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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 127 records · Page 7Linked to original sources
PubMed2001

Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation.

Allogeneic peripheral blood stem cell grafts contain about 10 times more T and B cells than marrow grafts. Because these cells may survive in transplant recipients for a long time, recipients of blood stem cells may be less immunocompromised than recipients of marrow. Immune reconstitution was studied in 115 patients randomly assigned to receive either allogeneic marrow or filgrastim-mobilized blood stem cell transplantation. Between day 30 and 365 after transplantation, counts of most lymphocyte subsets were higher in the blood stem cell recipients. The difference was most striking for CD4 T cells (about 4-fold higher counts for CD45RA(high) CD4 T cells and about 2-fold higher counts for CD45RA(low/-)CD4 T cells; P <.05). On assessment using phytohemagglutinin and herpesvirus antigen-stimulated proliferation, T cells in the 2 groups of patients appeared equally functional. Median serum IgG levels were similar in the 2 groups. The rate of definite infections after engraftment was 1.7-fold higher in marrow recipients (P =.001). The rate of severe (inpatient treatment required) definite infections after engraftment was 2.4-fold higher in marrow recipients (P =.002). The difference in the rates of definite infections was greatest for fungal infections, intermediate for bacterial infections, and lowest for viral infections. Death associated with a fungal or bacterial infection occurred between day 30 and day 365 after transplantation in 9 marrow recipients and no blood stem cell recipients (P =.008). In conclusion, blood stem cell recipients have higher lymphocyte-subset counts and this appears to result in fewer infections. (Blood. 2001;97:3380-3389)

Adult↗
PubMed2001

On the origin of the Hirudinea and the demise of the Oligochaeta.

The phylogenetic relationships of the Clitellata were investigated with a data set of published and new complete 18S rRNA gene sequences of 51 species representing 41 families. Sequences were aligned on the basis of a secondary structure model and analysed with maximum parsimony and maximum likelihood. In contrast to the latter method, parsimony did not recover the monophyly of Clitellata. However, a close scrutiny of the data suggested a spurious attraction between some polychaetes and clitellates. As a rule, molecular trees are closely aligned with morphology-based phylogenies. Acanthobdellida and Euhirudinea were reconciled in their traditional Hirudinea clade and were included in the Oligochaeta with the Branchiobdellida via the Lumbriculidae as a possible link between the two assemblages. While the 18S gene yielded a meaningful historical signal for determining relationships within clitellates, the exact position of Hirudinea and Branchiobdellida within oligochaetes remained unresolved. The lack of phylogenetic signal is interpreted as evidence for a rapid radiation of these taxa. The placement of Clitellata within the Polychaeta remained unresolved. The biological reality of polytomies within annelids is suggested and supports the hypothesis of an extremely ancient radiation of polychaetes and emergence of clitellates.

Animals↗
PubMed2001

Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins.

Pax-6 and microphthalmia transcription factor (Mitf) are required for proper eye development. Pax-6, expressed in both the neuroretina and pigmented retina, has two DNA-binding domains: the paired domain and the homeodomain. Mice homozygous for Pax-6 mutations are anophthalmic. Mitf, a basic helix-loop-helix leucine zipper (b-HLH-LZ) transcription factor associated with the onset and maintenance of pigmentation, identifies the retinal pigmented epithelium during eye development. Loss of Mitf function results in the formation of an ectopic neuroretina at the expense of the dorsal retinal pigmented epithelium. In the present study, we investigated the interaction between Pax-6 and Mitf. In transient transfection-expression experiments, we found that transactivating effects of Pax-6 and Mitf on their respective target promoters were strongly inhibited by co-transfection of both transcription factors. This repression was due to direct protein/protein interactions involving both Pax-6 DNA-binding domains and the Mitf b-HLH-LZ domain. These results suggest that Pax-6/Mitf interactions may be critical for retinal pigmented epithelium development.

Animals↗
PubMed2001

Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome.

