior mesenteric vessels was considered technically possible, this was attempted prior to endovascular repair. Follow-up CT was used to assess the presence of type II endoleak. RESULTS: Seventy-two patients were followed up for longer than 1 month. Embolization was attempted in 25 cases, successfully in 10, with partial success in 11, and failure in four. Twenty patients with successful or partly successful preoperative embolization were discharged and followed-up. Four (20%) had demonstrable type II endoleak during follow-up, with two of these persisting at latest follow-up. Of 43 patients without previous embolization, there were 10 (23.3%) type II endoleaks during the follow-up period, four of these persisting. In cases with type II endoleak, mean sac diameter change was -0.5 mm in the cases with previous embolization and +3.1 mm without. The mean period to onset of type II endoleak was 6.9 months without, and 15.3 months with, previous embolization. CONCLUSION: Although the cohort size is below a level that would confer significance, the trend of these findings is such as to suggest a lack of influence of aortic side branch embolization on the incidence of type II endoleak during the follow-up period.
Angiography↗
(+)-epi-Alpha-bisabolol [correction of bisbolol] is the wound-healing principle of Peperomia galioides: investigation of the in vivo wound-healing activity of related terpenoids.
Bioassay-guided investigation of the ethanol extract of Peperomia galioides using a tensile strength method in mice as a monitor led to the isolation of epi-alpha-bisabolol (1) (ED(50) 155 microg/mL). An in vivo healing study of selected commercially available monoterpenoids yielded two bioactive compounds, alpha-bisabolol (2) and alpha-terpineol (3) (ED(50) of 228 and 240 microg/g mouse[corrected], respectively).
3T3 Cells↗