Congenital nephrotic syndrome, Finnish type (CNF or NPHS1), is an autosomal recessive disease characterized by massive proteinuria and development of nephrotic syndrome shortly after birth. The disease is most common in Finland, but many patients have been identified in other populations. The disease is caused by mutations in the gene for nephrin which is a key component of the glomerual ultrafilter, the podocyte slit diaphragm. A total of 30 mutations have been reported in the nephrin gene in patients with congenital nephrotic syndrome worldwide. In the Finnish population, two main mutations have been found. These two nonsense mutations account for over 94% of all mutations in Finland. Most mutations found in non-Finnish patients are missense mutations, but they include also nonsense and splice site mutations, as well as deletions and insertions. This mutation update summarizes the nature of all previously reported nephrin mutations and, additionally, describes 20 novel mutations recently identified in our laboratory.

Codon, Nonsense↗
PubMed2001

Localized two-dimensional shift correlated MR spectroscopy of human brain.

A two-dimensional (2D) chemical shift correlated MR spectroscopic (COSY) sequence integrated into a new volume localization technique (90 degrees -180 degrees -90 degrees ) is proposed for whole-body MR spectroscopy (MRS). Using the product operator formalism, a theoretical calculation of the volume localization as well as the coherence transfer efficiencies in 2D MRS is presented. Phantom model solutions were used to test and optimize the efficiency of the proposed sequence. A combination of different MRI transmit/receive RF coils was used: a head MRI coil and a 3" surface coil receive combined with a body coil transmit. The J cross-peaks due to N-acetyl aspartate (NAA), glutamate/glutamine (Glx), myo-inositol (mI), creatine (Cr), choline (Ch), aspartate (Asp), gamma-aminobutyrate (GABA), taurine (Tau), glutathione (GSH), threonine (Thr), and macromolecules (MM) were identified. The cross-peak intensities excited by the proposed 2D sequence were asymmetric with respect to the diagonal peaks. Localized COSY (L-COSY) spectra of cerebral prefrontal and occipital gray/white matter regions in 15 healthy controls are presented. Magn Reson Med 46:58-67, 2001.

Adult↗
PubMed2001

A fluorescent reverse transcription-polymerase chain reaction assay to quantify the lipoprotein lipase messenger RNA.

Relative quantitative reverse transcription-polymerase chain reaction (rqRT-PCR), which allows an accurate quantification of the amount of mRNA in samples potentially differing in the quality of their RNA preparation, was used to quantify lipoprotein lipase (LPL) mRNA in ovine adipose tissue. A comparative evaluation of four rqRT-PCR procedures was carried out. The amount of LPL mRNA was assayed relative to either that of gamma-actin (ACT) or cyclophilin (CYC) mRNA, used as endogenous standard. Independent (INACT and INCYC procedures) or simultaneous (COACT and COCYC procedures) amplifications have been compared. Fluorescently labelled primers yielded PCR products which were quantitatively analysed using an automated DNA sequencer. After optimizing the PCR cycle number and verifying that the amounts of ACT and CYC mRNA varied only weakly according to the nutritional conditions studied, we have tested the ability of the four procedures to quantify specific variations in LPL mRNA. The repeatability of each step and the overall assay reproducibility were also examined. The COACT and INCYC procedures were finally retained to accurately quantify LPL mRNA in AT from nine underfed or refed ewes, and gave highly correlated results (r=0.98, p<0.01). In addition, significant correlations (r=0.83, p<0.01 and r=0.92, p<0.01 for COACT and INCYC, respectively) were observed with the LPL activity in AT.

Actins↗
PubMed2001

Functional MRI in patients with band heterotopia.

Functional activation associated with a motor task (fist movements) was studied in three patients with band heterotopias by fMRI. In two patients, additional visual fMRI studies were performed using a flickering checkerboard stimulus. In all patients activation of the outer cortex and of the inner neuronal band could be found during performance of the motor task. Visual stimulation elicited a normal activation pattern without activation of the ectopic neuronal layer in one patient; in another patient activation extended toward the ventricular wall, i.e., along the route of embryonic neuronal migration. The potential participation of ectopic neuronal tissue in physiologic cerebral functions is of clinical impact in patients with neuronal heterotopias suffering from medically intractable seizures prior to epilepsy surgery.

Adult↗
PubMed2001

Families and intergenerational relationships in aging societies: comparing the United States with German-speaking countries.

Industrialized nations have experienced many demographic changes favoring older adults during the last few decades of the 20th century. This article is a comparative examination of current and future trends in intergenerational relationships and aging in two societies: the United States and German-speaking countries. While comparing similarities and significant differences between the cultures, we examine five issues related to these trends for families and intergenerational relationships in the 21st century: (1) consequences of population aging for family structures and relationships--the emergence of the beanpole family structure and the longer years of linked lives across generations; (2) the debate about the decline of the family; (3) intergenerational solidarity over the life course; (4) intergenerational conflict across the life course; (5) prospects for solidarity and conflict between generations in the 21st century. Similarities between cultures include the demographic realities of population aging, the shift from pyramids to beanpoles, more years of shared lives between and across generations, more non-traditional family forms, and intergenerational conflicts in families. Differences include diverse replacement fertility rates, alternative approaches to governmental supports for families and aging members, and possible differences in cultural values regarding individualism.

Adolescent↗
PubMed2001

Platelet-derived growth factor B-chain of hematopoietic origin is not necessary for granulation tissue formation and its absence enhances vascularization.

The hypothesis that wound repair is augmented by delivery of platelet-derived growth factor (PDGF) from platelets and macrophages is an attractive extrapolation from the known activities of PDGF in cell culture and in vivo. To test this hypothesis in mice, we prepared hematopoietic chimeras, in which the hematopoietic system of a normal adult mouse was replaced by the hematopoietic system of a PDGF B-chain -/- or +/+ donor. We initiated local granulation tissue formation either by implanting small surgical sponges to elicit a foreign body granulation tissue response, or by ligating the left common carotid to form an organized thrombus. We found that the absence of hematopoietic PDGF B-chain did not decrease the extent of granulation tissue or vascular lesion formation, and that the vascularization of both lesions increased by approximately 100%. We conclude that PDGF B-chain from cells of hematopoietic origin, including platelets and macrophages, is not important for granulation tissue formation, and that it reduces vascularization of granulation issue, probably through disabling of the short-range chemotactic gradients of PDGF that are important for recruiting pericytes/smooth muscle cells to the endothelium of new vessels.

Animals↗
PubMed2001

"Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients.

The results of a novel approach to the use of ketamine in refractory cancer pain are reported. In this prospective, multicenter, unblinded, open-label audit, 39 patients (with a total of 43 pains) received a short duration (3 to 5 days) ketamine infusion. The initial dose of 100 mg/24 hr was escalated if required to 300 mg/24 hr and then to a maximum dose of 500 mg/24hr. The overall response rate was 29/43 (67%). Analysis of results according to pain mechanisms showed that 15/17 somatic and 14/23 neuropathic pains responded. In 5 patients who appeared to respond, it is possible that another concurrent intervention may have contributed in whole or part for the pain relief observed. After cessation of ketamine, 24/29 maintained good pain control, with a maximum documented duration of eight weeks. However, 5 of the initial 29 responders experienced a recurrence of pain within 24 hours, and ketamine was recommenced. Of these, 2 underwent another intervention for pain control while 3 continued on ketamine until their deaths between two and four weeks later. Twelve patients reported adverse psychomimetic effects, with the incidence rising with increasing dose. Four of these were non-responders and the ketamine was stopped. Eight were responders, and in 3 the adverse effects were rendered acceptable with dose reduction; the other 5 rejected a dose reduction. The results reported suggest the need for further investigation of the place of ketamine in cancer pain management.

Adult↗
PubMed2001

[Nutritional status and risk in hospitalized children].

BACKGROUND: A few studies report malnutrition in hospitalized patients. MATERIAL AND METHODS: This one-day cross-sectional survey performed in January 1999 assessed nutritional status and protein-energy intake in a pediatric population hospitalized in medicine or surgery units. Every child older than six months, hospitalized for more than 48 h and free of nutritional support (parenteral, enteral, or special regimens for metabolic diseases) was included. RESULTS: Fifty-eight children among the 183 present the day of the study met the inclusion criteria and were included in the statistical analysis. They were hospitalized in medicine (48%), psychiatry (31%) and surgery (21%). The body mass index (BMI) was below -2 standard deviations (DS) in 21% of them. Excluding patients with anorexia nervosa, BMI was < -2 SD, > +2 SD, or in between these limits in respectively 12, 14 and 74%. Energy intake measured at the hospital was below 75% of the recommended dietary allowances in two-thirds of the children whether malnourished or not. Fifty percent of the malnourished children had been referred to a dietician the day of the study. CONCLUSIONS: Malnutrition is frequent in a population of hospitalized children. Energy intake and referral to a dietician are insufficient.

Body Mass Index↗
PubMed2001

Insights into the structure, solvation, and mechanism of ArsC arsenate reductase, a novel arsenic detoxification enzyme.

BACKGROUND: In Escherichia coli bearing the plasmid R773, resistance to arsenite, arsenate, antimonite, and tellurite is conferred by the arsRDABC plasmid operon that codes for an ATP-dependent anion pump. The product of the arsC gene, arsenate reductase (ArsC), is required to efficiently catalyze the reduction of arsenate to arsenite prior to extrusion. RESULTS: Here, we report the first X-ray crystal structures of ArsC at 1.65 A and of ArsC complexed with arsenate and arsenite at 1.26 A resolution. The overall fold is unique. The native structure shows sulfate and sulfite ions binding in the active site as analogs of arsenate and arsenite. The covalent adduct of arsenate with Cys-12 in the active site of ArsC, which was analyzed in a difference map, shows tetrahedral geometry with a sulfur-arsenic distance of 2.18 A. However, the corresponding adduct with arsenite binds as a hitherto unseen thiarsahydroxy adduct. Finally, the number of bound waters (385) in this highly ordered crystal structure approaches twice the number expected at this resolution for a structure of 138 ordered residues. CONCLUSIONS: Structural information from the adduct of ArsC with its substrate (arsenate) and with its product (arsenite) together with functional information from mutational and biochemical studies on ArsC suggest a plausible mechanism for the reaction. The exceptionally well-defined water structure indicates that this crystal system has precise long-range order within the crystal and that the upper limit for the number of bound waters in crystal structures is underestimated by the structures in the Protein Data Bank.

Arsenates↗
PubMed2001

Targeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway.

Here we have addressed the role that zetaPKC plays in NF-kappaB activation using mice in which this kinase was inactivated by homologous recombination. These mice, although grossly normal, showed phenotypic alterations in secondary lymphoid organs reminiscent of those of the TNF receptor-1 and of the lymphotoxin-beta receptor gene-deficient mice. The lack of zetaPKC in embryonic fibroblasts (EFs) severely impairs kappaB-dependent transcriptional activity as well as cytokine-induced phosphorylation of p65. Also, a cytokine-inducible interaction of zetaPKC with p65 was detected which requires the previous degradation of IkappaB. Although in zetaPKC-/- EFs this kinase is not necessary for IKK activation, in lung, which abundantly expresses zetaPKC, IKK activation is inhibited.

Acetylcysteine↗
PubMed2001

[Qualitative assessment of labile blood product prescription in Le Havre Hospital].

This retrospective study assessed the conformity of prescriptions of labile blood products as well as the respect of legal requirements and recommendations concerning red blood cells specifications. This study was carried out in two phases one year apart, so as to be able to compare between them. It consisted in an analysis of the administrative and medical information present on the prescription forms and of the discrepancies between the prescribed product and that which was dispensed. Quality of prescriptions was overall better, but some points needed further improvement. The data moreover showed that some prescriptions of phenotyped and cross-matched red blood cells were incomplete. This did not improve over time. Out of 1000 prescriptions for red blood cells, 216 were altered by the transfusion service dispensing unit. A closer look at these changes showed that 49% were justified by statutory requirements or by local protocols. The discrepancies observed between the prescribed product and that which was dispensed were partly due to a poor understanding by the prescribers of statutory requirements. However they are mostly related to particular circumstances, such as emergencies. Furthermore, the prescribers expected the transfusion center to adapt the product in terms of the clinical context.

Documentation↗
PubMed2001

Goats' milk of defective alpha(s1)-casein genotype decreases intestinal and systemic sensitization to beta-lactoglobulin in guinea pigs.

Contradictory results have been reported on the use of goats' milk in cows' milk allergy. In this study the hypothesis was tested, using a guinea pig model of cows' milk allergy, that these discrepancies could be due to the high genetic polymorphism of goats' milk proteins. Forty guinea pigs were fed over a 20 d period with pelleted diets containing one of the following: soyabean proteins (group S), cows' milk proteins (group CM), goats' milk proteins with high (group GM1) or low (group GM2) alpha(s1)-casein content. Parenteral sensitization to GM1 and GM2 proteins as also assessed. The sensitization was measured (1) by systemic IgG1 antibodies directed against bovine or caprine beta-lactoglobulin (beta-lg), alpha-lactalbumin (alpha-la) and whole caseins, and (2) by intestinal anaphylaxis measured in vitro in Ussing chambers, by the rise in short-circuit current (delta Isc) in response to milk proteins. Guinea pigs fed on CM and GM1 developed high titres (> 1500) of anti-beta-lg IgG1, with an important cross reactivity between goat and cow beta-lg. However, in guinea pigs fed on GM2, anti-goat beta-lg IgG1 antibodies were significantly decreased compared with GM1 guinea pigs (mean IgG1 titres were 546 and 2046 respectively), and the intestinal anaphylaxis was significantly decreased (3.5+/-4.5 microA/cm2) compared with that observed in GM1 guinea pigs (8.3+/-7.6 microA/cm2). Animals receiving GM1 or GM2 proteins via the parenteral route developed a marked sensitization. These results suggest that the discrepancies observed in the use of goats milk in cows' milk allergy could be due, at least in part, to the high genetic polymorphism of goats' milk proteins.

Anaphylaxis↗
PubMed2001

Diagnostic and therapeutic potential of the endothelin system in patients with chronic heart failure.

There is now considerable evidence to support a role for the endothelin (ET) system in the pathogenesis and progression of chronic heart failure (CHF). As such, the potential exists for this system to be useful in both diagnosis (by measurement of peptide levels in plasma and other body fluids) and treatment (by pharmacological blockade) of this condition. Plasma levels of endothelin-1 (ET-1) are elevated in CHF and the magnitude of elevation correlates with disease severity. ET-1 levels in plasma predict subsequent mortality in patients with CHF. ET-1 may also contribute to symptoms associated with CHF, such as exercise intolerance. In the diagnosis of CHF, plasma levels of ET-1 appear to be a less powerful discriminator between patients with mild disease and control subjects with normal ventricular function on multivariate analyses, compared to brain natriuretic peptide (BNP), or its N-terminal fragment. ET-1 concentrations are also elevated in the saliva of patients with CHF and may represent an alternative approach to assessment of the status of the ET system in these patients. Specific ET receptor antagonists (both mixed and ET(A)-selective) have been developed. Studies with these agents in animal models of CHF have demonstrated beneficial effects via both haemodynamic and non-haemodynamic pathways. A number of short-term clinical studies have been performed demonstrating improvements in haemodynamic parameters without neurohormonal activation. Long-term clinical studies with ET receptor antagonists are currently underway to definitively test the impact of blockade of this system on mortality and major cardiovascular endpoints. Endothelin converting enzyme (ECE) inhibitors represent an alternative strategy of ET blockade, and early data from animal models suggest these agents may be of clinical utility, either alone or, more likely, in combination with other zinc metallopeptidases.

Animals↗
PubMed2001

Mechanisms of epithelial fusion and repair.

One of the principal functions of any epithelium in the embryonic or adult organism is to act as a self-sealing barrier layer. From the earliest stages of development, embryonic epithelia are required to close naturally occurring holes and to fuse wherever two free edges are brought together, and at the simplest level that is precisely what the epidermis must do to repair itself wherever it is damaged. Parallels can be drawn between the artificially triggered epithelial movements of wound repair and the naturally occurring epithelial movements that shape the embryo during morphogenesis. Recent in vitro and in vivo wound-healing studies and analysis of paradigm morphogenetic movements in genetically tractable embryos, like those of Drosophila and Caenorhabditis elegans, have begun to identify both the signals that initiate these movements and the cytoskeletal machinery that drives motility. We are also gaining insight into the nature of the brakes and stop signals, and the mechanisms by which the confronting epithelial sheets knit together to form a seam.

Actins↗